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Does competitive swimming during puberty affect lung development in pubertal females? Bovard, Joshua Maschio 2017

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    DOES COMPETITIVE SWIMMING DURING PUBERTY AFFECT LUNG DEVELOPMENT IN PUBERTAL FEMALES?  by  Joshua Maschio Bovard B.Sc., McGill University, 2012   A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF  MASTER OF SCIENCE  in  THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Kinesiology)    THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver)   August 2017  © Joshua Maschio Bovard, 2017  ii  ABSTRACT Whether the large lungs of competitive swimmers result from intensive swim training or genetic endowment has been widely debated. Given that peak growth velocities for the lungs occur during puberty, this longitudinal study aimed to determine if competitive swimming during puberty affected lung development. Female swimmers (n=11) and healthy controls (n=10) aged 11-14 years old were assessed before and after one competitive swimming season. Pulmonary function testing included lung volumes, spirometry, diffusion capacity (DL,CO), and maximal inspiratory (PIMAX) and expiratory (PEMAX) pressures. Ventilatory constraints, including end-expiratory lung volume (EELV), expiratory flow limitation (EFL), and utilization of ventilatory capacity (V̇E/V̇ECAP), were assessed during an incremental cycling test. Despite being of similar age (p=0.10), maturational development (p=0.27), and height (p=0.38) as controls, swimmers had a larger total lung capacity (p<0.01), forced vital capacity (p<0.01), and peak expiratory flow (p=0.03). Although DL,CO was greater in swimmers (p=0.01), there was no difference when expressed relative to alveolar volume (p=0.20). Both PIMAX (p=0.06) and PEMAX (p<0.001) were greater in swimmers. Swimmers and controls achieved a similar relative maximal oxygen consumption (p=0.32) and experienced similar ventilatory constraints as characterized by EELV (p=0.18), severity (p=0.95) and prevalence (p=0.71) of EFL, and V̇E/V̇ECAP (p=0.95). Changes over time were similar between groups (p>0.05). Pubertal female swimmers already had larger lung capacities, higher flows, and greater indices of respiratory muscle strength, but similar ventilatory constraints while cycling. One competitive swimming season did not further accentuate this enhanced function or alter exercise ventilatory mechanics, suggesting that competitive swimming during puberty did not affect lung development.   iii  LAY SUMMARY Whether the large lungs of competitive swimmers result from intensive swim training or genetic endowment has been widely debated. Because lung growth is greatest during puberty, this thesis compared lung function before and after one swimming season in 11-14-year-old, similarly-sized female swimmers and healthy controls. At the initial measurement, the swimmers already had larger lung capacities, higher flows, and greater indices of respiratory muscle strength that occurred irrespective of training experience. One swimming season did not further accentuate this enhanced lung function, and no associations between changes in lung function and swim training volume were found. Moreover, detailed analyses of physiological development of the lungs and the respiratory challenges imposed by swimming provided no unequivocal evidence that swimming can alter lung development. Despite having greater lung function, swimmers had similar ventilatory responses as controls while cycling. Thus, this thesis concluded that competitive swimming during puberty did not affect lung development.   iv  PREFACE This thesis contains original data collected and analyzed for partial fulfilment of Joshua Bovard’s Master of Science degree. All protocols were approved by the University of British Columbia’s Children’s and Women’s Clinical Research Ethics Board (approval certificate number: H15-00977). The research question and experimental protocol were developed by Joshua Bovard and Drs William Sheel, Kristin Houghton, Donald McKenzie, and James Potts. Data was collected and analyzed by Joshua Bovard.   v  TABLE OF CONTENTS ABSTRACT ................................................................................................................................... ii LAY SUMMARY ......................................................................................................................... iii PREFACE ..................................................................................................................................... iv TABLE OF CONTENTS ............................................................................................................. v LIST OF TABLES ....................................................................................................................... xi LIST OF FIGURES .................................................................................................................... xv LIST OF ABBREVIATIONS ................................................................................................... xix ACKNOWLEDGEMENTS .................................................................................................... xxiii INTRODUCTION ........................................................................................................................ 1 1.1 Competitive swimming and lung development ................................................................. 1 1.1.1 Swedish “girl swimmers” – the foundational studies on swimming and lung development ........................................................................................................................... 8 1.1.2 Lung volumes in young swimmers ............................................................................ 10 1.1.3 Longitudinal assessments of competitive swimming and lung volume development ............................................................................................................................................... 11 1.1.4 Competitive swimming and diffusion capacity during growth .............................. 12 1.1.5 Differences between and weaknesses of previous studies ....................................... 13 1.1.6 Summary ..................................................................................................................... 17 1.2 Ventilatory mechanics during growth ............................................................................. 18 1.2.1 The effect of training on ventilatory constraints during growth ............................ 21 1.2.2 The effect of ventilatory constraints on EIAH during growth ............................... 22 vi  1.3 Significance ........................................................................................................................ 23 1.4 Conclusion .......................................................................................................................... 23 1.5 Purposes ............................................................................................................................. 25 1.6 Hypotheses ......................................................................................................................... 25 METHODS .................................................................................................................................. 26 2.1 Subjects .............................................................................................................................. 26 2.2 Experimental overview ..................................................................................................... 26 2.3 Measurements and procedures ........................................................................................ 28 2.3.1 Spirometry ................................................................................................................... 28 2.3.2 Single-breath carbon monoxide diffusion and helium dilution technique ............ 28 2.3.3 Maximal static pressures............................................................................................ 28 2.3.4 Resting baseline........................................................................................................... 29 2.3.5 Forced vital capacity and graded forced vital capacity maneuvers ....................... 29 2.3.6 Graded maximal exercise test .................................................................................... 30 2.3.7 Data collection and processing .................................................................................. 30 2.4 Data analysis ...................................................................................................................... 31 2.4.1 Predictive values ......................................................................................................... 31 2.4.2 Dysanapsis ratio .......................................................................................................... 31 2.4.3 Maximum expiratory flow-volume curve ................................................................. 32 2.4.4 Metabolic data............................................................................................................. 33 2.4.5 Operational lung volumes .......................................................................................... 33 2.4.6 Tidal flow-volume loops ............................................................................................. 34 2.4.7 Expiratory flow limitation ......................................................................................... 34 2.4.8 Ventilatory capacity ................................................................................................... 35 vii  2.4.9 Composite maximum expiratory flow-volume curves and tidal flow-volume loops ............................................................................................................................................... 35 2.4.10 Statistical analysis ..................................................................................................... 36 RESULTS .................................................................................................................................... 38 3.1 Descriptive data ................................................................................................................. 38 3.2 Spirometry ......................................................................................................................... 41 3.3 Lung volumes ..................................................................................................................... 43 3.4 Diffusion capacity .............................................................................................................. 53 3.5 Maximal static pressures .................................................................................................. 54 3.6 Dysanapsis ratio ................................................................................................................ 55 3.7 Maximum expiratory flow-volume curve ....................................................................... 56 3.8 Maximal exercise test ........................................................................................................ 59 3.8.1 Metabolic and ventilatory responses......................................................................... 59 3.8.2 Ventilatory mechanics ................................................................................................ 65 3.8.3 Individual and composite maximum expiratory flow-volume curves and tidal flow-volume loops ......................................................................................................................... 72 DISCUSSION .............................................................................................................................. 76 4.1 Major findings ................................................................................................................... 76 4.1.1 Changes in pulmonary function due to competitive swim training during puberty ............................................................................................................................................... 76 4.1.1.1 Comparisons of training volume, swimming history, and pulmonary function to previous studies ............................................................................................................ 77 4.1.1.2 Differences in initial pulmonary function .......................................................... 80 4.1.1.3 Changes in pulmonary function after one season of competitive swimming . 84 4.1.1.4 Summary of changes in pulmonary function .................................................... 88 4.1.2 Mechanisms underlying differences in pulmonary function .................................. 88 viii  4.1.2.1 Development of the respiratory system .............................................................. 89 Development of the alveoli and the elastic properties of the lung. .............. 89 Development of the airways and the flow-resistive properties of the lung. 90 Dysanapsis. ........................................................................................................ 90 Development of the chest wall. ........................................................................ 92 4.1.2.2 Total lung capacity and chest wall size. ............................................................. 93 4.1.2.3 Total lung capacity, hypoxia, and induced postnatal lung growth ................. 94 Hypoxia. ............................................................................................................ 94 Immersion and the supine and prone positions. ............................................ 95 Breathing pattern and the ventilatory response to swimming. .................... 97 Controlled frequency breathing drills and sprint swimming....................... 99 Age of onset of training. ................................................................................. 102 Other stimulants inducing postnatal lung growth. ..................................... 104 Summary. ........................................................................................................ 105 4.1.2.4 Total lung capacity and respiratory musculature. .......................................... 105 4.1.2.5 Summary on total lung capacity ....................................................................... 107 4.1.2.6 Functional residual capacity. ............................................................................ 108 4.1.2.7 Residual volume. ................................................................................................ 111 4.1.2.8 Vital capacity ...................................................................................................... 113 4.1.2.9 Spirometry .......................................................................................................... 113 4.1.2.10 Dysanapsis ratio ............................................................................................... 117 4.1.2.11 Maximal static pressures and respiratory muscle force ............................... 118 Maximal static mouth pressures. .................................................................. 118 Respiratory muscle force. .............................................................................. 120 4.1.2.12 Diffusion capacity of the lungs ........................................................................ 121 ix  4.1.2.13 Summary ........................................................................................................... 122 4.1.3 Metabolic and ventilatory responses during cycling exercise .............................. 125 4.1.3.1 Metabolic and ventilatory responses during cycling ...................................... 125 4.1.3.2 Ventilatory mechanics during cycling exercise ............................................... 129 4.1.3.3 Individual responses .......................................................................................... 132 4.1.3.4 Summary of ventilatory and metabolic responses to cycling exercise .......... 132 4.2 Methodological considerations ....................................................................................... 133 4.2.1 Tanner level of maturation ...................................................................................... 133 4.2.2 Technique .................................................................................................................. 134 4.2.3 Predictive equations ................................................................................................. 136 4.2.4 Interpretation of changes in lung function ............................................................. 138 4.2.5 Exposure to chlorine and FEV1/FVC...................................................................... 139 4.3 Methodological improvements ....................................................................................... 140 4.3.1 Sample size and study duration ............................................................................... 140 4.3.2 Sex-based differences ............................................................................................... 142 4.3.3 Control group ............................................................................................................ 143 4.3.4 Additional measures of pulmonary structure and function ................................. 144 x  4.4 Unresolved questions and future directions ................................................................. 144 CONCLUSION ......................................................................................................................... 148 REFERENCES .......................................................................................................................... 149 APPENDICES ........................................................................................................................... 163 Appendix A: Individual subject data – group tables ......................................................... 163 Appendix B: Individual subject data – individual tables and figures .............................. 180 Appendix C: Questionnaires, forms, and documents ........................................................ 223 Appendix D: Predictive equations ....................................................................................... 231    xi  LIST OF TABLES Table 1 – Cross-sectional studies of competitive swim training on lung development. ................. 4 Table 1 – Cross-sectional studies of competitive swim training on lung development, continued 5 Table 2 – Longitudinal studies of competitive swim training on lung development. ..................... 6 Table 2 – Longitudinal studies of competitive swim training on lung development, continued .... 7 Table 3 – Weaknesses of selected previous studies on competitive swimming during development ...................................................................................................................... 14 Table 4 – Anthropometric data ..................................................................................................... 39 Table 5 – Activity levels and swim training history ..................................................................... 40 Table 6 – Spirometry .................................................................................................................... 42 Table 7 – Lung volumes ............................................................................................................... 46 Table 8 – Correlations between swimming history and pulmonary function ............................... 51 Table 9 – Correlations between weekly training volume and changes in pulmonary function .... 52 Table 10 – Diffusion capacity ....................................................................................................... 53 Table 11 – Maximal static pressures ............................................................................................. 54 Table 12 – Maximal expiratory flow-volume curve characteristics ............................................. 58 Table 13 – Interactions and main effects p-values for metabolic variables during the exercise test........................................................................................................................................... 61 Table 14 – Maximal exercise data ................................................................................................ 62 Table 15 – Interactions and main effects p-values for operational lung volumes during the exercise test ....................................................................................................................... 67 Table 16 – Operational lung volumes during maximal exercise .................................................. 68 Table 17 – Lung function of adolescent swimmers ...................................................................... 82 Table 18 – Percent-predicted lung function in competitive swimmers throughout development listed according to average age. ........................................................................................ 83 Table 19 – Summary of changes in pulmonary function ............................................................ 123 Table 20 – Metabolic responses at maximal cycling exercise in adolescent female swimmers. 128 xii  Table 21 – Individual anthropometric data for SWIM ............................................................... 163 Table 22 – Individual anthropometric data for CON .................................................................. 164 Table 23 – Individual physical activity questionnaire data (each question is scored out of 5) .. 165 Table 24 – Individual moderate and vigorous intensity physical activity data........................... 166 Table 25 – Individual training data for SWIM ........................................................................... 167 Table 26 – Individual spirometry data for SWIM ...................................................................... 168 Table 27 – Individual spirometry data for CON ......................................................................... 169 Table 28 – Individual lung volume data for SWIM .................................................................... 170 Table 29 – Individual lung volume data for CON ...................................................................... 171 Table 30 – Individual diffusion capacity data for SWIM ........................................................... 172 Table 31 – Individual diffusion capacity for CON ..................................................................... 173 Table 32 – Individual maximal static pressure data for SWIM .................................................. 174 Table 33 – Individual maximal static pressure data for CON .................................................... 175 Table 34 – Individual maximal exercise data for SWIM ............................................................ 176 Table 35 – Individual maximal exercise data for CON .............................................................. 177 Table 36 – Individual maximal exercise operational lung volume data for SWIM.................... 178 Table 37 – Individual maximal exercise operational lung volume data for CON ...................... 179 Table 38 – S01 selected anthropometric, pulmonary function, and maximal exercise data. ...... 181 Table 39 – S01 EFL severity and V̇E/V̇ECAP. .............................................................................. 182 Table 40 – S02 selected anthropometric, pulmonary function, and maximal exercise data. ...... 183 Table 41 – S02 EFL severity and V̇E/V̇ECAP. .............................................................................. 184 Table 42 – S04 selected anthropometric, pulmonary function, and maximal exercise data. ...... 185 Table 43 – S04 EFL severity and V̇E/V̇ECAP. .............................................................................. 186 Table 44 – S05 selected anthropometric, pulmonary function, and maximal exercise data. ...... 187 Table 45 – S05 EFL severity and V̇E/V̇ECAP. .............................................................................. 188 xiii  Table 46 – S06 selected anthropometric, pulmonary function, and maximal exercise data. ...... 189 Table 47 – S06 EFL severity and V̇E/V̇ECAP. .............................................................................. 190 Table 48 – S07 selected anthropometric, pulmonary function, and maximal exercise data. ...... 191 Table 49 – S07 EFL severity and V̇E/V̇ECAP. .............................................................................. 192 Table 50 – S08 selected anthropometric, pulmonary function, and maximal exercise data. ...... 193 Table 51 – S08 EFL severity and V̇E/V̇ECAP. .............................................................................. 194 Table 52 – S09 selected anthropometric, pulmonary function, and maximal exercise data. ...... 195 Table 53 – S09 EFL severity and V̇E/V̇ECAP. .............................................................................. 196 Table 54 – S10 selected anthropometric, pulmonary function, and maximal exercise data. ...... 197 Table 55 – S10 EFL severity and V̇E/V̇ECAP. .............................................................................. 198 Table 56 – S11 selected anthropometric, pulmonary function, and maximal exercise data. ...... 199 Table 57 – S11 EFL severity and V̇E/V̇ECAP. .............................................................................. 200 Table 58 – S12 selected anthropometric, pulmonary function, and maximal exercise data. ...... 201 Table 59 – S12 EFL severity and V̇E/V̇ECAP. .............................................................................. 202 Table 60 – C01 selected anthropometric, pulmonary function, and maximal exercise data. ..... 203 Table 61 – C01 EFL severity and V̇E/V̇ECAP. .............................................................................. 204 Table 62 – C02 selected anthropometric, pulmonary function, and maximal exercise data. ..... 205 Table 63 – C02 EFL severity and V̇E/V̇ECAP. .............................................................................. 206 Table 64 – C03 selected anthropometric, pulmonary function, and maximal exercise data. ..... 207 Table 65 – C03 EFL severity and V̇E/V̇ECAP. .............................................................................. 208 Table 66 – C04 selected anthropometric, pulmonary function, and maximal exercise data. ..... 209 Table 67 – C04 EFL severity and V̇E/V̇ECAP. .............................................................................. 210 Table 68 – C05 selected anthropometric, pulmonary function, and maximal exercise data. ..... 211 Table 69 – C05 EFL severity and V̇E/V̇ECAP. .............................................................................. 212 Table 70 – C08 selected anthropometric, pulmonary function, and maximal exercise data. ..... 213 xiv  Table 71 – C08 EFL severity and V̇E/V̇ECAP. .............................................................................. 214 Table 72 – C09 selected anthropometric, pulmonary function, and maximal exercise data. ..... 215 Table 73 – C09 EFL severity and V̇E/V̇ECAP. .............................................................................. 216 Table 74 – C10 selected anthropometric, pulmonary function, and maximal exercise data. ..... 217 Table 75 – C10 EFL severity and V̇E/V̇ECAP. .............................................................................. 218 Table 76 – C11 selected anthropometric, pulmonary function, and maximal exercise data. ..... 219 Table 77 – C11 EFL severity and V̇E/V̇ECAP. .............................................................................. 220 Table 78 – C12 selected anthropometric, pulmonary function, and maximal exercise data. ..... 221 Table 79 – C12 EFL severity and V̇E/V̇ECAP. .............................................................................. 222 Table 80 – Predictive equations and the limits of abnormality .................................................. 231    xv  LIST OF FIGURES Figure 1 – Composite maximum expiratory flow-volume curve from the pulmonary function test. From left to right, data points represent total lung capacity, peak expiratory flow (PEF), forced expiratory flow when 25% (FEF25%), 50% (FEF50%), and 75% (FEF75%) of the forced vital capacity (FVC) has been expired, and residual volume (RV). ...................... 43 Figure 2 – Total lung capacity for individual subjects in relation to their height. Individual data are presented with an open symbol connected by a solid line, while group averages have a closed symbol connected by a hashed line. ...................................................................... 45 Figure 3 – Percent-predicted total lung capacity (TLC), vital capacity (VC), functional residual capacity (FRC), and residual volume (RV) for each group during the PRE and POST visits. Bars are presented as mean ± SE. #p<0.05, significant difference between PRE to POST. *p<0.05, significant difference within group between PRE and POST. ............... 47 Figure 4 – Percent-predicted total lung capacity at the initial measurement compared to the number of years of swimming experience for each swimmer. ......................................... 48 Figure 5 – Relative change in total lung capacity from PRE to POST compared to the average weekly swim training volume for each swimmer. ............................................................ 49 Figure 6 – Relative change in total lung capacity from PRE to POST compared to the average daily moderate-vigorous physical activity in all subjects. ................................................ 50 Figure 7 – A) Diffusion capacity, B) alveolar volume, and C) DL,COc/VA for swimmers (○) and controls (Δ) during PRE and POST time points. Individual data are presented with an open symbol, while group averages have a closed symbol. ............................................. 54 Figure 8 – A) Maximal inspiratory pressure B) maximal expiratory pressure for swimmers (○) and controls (Δ) during PRE and POST time points. Individual data are presented with an open symbol, while group averages have a closed symbol. ............................................. 55 Figure 9 – Dysanapsis ratio for swimmers (○) and controls (Δ) during PRE and POST time points. Individual data are presented with an open symbol, while group averages have a closed symbol.................................................................................................................... 56 Figure 10 – Instantaneous slope ratio. The box represents the range of values (0.5-2.5) for homogenous emptying of the lung. ................................................................................... 58 Figure 11 – Mean A) heart rate, B) oxygen consumption, C) carbon dioxide production D) breathing frequency, E) tidal volume, and F) VT/FVC responses during the maximal exercise test. All exercise stages were significantly increased from baseline (BL). # significant difference between PRE and POST. Statistical significance was set at the level of p<0.05. .......................................................................................................................... 64 Figure 12 – EFL prevalence for each group and time point. ........................................................ 65 xvi  Figure 13 – Mean A) V̇E (line and symbols) and V̇ECAP (line only) and B) V̇E/V̇ECAP during the maximal exercise test. * significant difference between resting baseline and exercise stage for all groups (combined). # significant difference between PRE and POST. For V̇E and V̇E/V̇ECAP, all exercise stages were significantly increased from baseline (BL). Statistical significance was set at the level of p<0.05. ...................................................... 66 Figure 14 – Absolute operational lung volumes for A) swimmers PRE vs. POST, B) controls PRE vs. POST, C) PRE swimmers vs. controls, and D) POST swimmers vs. controls. As shown in (A), the top lines represent end-inspiratory lung volume (EILV) and the bottom lines end-expiratory lung volume (EELV). Data points are presented as mean ± SE. For all exercise stages, EILV and EELV were significantly increased and decreased from baseline (BL), respectively. Statistical significance was set at the level of p<0.05. ........ 69 Figure 15 – Relative operational lung volumes for A) swimmers PRE vs. POST, B) controls PRE vs. POST, C) PRE swimmers vs. controls, and D) POST swimmers vs. controls. Data points are presented as mean ± SE. EILV/FVC and EELV/FVC were significantly increased and decreased from baseline (BL), respectively, for all stages except PREx100% for EELV. There were no differences between PRE and POST except for 50% for EILV/FVC and 30% for EELV/FVC. Statistical significance was set at the level of p<0.05. .......................................................................................................................... 70 Figure 16 – Mean A) inspiratory reserve volume, B) IRV/FVC, C) inspiratory capacity, and D) IRV/IC during the maximal exercise test. All exercise stages were significantly decreased from baseline (BL) for IRV, IRV/FVC, and IRV/IC and increased for IC (except PREx100%). # significant difference between PRE and POST. Statistical significance was set at the level of p<0.05. .................................................................................................. 71 Figure 17 – Individual MEFV and FVL for swimmers. ............................................................... 73 Figure 18 – Individual MEFV and FVL for controls. ................................................................... 74 Figure 19 – Composite MEFV and FVL for A) swimmers PRE, B) swimmers POST, C) controls PRE, and D) controls POST.............................................................................................. 75 Figure 20 – S01 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 181 Figure 21 – S01 ventilatory mechanics. ...................................................................................... 182 Figure 22 – S02 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 183 Figure 23 – S02 ventilatory mechanics. ...................................................................................... 184 Figure 24 – S04 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 185 Figure 25 – S04 ventilatory mechanics. ...................................................................................... 186 Figure 26 – S05 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 187 xvii  Figure 27 – S05 ventilatory mechanics. ...................................................................................... 188 Figure 28 – S06 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 189 Figure 29 – S06 ventilatory mechanics. ...................................................................................... 190 Figure 30 – S07 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 191 Figure 31 – S07 ventilatory mechanics. ...................................................................................... 192 Figure 32 – S08 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 193 Figure 33 – S08 ventilatory mechanics. ...................................................................................... 194 Figure 34 – S09 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 195 Figure 35 – S09 ventilatory mechanics. ...................................................................................... 196 Figure 36 – S10 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 197 Figure 37 – S10 ventilatory mechanics. ...................................................................................... 198 Figure 38 – S11 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 199 Figure 39 – S11 ventilatory mechanics. ...................................................................................... 200 Figure 40 – S12 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 201 Figure 41 – S12 ventilatory mechanics. ...................................................................................... 202 Figure 42 – C01 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 203 Figure 43 – C01 ventilatory mechanics. ..................................................................................... 204 Figure 44 – C02 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 205 Figure 45 – C02 ventilatory mechanics. ..................................................................................... 206 Figure 46 – C03 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 207 Figure 47 – C03 ventilatory mechanics. ..................................................................................... 208 Figure 48 – C04 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 209 Figure 49 – C04 ventilatory mechanics. ..................................................................................... 210 Figure 50 – C05 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 211 Figure 51 – C05 ventilatory mechanics. ..................................................................................... 212 xviii  Figure 52 – C08 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 213 Figure 53 – C08 ventilatory mechanics. ..................................................................................... 214 Figure 54 – C09 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 215 Figure 55 – C09 ventilatory mechanics. ..................................................................................... 216 Figure 56 – C10 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 217 Figure 57 – C10 ventilatory mechanics. ..................................................................................... 218 Figure 58 – C11 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 219 Figure 59 – C11 ventilatory mechanics. ..................................................................................... 220 Figure 60 – C12 MEFV and FVL for PRE (top) and POST (bottom). ....................................... 221 Figure 61 – C12 ventilatory mechanics. ..................................................................................... 222    xix  LIST OF ABBREVIATIONS A-aDO2 Alveolar-arterial oxygen difference AHR Airway hyperresponsiveness ANOVA Analysis of variance β° β-angle BL Resting baseline BMI Body mass index bpm Beats per minute BSA Body surface area BTPS Body temperature and pressure, saturated Cdyn Dynamic compliance CFB Controlled frequency breathing CO Carbon monoxide CO2 Carbon dioxide CON Controls Cst Static compliance CRS Respiratory system compliance CV Closing volume CVE Central vascular engorgement CW Chest wall compliance DL,CO Diffusion capacity for the lungs measured using carbon monoxide DL,COc DL,CO corrected for hemoglobin DR Dysanapsis ratio EELV End-expiratory lung volume EFL Expiratory flow limitation EIAH Exercise-induced arterial hypoxemia EILV End-inspiratory lung volume EPL Exercise Physiology Laboratory in the Children’s Heart Centre ERV Expiratory reserve volume EVH Eucapneic voluntary hyperpnea fB Breathing frequency xx  FECO2 Fraction of expired carbon dioxide FEF Forced expiratory flow  FEF25-75% Maximum mid-expiratory flow (between 25% and 75% of the FVC) FEF25% Maximum expiratory flow when 25% of the FVC has been expired FEF50% Maximum expiratory flow when 50% of the FVC has been expired FEF75% Maximum expiratory flow when 75% of the FVC has been expired FEO2 Fraction of expired oxygen FEV1 Forced expiratory volume in one second FR Flow ratio FRC Functional residual capacity FSB Freestyle breathing pattern (“hypoxic training”) FVC Forced vital capacity FVL Tidal flow-volume loop Gaw Airway conductance gFVC Graded forced vital capacity GH Growth hormone Hb Hemoglobin **He Helium HR Heart rate IC Inspiratory capacity IRV Inspiratory reserve volume KCO Transfer coefficient of the lung (i.e., DL,CO/VA) MCh Methacholine MEFV  Maximum expiratory flow-volume curve  MVV Maximum voluntary ventilation O2 Oxygen PaCO2 Arterial carbon dioxide tension PaO2 Arterial oxygen tension PAQ Physical activity questionnaire PEF Peak expiratory flow PEMAX Maximum expiratory pressure xxi  PFT Pulmonary function test PGV Peak growth velocity PIMAX Maximum inspiratory pressure POST Follow-up visit PRE Initial visit Pst(L) Static recoil pressure of the lungs Pst(L)50 Static recoil pressure of the lungs at 50% of VC Q̇ Cardiac output Raw Airway resistance RC Respiratory Clinic RER Respiratory exchange ratio RPE Rating of perceived exertion rpm Revolutions per minute RT Respiratory therapist RV Residual volume SaO2 Arterial oxygen saturation SD Standard deviation SE Standard error of the mean sGaw Specific airway conductance SMR Sexual maturity rating SR Slope ratio SS Snorkel set  STPD Standard temperature and pressure, desaturated SV Stroke volume SWIM Swimmers TLC Total lung capacity UK Underwater (dolphin or breast) kick VA Alveolar volume V̇A/Q̇ Ventilation-perfusion ratio Vc Pulmonary capillary blood volume VC Vital capacity xxii  V̇CO2 Carbon dioxide production V̇E Expired minute ventilation V̇ECAP Ventilatory capacity V̇E/V̇CO2 Ventilatory equivalent for carbon dioxide V̇E/V̇ECAP Utilization of ventilatory capacity V̇E/V̇O2 Ventilatory equivalent for oxygen V̇I Inspired minute ventilation V̇O2 Oxygen consumption V̇O2MAX Maximal oxygen consumption  VT Tidal volume WMAX Peak work rate WOB Work of breathing   xxiii  ACKNOWLEDGEMENTS I would like to acknowledge my supervisor, Dr. William Sheel, for his invaluable support, guidance, and patience over the past three years. You have been a superb role model both inside and beyond the laboratory, and I hope that we will continue to work together in the future. Thank you! I would also like to acknowledge my committee, Dr. Kristin Houghton, Dr. Don McKenzie, and Dr. Jim Potts. Thank you all for your patience, expertise, and guidance with my graduate work and career perspectives. A big thanks to Barb, Opi, and all the volunteers who graciously gave up their time on weekends to help with data collection and create an enjoyable and comfortable atmosphere for the participants. On that note, to all the participants and parents, thank you so much for donating your time and energy to my project. To the swimmers, good luck with your swimming careers! I would also like to thank Dr. Carolyn McEwen for her help with the statistical analysis. HIP lab members: Paolo and Yannick, thanks for always answering my questions; Carli, thanks for continually showing me how to take that next step in my MSc; and Joe, mate, this thesis would not have been completed without you. I would also like to acknowledge many more individuals who made my graduate work so enjoyable. Kelcey Bland, Dr. Kristin Campbell, Dr. Victoria Claydon, Dr. Amy Kirkham, Matthew Lloyd, NExT and EXIT participants, Dr. Anita Cote, Astrid de Souza, Dr. George Sandor, Dr. Rick Celebrini, Dr. Ben Sporer, Nadine Sinnen, Chad Cardoso, Duarte Rosario, Dr. Neil Eves, and Dr. Mike Koehle. Each and all of you have made me a better scientist, clinician, and person, and I thank you for that. Special thanks to Mom, Dad, Jo Ann, Tim, and the rest of my family who have provided endless support, encouragement, and food. Kibo, thanks for waiting patiently when a walk was delayed because of writing. Most importantly, Amy, I can’t wait for our next adventure.   1  INTRODUCTION The respiratory system is generally thought to be ideally designed to meet the demands of exercise in healthy young adults (1). However, unlike the cardiovascular and musculoskeletal systems, the respiratory system does not exhibit significant beneficial adaptations to endurance training (2, 3). There are no known measurable beneficial structural adaptations, and, of the limited number of functional adaptations, the majority are related to changes in respiratory musculature (e.g., increased respiratory muscle endurance or strength) (2). As a result, the respiratory system can become a limiting factor of performance in highly trained athletes (2-4) and can negatively adapt to exercise in cold (5) or chlorinated (6) environments. While chronic exercise training appears to confer no change to the respiratory system, an exception may be in young, competitive swimmers.  1.1 Competitive swimming and lung development The pulmonary function of competitive swimmers is characterized by large lung capacities (7-31), greater expiratory flows (11, 14, 18, 29-31), and increased diffusion capacities (19, 22, 24, 29, 31-35). This enhanced function has been suggested to be beneficial for swimming (14). For example, increased functional residual capacity (FRC) may act as a reservoir for gas exchange, thereby attenuating oscillations in arterial blood gases between breaths (14). Additional benefits may include greater buoyancy in the water to decrease drag and improved ventilatory capacity (14). In fact, it has been suggested that having large lungs is a pre-requisite for becoming a top swimmer (12). However, it has been widely debated whether this enhanced pulmonary profile is an adaptation to swim training (8, 13, 16, 18, 21, 33), the result of young athletes self-selecting into swimming based on favourable genetic endowments (17), or both (9-11, 14, 15, 23, 27). 2  The argument for adaptive growth is based on four unique challenges that competitive swimming places upon the developing respiratory system. First, swimming is performed in the prone or supine position with the body partially or fully submerged (36). Second, swimmers use an “obligatory, controlled frequency” breathing pattern that is dependent on both physiological need and timing of arm strokes (36). Third, swim training often involves breath control drills, including “hypoxic training”, and sprint swimming where breathing frequency is reduced. Lastly, intense and structured swim training begins as early as 5 y old (17). Hypothetically, the first three stressors may cause changes in ventilatory mechanics, greater inspiratory pressures (14), and excessive upper body work (14) and/or require transient breath-holding maneuvers (11). These have been suggested to augment growth of the thoracic cavity and musculature (14) and/or create an intermittent hypoxic stimulus for lung growth (29). However, mechanistic evidence is lacking. More importantly, competitive swimmers are exposed to these stressors during periods of maximal lung growth between 1 month and 7 years of age (37) and during puberty (38). Thus, if the growing respiratory system is sensitive to induced growth, then competitive swimming during these critical periods is likely to elicit the greatest effects. Table 1 andTable 2 list 18 cross-sectional (20-34, 39-41) and 16 longitudinal (6 <1 year (7, 14, 19, 35, 42, 43) and 10 ≥1 year (8-13, 15-18)) studies that have reported pulmonary function data in young swimmers throughout development. Overall, increased lung volumes of competitive swimmers have been observed compared to predicted values (13, 24, 25, 29, 31), population norms (8-10, 12, 21), and measurements in controls (7, 11, 14-18, 20, 22, 26-30, 40, 41). Greater expiratory flows have been measured in competitive swimmers compared to controls (11, 14, 16, 18, 20, 22, 28-30, 40) and predicted values (24, 25, 29, 31), as have diffusion capacities compared to controls (11, 22, 29, 34, 39) and predicted values (24, 29, 31-33, 35). Conversely, maximal static 3  mouth pressures, which have been seldom reported, have often been found to be similar in swimmers relative to controls (15, 27-29). However, within the published literature there is considerable between-study variation in the competitive level of the swimmers (e.g., experience and training volume), study length, and experimental design and analysis. Moreover, some have not observed any differences in lung volumes between swimmers and a control group (33, 39, 42, 43). Therefore, a more detailed review of this literature is necessary to provide a comprehensive understanding of the relationship between competitive swimming and lung development. This includes addressing the following questions: 1. At what age are swimmers first reported to have larger lung capacities compared to a normal control group or predicted values? 2. Given that lung volume increases 13-fold between 1 month and 7 y (37), does swim training prior to age 7 y have any effect on lung capacities? 3. When children begin intensive swim training, do they already have greater lung capacities? 4. Do longitudinal analyses show greater-than-expected growth of lung capacities? 5. If there is accentuated growth, is it most evident during puberty when the lungs reach their peak growth velocities (PGV)? 6. At what age are swimmers first reported to have a higher diffusion capacity, and does swim training increase it further? 7. What are the main differences between and weaknesses of these studies on competitive swimming and lung development?    4  Table 1 – Cross-sectional studies of competitive swim training on lung development. Study Sex N Age (y) Swimming history Training volume Volume Flow Pressure Diffusion capacity Endowment or swim training? Other conclusions Newman et al., 1961 (20) M 15 S 10 C 16.1 (13-17) “Leading British swimmers” - ↑ FVC ↑ FEV1 ↑ PEMAX - - Swimmers had greater standing and seated height F 15 S 9 C Astrand et al., 1963 (21) F 30 S 12-16 Started training at 10-15 y 6-28 h and 6-65 km per week TLC, FRC, FVC > predicted by body size - - - Swim training ↑ height due to early menarche Mostyn et al., 1963 (34) M&F 5 S 6 R 19.0 University team >9 h/week - - - Similar DL,CO during exercise Either DL,CO of champion swimmers > university swimmers  Greater DL,CO due to ↑ Vc 8 S 24 O 19.3 Canadian National or Olympic swim team - - - - ↑ absolute and relative DL,CO during exercise Magel and Andersen, 1969 (22) M 10 S 9 C 17.3 ± 1.4 17.1 ± 1.3 Well-trained - ↑ TLC, FRC, VC ↑ FEV1 - ↑ DL,CO at rest & exercise ↑ KCO at max exercise - - Ness et al., 1974 (39) F 20 S 13 C 10.2 ± 0.7 9.8 ± 0.8 No prior swimming experience - TLC, VC, FRC not significantly larger No difference in FEV1 - ↑ DL,CO at submaximal exercise - Minimal differences in lung function in parents Vaccaro et al., 1977 (32) M&F 16 S 10-18 - Daily, 3000-13,000 yards per day  - - - Dl,,CO > predicted Either - Eriksson et al., 1978 (23) M 18 S 10.1 (7.6-11.8) Just started swimming - TLC, FRC, RV, FVC > predicted by body size - - - Endowment more likely - Vaccaro et al., 1980 (24) M 12 S 15.1 ± 1.7 ≥6 y swim training 4x/week 3600-6400 m per session TLC, FRC, RV > predicted FEV1 > predicted - DL,CO > predicted Potentially swim training - Yost et al., 1981 (33) M&F 12 S 12 C 13.9 ± 2.2 14.0 ± 2.4 2-12 y intense swim training Daily 3-12 km per session No difference in FVC - - ↑ DL,CO at rest & exercise and > predicted Swim training DL,CO at rest and exercise, FVC ↑ after 10 months in 10 S McKay et al., 1983 (25) M&F 25 S Youngest: 14.1 ± 0.9 Oldest: 18.6 ± 1.3 Scottish National or Youth swim team members - FVC 9-25% above predicted FEV1 19-25% above predicted - - Either - Bloomfield et al., 1984 (26) M 53 S 106 C 7-12 State Championship finalists - ↑ FVC No difference in FEV1 - - - - F 62 S 123 C Bradley et al., 1985 (31) M 18 S 20.3 (17-25) US Olympic team - TLC, FRC, RV, FVC > predicted PEF, FEV1 > predicted - DL,CO > predicted Either Greater than other Olympic athletic groups F 20 S 18.4 (15-23)  5  Table 1 – Cross-sectional studies of competitive swim training on lung development, continued Study Sex N Age (y) Swimming history Training volume Volume Flow Pressure Diffusion capacity Endowment or swim training? Other conclusions Zinman and Gaultier, 1986 (27) F 7 S 15 C 7.0-8.9 14.7 ± 7.7 mo 5 h per week ↑ TLC, FRC, VC - No difference in PEMAX or PIMAX at TLC, FRC, or RV - Both ↑ chest wall dimensions, surface area 15 S 17 C 9.0-10.9 27.2 ± 15.0 mo 5-12.5 h per week ↑ chest wall dimensions, surface area; ↑ FImax at FRC 16 S 27 C 11.0-13.3 44.7 ± 19.5 mo 12.5 h per week ↑ TLC, FRC, RV, VC - ↓ PEMAX at FRC, PIMAX at FRC, RV - ↑ chest wall dimensions, surface area Pherwani et al., 1989 (40) M&F 45 S 45 C  6 months to >5 years 6x/week, 2000-5000 m per session ↑ FVC ↑ FEV1, FEF25% - - -  Cordain et al., 1990 (28) F 11 S 11 R 10 C 19.0 ± 0.6 Collegiate Division 1 swimmers (9.4 ± 2.8 y start swim) 3000-7000 m per day ↑ TLC, FRC, RV, FVC ↑ FEV1 No difference in PIMAX, PEMAX - Either - Armour et al., 1993 (29) M 8 S 8 R 8 C 18 ± 2.4 24 ± 3.2 22 ± 4.8 Start: 11.0 ± 2 y Experience: 6.5 ± 1.9 y 69.4 ± 22.1 km per week ↑ TLC, FRC, VC, RV, FVC ↑ FEV1, FEF50%, PEF No difference in PIMAX, PEMAX ↑ DL,CO, no difference in KCO More likely to be swim training ↑ chest wall dimensions, no difference in FEmax, FImax, or lung recoil Doherty and Dimitriou, 1997 (30) M 82 S 90 O 66 C 15.1 ± 3.0 14.1 ± 2.6 13.8 ± 2.7 Some were National swimmers ≥3x/week ↑ FVC ↑ FEV1, PEF - - Either Swimmers were taller and, in males, older F 78 S 72 O 70 C 14.5 ± 2.4 14.4 ±2.6 14.0 ± 2.5 Lazovic-Popopvic et al., 2016 (41) M 38 S 271 O 100 C 20.9 ± 2.4 20.2 ± 3.6 21.2 ± 3.9 Start: 9.4 ± 2.6 y Experience: 12.8 ± 3.0 y 22.0 ± 7.9 h/week ↑ FVC and > predicted ↑ FEV1 and > predicted, PEF same - - Genetic endowment likely No relationship between % predicted and starting age, experience, or training volume Values are expressed as means ± SD. M, male; F, female; swim, competitive swimmers; con, controls; land, land-based athletes; TLC, total lung capacity; FRC, functional residual capacity; VC, vital capacity; RV, residual volume; FVC, forced vital capacity; FEV1.0, forced expiratory volume in one second; FEF50%, forced expiratory flow at 50% of FVC; PEF, peak expiratory flow; PEmax, maximal static expiratory pressure at the mouth; PImax, maximal static inspiratory pressure at the mouth; DLCO, diffusion capacity of the lungs for carbon monoxide; KCO, transfer factor; FImax, maximal inspiratory respiratory muscle force; FEmax, maximal expiratory respiratory muscle force; Vc, pulmonary capillary blood volume.   6  Table 2 – Longitudinal studies of competitive swim training on lung development. Study Length Sex N Starting Age (y) Swimming history Training volume Volume Flow Pressure Diffusion capacity Endowment or swimming? Other conclusions Bachman and Horvath, 1966 (7) 4 mo M 12 S 9 C 18.8 ± 1.1 Collegiate - Swim had ↑ FVC, ↓ FRC, RV, RV/TLC - - - - - Eriksson et al., 1967 (8) 4 y F 30 S 12-16 See Astrand et al., 1963 Only 4 were still actively training Pre: see Astrand 1963 Post: still had ↑ FVC - - - Swimming - Gibbins, 1971 (42) 6 mo F 8 S 6 C 9-10 - 3-4x/week 1000 yards per session Pre/post: same TLC, FRC, FVC Pre/post: same FEV1 - Same DL,CO Neither - Engstrom et al., 1971 (9) 3.6 (1-5) y F 29 S 9-13 2 (0-5) y training experience - Pre/post: ↑ TLC, FRC Swim had ↑ VC during 1-5 y - - - Both - Eriksson et al., 1971 (10) 7-8 F 30 S 12-16 Started training at 10-13 y Had stopped training for 5 (0-7) y Pre: see Astrand 1963 Post: still had ↑ FVC - - - Both - Andrew et al., 1972 (11) 3 y M 71 S 40 C 8-18 - - ↑ TLC, VC, no difference in FRC; with ↑ height the greater volumes were more evident ↑ maximal mid-expiratory flow - ↑ DL,CO at exercise only in males No difference in DL,CO/TLC Both By age 12 the swimmers were taller than average F 32 S 73 C Eriksson et al., 1978 (12) 10 y F 30 S 12-16 See Astrand et al., 1963 All had stopped training (see Eriksson et al., 1971) Pre/post: ↑ TLC, VC, FRC - - - Both - Vaccaro and Clarke, 1978 (43) 7 mo M&F 15 S 15 C 9-11 Just started (in 1st year of swim training) 4x/week 3000-10,000 yards per session Pre/post: same FVC No difference in ↑ in FVC No difference in in FEV1 - - Neither - Zauner and Benson, 1981 (13) 3 y M 8 S 13.7 (9-19) Each had competitively swam ≥50% of their life ≥6x/week ≥5000 m per session Pre: FVC = predicted Post: FVC > predicted - - - Swimming - F 7 S Clanton et al., 1987 (14) 12 w F 8 S 4 C 18.9 ± 1.2 20.8 ± 1.0 Varsity swimmer for collegiate team ≥5 days per week, 2300-9000 m per day Pre/post: ↑ TLC, VC, FRC, RV Swim had ↑ VC, FRC during 12 w Pre/post: ↑ FEV1, PEF, FIV1, PIF Pre: no difference Post: ↑ PIMAX - Both ↑ Inspiratory muscle endurance   7  Table 2 – Longitudinal studies of competitive swim training on lung development, continued Study Length Sex N Starting Age (y) Swimming history Training volume Volume Flow Pressure Diffusion capacity Endowment or swimming? Other conclusions Zinman and Gaultier, 1987 (15) 1 y F 7 S 7-10 See Zinman and Gaultier, 1986 See Zinman and Gaultier, 1986 Pre/post: ↑ TLC, VC Swim had ↑ TLC, VC during 1 y   - ↑ PEMAX - Both - 10 S 10-12 No change in PIMAX or PEMAX Miller et al., 1989 (35) 5 mo M 22 S 18-22 y Collegiate swim team - Pre/post: similar VC - - Pre/post: similar DL,CO, > predicted Either Performance and lung function were independent Bloomfield et al., 1990 (16) 5 y M 38 S 57 C 8-12 Group selected from State finalists 5x/week ↑ FVC from stage 2 ↑ FEV1 from stage 3 - - Swimming ↑ chest depth and girth F 57 S 64 C ↑ FVC from stage 4 ↑ FEV1 from stage 4 Baxter-Jones and Helms, 1996 (17) 3 y M&F 114 S 339 O 8-16 - 9-13 h per week ↑ FVC at start compared to others, no further ↑ after - - - Endowment Swimmers were taller after adjusting for age and pubertal status Courteix et al., 1997 (18) 1 y F 5 S 11 C 9.3 ± 0.5 9.4 ± 0.5 - 8-12 h per week 10-20 km per week Pre: no difference  Post: ↑ TLC, VC, FRC Pre: no difference  Post: ↑ FEV1, PEF, FEF25%, FEF50%, FEF75% - - Swimming No difference in Raw; not-significantly taller Mickleborough et al., 2008 (19) 12 w M&F 10 S 18.2 ± 1.6 National and international swimmers 10-12x/week 40-60 km per week ↑ TLC, FVC, no difference RV ↑ FEV1, FIV1 ↑ PIMAX, PEMAX ↑ DL,CO, no change K,CO   This thesis 7 mo F 11 S 10 C 12.4 ± 0.8 13.2 ± 1.3 3.2 ± 1.8 y 9.1 ± 3.6 h per week 19 ± 8 km per week Pre/Post: ↑ TLC, FVC, VC Pre/Post: ↑ PEF, FEV1, FEF Pre/Post: ↑ PIMAX (p=0.06), PEMAX Pre/Post: ↑ DL,CO, similar K,CO Endowment Similar ventilatory constraints during cycling Values are expressed as means ± SD. M, male; F, female; swim, competitive swimmers; con, controls; TLC, total lung capacity; FRC, functional residual capacity; VC, vital capacity; RV, residual volume; FVC, forced vital capacity; FEV1.0, forced expiratory volume in one second; PEF, peak expiratory flow; FIV, forced inspiratory volume in one second; PIF, peak inspiratory flow; FEF25% FEF50%, and FEF75%, forced expiratory flow at 25%, 50%, and 75% of FVC, respectively; PEMAX, maximal static expiratory pressure at the mouth; PIMAX, maximal static inspiratory pressure at the mouth; DLCO, diffusion capacity of the lungs for carbon monoxide; KCO, transfer factor; Raw, airway resistance; IMT, inspiratory muscle training.    8  1.1.1 Swedish “girl swimmers” – the foundational studies on swimming and lung development The foundational research into physiological adaptations to competitive swimming during development came from analyses of three different cohorts of Swedish swimmers (summarized elsewhere (44)). The original was a longitudinal analysis of 30 “girl swimmers”, examined first at 12-16 y old by Astrand et al. (21) and again after 2, 4 (8), 7 (10), and 10 y (12). Initially, the girls had significantly larger lung volumes (i.e., total lung capacity (TLC), forced vital capacity (FVC), and FRC) that were 11-13% greater than the average value for their height (21). These larger lung volumes for a given height were maintained throughout the follow-up period, even upon cessation of swimming (12). At the first measurement, significant correlations between lung volume (expressed as the %-deviation in TLC or vital capacity (VC) from the average value for height) and training volume (expressed either as training experience or training volume in metres or hours per week) suggested that the intensity of swim training influenced functional development of the respiratory system (21). Therefore, different training regimens were compared by separating the swimmers into two groups such that 9 top swimmers from one club who trained the most (up to 65,000 m and 28 h per week) were compared to the other 21 swimmers (6,000-30,000 m and 6-20 hours per week). While the top swimmers initially had a larger FVC but statistically similar TLC, FRC, and residual volume (RV), differences between the groups did not change throughout the follow-up period (12). This suggested that intense training did not further increase lung volumes in the top swimmers; however, the question of whether the larger lungs of all swimmers at the initial measurement were due to intense training or genetic endowment was unresolved. A subsequent longitudinal analysis conducted with 29 9-13 y old Swedish girl swimmers confirmed some of these findings (9). At the initial measurement, TLC and FRC in relation to 9  height were already significantly larger than normal whereas FVC was not. By the final measurement 3.6 y (range 1-5 y) later, FVC in relation to height had increased significantly while TLC and FRC remained constant. Interestingly, when the girls were stratified into two groups based on training experience before the first measurement, the 18 girls who had been training at least 3 times per week for ≥1 year had significantly increased lung volumes (TLC, FRC, and FVC in relation to height) whereas those who had trained for ≤1 year did not. Moreover, when lung volumes were analyzed from 12 to 14 y old, the girls that trained during this period had a significant increase in FVC in relation to both height and TLC, while TLC grew as expected. From these observations, the authors concluded that lung volumes in swimmers are larger at the start of training, and further increases in FVC but not TLC with continued training point to functional rather than anatomical growth. However, no explanation was provided for why the swimmers with more experience had greater lung volumes. The third study by Eriksson et al. assessed 18 boys aged 10.1 y (range 7.6-11.8 y) who had minimal training experience (less than a few months) but had just been selected to competitively swim with the top clubs in Sweden (23). Despite not yet having started intensive swim training, their lung volumes (TLC, FRC, RV, and FVC) already exceeded normal values in relation to height, strongly suggesting that the initially larger lungs of competitive swimmers were due to genetic endowment. A similar result was found in a study comparing untrained girls trying out for a competitive swimming team (39). The 11 girls who qualified for the team had an average TLC of 3.08±0.73 l compared to 2.52±0.39 l in the 9 girls of similar age, maturity, and body size who did not. Furthermore, the fathers of the girls who qualified had a greater TLC and FRC than the fathers of those who did not, strongly pointing to a genetic endowment whereby swimmers with constitutionally larger lungs may select into swimming. 10   1.1.2 Lung volumes in young swimmers Other studies have also reported differences in young swimmers. In a 3-year longitudinal analysis of over 70 8-18 y old competitive swimmers (compared to 83 controls analyzed cross-sectionally), Andrew et al. found greater lung volumes (TLC and VC) which were apparent even in the youngest swimmers (11). Zinman and Gaultier cross-sectionally assessed 38 7-13 y old trained female swimmers and 59 age- and size-matched controls, and found significantly greater lung volumes (TLC, VC, and FRC) in all ages of swimmers (27). In a cross-sectional analysis of 112 7-12 y old trained swimmers compared to tennis players and non-athletes, Bloomfield et al. found a significantly greater FVC that was apparent across all ages (26). Lastly, a large, longitudinal study of 453 8-16 y old young athletes (swimmers, gymnasts, tennis players, and soccer players) found that FVC (adjusted for height, weight, and maturation) was ≥20% larger in swimmers compared to the other athletes at the initial measurement (17). Cumulatively, these results suggest that swimmers as young as 7-8 y old already have greater lung volumes However, this has not been the case for all studies. As mentioned, Engstrom et al. did not find any initial differences in TLC or FVC in the 9-13 y old swimmers who had less than 1 year of training (9). Similarly, Vaccaro and Clarke compared 15 9-11 y old children in their first year of swim training (3,000-10,000 yards per training session) with 15 controls, but reported no differences in FVC (43). Gibbins and Courteix et al. did not find any differences in TLC, FRC, FVC, or VC between 8 9-10 y old female swimmers and 6 controls (42) and 5 9-10 y old prepubertal competitive swimmers and 11 age-, sex-, and size-matched controls (18), respectively. Unfortunately, swimming history was not reported in either of these studies. Zauner and Benson 11  measured FVC in extensively trained 9-19 y old swimmers and found no initial difference compared to predicted values (13). There is no clear reason for these opposing results.  1.1.3 Longitudinal assessments of competitive swimming and lung volume development Longitudinal assessments of lung function in growing swimmers are also contradicting, as four different conclusions have been reported. First, there was no difference in lung function before or after a 6-7 month period of training in 8 9-10 y (42) and 15 9-11 y (43) old swimmers compared to control groups. Second, despite similar lung capacities initially, greater lung capacities were measured in 5 9-10 y old swimmers compared to 11 matched controls after 1 y of training (18), 95 8-12 y old trained swimmers compared to 102 maturation-matched controls over 5 y of assessments (16), and 15 9-19 y old very competitive swimmers compared to predicted values after 3 y of training (13). Third, swimmers initially had larger lungs and these did not increase further over 3 y of training in 114 8-16 y old swimmers compared to other athletes (17), 3 y of training in >70 8-18 y old swimmers compared to non-athletes (11), and 1-5 y of training in 29 female swimmers aged 9-13 y compared to population norms (9). Finally, trained swimmers aged 7-12 y initially had larger lungs and these further increased after 1 y of training as compared to a control group analyzed cross-sectionally (15). Unfortunately, no study has assessed lung function in competitive swimmers before 7 y (this may be related to some measurements requiring maximal maneuvers that are not reliable until 8 y (37, 45-47)). Moreover, only 4 of the aforementioned studies have provided analysis during puberty and the conclusions are conflicting. Engstrom et al. found that VC, but not TLC, grew more than expected between 12 and 14 y old (9), whereas Zinman and Gaultier reported accentuated growth of both TLC and VC in 10-12 y old trained swimmers (15). While Bloomfield et al. found that 12  FVC was only statistically significantly larger from stage 2 (puberty) onwards in males and stage 4 (puberty) onwards in females (16), Baxter-Jones and Helms reported that FVC was initially larger and did not increase further during puberty (17). Clearly, more work is needed to determine if competitive swimming affects the development of lung volumes during growth.  1.1.4 Competitive swimming and diffusion capacity during growth Differences in diffusion capacity may highlight structural or functional changes in the gas exchanging ability of the lungs. Like lung volumes, greater diffusion capacities have been observed in swimmers. One study suggested the greater diffusion capacity for carbon monoxide (DL,CO) was partly due to an adaptation to swim training (33). Yost et al. observed a greater absolute DL,CO at rest and during submaximal exercise at 170 bpm in 12 9-17 y old competitive swimmers (2-12 y experience, 3-12 km per session) compared to 12 matched controls (33). They re-tested 10 of the swimmers after 10 months of training and found that exercise DL,CO increased more than expected by growth, leading them to suggest that swim training increased DL,CO to a greater extent than expected by growth. However, resting DL,CO increased only slightly (and as expected given their somatic growth), and the greater exercise DL,CO could be explained by the swimmers exercising at a greater metabolic rate (oxygen consumption (V̇O2) at 170 bpm was significantly increased) at the second examination. Moreover, when resting DL,CO was correlated with height, the slope between DL,CO and height was identical for swimmers and controls, suggesting that DL,CO was equally greater across all heights studied. This could have been related to greater lung volumes in the swimmers (FVC 4.12±0.93 vs. 3.61±0.86 l), although differences in FVC did not reach statistical significance. Such a difference was found in the longitudinal analysis by Andrew et al., where the greater exercise DL,CO across all heights in 8-18 y old male 13  swimmers compared to non-athletic male controls (no differences were found between the female cohorts) was no longer apparent when expressed relative to TLC (11). Greater absolute DL,CO but similar relative DL,CO have also been reported in older adolescent (22) and young adult (29) elite swimmers. Thus, the greater diffusion capacity of swimmers is apparent across all heights and ages and is related to their larger lung volumes, yet no conclusive evidence has shown that competitive swim training accentuates the development of DL,CO during development.  1.1.5 Differences between and weaknesses of previous studies While there is a myriad of literature on competitive swimming and lung development, heterogeneities between studies have made it difficult to systemically analyze and resolve the question of “genetic endowment, training adaptation, or both?”. These include differences in participant age; swimming history and level of competition; training status; design and length of study; lung function measurements; comparisons to controls, predictive values, or population norms; and statistical analysis. Moreover, as outlined in Table 3, previous studies have been weakened by short study periods (≤7 months (43)), not differentiating boys and girls, not assessing or matching for maturational stage, small sample size (<10 subjects in group), no control group, not statistically comparing swimmers with the control group or reference values, or not performing a comprehensive assessment of lung function (e.g., only FVC and forced expiratory volume in one second (FEV1), but no lung volumes).    14  Table 3 – Weaknesses of selected previous studies on competitive swimming during development  Short study period (≤7 months) * Did not separate sexes Did not match for maturational stage Small sample size (<10 subjects in group) No control group No statistical comparison to controls or reference values Few measures of lung function (e.g., only FVC, FEV1) Other notes Gibbins, 1971 (42) X   X    Swim history not stated, training stimulus low Andrew et al., 1972 (11)      X  Controls assessed cross-sectionally but swimmers longitudinally Ness et al., 1974 (39)    X     Vaccaro et al., 1977 (32)  X   X  X  Vaccaro and Clarke, 1978 (43) X X X    X Did not state if groups were sex-matched Vaccaro et al., 1980 (24)     X    Yost et al., 1981 (33)  X X    X  Zauner and Benson, 1981 (13)   X   X  X  Bloomfield et al., 1984 (26)  ** X    X  Zinman and Gaultier, 1986 (27)   X      Zinman and Gaultier, 1987 (15)   X   X  Controls assessed cross-sectionally but swimmers longitudinally Bloomfield et al., 1990 (16)       X Mixed-longitudinal analysis Baxter-Jones and Helms, 1996 (17)       X  Courteix et al., 1997 (18)    X    Unusually small lung growth in control group Doherty and Dimitriou, 1997 (30)   X    X  *Only for longitudinal studies. **Did not find significant effect of sex, therefore dropped from further statistical analysis. FVC, forced vital capacity; FEV1, forced expiratory volume in one second.  15  Vaccaro and Clarke reported similar lung function in 15 9-11 y old swimmers (training 3,000-10,000 yards per session, 3-4 times per week) and 15 age- and size-matched controls before and after a 7-month season of competitive swimming, leading them to suggest that study durations less than 7 months are too short to measure significant differences in lung development (43). The short time period may also underlie the lack of differences in the 6-month swim training study by Gibbins (42). To note, the very low training stimulus (1000 yards per session, 3-4 sessions per week) may have contributed to the negative finding. Vaccaro and Clarke did not specify if the groups were matched for sex. A variety of sex-based differences in lung growth (48, 49), which lead to differential timing and rates of growth of alveoli and small and large airways between boys and girls, may have caused no effect of competitive swimming on lung development to be observed in this study (43) and affected the results of others (13, 33). While Zinman and Gaultier found significantly greater (27) and accentuated growth (15) of lung volumes in 7-13 y old swimmers compared to similarly-aged controls, it is not clear if they were matched for maturational stage. Male swimmers tend to be early maturers (50, 51); conversely, female swimmers tend to have a slightly intrinsically later (not delayed) menarchal age (13.3-13.4 y (52, 53) compared to the reference 13.0 y (52)) with the best performers having the latest menarchal ages (54). Considering that, first, females who are late maturers might also have a prolonged pubertal growth spurt (55), second, the growth velocity of the lungs differs depending on pubertal stage (56), and, third, a mixed-longitudinal study of swimmers and non-athletes showed different amounts of growth in FVC depending on the maturational stage (16), there is clear need for maturational matching when comparing swimmers with their healthy counterparts. Therefore, differences in maturational stage may have contributed to the larger lungs 16  of the swimmers in the studies by Zinman and Gaultier and affected the results of others (26, 30, 33, 43). In the longitudinal analysis by Courteix et al., they found similar lung volumes initially but significantly greater volumes after 1 y of intense swim training in 5 9-10 prepubescent swimmers and maturity- and age-matched controls (18). However, the control group grew an average of 5 cm in height but only 90 ml in TLC, which appears abnormally small compared to reference values for their age and somatic growth (57). Therefore, the difference may have been due to the control group’s minimal increase in lung volumes. Moreover, the authors cited the need for a larger group of swimmers.  While comparisons to predicted values provide an idea of lung function relative to population standards, they require predictive equations. These depend on the design (cross-sectional versus longitudinal) of the reference study, size of the reference population, and quality of the statistical modelling. Moreover, selecting the appropriate predictive equations requires demographic similarities between the study sample and reference population as well as methodological similarities between the study and reference measurements. Thus, conclusions from studies lacking a control group (13, 24, 32) must be interpreted with caution. Longitudinal assessments of swimmers by Andrew et al. (11) and Zinman and Gaultier (15) were compared to control groups who were cross-sectionally analyzed using regression lines (with a 95% confidence interval). Although plots of longitudinal changes against these regression lines provided graphical illustration of changes in lung function, neither study statistically analyzed if the changes in swimmers’ lung function reached statistical significance. Lastly, many studies have used only FVC as an indicator of lung size and FEV1 of airway function (Table 3). More comprehensive analysis of lung volumes (i.e., measuring TLC, FRC, and 17  RV), flows (i.e., measuring expiratory flow rates and analyzing maximum expiratory flow-volume curves (MEFV)), diffusion capacity, and static pressures are necessary to draw thorough conclusions about the effect of competitive swimming on lung development. Specifically, assessing changes in TLC and DL,CO may elucidate irreversible anatomical adaptations, whereas FVC may only be indicative of functional changes (9).  1.1.6 Summary Thus, the following key points can be concluded from the current literature:  1. While two small studies have observed no differences in TLC in 9-10 y old (18) or FVC in 9-11 y old (43) swimmers, greater lung volumes have been observed in large cohorts of swimmers as young as 7-8 y (11, 17, 23, 26, 27). This suggests even the youngest swimmers already have enhanced lung function.  2. Whether this difference is due to genetic endowment or an adaptation to swim training at an early age is not clear, as lung function has not been measured in swimmers prior to age 7 y. 3. Reports of lung volumes in swimmers at the beginning of training are conflicting, as greater lung capacities have been reported in 7-12 y (23) but not in 9-11 y (43) or 9-13 y (9) old children in their first year of swim training. 4. Longitudinal analyses has provided four different conclusions regarding changes in lung capacities with swim training: first, no differences before or after (42, 43); second, no differences before but greater capacities after (13, 16, 18); third, greater capacities 18  before that did not increase further (9, 11, 17); and, fourth, greater capacities before that further increased (15). 5. Studies longitudinally assessing lung volumes in swimmers during puberty have found conflicting results. Some have found FVC (9, 16) and TLC (15) increased more than can be expected due to maturational growth alone, while others have not (FVC (17), TLC (9)). 6. A greater diffusion capacity has been observed across all ages and heights of swimmers (11, 33), which is likely related to their larger lung volumes. There is no conclusive evidence that competitive swimming accentuates increases in DL,CO. 7. Differences between and weaknesses of previous studies underlie the difficulty in determining whether differences are due to genetic endowment, a training adaptation, or both.  There is need for a longitudinal study that comprehensively assesses lung function (i.e., lung volumes, spirometry, diffusion capacities, and pressures) in pubertal competitive swimmers compared to healthy controls of similar age, size, and sexual maturity to further our understanding of pulmonary adaptations to competitive swimming. Moreover, whether competitive swimming affects ventilatory mechanics during exercise has not been studied and warrants investigation.  1.2 Ventilatory mechanics during growth Smaller lungs and airways, such as those found in adult women in comparison to adult men, can lead to more constrained ventilatory mechanics during exercise and subsequently an augmented oxygen cost of breathing (58), increased likelihood of experiencing exercise-induced 19  arterial hypoxemia (EIAH) (59), and, ultimately, impaired exercise performance (4). Moreover, higher levels of aerobic fitness and therefore an increased ventilatory demand may also lead to the development of expiratory flow limitation (EFL) at maximal exercise (60). Because children have similar lung structures and hyperventilatory responses to exercise as do adult women, it is possible that they are predisposed to the same ventilatory constraints during exercise (61). However, while much work has been done in adults, only a handful of reports have studied ventilatory mechanics in the healthy pediatric population (61-65).  Ventilatory mechanics can be assessed quantitatively using (1) the degree of EFL, (2) breathing strategy (i.e., regulation of operational lung volumes), and (3) the utilization of ventilatory capacity (V̇E/V̇ECAP) (66) and qualitatively by superimposing tidal flow-volume loops (FVL) on a graph of the maximum expiratory flow-volume curve (MEFV). Expiratory flow limitation occurs when expiratory flow does not change despite increases in transpulmonary pressure (67). In other words, for a given volume no greater expiratory flow can be generated, thus a shift towards higher operating lung volumes is necessitated to increase flow further. This, however, comes at a cost because operating volumes dictate muscle length (i.e., length-tension relationship) and the work required to overcome the elastic properties of the lung (i.e., pressure-volume relationship). Estimating the ventilatory capacity (V̇E/V̇ECAP) provides another useful tool, as one can determine the ventilatory demand imposed by the given breathing strategy (66). The prevalence of EFL in prepubescent children is high, ranging from 56% (63) to 93% (61) at maximal exercise, and both boys and girls are equally susceptible. However, the reason for this high prevalence is unclear. Nourry et al. compared 10 flow-limited and 8 non-flow-limited prepubescent children, finding that the two groups had different breathing strategies as exercise progressed despite similar resting pulmonary function (63). In the non-flow-limited group, the 20  decrease in operational lung volumes upon starting exercise was followed by a leftward shift towards greater operating lung volumes as intensity increased, enabling them to breathe at higher expiratory flows that prevented the onset of EFL. Conversely, the flow-limited group initially decreased and then maintained their end-expiratory lung volume (EELV), operating at lower lung volumes with smaller expiratory flows that made them susceptible to EFL. The leftward shift meant that the non-flow limited group was able to reach higher peak values for minute ventilation (V̇E) and V̇O2 and utilize a greater percentage (>90%) of their estimated maximum voluntary ventilation (MVV). The study by Swain et al. observed the opposite operating lung volume response (61). They studied 20 prepubescent boys and 20 prepubescent girls, finding a significant correlation between the increase in expiratory reserve volume (ERV) relative to FVC (ERV/FVC) from rest (i.e., the amount of dynamic hyperinflation) and the extent of EFL. In other words, they observed that EFL was associated higher operating lung volumes, a finding consistent with healthy adult populations (61). Given that no relationships were found between the severity of EFL and TLC, peak V̇E, or peak V̇O2, the authors suggested that prepubescent girls and boys experience similar rates of EFL but for different reasons. Prepubescent girls were limited by their capacity, as their smaller lung volumes and expiratory flows led to a smaller MEFV that then provided the main ventilatory constraint to exercise. On the other hand, prepubescent boys were constrained due to their increased demand. They had a bigger MEFV because of their larger lung volumes and expiratory flows, but it was still encroached upon because they had a higher metabolic demand (as evidenced by a higher peak V̇O2 than girls) (61). The boys (65.5 ± 6.1%) and girls (64.4 ± 5.7%) utilized a similar percentage of estimated MVV at peak exercise, values that may be lower than the previous study because they had a lower fitness level.  21  A follow-up study done five years later in 21 (11 boys, 10 girls) of the 40 prepubescent children provides the only observation of ventilatory mechanics in postpubescent children (62). The prevalence of EFL was 45% and 20% in boys and girls, respectively, much lower than prepubescent rates despite both the postpubescent boys and girls operating at higher lung volumes at maximal exercise. The authors suggested this was possible because greater growth of lung volumes and expiratory flows compared to improvements in exercise capacity increased the ventilatory capacity well beyond the metabolic demand. Thus, the postpubescent children could operate at higher lung volumes as a strategy to avoid EFL (62). Moreover, maturation may have lowered the sensitivity to CO2 during exercise (the authors noted a decreased ventilatory equivalent for carbon dioxide (V̇E/V̇CO2) at maximal exercise in postpubescence compared to prepubescence) which relatively decreased the ventilatory demand, further decreasing the likelihood of EFL. Unfortunately, no estimate of ventilatory capacity was provided postpubescence.   1.2.1 The effect of training on ventilatory constraints during growth How training affects ventilatory mechanics in children has only been assessed in one cross-sectional study. Comparing trained and untrained prepubescent children, larger lungs and therefore a greater MEFV in the trained group was associated with the leftward shift in operational lung volumes observed at maximal exercise (65), similar to the aforementioned difference from pre- to post-puberty. However, the prevalence of EFL was similar between the two groups (69 and 73% in trained and untrained, respectively) and the trained subjects utilized a higher proportion of their MVV. The authors suggested that the equal prevalence of EFL was due to trained subjects having a substantially greater ventilatory drive occupying more of the larger MEFV, while the untrained subjects simply had a smaller MEFV. There was a cost associated with this greater ventilatory 22  drive, as the trained subjects operated at a higher EELV which may have negatively impacted dyspnea and arterial saturation at maximal exercise. More research is needed on this topic, specifically comparing trained and untrained children with similar resting pulmonary structure and function.  1.2.2 The effect of ventilatory constraints on EIAH during growth Whether these ventilatory constraints ultimately lead to EIAH is unknown. Arterial desaturation during exercise in adults is the result of relative alveolar hypoventilation, increased ventilation-perfusion mismatching, and an alveolar-to-capillary diffusion limitation (64). The small and more mechanically constrained lungs of adult women can directly or indirectly lead to an increased susceptibility to EIAH by preventing an adequate alveolar hyperventilatory response (59). In prepubescent children, EIAH measured noninvasively with pulse oximetry at the ear was reported in approximately 30% of active children at maximal exercise and associated with smaller lungs (as measured by FVC) and greater ventilatory constraints (as assessed using breathing reserve) (64). Conversely, two other studies of prepubescent girls (68) and both boys and girls (61) found that EIAH did not occur in any subjects during maximal exercise, suggesting that the ventilatory constraints experienced were not of sufficient magnitude to cause arterial desaturation. Moreover, in a follow-up of the latter study, no postpubescent boys and girls desaturated during maximal exercise (62). More work is needed to clarify the prevalence of EIAH and its significance during growth. Since ventilatory capacity is primarily determined by anatomical features (i.e., lung size, airway size and geometry) (69), the larger lung volumes and expiratory flows of swimmers may be advantageous during exercise if it leads to a larger ventilatory capacity that makes them less 23  susceptible to ventilatory constraints during exercise. They may be able to generate higher flows at similar lung volumes, decreasing their susceptibility to EFL and allowing them to operate at lower relative lung volumes that may lower their work of breathing (WOB). Alternatively, the increased capacity could facilitate an increased metabolic and ventilatory demand within similar ventilatory constraints. Exploratory work is needed in swimmers to determine if they are afforded any benefits from their larger lungs.  1.3 Significance As mentioned, increased lung volumes and diffusion capacity may facilitate improved arterial oxygen saturation, increase ventilatory capacity, and provide greater buoyancy in the water. Cumulatively, these may lead to greater performance in meets and success in swimming. There is also benefit for the general population from studying the effect of swim training on lung development. Adolescence is a critical period during which physiological changes can significantly influence health throughout the lifespan (70). Years of competitive swim training during this period may lead to improvements in lung function that can persist into adulthood (12). However, increased exposure to chlorine derivatives while swimming may increase the likelihood of developing reactive airway disease later into a swimmer’s career (71). Therefore, studying changes in lung development will give us a greater understanding of the potential benefits and harms of competitive swimming during youth.  1.4 Conclusion Typically, the lungs do not beneficially adapt to physical activity. However, competitive swimmers consistently display exceptional pulmonary function. Whether this is an inherited or 24  acquired trait has been widely debated. Previous cross-sectional findings suggest that swimmers as young as 7 y old already have enhanced function, but swimmers before this age have not been examined. Longitudinal analyses of competitive swimmers during growth present contradicting results, and a limited number of studies have focused on changes during puberty. Moreover, a myriad of differences between and weaknesses of previous studies make it difficult to draw definitive conclusions regarding the relationship between competitive swimming and lung development. Additionally, whether this enhanced function improves ventilatory capacity and/or alters ventilatory mechanics during exercise has not been assessed. Given that the PGV for FVC (57, 72) and lung and chest wall dimensions (73) occur between 11-14 y old or Tanner stages 2-4 (16) in girls, a comprehensive and longitudinal assessment of lung function during this period of rapid growth is needed to provide further answers to the question: “genetic endowment, training adaptation, or both?”.   25  1.5 Purposes This thesis was designed to address the following questions: 1. Does competitive swim training during puberty affect lung development in healthy, pubescent girls? 2. Does competitive swim training during puberty affect ventilatory mechanics during exercise in healthy, pubescent girls?  Thus, the primary purpose of this longitudinal study was to determine if one season of competitive swimming during puberty affects lung development in female competitive swimmers as compared to healthy controls of similar age, sex, size, and maturity. The secondary purpose was to characterize their ventilatory mechanics during cycling exercise.   1.6 Hypotheses This thesis hypothesized that: 1. Swimmers will have greater increases in pulmonary function measurements. 2. Swimmers will have less ventilatory constraints due to their larger lungs.  Specifically, it was hypothesized that swimmers would have a greater increase in TLC as compared to a healthy control group. Moreover, because ventilatory capacity is primarily determined by anatomical features (i.e., lung size) (69), it was further hypothesized that the larger lungs of swimmers would be associated with an increased V̇ECAP and make them less susceptible to ventilatory constraints (i.e., higher operational lung volumes and decreased prevalence and/or severity of EFL) during exercise. 26  METHODS 2.1 Subjects Twenty-four healthy females (12 SWIM and 12 CON) aged 11-14 y old were recruited to participate in the study. All of the subjects had no history of smoking, no previous exposure to hypoxia (i.e., altitude) for a period greater than 6 weeks, no pre-existing reactive airway disease (e.g., asthma), and no previous use of an inhaler. The swimming group (SWIM) consisted of 12 competitive swimmers from 7 Greater Vancouver swim clubs, where each swimmer was required to maintain a vigorous training volume as instructed by her coach. Ten swimmers competed in regional or provincial meets, including one who competed at the national level. An eleventh swimmer trained predominantly for water polo during the study period, but was still included because her training involved weekly speed swimming sessions and she competitively swam during the summer season. A twelfth subject in the SWIM group was excluded from analysis due to a non-cardiorespiratory illness that interrupted her swim training. Twelve controls (CON) were recruited from family and friends of the hospital and university staff and the University of British Columbia’s recreational activities programs. They primarily participated in gymnastics, dance, and team sports, but none of them competed in any sports or activities that required sport-specific endurance training. Two controls declined to return for the follow-up visit. Thus, 11 swimmers and 10 controls completed the entire experimental protocol and were included in the analysis.  2.2 Experimental overview Testing was performed in the Respiratory Clinic (RC) and Exercise Physiology Laboratory in the Children’s Heart Centre (EPL) at BC Children’s Hospital. Each subject completed two identical visits; the first at the beginning of the swim season between September and November 27  (PRE), and the second at the end of the swim season in May or June (POST). Subjects were accompanied by a parent or guardian at all visits. All measurements and procedures were approved by the University of British Columbia’s Children’s and Women’s Clinical Research Ethics Board (approval certificate number: H15-00977), which conforms to the Declaration of Helsinki. After being greeted outside the RC, subjects completed an informed assent (11-13 y old) or adolescent assent (14 y old) form and the parent or guardian provided medical history and informed consent. Sexual maturity rating (SMR) was assessed at all visits using a validated form (74) containing sex-specific illustrations and written descriptions of pubic hair and breast development (Appendix C) corresponding to Tanner’s five pubertal stages (75). Each subject had the option of self-reporting her SMR or being evaluated by her parent or guardian. Subjects were then taken into the RC where a respiratory therapist (RT), experienced in working with pediatric patients, measured their height (seca 217, seca GmbH & Co. KG., Hamburg, Germany), weight (Scale-Tronix, White Plains, NY, USA), and hemoglobin (Hb) (Pronto-7, Masimo Corp., Irvine, CA, USA). A pulmonary function test (PFT), consisting of spirometry, lung volumes, and diffusion capacity (MasterScreen™ PFT system, Jaeger, CareFusion Corp., San Diego, CA, USA), was completed with the subject sitting and wearing nose clips. Subjects were then taken into the EPL where maximal static pressure maneuvers (Mouth Pressure Meter, Micro Direct, Inc., Lewiston, ME, USA) and a graded maximal exercise test on a cycle ergometer (Excalibur Sport, Lode BV, Groningen, Netherlands) were performed. Before the exercise test, five minutes of seated resting metabolic data were obtained, followed by multiple FVC and graded forced vital capacity (gFVC) maneuvers. Forced vital capacity and gFVC maneuvers were also performed after the exercise test. After the second visit, subjects filled out a modified version of a validated 28  physical activity questionnaire (PAQ) (76-78) and coaches reported the training load during the study period for the SWIM group (Appendix C).   2.3 Measurements and procedures 2.3.1 Spirometry With the RT, subjects performed FVC maneuvers according to ATS/ERS guidelines (79) to determine FVC, FEV1, FEV1/FVC, peak expiratory flow (PEF), maximum mid-expiratory flow (FEF25-75%), and forced expiratory flows (FEF) when 25%, 50%, and 75% of the FVC had been expired (FEF25%, FEF50%, and FEF75%, respectively).   2.3.2 Single-breath carbon monoxide diffusion and helium dilution technique Using the single-breath technique, FRC, inspiratory capacity (IC), and ERV were measured by helium dilution and DL,CO and alveolar volume (VA) by carbon monoxide (CO) diffusion according to ATS/ERS guidelines (80, 81). Total lung capacity, RV, and VC were calculated as follows: TLC = FRC + IC, RV = FRC – ERV, and VC = TLC – RV. The transfer coefficient for carbon monoxide (DL,CO/VA), a measurement of diffusion capacity standardized to alveolar volume, was determined by dividing DL,CO by VA. Because DL,CO depends on the concentration of Hb in the blood, measurements were corrected for Hb (DL,COc) using the equation: 𝐷𝐿,𝐶𝑂𝑐 =𝐷𝐿,𝐶𝑂×1.79.38+𝐻𝑏 (81).  2.3.3 Maximal static pressures Maximum inspiratory pressure (PIMAX) from RV and maximum expiratory pressure (PEMAX) from TLC were measured at the mouth using a handheld device according to ATS/ERS 29  guidelines (82). Maneuvers were performed in the sitting position a minimum of 3 and a maximum of 9 times, with at least one minute of rest in between.  2.3.4 Resting baseline Subjects then sat on the cycle ergometer for five minutes and breathed quietly through a low-resistance, two-way non-rebreathing valve (model 2700B, Hans Rudolph, Kansas City, MO, USA). The valve was connected by large bore tubing to independently calibrated pneumotachographs (model 3813, Hans Rudolph, Kansas City, MO, USA) to separately measure inspiratory and expiratory flow. Expired gas was collected in a mixing chamber from which independent sampling lines were drawn through Nafion tubing and a de-humidification chamber containing Drierite and into calibrated O2 and CO2 analyzers (#17625 Fast Response O2 Analyzer and #17630 Silver Edition CO2 Analyzer, respectively, VacuMed, Ventura, CA, USA). Heart rate (HR) was measured using a HR monitor (T34, Polar Electro, Kempele, Finland) worn around the chest. At the end of the five-minute period, subjects were instructed to perform several IC maneuvers using the instructions, “at the end of a normal breath out, take a maximal breath all the way in until you fill up your lungs, then return to normal breathing.”  2.3.5 Forced vital capacity and graded forced vital capacity maneuvers While still seated on the cycle ergometer, subjects performed multiple FVC and gFVC maneuvers to construct the MEFV. The FVC maneuvers were performed according to ATS/ERS guidelines (79), while the gFVC maneuvers were performed with extensive coaching to ensure the subjects inspired maximally but expired maximal volumes at sub-maximal efforts (83). Both maneuvers were repeated after the maximal exercise test, as gFVC maneuvers minimize thoracic 30  gas compression and post-exercise maneuvers may reflect exercise-induced bronchodilation, together leading to better representation of the MEFV (83).  2.3.6 Graded maximal exercise test After warming-up on the cycle ergometer for three minutes at 20 W, intensity was increased stepwise by 20 W every two minutes until exhaustion to ensure a test duration of less than 20 minutes. Subjects were instructed to maintain a pedalling frequency of 60 revolutions per minute (rpm) throughout the test, which was terminated when the subject could no longer maintain 50 rpm for at least five seconds despite strong verbal encouragement from the researchers. During each stage, subjects were asked to perform two IC maneuvers; the first around one minute and 10 seconds (1:10) into the stage and the second approximately 10 seconds before the end of each stage (1:50). Following the first IC maneuver, subjects were asked to provide their rating of perceived exertion (RPE) using the validated Children’s OMNI Scale of Perceived Exertion (84).  2.3.7 Data collection and processing Summary data for spirometry, lung volumes, and diffusion capacity were listed on a standard lab report printed and provided by the RT. Raw ventilatory and metabolic data were recorded continuously during the resting baseline period and exercise test using a 16-channel analog-to-digital data acquisition system (PowerLab/16SP model ML 795, ADInstruments, Colorado Springs, CO, USA) and stored on a laboratory computer for subsequent analysis (LabChart v6.1.3, ADInstrument, Colorado Springs, CO, USA).  31  2.4 Data analysis 2.4.1 Predictive values Predictive regression equations used to generate reference values for each subject are listed in Appendix D. Spirometric measurements and lung volumes were compared to predicted values determined using age-, height-, and sex-based regression equations from a large, longitudinal study comprising of subjects with similar age and ethnicity (85). As recommended, predictive values for FRC/TLC, RV/TLC, and VC were derived from those for TLC, FRC, and RV (86). Predictive values for diffusion capacity, VA, and DL,CO/VA were determined from age-, height-, and sex-based regression equations from a large, multi-centre cross-sectional study that also comprised of subjects with similar age and ethnicity (87). Regression equations based on age, height, weight, and sex and generated from a large cross-sectional study were used to calculate reference values for PIMAX and PEMAX (45). A sex- and weight-based regression equation for maximal oxygen consumption (V̇O2MAX) measured using a similar cycling protocol and 6-17 year old children was used as the reference value for V̇O2MAX (88). When the limits of abnormality based upon the predictive equation’s 95% confidence intervals were provided, each subject’s %-predicted value was identified as normal or abnormal (85) (Appendix A).  2.4.2 Dysanapsis ratio The dysanapsis ratio (DR) was calculated according to the equation: 𝐷𝑅 =𝐹𝐸𝐹50%𝑉𝐶 × 𝑃𝑠𝑡(𝐿)50, where Pst(L)50 was the static recoil pressure at 50% of VC (89). Because static recoil pressures were not measured directly, Pst(L)50 was estimated using a height-based regression equation derived from elastic recoil measurements in 130 children and adolescents aged 6-17 years old: 𝑃𝑠𝑡(𝐿)50 = 0.0770×𝐻𝑒𝑖𝑔ℎ𝑡 − 3.3871 (90). Because there is no evidence of a difference in lung 32  elasticity in swimmers (29), the same regression equation was used for both swimmers and controls.  2.4.3 Maximum expiratory flow-volume curve Maximum expiratory flow-volume curves were created by superimposing all FVC and gFVC maneuvers and determining the highest flow for each 10 ml volume increment of the FVC. Constructed curves were used to calculate numerical descriptions of the MEFV: the slope ratio (SR), β-angle (β°), and flow ratio (FR). Slope ratio, a quantity describing the emptying of the lungs, was calculated instantaneously at each 10 ml volume increment by comparing the ratio of the tangent to the chord slopes (91). To determine the tangent slope, flows and volumes 200 mL above and below the point of interest were used (92). While tangent slopes were also calculated with increments of 50, 100, and 150 ml, no differences in SR were found; therefore, 200 ml was selected to minimize small oscillatory noise. The instantaneous SR were filtered down to 31 discrete points in 2% increments between 80 and 20% of the expired FVC to ensure all subjects could be compared, regardless of FVC size (92). These filtered values were also averaged to provide an overall SR. The β°, which describes the curvature of the MEFV around 50% of the FVC, was calculated as the angle above and to the right of the MEFV, created from three points: (1) the PEF, (2) the FEF50%, and (3) the point of zero flow and volume (93). Lastly, the FR characterized the curvature at low lung volumes by comparing the FEF75% with an “ideal” FEF75% (94). The latter was calculated by multiplying the FEF50% by 0.5, thus quantifying the flow had it decreased linearly from 50% of the expired FVC.   33  2.4.4 Metabolic data The customized metabolic cart used tidal volume (VT) and breathing frequency (fB) measured from expiratory flow to calculate expired V̇E; V̇E and the Haldane conversion to calculate inspired minute ventilation (V̇I); and V̇E, V̇I, and the mixed expiratory fractions of O2 (FEO2) and CO2 (FECO2) to determine V̇O2, carbon dioxide production (V̇CO2), and the respiratory exchange ratio (RER). All ventilatory parameters (e.g., VT, V̇E) were reported in BTPS and metabolic parameters (i.e., V̇O2, V̇CO2) in STPD. Baseline and exercise data were presented as the 20-30 second average before the IC maneuver used in the calculation of operational lung volumes (see below). Maximal exercise data were presented as the 20-30 second average before the final successful IC maneuver. Subjects were pooled together according to their group (SWIM vs. CON), time point (PRE vs. POST), and work rate. Because the subject with the shortest test finished during the fifth stage (and other subjects completed up to 10 stages), pooled exercise data was compared at six work rates expressed relative to peak work rate (WMAX) (resting baseline (BL), 30%, 50%, 70%, 90%, and 100% of WMAX).   2.4.5 Operational lung volumes End-expiratory lung volume was determined by subtracting the IC volume (corrected for pneumotachograph drift using the 5-12 breaths preceding the maneuver) from the subject’s FVC, while end-inspiratory lung volume (EILV) was calculated by summing VT and EELV. The difference between the IC and EILV was the inspiratory reserve volume (IRV). By default, the first IC maneuver of the stage and the preceding 20-30 seconds were used to determine the operational lung volumes and metabolic data, respectively. However, in the case where the first IC maneuver was not performed properly (as assessed using the inspiratory flow), the second IC 34  maneuver during the stage and its preceding 20-30 second period were used. The last successful IC maneuver in the test was used for maximal exercise data. This meant that both maneuvers were analyzed for subjects who performed two IC maneuvers during their last stage.  2.4.6 Tidal flow-volume loops Average tidal flow-volume loops (FVL) were generated for each stage by averaging the flows over the 10 ml volume increments of the VT from the tidal breaths in the same 20-30 second period preceding the IC maneuver as was used for the metabolic data. Thus, FVL were composed of a minimum of 5 tidal breaths during resting baseline to a maximum of 30 tidal breaths during maximal exercise. Apneic and double breaths were excluded. To provide a qualitative assessment of ventilatory constraints, the FVL were then superimposed onto the MEFV by aligning the VT with the EELV.  2.4.7 Expiratory flow limitation Expiratory flow limitation EFL was determined by calculating the amount of overlap between the tidal FVL and MEFV. For each 10 m increment of the VT, the FVL’s expiratory flow was compared with the corresponding MEFV’s flow. Increments where the FVL’s expiratory flow exceeded that of the MEFV were considered flow limited. The number of flow-limited increments could be expressed as a percentage of the total number of increments (i.e., as a percentage of the VT), and subjects whose VT was greater than 5% flow limited were deemed to exhibit EFL (95).    35  2.4.8 Ventilatory capacity Ventilatory capacity, which is the theoretical maximum minute ventilation based on the subject breathing at the maximum expiratory flow across the entire range of the tidal breath, was calculated for each stage from the MEFV, VT, EELV, and ratio of inspiratory-to-expiratory time (96, 97). This was accomplished by dividing the VT into 20-30 ml volume segments and determining the maximum expiratory flow for each. The minimum expiratory time was found by dividing the maximum expiratory flow by the volume segment and summing the resulting times for each volume segment. Using the ratio of inspiratory-to-expiratory time, the minimum inspiratory time was calculated and added to the minimum expiratory time, from which the reciprocal was the theoretical maximum fB for the given VT and EELV. The maximum fB was multiplied by the VT to produce the V̇ECAP, which was then compared with the V̇E to provide a quantitative assessment of the extent to which each subject was encroaching on their breathing reserve (expressed as V̇E/V̇ECAP).  2.4.9 Composite maximum expiratory flow-volume curves and tidal flow-volume loops  Composite MEFV and FVL were created for each group (SWIM and CON) at both time points (PRE and POST) to qualitatively characterize the ventilatory constraints during the maximal exercise test. To construct the composite MEFV, each subject’s MEFV had to be reduced to the same number of volume data points by filtering the % FVC expired according to the subject with the smallest FVC. Then, for each % FVC expired increment, the expiratory flow and absolute FVC expired were averaged. A similar process was used to construct composite FVL, except the % VT expired and subject with the smallest VT for a given relative work rate were used.  36  2.4.10 Statistical analysis Two-way mixed-factorial analysis of variance (ANOVA) tests were used to determine statistically significant interactions and main effects between the groups and time points for descriptive characteristics, spirometry, lung volumes, diffusion capacity, maximal static pressures, DR, MEFV quantities (SR, β°, and FR), and V̇O2MAX. For these tests, group served as the between-subjects independent variable (two levels: SWIM and CON) and time point was the within-subjects independent variable (two levels: PRE and POST). Three-way mixed-factorial ANOVA compared the exercise response between the groups, time points, and work rates for all metabolic and ventilatory parameters except RPE. In addition to the independent variables (group and time point), relative work rate was the second within-subjects independent variable (six levels: BL, 30%, 50%, 70%, 90%, and 100% of WMAX). A generalized estimating equation was used to assess SMR and RPE, as data for these variables were ordinal. A generalized estimating equation was also used to determine if the prevalence of EFL was different between SWIM and CON at PRE and POST. A three-way mixed-model ANOVA compared instantaneous SR for the groups and time points across the expired FVC. Normality for each combination of levels (e.g., SWIMxPRExBL) was assessed qualitatively by visually inspecting descriptive statistics (including kurtosis), histograms, and Q-Q plots and quantitatively using a suitable Shapiro-Wilk test for small samples, as recommended by Tabachnick and Fidell (98). Outliers were identified through visual inspection of box and whisker plots and were kept in the analysis to maintain sample size, for theoretical reasons (i.e., to avoid subjectively removing data points), and because ANOVA are quite robust to violations of normality. Homogeneity of variances between the groups (i.e., between-subjects factor) for each combination of time point and work rate (i.e., within-subject factors) was tested using Levene’s 37  Test of Equality of Error Variances. Given similar group sizes, data that moderately departed from the assumption of equal variances were still interpreted unless qualitative assessments of positive correlations between group and level (i.e., the group with the larger variance also had the greater mean) were found. Mauchly’s Test of Sphericity was used to test if the variances of the differences between levels of the within-subject factors for both groups of the between-subjects factor were equal. When a significant difference rejected the assumption of sphericity, the Greenhouse-Geisser adjusted test was interpreted. Statistically significant F-ratios, as well as those approaching statistical significance (i.e., p≤0.10), were further analyzed for magnitude and direction using independent and paired t-tests for between- and within-subject data, respectively (Bonferonni-corrected levels of significance were not used (99)). Main effects were not interpreted if statistically significant interactions were found. Independent t-tests were used to compare the time between visits and self-reported physical activity levels. Associations between swimming history and pulmonary function as well as swim training volume and changes in pulmonary function were quantified using Pearson’s correlation coefficient. A level of significance of p<0.05 was used for all statistical comparisons, and a suitable Shapiro-Wilk test for small samples assessed the assumption of a normal distribution. Statistical tests were performed using SPSS statistics (Version 20, IBM Corporation, Armonk, NY, USA).    38  RESULTS 3.1 Descriptive data Anthropometric data is presented for both groups in Table 4. The two groups had similar age (p=0.10) and height (p=0.38) during both PRE and POST; SWIM tended to be heavier (p=0.10) with a larger body mass index (BMI) (p=0.10) and body surface area (BSA) (p=0.12), but these differences were not statistically significant. Most subjects listed their SMR as pubertal (between Tanner stage 2 and 4), and there were no differences between groups (p=0.27). Hemoglobin was similar for all groups (p=0.89) and time points (p=0.15). There were no statistically significant interactions between group and time point and no main effect of group for any anthropometric variable. The average follow-up time was similar between the two groups (7.3 ± 0.5 and 7.6 ± 0.4 months for SWIM and CON, respectively; p=0.16).   39  Table 4 – Anthropometric data   Swimmers (n=11) Controls (n=10) Interaction p-value Group p-value Time point p-value Age (y) PRE 12.4 ± 0.8 13.2 ± 1.3 0.53 0.10 <0.001  POST 13.0 ± 0.8 13.8 ± 1.3   POST > PRE Height (cm) PRE 161.3 ± 7.9 158.3 ± 7.4 0.59 0.38 <0.001  POST 163.4 ± 6.9 160.7 ± 7.0   POST > PRE Weight (kg) PRE 52.4 ± 10.8 46.3 ± 5.4 0.71 0.10 <0.001  POST 55.8 ± 9.8 49.4 ± 5.6   POST > PRE BMI (kg·m-2) PRE 19.9 ± 2.5 18.5 ± 1.7 0.54 0.10 <0.001  POST 20.8 ± 2.3 19.1 ± 1.6   POST > PRE BSA (m2) PRE 1.53 ± 0.19 1.43 ± 0.11 0.91 0.12 <0.001  POST 1.59 ± 0.17 1.48 ± 0.11   POST > PRE Hb (g·dl-1) PRE 13.3 ± 1.5 13.5 ± 0.6 0.64 0.89 0.15  POST 13.8 ± 1.0 13.7 ± 1.3    SMR pubic hair#    0.81 0.27 <0.001  I PRE 1 (9%) 1 (10%)   POST > PRE   POST 0 (0%) 0 (0%)     II PRE 1 (9%) 1 (10%)      POST 1 (9%) 1 (10%)     III PRE 2 (18%) 5 (50%)      POST 1 (9%) 4 (40%)     IV PRE 6 (55%) 2 (20%)      POST 6 (55%) 3 (30%)     V PRE 1 (9%) 1 (10%)      POST 3 (27%) 2 (20%)    SMR breasts#    0.54 0.23 <0.01  I PRE 0 (0%) 1 (10%)   POST > PRE   POST 0 (0%) 0 (0%)     II PRE 2 (18%) 1 (10%)      POST 0 (0%) 0 (0%)     III PRE 1 (9%) 4 (40%)      POST 1 (9%) 4 (40%)     IV PRE 8 (73%) 3 (30%)      POST 8 (73%) 5 (50%)     V PRE 0 (0%) 1 (10%)      POST 2 (18%) 1 (10%)    Values are expressed as mean ± SD except # presented as count (relative frequency). BMI, body mass index; BSA, body surface area; Hb, hemoglobin; POST, follow-up visit; PRE, initial visit; SMR, sexual maturity rating.  Self-reported physical activity levels for both groups and swim training history for SWIM are found in Table 5. Both groups self-reported similar levels of physical activity, with 8 out of 10 40  CON subjects and 10 of the SWIM subjects (1 swimmer did not complete the questionnaire) meeting the Canadian Society for Exercise Physiology’s guideline of 60 minutes of moderate-to-vigorous intensity physical activity per day (100). The swimmers had a diversity of training backgrounds, with the age of onset of swim training ranging from 6.0 to 10.1 y old and experience ranging from 1.1 to 6.3 y. The 10 year-round swimmers trained 5-7 times per week, ranging from 2.5-4.8 km per session and 7.5-15.5 h and 10-30 km per week. All of them completed weekly breath control drills, with underwater dolphin or breast kick off of the wall being the most common drill. Only 3 swimmers performed freestyle breathing pattern drills (“hypoxic training”). The 11th swimmer’s weekly training regimen consisted of seven water polo (totalling 12 h in the pool) and one 3 km speed swimming sessions, but these did not include any breath control drills. Table 5 – Activity levels and swim training history  Swimmers (n=11) Controls (n=10) p-value PAQσ 3.1 ± 0.4 3.1 ± 0.5 0.58 Daily activity (min)σ 121 ± 25 110 ± 55 0.76 Starting swimming age (y) 9.2 ± 1.4 - - Swimming experience (y) 3.2 ± 1.8 - - Swim distance per week (km) 19 ± 8 - - Swim time per week (h) 9.1 ± 3.6 - - Non-swim training time per week (h) 1.0 ± 0.6 - - Breath control drills time per week (h) 1.3 ± 1.1 - - Breath control drills#     Underwater kick 8 (73%) - -  Freestyle breathing pattern (“hypoxic training”) 3 (27%) - -  Snorkel sets 1 (9%) - -  Other 1 (9%) - -  None 1 (9%) - - All values are expressed as means ± SD. σ swimmers n=10. # data presented as count (relative frequency). NS, not statistically significant. PAQ, self-reported physical activity questionnaire score.  41  3.2 Spirometry Swimmers had statistically significantly larger values for all spirometric measurements except FEV1/FVC (p=0.49) and FEF25% (p=0.08) (Table 6). This is illustrated in Figure 1, where the average MEFV for SWIM at both time points has a wider FVC and higher peak flow. However, the figure also suggests that SWIM and CON produced a similar flow for a given FVC. There was no change in FEV1/FVC in either SWIM or CON. Comparing the groups to their reference values, swimmers consistently exceeded their predicted function (means ranging from 97 to 125%) and had, on average, an abnormally high FVC. The controls were more similar to their predicted function, on average ranging from 78 to 102% of their reference values. Assessing the pulmonary function data individually, seven swimmers had a %-predicted FVC during at least one visit that was above the limits of abnormality (Appendix A). None had a spirometric value below the limits of abnormality. Conversely, four controls had at least one abnormally low spirometric value and none had a measurement that was abnormally high. While a main effect of group was noted for almost all spirometric measurements (except FEV1/FVC (p=0.49) and FEF25% (p=0.08)), no statistically significant interactions were found.  42  Table 6 – Spirometry   Swimmers (n=11) Controls (n=10) Interaction p-value Group p-value Time point p-value FVC (l) PRE 3.92 ± 0.71 3.13 ± 0.50 0.27 <0.01 <0.001  POST 4.15 ± 0.61 3.28 ± 0.54  SWIM > CON POST > PRE FVC (% pred) PRE 123 ± 11 102 ± 11 0.24 <0.001 0.28  POST 125 ± 10 101 ± 11  SWIM > CON  FEV1 (l) PRE 3.34 ± 0.61 2.61 ± 0.43 0.23 <0.01 <0.001  POST 3.55 ± 0.57 2.74 ± 0.43  SWIM > CON POST > PRE FEV1 (% pred) PRE 117 ± 11 95 ± 13 0.21 <0.001 0.35  POST 119 ± 10 94 ± 12  SWIM > CON  FEV1/FVC (%) PRE 85 ± 2 84 ± 7 0.98 0.49 0.63  POST 85 ± 3 84 ± 7    PEF (l·s-1) PRE 6.48 ± 0.92 5.70 ± 0.86 0.21 0.03 <0.001  POST 6.97 ± 0.84 6.00 ± 0.77  SWIM > CON POST > PRE PEF (% pred) PRE 97 ± 9 86 ± 10 0.24 <0.01 0.02  POST 101 ± 8 87 ± 10  SWIM > CON POST > PRE FEF25-75% (l·s-1) PRE 3.56 ± 0.73 2.74 ± 0.81 0.47 0.02 0.04  POST 3.76 ± 0.84 2.85 ± 0.83  SWIM > CON POST > PRE FEF25-75% (% pred) PRE 100 ± 15 79 ± 22 0.64 0.01 0.80  POST 101 ± 15 78 ± 22  SWIM > CON  FEF25% (l·s-1) PRE 5.66 ± 0.87 4.82 ± 1.22 0.57 0.08 <0.001  POST 6.10 ± 0.99 5.16 ± 1.31   POST > PRE FEF25% (% pred) PRE 115 ± 10 98 ± 23 0.65 0.04 0.09  POST 119 ± 14 101 ± 24  SWIM > CON  FEF50% (l·s-1) PRE 4.03 ± 0.85 3.08 ± 0.90 0.74 0.02 0.14  POST 4.20 ± 0.95 3.19 ± 0.87  SWIM > CON  FEF50% (% pred) PRE 118 ± 20 91 ± 25 0.96 <0.01 0.75  POST 117 ± 18 90 ± 23  SWIM > CON  FEF75% (l·s-1) PRE 1.90 ± 0.44 1.39 ± 0.43 0.16 <0.01 <0.01  POST 2.19 ± 0.59 1.48 ± 0.42  SWIM > CON POST > PRE FEF75% (% pred) PRE 107 ± 17 80 ± 24 0.22 <0.01 0.16  POST 116 ± 22 81 ± 23  SWIM > CON  All values are expressed as mean ± SD. FVC, forced vital capacity; FEV1, forced expiratory volume in one second; PEF, peak expiratory flow; FEF, forced expiratory flow; SWIM, swimmers; CON, controls; POST, follow-up visit; PRE, initial visit. 43   Figure 1 – Composite maximum expiratory flow-volume curve from the pulmonary function test. From left to right, data points represent total lung capacity, peak expiratory flow (PEF), forced expiratory flow when 25% (FEF25%), 50% (FEF50%), and 75% (FEF75%) of the forced vital capacity (FVC) has been expired, and residual volume (RV).   3.3 Lung volumes Individually, swimmers had a greater TLC than controls for nearly all heights (Figure 2), meaning that the swimmers as a group had a larger TLC at both PRE and POST (Table 7). However, there was no statistically significant interaction between group and time point for TLC (p=0.29). Because RV was the same between groups, the greater TLC in swimmers was due to a larger VC whilst RV/TLC tended to be smaller in swimmers compared to controls (p=0.07). Similar to the spirometry results, swimmers exceeded their predictions for TLC (ranging 100-44  123%) whereas controls were around their expected values (81-106%; Figure 3). Two swimmers, but no controls, had a TLC considered to be abnormally large. There was no correlation between starting age of swimming and TLC (r=-0.39, p=0.23) or %-predicted TLC (r=0.20, p=0.56), or years of training history and %-predicted TLC (r=-0.12, p=0.72) (Figure 4). Moreover, there were no significant correlations between swim training per week (km) and absolute (r=0.09, p=0.78) or relative (r=-0.02, p=0.95) change in TLC (Figure 5). In fact, there were no trends or significant correlations between any pulmonary function parameter and starting age or training history (for %-predicted values) whereby an earlier age of swimming onset or more years of swim training experience correlated with a greater absolute or %-predicted value (Table 8). Similarly, no significant correlations were found between the absolute or relative change in a pulmonary function parameter and training per week (expressed either in hours or kilometres) (Table 9). Lastly, when the swimmers and controls were combined into one group, no association was found between daily moderate-vigorous physical activity levels and relative change in TLC (r=0.08, p=0.75) (Figure 6).  Statistically significant interactions between group and time point were observed for FRC (p=0.04), %-predicted FRC (p=0.01), and FRC/TLC (p=0.03). Post-hoc comparisons showed that swimmers increased FRC from PRE to POST (p<0.01), but there were no differences between PRE and POST for controls (p=0.80) or between the two groups (PRE: p=0.94, POST: p=0.28). There was no difference in %-predicted FRC between swimmers and controls at PRE (p=0.88), whereas at POST the swimmers were larger (p=0.05). There was no change from PRE to POST in swimmers (p=0.16), while in controls %-predicted FRC decreased (p=0.04). Conversely, FRC/TLC tended to decrease from PRE to POST in the controls (p=0.06) and was larger than the swimmers at PRE (p=0.001) and POST (p=0.07). 45   Figure 2 – Total lung capacity for individual subjects in relation to their height. Individual data are presented with an open symbol connected by a solid line, while group averages have a closed symbol connected by a hashed line.    46  Table 7 – Lung volumes   Swimmers (n=11) Controls (n=10) Interaction p-value Group p-value Time point p-value TLC (l) PRE 4.73 ± 0.73 3.93 ± 0.46 0.29 <0.01 <0.001  POST 5.08 ± 0.68 4.19 ± 0.64  SWIM > CON POST > PRE TLC (% pred) PRE 110 ± 7 94 ± 7 0.18 <0.001 0.15  POST 112 ± 8 94 ± 7  SWIM > CON  FRC (l) PRE 2.18 ± 0.43 2.19 ± 0.28 0.04 - -  POST 2.40 ± 0.39** 2.21 ± 0.40    FRC (% pred) PRE 102 ± 14 103 ± 4 0.01 - -  POST 106 ± 14 96 ± 7*    RV (l) PRE 0.99 ± 0.16 0.96 ± 0.20 0.97 0.70 0.01  POST 1.04 ± 0.19 1.01 ± 0.25   POST > PRE RV (% pred) PRE 96 ± 13 91 ± 14 0.85 0.39 0.46  POST 95 ± 16 90 ± 16    VC (l) PRE 3.74 ± 0.65 2.98 ± 0.45 0.24 <0.01 <0.001  POST 4.03 ± 0.61 3.18 ± 0.55  SWIM > CON POST > PRE VC (% pred) PRE 114 ± 9 94 ± 12 0.17 <0.001 0.02  POST 118 ± 11 95 ± 12  SWIM > CON POST > PRE FRC/TLC PRE 0.46 ± 0.05### 0.56 ± 0.04 0.03 - -  POST 0.47 ± 0.06 0.53 ± 0.05    FRC/TLC (% pred) PRE 93 ± 10### 110 ± 8 0.02 - -  POST 95 ± 13 103 ± 10*    RV/TLC PRE 0.21 ± 0.03 0.24 ± 0.05 0.92 0.07 0.72  POST 0.21 ± 0.03 0.24 ± 0.05    RV/TLC (% pred) PRE 88 ± 13 99 ± 20 0.83 0.15 0.10  POST 85 ± 15 96 ± 21    All values are expressed as mean ± SD. *p<0.05, **p<0.01 statistically significant difference within group between PRE and POST. #p<0.05, ###p<0.001 statistically significant difference within time point between SWIM and CON. TLC, total lung capacity; FRC, functional residual capacity; RV, residual volume; VC, vital capacity; SWIM, swimmers; CON, controls; POST, follow-up visit; PRE, initial visit. 47   Figure 3 – Percent-predicted total lung capacity (TLC), vital capacity (VC), functional residual capacity (FRC), and residual volume (RV) for each group during the PRE and POST visits. Bars are presented as mean ± SE. #p<0.05, significant difference between PRE to POST. *p<0.05, significant difference within group between PRE and POST.  48   Figure 4 – Percent-predicted total lung capacity at the initial measurement compared to the number of years of swimming experience for each swimmer.  49   Figure 5 – Relative change in total lung capacity from PRE to POST compared to the average weekly swim training volume for each swimmer.    50   Figure 6 – Relative change in total lung capacity from PRE to POST compared to the average daily moderate-vigorous physical activity in all subjects.    51  Table 8 – Correlations between swimming history and pulmonary function  Starting age (y) Years experience (y)  r P-value r P-value TLC (l) -0.39 0.23 0.65 0.03 TLC (% pred) 0.20 0.56 -0.12 0.72 FRC (l) -0.49 0.13 0.72 0.01 FRC (% pred) -0.18 0.59 0.22 0.51 RV (l) -0.06 0.87 0.35 0.29 RV (% pred) 0.45 0.17 -0.40 0.22 VC (l) -0.42 0.19 0.64 0.03 FRC/TLC -0.28 0.41 0.32 0.34 RV/TLC 0.34 0.31 -0.29 0.39 FVC (l) -0.42 0.20 0.64 0.03 FVC (% pred) -0.08 0.81 0.18 0.59 FEV1 (l) -0.38 0.25 0.62 0.04 FEV1 (% pred) -0.03 0.92 0.16 0.64 FEV1/FVC 0.25 0.46 -0.10 0.77 PEF (l·s-1) -0.36 0.28 0.68 0.02 PEF (% pred) -0.14 0.67 0.43 0.18 FEF25-75% (l·s-1) -0.26 0.44 0.50 0.11 FEF25-75% (% pred) -0.01 0.98 0.17 0.62 FEF25% (l·s-1) -0.38 0.25 0.66 0.03 FEF25% (% pred) -0.09 0.79 0.26 0.43 FEF50% (l·s-1) -0.31 0.35 0.50 0.12 FEF50% (% pred) -0.08 0.81 0.16 0.64 FEF75% (l·s-1) -0.20 0.56 0.44 0.17 FEF75% (% pred) 0.15 0.66 -0.01 0.97 DL,CO (ml·min-1·mmHg-1) 0.04 0.91 0.26 0.43 DL,CO (% pred) 0.61 0.04 -0.49 0.13 DL,COc (ml·min-1·mmHg-1) 0.15 0.66 0.08 0.81 DL,COc (% pred) 0.67 0.02 -0.67 0.02 VA (l) -0.39 0.24 0.65 0.03 VA (% pred) 0.21 0.54 -0.13 0.71 DL,COc/VA (ml·min-1 ·mmHg-1·l-1) 0.62 0.04 -0.71 0.01 DL,COc/VA (% pred) 0.55 0.08 -0.59 0.05 PIMAX (cm H2O) 0.12 0.71 0.00 1.00 PIMAX (% pred) 0.34 0.30 -0.31 0.36 PEMAX (cm H2O) -0.46 0.15 0.67 0.02 PEMAX (% pred) -0.43 0.19 0.54 0.09 TLC, total lung capacity; FRC, functional residual capacity; RV, residual volume; VC, vital capacity; FVC, forced vital capacity; FEV1, forced expiratory volume in one second; PEF, peak expiratory flow; FEF, forced expiratory flow; DL,CO, diffusion capacity of the lung for carbon monoxide; DL,COc, DL,CO corrected for hemoglobin; VA; alveolar volume; PIMAX, maximal inspiratory pressure; PEMAX, maximal expiratory pressure; SWIM, swimmers; CON, controls. 52  Table 9 – Correlations between weekly training volume and changes in pulmonary function  Training per week (h) vs. Δ in variable Training per week (h) vs. % Δ in variable Training per week (km)  vs. Δ in variable Training per week (km) vs. % Δ in variable  r P-value r P-value R P-value r P-value TLC (l) 0.35 0.29 0.14 0.67 0.09 0.78 -0.02 0.95 TLC (% pred) 0.46 0.15 0.47 0.14 0.17 0.62 0.20 0.56 FRC (l) -0.30 0.38 -0.21 0.54 0.05 0.87 0.16 0.63 FRC (% pred) -0.22 0.51 -0.17 0.62 0.14 0.68 0.21 0.54 RV (l) -0.07 0.84 -0.06 0.86 -0.24 0.47 -0.22 0.51 RV (% pred) 0.00 1.00 -0.01 0.97 -0.17 0.61 -0.19 0.58 VC (l) 0.34 0.30 0.16 0.64 0.25 0.46 0.12 0.72 FRC/TLC -0.35 0.30 -0.29 0.38 0.11 0.76 0.16 0.64 RV/TLC -0.10 0.76 -0.10 0.76 -0.23 0.50 -0.21 0.53 FVC (l) -0.01 0.98 -0.06 0.86 0.10 0.78 0.06 0.86 FVC (% pred) 0.19 0.57 0.19 0.57 0.25 0.45 0.29 0.38 FEV1 (l) -0.12 0.72 -0.25 0.45 -0.22 0.51 -0.26 0.43 FEV1 (% pred) 0.04 0.90 0.01 0.97 -0.11 0.74 -0.09 0.78 FEV1/FVC -0.15 0.66 -0.14 0.67 -0.33 0.32 -0.33 0.33 PEF (l·s-1) -0.40 0.22 -0.41 0.21 -0.39 0.23 -0.41 0.21 PEF (% pred) -0.30 0.36 -0.31 0.36 -0.32 0.33 -0.32 0.34 FEF25-75% (l·s-1) 0.29 0.38 0.22 0.51 0.00 1.00 -0.02 0.95 FEF25-75% (% pred) 0.30 0.37 0.30 0.37 0.04 0.91 0.04 0.91 FEF25% (l·s-1) 0.16 0.63 0.10 0.77 0.13 0.71 0.13 0.70 FEF25% (% pred) 0.22 0.53 0.19 0.58 0.20 0.56 0.20 0.56 FEF50% (l·s-1) 0.42 0.20 0.37 0.26 0.23 0.49 0.23 0.51 FEF50% (% pred) 0.39 0.24 0.42 0.20 0.26 0.44 0.26 0.43 FEF75% (l·s-1) -0.20 0.56 -0.33 0.33 -0.30 0.37 -0.34 0.31 FEF75% (% pred) -0.23 0.50 -0.26 0.43 -0.30 0.37 -0.30 0.38 DL,CO (ml·min-1·mmHg-1) 0.10 0.78 0.10 0.78 0.07 0.83 0.04 0.91 DL,CO (% pred) 0.25 0.45 0.20 0.56 0.16 0.64 0.12 0.73 DL,COc (ml·min-1·mmHg-1) 0.13 0.70 0.22 0.52 0.10 0.78 0.09 0.79 DL,COc (% pred) 0.30 0.37 0.24 0.48 0.19 0.57 0.16 0.64 VA (l) 0.36 0.28 0.16 0.65 0.09 0.78 -0.02 0.96 VA (% pred) 0.59 0.05 0.60 0.05 0.26 0.45 0.29 0.39 DL,COc/VA (ml·min-1 ·mmHg-1·l-1) 0.19 0.58 0.08 0.81 0.17 0.61 0.10 0.76 DL,COc/VA (% pred) 0.11 0.75 0.04 0.90 0.12 0.72 0.07 0.83 PIMAX (cm H2O) -0.14 0.69 -0.42 0.20 -0.33 0.32 -0.51 0.11 PIMAX (% pred) -0.17 0.62 -0.33 0.32 -0.40 0.23 -0.47 0.15 PEMAX (cm H2O) 0.13 0.70 0.05 0.89 0.16 0.63 0.09 0.79 PEMAX (% pred) 0.07 0.83 0.04 0.90 0.11 0.75 0.09 0.78 TLC, total lung capacity; FRC, functional residual capacity; RV, residual volume; VC, vital capacity; FVC, forced vital capacity; FEV1, forced expiratory volume in one second; PEF, peak expiratory flow; FEF, forced expiratory flow; DL,CO, diffusion capacity of the lung for carbon monoxide; DL,COc, DL,CO corrected for hemoglobin; VA; alveolar volume; PIMAX, maximal inspiratory pressure; PEMAX, maximal expiratory pressure; SWIM, swimmers; CON, controls.  53  3.4 Diffusion capacity Swimmers had a statistically significantly greater DL,COc (p=0.01) and VA (p<0.01) than controls (Table 10). However, when DL,COc was expressed relative to VA, there were no differences between the groups (p=0.20). Group averages for diffusion capacity did not change from PRE to POST in SWIM or CON, as illustrated in panel A of Figure 7. Conversely, VA increased (Figure 7B) and DL,COc/VA decreased (Figure 7C) from PRE to POST. While the swimmers had high %-predicted values for DL,COc and VA, controls were within normal limits. No statistically significant interactions were found.  Table 10 – Diffusion capacity   Swimmers (n=11) Controls (n=10) Interaction p-value Group p-value Time point p-value DL,CO (ml·min-1·mmHg-1) PRE 23.29 ± 2.87 20.76 ± 1.93 0.39 0.01 0.09  POST 24.33 ± 2.16 21.13 ± 3.10  SWIM > CON  DL,CO (% pred) PRE 121 ± 11 110 ± 8 0.28 <0.01 0.61  POST 122 ± 12 107 ± 8  SWIM > CON  DL,COc (ml·min-1·mmHg-1) PRE 23.43 ± 2.58 20.73 ± 1.88 0.63 <0.01 0.26  POST 24.09 ± 1.83 21.00 ± 3.18  SWIM > CON  DL,COc (% pred) PRE 122 ± 12 110 ± 8 0.55 <0.01 0.31  POST 121 ± 13 107 ± 9  SWIM > CON  VA (l) PRE 4.61 ± 0.71 3.83 ± 0.45 0.28 <0.01 <0.001  POST 4.96 ± 0.66 4.08 ± 0.64  SWIM > CON POST > PRE VA (% pred) PRE 114 ± 7 98 ± 7 0.17 <0.001 0.05  POST 117 ± 8 99 ± 8  SWIM > CON  DL,COc/VA (ml·min-1 ·mmHg-1·l-1) PRE 5.14 ± 0.60 5.44 ± 0.44 0.65 0.20 <0.001  POST 4.91 ± 0.56 5.16 ± 0.38   PRE > POST DL,COc/VA (% pred) PRE 101 ± 10 106 ± 8 0.68 0.25 <0.01  POST 97 ± 9 101 ± 8   PRE > POST All values are expressed as mean ± SD. DL,CO, diffusion capacity of the lung for carbon monoxide; DL,COc, DL,CO corrected for hemoglobin; VA; alveolar volume; SWIM, swimmers; CON, controls; POST, follow-up visit; PRE, initial visit.  54   Figure 7 – A) Diffusion capacity, B) alveolar volume, and C) DL,COc/VA for swimmers (○) and controls (Δ) during PRE and POST time points. Individual data are presented with an open symbol, while group averages have a closed symbol.  3.5 Maximal static pressures Maximal inspiratory mouth pressure tended to be greater in swimmers (p=0.06), and while PEMAX was significantly greater in swimmers (p=0.001) compared to controls (Table 11). Both groups increased PIMAX and PEMAX from PRE to POST (Figure 8), but no statistically significant interactions were noted. Table 11 – Maximal static pressures   Swimmers (n=11) Controls (n=10) Interaction p-value Group p-value Time point p-value PIMAX (cm H2O) PRE 87 ± 26 71 ± 24 0.19 0.06 <0.001  POST 103 ± 22 79 ± 26   POST > PRE PIMAX (% pred) PRE 96 ± 26 82 ± 30 0.23 0.13 <0.01  POST 109 ± 19 87 ± 30   POST > PRE PEMAX (cm H2O) PRE 112 ± 17 85 ± 16 0.77 <0.001 <0.01  POST 127 ± 17 98 ± 18  SWIM > CON POST > PRE PEMAX (% pred) PRE 104 ± 13 77 ± 19 0.83 <0.001 0.02  POST 114 ± 13 84 ± 19  SWIM > CON POST > PRE All values are expressed as mean ± SD. PIMAX, maximal inspiratory pressure; PEMAX, maximal expiratory pressure; SWIM, swimmers; CON, controls; POST, follow-up visit; PRE, initial visit.  55   Figure 8 – A) Maximal inspiratory pressure B) maximal expiratory pressure for swimmers (○) and controls (Δ) during PRE and POST time points. Individual data are presented with an open symbol, while group averages have a closed symbol.  3.6 Dysanapsis ratio As shown in Figure 9, the DR was similar between swimmers and controls for PRE (0.12 ± 0.02 vs. 0.12 ± 0.03 for SWIM and CON, respectively) and POST (0.11 ± 0.01 vs. 0.11 ± 0.03) (p=0.95). No significant interaction was found (p=0.61) and DR tended to decrease from PRE to POST (p=0.09). 56   Figure 9 – Dysanapsis ratio for swimmers (○) and controls (Δ) during PRE and POST time points. Individual data are presented with an open symbol, while group averages have a closed symbol.  3.7 Maximum expiratory flow-volume curve No differences between groups or time points were found for any characteristic of the MEFV curve, including FR, β°, and SR (  57  Table 12). When instantaneous SR was plotted versus FVC (Figure 10), there was a statistically significant main effect for instantaneous SR (p<0.001) but not for group (p=0.28) or time point (p=0.44). There were no significant interactions (Figure 10).    58  Table 12 – Maximal expiratory flow-volume curve characteristics   Swimmers (n=11) Controls (n=10) Interaction p-value Group p-value Time point p-value FR (%) PRE -3 ± 19 -5 ± 8 0.41 0.71 0.73  POST -5 ± 17 0 ± 10    β° (°) PRE 195 ± 9 194 ± 15 0.60 0.64 0.52  POST 194 ± 14 191 ± 12    SR (au) PRE 0.83 ± 0.23 0.89 ± 0.23 0.50 0.28 0.43  POST 0.83 ± 0.21 0.96 ± 0.23    All values are expressed as mean ± SD. FR, flow ratio; β°, β-angle; SR, slope ratio.     Figure 10 – Instantaneous slope ratio. The box represents the range of values (0.5-2.5) for homogenous emptying of the lung.  59   3.8 Maximal exercise test 3.8.1 Metabolic and ventilatory responses The metabolic response to exercise is displayed for selected variables in Figure 11, and maximal exercise data is listed in Table 13. Generally, subjects exercised longer and reached a higher work rate during the follow-up visit. The average RER at peak exercise was greater than 1.1 at both time points for SWIM and CON, suggesting that the tests were maximal. There were no statistically significant three-way interactions between group, time point, and relative work rate (Table 14), although VT approached statistical significance (p=0.08). Moreover, no statistically significant two-way interactions were found between group and time point. The only statistically significant two-way interactions involving group were with relative work rate for V̇O2 (p=0.02) and RER (p=0.01), with V̇CO2 approaching significance (p=0.08). Focusing on the main effects of competitive swimming, SWIM tended to have a higher work rate than CON throughout the exercise test (p=0.10); however, when work rate was expressed relative to body mass, there was no difference between groups (p=0.83). Thus, the larger size and therefore absolute work rate of the swimmers may have lead to the greater V̇CO2 (p=0.02), stimulating an increased V̇E (p=0.02) which was achieved by a similar fB (p=0.99) but greater VT (p=0.02). Although V̇O2 was greater in SWIM at each stage (p<0.05), these differences were abolished when expressed relative to body mass (p=0.26). Therefore, absolute V̇O2MAX was greater in swimmers initially (p<0.01) and at the follow-up measurement (p<0.001), but there were no differences in relative V̇O2MAX between groups (p=0.32) or time points (p=0.11). Swimmers had a smaller RER only at 50% WMAX (p=0.04) and 70% WMAX (p=0.04). Lastly, the HR response (p=0.39) and RPE 60  (p=0.85) were similar between the groups. Results were similar when compared at absolute work rates.   61  Table 13 – Interactions and main effects p-values for metabolic variables during the exercise test  3-way Group x work rate Time x work rate Group x time Work rate Group Time Work rate (W) 0.63 0.13 <0.001 0.31 - 0.10 - Work rate (W·kg-1) 0.68 0.83 0.08 0.39 <0.001 0.99 <0.01        POST > PRE HR (bpm) 0.94 0.70 0.56 0.36 <0.001 0.39 0.04        POST > PRE RPE 0.67 0.52 0.57 0.05 <0.001 0.61 0.97 VT (l) 0.08 0.62 <0.01 0.16 - 0.02 -       SWIM > CON  VT/FVC (%) 0.17 0.39 0.10 0.69 <0.001 0.32 0.69 fB (breaths per minute) 0.78 0.46 0.03 0.19 - 0.99 - V̇E (l·min-1) 0.53 0.11 <0.001 0.37 - 0.02 -       SWIM > CON  V̇O2 (l·min-1) 0.84 0.02 <0.01 0.85 - - - V̇O2 (ml·kg-1·min-1) 0.89 0.43 0.30 0.98 <0.001 0.26 0.17 V̇CO2 (l·min-1) 0.66 0.08 <0.001 0.50 - 0.02 -       SWIM > CON  RER 0.08 0.01 <0.01 0.61 - - - V̇E/V̇O2 0.46 0.48 <0.01 0.69 - 0.76 - V̇E/V̇CO2 0.69 0.65 <0.01 0.87 - 0.95 - EFL (% VT) 0.58 0.80 0.09 0.99 <0.001 0.95 0.07 V̇ECAP (l·min-1) 0.17 0.15 0.29 0.70 <0.001 0.23 0.25 V̇E/V̇ECAP (%) 0.44 0.75 <0.001 0.90 - 0.96 - HR, heart rate; RPE, rating of perceived exertion; VT, tidal volume; FVC, forced vital capacity; fB, breathing frequency; V̇E, expired minute ventilation; V̇O2, oxygen consumption; V̇CO2, carbon dioxide production; RER, respiratory exchange ratio; EFL, expiratory flow limitation; V̇ECAP, ventilatory capacity; SWIM, swimmers; CON, controls; POST, follow-up visit; PRE, initial visit.  62  Table 14 – Maximal exercise data   Swimmers (n=11) Controls (n=10) Duration (min) PRE 14.3 ± 3.0 12.8 ± 2.7  POST 16.5 ± 1.5 14.6 ± 2.7 Work rate (W) PRE 167 ± 29 154 ± 25  POST 191 ± 16 170 ± 27 Work rate (W·kg-1) PRE 3.3 ± 0.5 3.3 ± 0.4  POST 3.5 ± 0.6 3.5 ± 0.5 HR (bpm) PRE 192 ± 10 196 ± 7  POST 195 ± 8 198 ± 8 RPE PRE 9.3 ± 1.8 9.3 ± 1.0  POST 9.5 ± 1.0 9.4 ± 0.9 VT (l) PRE 1.59 ± 0.33 1.44 ± 0.25  POST 1.77 ± 0.26 1.55 ± 0.26 VT/FVC (%) PRE 48 ± 8 52 ± 5  POST 47 ± 6 52 ± 5 fB (breaths per minute) PRE 56 ± 16 50 ± 8  POST 58 ± 13 56 ± 7 V̇E (l·min-1) PRE 85.5 ± 20.8 72.0 ± 15.6  POST 100.4 ± 17.6 85.3 ± 12.5 V̇O2 (l·min-1) PRE 2.20 ± 0.35 1.85 ± 0.25  POST 2.42 ± 0.23 2.07 ± 0.27 V̇O2 (ml·kg-1·min-1) PRE 42.9 ± 6.8 40.1 ± 4.2  POST 44.4 ± 8.1 42.1 ± 5.2 V̇O2MAX (% pred) PRE 125 ± 18 115 ± 12  POST 131 ± 21 122 ± 14 V̇CO2 (l·min-1) PRE 2.45 ± 0.42 2.13 ± 0.38  POST 2.77 ± 0.25 2.43 ± 0.33 RER PRE 1.11 ± 0.05 1.15 ± 0.09  POST 1.15 ± 0.05 1.18 ± 0.06 V̇E/V̇O2 PRE 39 ± 5 39 ± 6  POST 42 ± 6 42 ± 5 V̇E/V̇CO2 PRE 35 ± 4 34 ± 4  POST 36 ± 4 35 ± 4 EFL (% VT) PRE 19 ± 24 13 ± 25  POST 28 ± 28 28 ± 21 V̇ECAP (l·min-1) PRE 122.8 ± 39.2 110.3 ± 32.8  POST 132.9 ± 37.8 105.3 ± 21.2 V̇E/V̇ECAP (%) PRE 73 ± 19 69 ± 23  POST 80 ± 21 82 ± 13 All values are expressed as mean ± SD. HR, heart rate; bpm, beats per minute; RPE, rating of perceived exertion; VT, tidal volume; FVC, forced vital capacity; fB, breathing frequency; V̇E, expired minute ventilation; V̇O2, oxygen consumption; V̇CO2, carbon dioxide production; RER, 63  respiratory exchange ratio; EFL, expiratory flow limitation; V̇ECAP, ventilatory capacity; SWIM, swimmers; CON, controls; POST, follow-up visit; PRE, initial visit.64    Figure 11 – Mean A) heart rate, B) oxygen consumption, C) carbon dioxide production D) breathing frequency, E) tidal volume, and F) VT/FVC responses during the maximal exercise test. All exercise stages were significantly increased from baseline (BL). # significant difference between PRE and POST. Statistical significance was set at the level of p<0.05.   65  3.8.2 Ventilatory mechanics As shown in Figure 12, the prevalence of EFL was similar in both groups (p=0.72) but increased from PRE to POST (p=0.03). The interaction was not statistically significant (p=0.12). Moreover, no difference between groups was found for the severity of EFL (p=0.95), V̇ECAP (Figure 13A) (p=0.23), or V̇E/V̇ECAP (Figure 13B) (p=0.96).   Figure 12 – EFL prevalence for each group and time point.  66   Figure 13 – Mean A) V̇E (line and symbols) and V̇ECAP (line only) and B) V̇E/V̇ECAP during the maximal exercise test. * significant difference between resting baseline and exercise stage for all groups (combined). # significant difference between PRE and POST. For V̇E and V̇E/V̇ECAP, all exercise stages were significantly increased from baseline (BL). Statistical significance was set at the level of p<0.05.  There were no statistically significant three-way interactions involving group for operational lung volumes (Table 15); however, two-way interactions between group and relative work rate approached significance for EILV (p=0.10), EELV (p=0.11), EELV/FVC (p=0.07), and IRV (p=0.10). A main effect of swimming was found for IRV (p<0.01) such that swimmers had a larger IRV, while differences in EILV (p=0.05), EILV/FVC (p=0.08) and IRV/FVC (p=0.08) approached statistical significance. Swimmers utilized a similar absolute EELV (p=0.18). Although there was a significant interaction between group and time point for IC (p=0.02), IC was greater in SWIM compared to CON at PRE and POST (both p<0.001) and increased from PRE to POST for both SWIM (p<0.01) and CON (p<0.001). The interaction between time and work rate was or approached significance for all volumes. The absolute and relative operational lung 67  volumes are displayed in Figure 14 andFigure 15, respectively, and IRV, IRV/FVC, IC, and IRV/IC are displayed in Figure 16. Values are maximal exercise are presented in Table 16.  Table 15 – Interactions and main effects p-values for operational lung volumes during the exercise test  3-way Group x work rate Time x work rate Group x time Work rate  Group Time EILV (l) 0.17 0.10 0.06 0.70 <0.001 0.05 <0.001        POST > PRE EILV/FVC (%) 0.37 0.64 0.04 0.27 - 0.08 - EELV (l) 0.32 0.11 0.09 0.64 <0.001 0.18 <0.001        POST > PRE EELV/FVC (%) 0.31 0.07 0.03 0.15 - 0.46 - IRV (l) 0.17 0.10 0.06 0.11 <0.001 <0.01 0.13       SWIM > CON  IRV/FVC (%) 0.37 0.64 0.04 0.27 - 0.08 - IC (l) 0.32 0.11 0.09 0.02 <0.001 - - IRV/IC (%) 0.81 0.81 0.10 0.58 <0.001 0.10 0.37 EILV, end-inspiratory lung volume; FVC, forced vital capacity; EELV, end-expiratory lung volume; IRV, inspiratory reserve volume; IC, inspiratory capacity; VT, tidal volume: SWIM, swimmers; CON, controls; POST, follow-up visit; PRE, initial visit.    68  Table 16 – Operational lung volumes during maximal exercise   Swimmers (n=11) Controls (n=10) EILV (l) PRE 2.71 ± 0.73 2.34 ± 0.46  POST 3.02 ± 0.70 2.48 ± 0.55 EILV/FVC (%) PRE 80 ± 7 84 ± 3  POST 80 ± 7 83 ± 6 EELV (l) PRE 1.12 ± 0.38 0.90 ± 0.27  POST 1.25 ± 0.43 0.93 ± 0.22 EELV/FVC (%) PRE 33 ± 5 32 ± 7  POST 33 ± 7 31 ± 5 IRV (l) PRE 0.67 ± 0.27 0.42 ± 0.06  POST 0.74 ± 0.26 0.52 ± 0.20 IRV/FVC (%) PRE 20 ± 7 16 ± 3  POST 20 ± 7 17 ± 6 IC (l) PRE 2.26 ± 0.41 1.87 ± 0.29  POST 2.51 ± 0.32 2.07 ± 0.37 IRV/IC (%) PRE 29 ± 10 23 ± 4  POST 29 ± 8 25 ± 7 All values are expressed as mean ± SD. EILV, end-inspiratory lung volume; FVC, forced vital capacity; EELV, end-expiratory lung volume; IRV, inspiratory reserve volume; IC, inspiratory capacity; VT, tidal volume: SWIM, swimmers; CON, controls; POST, follow-up visit; PRE, initial visit.  69    Figure 14 – Absolute operational lung volumes for A) swimmers PRE vs. POST, B) controls PRE vs. POST, C) PRE swimmers vs. controls, and D) POST swimmers vs. controls. As shown in (A), the top lines represent end-inspiratory lung volume (EILV) and the bottom lines end-expiratory lung volume (EELV). Data points are presented as mean ± SE. For all exercise stages, EILV and EELV were significantly increased and decreased from baseline (BL), respectively. Statistical significance was set at the level of p<0.05.  70    Figure 15 – Relative operational lung volumes for A) swimmers PRE vs. POST, B) controls PRE vs. POST, C) PRE swimmers vs. controls, and D) POST swimmers vs. controls. Data points are presented as mean ± SE. EILV/FVC and EELV/FVC were significantly increased and decreased from baseline (BL), respectively, for all stages except PREx100% for EELV. There were no differences between PRE and POST except for 50% for EILV/FVC and 30% for EELV/FVC. Statistical significance was set at the level of p<0.05.   71   Figure 16 – Mean A) inspiratory reserve volume, B) IRV/FVC, C) inspiratory capacity, and D) IRV/IC during the maximal exercise test. All exercise stages were significantly decreased from baseline (BL) for IRV, IRV/FVC, and IRV/IC and increased for IC (except PREx100%). # significant difference between PRE and POST. Statistical significance was set at the level of p<0.05.   72  3.8.3 Individual and composite maximum expiratory flow-volume curves and tidal flow-volume loops Figure 17 andFigure 18 present the individual MEFV and FVL for swimmers and controls, respectively. Composite MEFV and FVL are displayed in Figure 19. 73   Figure 17 – Individual MEFV and FVL for swimmers.  74   Figure 18 – Individual MEFV and FVL for controls.  75   Figure 19 – Composite MEFV and FVL for A) swimmers PRE, B) swimmers POST, C) controls PRE, and D) controls POST.   76  DISCUSSION 4.1 Major findings The primary purpose of this thesis was to determine if one season of competitive swimming during puberty affected lung development in female competitive swimmers in comparison to healthy controls matched for age, sex, size, and maturity. A secondary purpose was to characterize and compare their ventilatory mechanics during cycling exercise. Thus, the two major findings of this thesis were: first, the swimmers initially had an enhanced pulmonary profile as characterized by larger lung capacities, increased expiratory flows, greater diffusion capacity, and greater indices of respiratory muscle strength. These occurred regardless of the starting age of swimming or years of experience, and did not increase further after one competitive swimming season as compared to healthy controls. Second, the competitive swimmers experienced similar ventilatory constraints while cycling, as evidenced by similar EELV, prevalence and severity of EFL, and utilization of V̇ECAP.  4.1.1 Changes in pulmonary function due to competitive swim training during puberty The primary finding of this thesis was that one season (seven months) of competitive swimming during puberty did not accentuate growth of the lungs in 11-14 y old female swimmers. The swimmers had bigger lungs than controls of similar age, size, and maturational development at the initial visit, but TLC did not become significantly larger over time.    77  4.1.1.1 Comparisons of training volume, swimming history, and pulmonary function to previous studies In this thesis, the swimmers averaged 3.6 ± 0.8 km per swim training session and 5.3 ± 1.6 sessions per week for totals of 9.1 ± 3.6 h and 19 ± 8 km per week of swim training. They had a mean 3.2 ± 1.8 y of competitive swimming experience, with a range of starting ages from 6.0 to 10.1 y old. These are congruent with previously reported training volumes and swimming histories of adolescent competitive swimmers, including: Courteix et al.’s 9-10 y old female swimmers (8-12 h and 10-20 km per week) (18), Zinman and Gaultier’s 7-13 y old female swimmers (5 h per week and 1.2 ± 0.6 y experience in the youngest 7-8 y old cohort, 12.5 h per week and 3.3 ± 1.7 y experience in the oldest 11-13 y old cohort) (27), Bloomfield et al.’s Australian state finalist 8-12 y old swimmers (average 5 swimming sessions per week) (16), and Baxter-Jones and Helm’s 114 8-16 y old swimmers (9-13 h per week) (17). The training volume of the 30 female swimmers (1-4 y experience with starting age ranging from 10-15 y old) from Astrand et al.’s study varied depending on swim club, with 21 females from 3 clubs training 6-20 h and 6-30 km per week and 9 females from the most competitive club swimming upwards of 28 h and 65 km per week (21). Thus, the swimmers in this thesis had comparable swimming histories and training volumes to previous reports of competitive, adolescent female swimmers.  The pulmonary function of the swimmers in this thesis is also in accordance with previous reports of adolescent female swimmers (Table 17). In particular, TLC, RV, RV/TLC, and FVC were nearly identical to the 30 girls studied by Astrand et al. who had a comparable age and height (21). The 9 most competitive swimmers in the study by Astrand et al. (selected from >600 applicants and included 5 Swedish champions, 3 European record holders, and 2 world record holders) had an average age of ~15.0 y, height of 167.6 ± 6.1 cm, and TLC of 5.37 ± 0.81 l (21). 78  While these champion swimmers are slightly older and bigger, their pulmonary function falls in line with potential future values for the swimmers in this thesis when they reach an equivalent age. Wells et al. mixed-longitudinally assessed the Canadian National and Youth National Teams, including sprint, middle-distance, and long-distance swimmers (101). The 12 and 13 y old cohorts of female swimmers had a height (163.3±7.5 (n=12) and 164.6±6.1 cm (n=44), respectively), mass (53.2±6.8 (n=12) and 54.9±6.3 kg (n=44)), FVC (4.3±0.58 (n=8) and 4.2±0.5 l (n=32)), and hemoglobin (13.6±0.6 (n=8) and (13.5±0.9 g·dl-1 (n=34)) that were nearly identical to the swimmers in this thesis. Moreover, at the initial measurement the swimmers in this thesis had a similar TLC, FRC, FRC/TLC, PIMAX, and PEMAX to Zinman and Gaultier’s eldest cohort of 15 similarly-aged, but slightly shorter, swimmers with the same amount of competitive swimming experience (27). Lastly, initial and follow-up DL,CO were similar to 12 extensively-trained, comparably-sized adolescent swimmers studied by Yost et al. (33). Thus, the swimmers in this thesis had similar pulmonary function to previously reports of competitive, pubescent female swimmers, including the Canadian Youth National and National Teams. The swimmers in this thesis grew an average of 2.1 cm in height and 350 ml in TLC over the 7-8-month duration, equivalent to 3.4 cm and 560 ml per year, respectively. Changes in TLC of other longitudinal assessments have varied based on age. In 8 9-10 y old female swimmers, Gibbins et al. observed an average increase of 2.6 cm in height but only 80 ml in TLC after 6 months of swimming 1000 yards 3-4 times per week (42). Courteix et al. examined 5 prepubescent 9-10 y old swimmers before and after one year of intensive training, measuring average increases of 7 cm and 420 ml in height and TLC, respectively (18). Zinman and Gaultier assessed two cohorts before and after one year of training (15). In the 7-9 y old group, seven swimmers had a mean increase in height of 7 cm and TLC of 445 ml; the older cohort (10-12 y old), grew 6.9 cm 79  and 738 ml. The aforementioned 9 most competitive swimmers from Astrand et al.’s study grew, on average, 2.4 cm in height and 610 ml in TLC over 2 years (equivalent 1.2 cm and 305 ml over 1 year) of intensive swimming training from ~15 to 17 y old (to note, one swimmer had stopped training by the time of the follow-up measurement) (12). This may reflect that, in females, lung volumes continue to increase even when standing height is approaching or has reached adult values (57, 102-104). Thus, in comparison to other studies which included pre- or peri-pubescent (<15 y old) competitive swimmers, the swimmers in this thesis experienced the greatest change in TLC for the given somatic growth. This validates the thesis design, which focused on the pubertal growth spurt when lung growth is greatest. In terms of training volume, swimming history, and pulmonary function, the swimmers in this thesis were much like previous reports of competitive adolescent female swimmers. The controls also appeared to have “normal” function, as evidenced by mean %-predicted values ranging between 90-105% for most measures. For example, the %-predicted values for TLC were identical before and after (94 ± 7%) and within the limits of normality (85), suggesting normal growth of the lungs. Therefore, both groups appear representative of their respective populations. Additionally, %-predicted values were generally similar at PRE and POST within each group. Thus, discrepancies between the groups in pulmonary function are unlikely to be the result of abnormal results (e.g., the swimmers initially having extraordinarily large lungs compared to other groups of swimmers or the control group having too small of a change in TLC for a given the change in height) and instead signify real physiological differences typical of swimmers vs. non-swimmers.   80  4.1.1.2 Differences in initial pulmonary function At the initial visit, the swimmers already had enhanced lung function (i.e., TLC, FVC, FEV1, PEF, mid-expiratory flows, DL,CO, PEMAX, and PIMAX) compared to both reference values and the healthy controls, including individually greater TLC than controls for nearly all heights (Figure 2). Individually, swimmers consistently exceeded their predicted values for initial measurements of TLC (range 100-122%), FVC (106-143%), DL,COc (100-142%), and PEMAX (84-125%). This occurred regardless of the starting age of swimming or training history (i.e., number of years of experience), as shown in Table 8. Moreover, as a group the swimmers had an average %-predicted value ≥110% for initial TLC, FVC, FEV1, FEF25%, FEF50%, DL,CO, DL,COc, and VA. In comparison to the control group, the swimmers initially had a 20% greater TLC and 25% greater FVC. Table 18 shows that these %-predicted means are akin to those reported in previous studies of competitive swimmers, including the observations by Astrand et al. on 30 adolescent female swimmers (21). Interestingly, %-predicted pulmonary function does not show an increase over time, suggesting that it is relatively constant in competitive female swimmers throughout adolescence and into adulthood. For example, the swimmers in this study and the female members of the 1984 U.S. Olympic swim team (aged 15-23 y) (31) had nearly identical mean %-predicted function for TLC (110 vs. 115%), RV (both 96%), FVC (both 123%), FEV1 (117 vs. 116%), and DL,CO (121 vs. 127%). The 20-25% larger values compared to the control group are similar to the 20% greater TLC reported by Cordain et al. (28) in 11 Division I collegiate swimmers (aged 19.0 ± 0.6 y) and 20% greater FVC throughout development by Baxter-Jones and Helms (17) in 114 swimmers aged 8-16 y. 81  Taken altogether, two conclusions can be made. First, the lung function of competitive swimmers is already enhanced by the time they reach puberty, regardless of swimming history. Second, the extent of this enhanced function, relative to either a control group or reference values, is fairly constant throughout development, suggesting that the differences in pulmonary function may be based upon genetic endowments in swimmers that are not accentuated by competitive swim training. Moreover, these findings support the conclusion by Baxter-Jones and Helms that children with endowments favourable to swimming success may select themselves into the sport (17). It is possible that competitive swimming leads to early attainment of peak pulmonary function, but reports of children at the start of their competitive swimming career already having larger lungs may refute this claim (23, 39).   82  Table 17 – Lung function of adolescent swimmers  Bloomfield et al., 1990* (n=34)# Zinman and Gaultier, 1986 (n=15) This study PRE (n=11) Astrand et al., 1963 (n=30) This study POST (n=11) Bloomfield et al., 1990* (n=51)## Yost et al., 1981* (n=12) Age (y) 12.2 ± 1.0 12.4 (11.0-13.3) 12.4 ± 0.8 12.9 13.0 ± 0.8 13.1 ± 0.9 14.0 ± 2.4 Height (cm) 152.5 ± 6.0 150 ± 8 161.3 ± 7.9 164.8 ± 6.5 163.4 ± 6.9 158.8 ± 6.7 159.3 ± 11.8 Experience (y) - 3.7 ± 1.6 3.2 ± 1.8 1-4 y - - 2-12 y TLC (l) - 4.58 ± 0.70 4.73 ± 0.73 4.91 ± 0.81 5.08 ± 0.68 - - VC (l) - 3.40 ± 0.51 3.74 ± 0.65 - 4.03 ± 0.61 - - FRC (l) - 2.25 ± 0.41 2.18 ± 0.43 2.04 ± 0.40 2.40 ± 0.39 - - RV (l) - 1.19 ± 0.33 0.99 ± 0.16 0.95 ± 0.28 1.04 ± 0.19 - - FRC/TLC - 0.49 ± 0.03 0.46 ± 0.05 0.42 ± 0.04 0.47 ± 0.06 - - RV/TLC - 0.25 ± 0.06 0.21 ± 0.03 0.19 ± 0.04 0.21 ± 0.03 - - FVC (l) 2.78 ± 0.49 - 3.92 ± 0.71 4.00 ± 0.67 4.15 ± 0.61 3.31 ± 0.60 4.12 ± 0.93 FEV1 (l·s-1) 2.45 ± 0.46 - 3.34 ± 0.61 - 3.55 ± 0.57 2.91 ± 0.49 - DL,CO (ml·min-1·mmHg-1) - - 23.29 ± 2.87 - 24.33 ± 2.16 - 22.40 ± 6.10 PIMAX (cm H2O) - 85 ± 23 87 ± 26 - 103 ± 22 - - PEMAX (cm H2O) - 110 ± 25 112 ± 17 - 127 ± 17 - - *males and females. #Tanner stage 3. ##Tanner stage 4. TLC, total lung capacity; VC, vital capacity; FRC, functional residual capacity; RV, residual volume; FVC, forced vital capacity; FEV1, forced expiratory volume in one second; PEF, peak expiratory flow; DL,CO, diffusion capacity for carbon monoxide; PIMAX, maximal inspiratory pressure; PEMAX, maximal expiratory pressure.    83  Table 18 – Percent-predicted lung function in competitive swimmers throughout development listed according to average age.  Age (y) N, Sex TLC FRC RV FVC FEV1 PEF DL,CO DL,CO/VA This study 12.4 ± 0.8 11 F 110 ± 7 102 ± 14 96 ± 13 123 ± 11 117 ± 11 97 ± 9 121 ± 12 101 ± 10 Astrand et al., 1963 12.9 30 F 112 ± 11 110 ± 14 100 ± 22 113 ± 12 115 ± 14 - -  This study 13.0 ± 0.8 11 F 112 ± 8 106 ± 14 95 ± 16 125 ± 10 119 ± 10 101 ± 8 122 ± 13 97 ± 9 Zauner and Benson, 1981 13.7 (9-19) 8 M, 7 F - - - 104-109* - - - - McKay et al., 1983 14.1 ± 0.9 10 F - - - 118 - - - - McKay et al., 1983 14.7 ± 0.5 6 M - - - 132 - - - - Vaccaro et al., 1980 15.1 ± 1.7 12 M 116 109 105 115 110 - 113 - McKay et al., 1983 17.5 ± 0.6 4 M - - - 130 - - - - Armour et al., 1993 18 ± 2.4 8 M 145 ± 22 137 ± 23 151 ± 37 149 ± 23 131 ± 16 116 ± 11 117 ± 18 93 ± 15 Bradley et al., 1985 18.4 (15-23) 20 F 115 - 96 123 116 113 127 - McKay et al., 1983 18.6 ± 1.3 5 F - - - 135  - - - Miller et al., 1989 18-22 22 M - - - - -  114 ± 15 - Bradley et al., 1985 20.3 (17-25) 18 M 119 - 91 127 120 110 139 - Lazovic-Popovic et al., 2016 20.9 ± 2.4 38 M - - - 115 ± 12 112 ± 10 104 ± 13 - - *Range of average %-predicted FVC over 3 consecutive years. TLC, total lung capacity; FRC, functional residual capacity; RV, residual volume; FVC, forced vital capacity; FEV1, forced expiratory volume in one second; PEF, peak expiratory flow; DL,CO, diffusion capacity for carbon monoxide; VA, alveolar volume.   84  4.1.1.3 Changes in pulmonary function after one season of competitive swimming Over the study duration, nearly all anthropometric and absolute pulmonary function measures significantly increased from PRE to POST for both swimmers and controls (the exceptions were hemoglobin, FEV1/FVC, FEF50%, RV/TLC, and diffusion capacity). Both groups had similar amounts of somatic growth in height (mean 2.1 vs. 2.3 cm for swimmers and controls, respectively) and mass (mean 3.4 vs. 3.1 kg), and changes in SMR were similar (p=0.23). Although swimmers had, on average, 800 ml greater TLC at the initial measurement, growth in TLC was comparable between the swimmers (350 ml) and controls (260 ml). This was also the case for almost all spirometry values, including FVC and PEF. While diffusion capacity (DL,CO and DL,COc) was greater in swimmers, neither group significantly changed over time. When expressed relative to lung volume (DL,COc/VA), decreases were observed from PRE to POST but no group differences were found at either time point. Thus, the lack of significant interactions between group and time for TLC, spirometry, and diffusion capacity suggests that, contrary to the first hypothesis, competitive swimming during puberty does not accentuate lung development. Whereas changes in absolute pulmonary function can be ascribed to normal somatic and lung growth, changes in relative (%-predicted) lung function may be indicative of lung growth beyond expected for a given increase in age and height. Since measures of lung volumes and spirometry ‘track’ (i.e., follow percentile curves) growth charts in healthy children (105), deviations in swimmers may indicate an effect of competitive swimming on lung growth. However, almost all subjects in this thesis had similar %-predicted TLC at PRE and POST as evidenced by the change in %-predicted TLC being ≤5% for 9/11 swimmers and 8/10 controls. Moreover, there were almost no significant two-way interactions for any %-predicted measure of lung function and the values were generally similar at PRE and POST. Therefore, the changes in 85  relative lung function do not suggest an effect of competitive swimming on lung development during puberty. The individual changes in lung function in swimmers occurred irrespective of the training volume, as no significant correlations were found between training volume (expressed as time (h) or distance (km) per week) and change in any measure of pulmonary function (Table 9). This thesis also quantified time spent performing breath control drills, which included underwater kick, freestyle breathing pattern (“hypoxic training”), snorkel sets, or any other as defined by the swimming coach (listed for each swimmer in Table 25 in Appendix A). On average, only 1.3 ± 1.1 h per week were spent performing these drills. Furthermore, no consistent qualitative association was observed between the amount of time spent performing breath control drills and change in pulmonary function. In fact, some of the swimmers (e.g., S04, S09, S10) who spent minimal training time performing breath control drills (0.25-0.5 h per week) had some of the greatest changes in TLC. Thus, the lack of association between training time and change in pulmonary function suggest that any effect of competitive swimming during puberty is not a dose-response relationship. Moreover, the lack of association between relative change in TLC and daily moderate-vigorous physical activity levels in all of the subjects suggest that growth of the lungs occurs irrespective of one’s activity level. The primary finding that changes in pulmonary function are not accentuated by competitive swimming is supported by three large longitudinal studies of adolescent swimmers. First, it is similar to that of Engstrom et al., who reported that TLC in 29 female swimmers age 9-13 y was initially larger compared to population norms and did not increase further up to age 16 (9). The finding also agrees with the observations of a large, longitudinal study by Baxter-Jones and Helms who found that, after adjusting for height, weight, and pubertal stage, the FVC of 114 8-16 y old 86  swimmers was ≥20% larger than 339 other young athletes at the initial measurement and also did not increase further (17). Lastly, it is in accordance with that of Andrew et al., who observed a greater TLC, VC, maximal mid-expiratory flow, and DL,CO (males only), but not FRC or DL,CO/TLC, across all ages in >70 8-18 y old swimmers compared to non-athletes (11).  However, other longitudinal reports of young swimmers compared to healthy controls have reported contrasting results. First, Gibbins (42) and Vaccaro and Clarke (43) found no difference in lung function before or after 6-7 months of training in 8 9-10 y and 15 9-11 y old swimmers compared to control groups, respectively. Compared to this thesis, the training volume in Gibbins’s thesis was relatively low as participants only swam 1000 yards 3-4 times per week. This suggests that the lack of differences in pulmonary function may be explained by participants not qualifying as “competitive swimmers.” Moreover, despite mean height increases of 2.7 and 3.2 cm in the swimmers and controls, average TLC increased by only 80 ml in swimmers and did not change in the controls. In fact, one swimmer’s TLC is listed as decreasing from 3.769 to 2.956 l. These are unusual results when considering their initial age and change in height (57), raising concerns regarding the validity of their measurements. On the other hand, the 15 swimmers in the study by Vaccaro and Clarke had a similar training volume (3,000-10,000 yards 3-4 times per week) and were tested before and after a similar duration (7 months) as the present study. Yet, they observed a similar FVC between swimmers and controls. This lack of difference may have been related to the controls being, on average, 5 cm taller than the swimmers, although this difference was not statistically significant. Alternatively, the groups may not have been matched for sex (sex distribution of the control group was not stated) or maturity (not measured), both of which can lead differential timing and rates of lung growth during development (48, 49, 56). 87  Second, significantly increased lung function after training despite no initial differences were found in longitudinal studies of 5 9-10 y old prepubescent female (18) and 95 8-12 y old (26) swimmers. The swimmers observed by Courteix et al. were comparable to this thesis with regards to training volume and competitive status, and had a similar amount of somatic and lung growth as the 7-9 y old competitive swimmers in Zinman and Gaultier’s one-year longitudinal assessment (15). However, over one year their age- and maturity-matched control group grew 6 cm in height but only 90 ml in TLC; again, this appears abnormally small compared to reference values for their age and somatic growth (57) and may underlie the contrasting results. Bloomfield et al. performed a five-year mixed-longitudinal analysis of 95 8-12 y old competitive swimmers and 102 matched non-competitors, separating the groups based on sex and Tanner maturational stage (26). A qualitatively larger FVC was found in swimmers throughout all maturational stages, and was particularly evident in the male cohort. In fact, they found a statistically significant main effect for swimming whereby FVC was larger in swimmers for both sexes, regardless of maturity, and no statistically significant interactions between swimming and maturational stage – this is in agreement with the results of the present thesis. However, only upon interpreting post-hoc tests did Bloomfield et al. state that the qualitative differences in FVC became statistically significant at stage 2 in males and stage 4 in females. Lastly, Zinman and Gaultier studied 17 7-12 y competitive swimmers and observed a greater TLC before and a larger increase in TLC after one year of training (15). While the greater TLC measured initially is in accordance with this study, the observation of a larger increase in TLC due to swim training is not. Their older cohort (the 10-12 y old swimmers) grew, on average, 6.9 cm in height and 738 ml in TLC. As mentioned previously, when these changes in TLC are expressed relative to height, Zinman and Gaultier’s swimmers had lower rates of lung growth 88  compared to the present thesis. Thus, the differing results may be related to the experimental design. Their control group was analyzed cross-sectionally, and no inferential statistics comparing the swimming and control groups were provided. Although the onset of puberty was assessed, there was no further quantification of maturational age and therefore the extent of maturational development of the swimmers was unknown.  4.1.1.4 Summary of changes in pulmonary function Overall, the swimmers in this thesis were much like previous reports of competitive adolescent female swimmers in terms of training volume, swimming history, and pulmonary function. Their lung function was already enhanced by the time they reached puberty, regardless of swimming history. The lack of significant interactions between group and time for TLC, spirometric values, diffusion capacity, and maximal static mouth pressures suggests that contrary to the first hypothesis, competitive swimming during puberty does not accentuate lung development. This is supported by three large longitudinal studies of adolescent swimmers (9, 11, 17); contrasting results may be explained by discrepancies in the control group used (18, 42, 43) or experimental design and analysis (15, 16), but not by effects of competitive swimming. Collectively, these findings suggest that the differences in pulmonary function may be based upon genetic endowments in swimmers, but are not accentuated by competitive swim training.  4.1.2 Mechanisms underlying differences in pulmonary function A thorough review of the development of the respiratory system and its mechanical properties is necessary to speculate why the pulmonary function of the swimmers in this thesis was not affected by intensive swim training. However, anatomical, morphological, and 89  physiological changes of the lungs and chest wall during growth are complex, not completely understood, and difficult to measure in healthy humans. Therefore, it is difficult to make inferences of their numerous interactions into causative mechanisms that determine the static and dynamic properties of the respiratory system and its measurable pulmonary function. It is also important to note that this thesis was not designed to address why differences in pulmonary function existed. Thus, this section will attempt to provide a brief review of developmental processes and speculate how they may be affected by the unique challenges imposed by competitive swimming. Then, the extent to which each measure of pulmonary function may be influenced by competitive swimming will be discussed within the context of the results of this thesis. More comprehensive reviews of respiratory mechanics in children (46), biochemical and structural changes during growth (106), and functional development from gestation to adulthood (107) can be found elsewhere.   4.1.2.1 Development of the respiratory system Development of the alveoli and the elastic properties of the lung. Alveoli appear around 30 weeks of gestational age (48). Extensive alveolar multiplication from alveolar ducts in the first 2-3 years of life form the bulk of the alveoli (108), then alveolar multiplication and hypertrophy continue throughout childhood and adolescence and into early adulthood (38). This normal development of the lung after birth happens through a feedback loop whereby outward recoil of the growing rib cage mechanically stimulates alveolar growth and then alveolar growth relieves the mechanical tension to allow further expansion of the rib cage (109). There is also an increase in the amount and change in the distribution of elastin, collagen, and smooth muscle during growth (46, 110). Combined with alveolar multiplication, these lead to changes in surface and tissue forces and therefore the elastic properties of the lungs (46, 111); more specifically a progressive increase 90  in lung elastic recoil pressure (Pst(L)) (37, 90, 112-114), a greater Pst(L) for a given fractional lung volume (i.e., % TLC) (37, 90, 113, 115), and a rightward shift and flattening of the pressure-volume (PV) curve (i.e., changes were more dramatic at larger (~90% TLC) than mid-range (~60% TLC) lung volumes) (37, 90, 113, 115).  Thus, although static (Cst) (90, 113, 116) and dynamic (Cdyn) (90, 117-119) lung compliances increase with growth (because of the increase in anatomical size), Cst relative to TLC (90) and FRC (90, 113) (“specific” Cst) decrease as a result of stiffer, more elastic lungs (90).  Development of the airways and the flow-resistive properties of the lung. Unlike the alveoli, the airways do not increase in number after birth (120). The airways are formed by ~16 weeks of gestational age (120), and by birth, the conducting regions of the lungs are a miniature version of the adult whereby the conducting airways can only increase in length and diameter during growth (121). There is an increase in anteroposterior and transverse diameters of the trachea (122) and a decrease in specific compliance of the trachea and main-stem bronchi (123). It is likely that the airway walls also undergo morphological changes, as the airway walls are much more compliant in children compared to adults (46). These changes lead to an increase in upstream (112) and total airway conductance (112, 124) and, reciprocally, a 10-fold decrease in airway resistance (Raw) from infancy to adulthood (46). The susceptibility of the peripheral airways to dynamic compression during expiration does not change during childhood and adolescence and into adulthood, therefore the trachea or main-stem bronchi remain the location of the flow-limiting segment (112).  Dysanapsis. The differing patterns of and disproportionate growth between airways and alveoli is termed dysanapsis (dys = unequal, anapitxy = growth) (69). One measure that quantifies dysanapsis is specific airway conductance (sGaw), calculated as the ratio of airway conductance 91  (sensitive to airway size) to the lung volume at which it is measured (sensitive to lung size) (46). Decreases in sGaw reflect periods when alveolar growth predominates, whereas increases suggest relatively more airway growth. The ratio is highest during infancy, then from birth until 5 years old, it decreases when alveolar growth is greatest (125-127). During childhood and early adolescence, sGaw remains fairly constant or slightly decreases (46); after puberty, increases in sGaw may be due to late airway growth that stabilizes sGaw into adulthood (125). Thus, dysanapsis is likely to be most prominent when lung growth is greatest in infancy and early childhood (37), and continues into puberty when PGV occur.  Puberty, also known as the adolescent growth spurt, occurs as early as age 7 y in girls and 9 y in boys (75). Lung growth during this stage can be characterized by four phases: (1) prepubescent steady-state lung growth continuing from childhood; (2) maximal acceleration of lung growth at the onset of puberty; (3) postpubescent growth at progressively slower rates; and (4) cessation of lung growth during post-adolescence and early adulthood (56). Mathematical modelling of longitudinal changes in FEV1 (sensitive to airway size) and FVC (sensitive to lung volume) showed that growth velocities for FVC were consistently greater than FEV1 throughout puberty until 13-14 years of age (72). Moreover, PGV for lung volume preceded those for flow by one year (48). The relationship between volume and flow can be quantified by the dysanapsis ratio, which, as mentioned, is the ratio of mid-expiratory flow corrected for Pst(L)50 (index of airway size) to VC (index of lung size) (89). From late childhood and through adolescence the ratios steadily decrease, suggesting disproportionate growth before, during, and after the adolescent growth spurt (57). However, caution is warranted when assessing changes in DR over time, as interpretation of decreases in DR may reflect isotropic (i.e., proportional) or dysanaptic growth depending on the assumption of turbulent flow during the expiratory maneuver (46, 89). A recent 92  longitudinal study accounted for this assumption and showed that an estimated DR (using Pst(L)50 calculated from a regression equation) decreased from prepubescence to postpubescence in a manner that suggested dysanaptic growth indeed occurs during puberty (128).  Development of the chest wall. The main static change of the respiratory system during development is an increased outward recoil of the chest wall (129). Infants have a chest wall compliance (Cw) that is nearly three times greater than lung compliance (130). However, within the first few years of life, the shape of the thorax changes as the ribs, which extend horizontally at birth, tend downwards and the diaphragm becomes less horizontal (131). Moreover, the ribs mineralize, the gravitational effect of the abdominal contents increases, and the respiratory musculature develops. These changes, especially within the first 2 y of life, cause a substantial reduction in specific Cw (130) such that, throughout the rest of development (132) and into adulthood (133), the contributions of Cst and Cw to total respiratory system compliance (CRS) are nearly equal. As with Cst, Cw and CRS increase with growth (116, 132); but when expressed relative to lung volume, specific Cw (46, 129) and specific CRS (132, 134) decrease. Further changes in size and shape of the chest wall occur during puberty, as the thorax elongates due to relatively greater thoracic height growth (135). Measurements of sternal length, chest width, and chest depth and estimations of chest wall surface area and thoracic volume index have been shown to increase before and during puberty (102, 136, 137). Furthermore, chest and lung widths reach their PGV simultaneously during puberty, while lung length and chest depth reach PGV six months later (73). Thus, growth of the thorax and, due to the feedback loop, lungs occur until their dimensions stabilize when somatic maturity is reached and epiphyses close (109).    93  4.1.2.2 Total lung capacity and chest wall size. The tight coupling between chest wall and lung growth has important implications on the development of pulmonary function. Static lung volumes are determined by lung size, the ability of the inspiratory and expiratory muscles to generate pressure, antagonistic muscle activity, and the elastic recoil pressures of the lungs and chest wall (138). Of these, lung size, inspiratory muscle force generation, and the inwards elastic recoils of the lungs and chest wall interact to determine TLC (139). During childhood, increases in TLC are due primarily to somatic growth of the chest wall (140) and, consequentially, lung size.  Thus, because TLC is primarily determined by lung size and lung size is directly related to chest wall size, it is likely that the greater TLC of the swimmers in this study were related to larger chests. Although not measured here, chest wall dimensions were observed to be larger in competitive swimmers (16, 27, 29). Zinman and Gaultier measured the anteroposterior diameter (i.e., chest depth) at the sternal angle and transthoracic diameter (i.e., chest width) at the xyphoid process at TLC, FRC, and RV, as well as sternal length (27). From these dimensions, they also estimated chest wall surface area at FRC and TLC. They found the dimensions and surface area to be larger in all three cohorts of female competitive swimmers (7-8, 9-10, and 11-13 y old), with all differences becoming statistically significant in the 9-10 and 11-13 y old swimmers. Armour et al. performed the same measurements in 24 collegiate male swimmers, runners, and controls (8 each), finding a greater chest width at TLC (but not chest depth) and chest wall surface area at TLC, FRC, and RV in 8 swimmers compared to 8 runners (differences between swimmers and 8 controls did not reach statistical significance) (29). They also found a significant correlation between increased chest wall surface area and TLC, whereby the swimmers with the largest surface area had the greatest TLC. Lastly, Bloomfield et al. measured chest depth and width in 95 8-12 y 94  old competitive swimmers and 102 matched non-competitors (16). They found a statistically significant main effect for both depth and girth in males and females. Post-hoc testing suggested that males and females had significantly greater chest depth from maturational stage 4, while chest width was greater at each stage in males. Interestingly, significant differences in FVC between swimmers and non-competitors nearly mirrored those of chest dimensions, as FVC was greater in male swimmers from stage 2 onwards and in female swimmers from stage 4 onwards. The observation that greater chest dimensions in swimmers as young as 7-8 y old persisted into young adulthood and were correlated with larger TLC provide further evidence that children with larger chests, and thus lungs, are likely selected into swimming.  4.1.2.3 Total lung capacity, hypoxia, and induced postnatal lung growth Armour et al. suggested that a periodic hypoxic stimulus and enhanced growth hormone response while swimming, specifically during the adolescent growth spurt, may elicit accentuated alveolar hyperplasia in response to the enlarging chest cavity (29). In other words, intermittent hypoxia may be a mediator of greater lung growth in developing swimmers. However, it is not clear if there is a connection between the mechanisms of induced postnatal lung growth (3, 109), including hypoxia, and the unique stressors of intense swim training. Hypoxia. Exposure to chronic hypoxia is one of the main stimulants of induced postnatal lung growth (109). As explained earlier, growth of the lung occurs via a feedback loop until epiphyseal union of the ribs occurs, at which point the size of the lungs is matched to and limited by the size of the thorax (109). This is critical to speculating the response to chronic hypoxia, because its effect may be dose-dependent whereby moderate levels stimulate lung growth but severe levels retard rib cage growth (109). Comparisons of animal models at different altitudes 95  effectively describe this interplay (109). At moderate altitudes, hypoxia primarily stimulates lung growth, with passive rib cage expansion and lowering of the diaphragm providing the space for more alveoli. The balance is more delicate at higher altitudes, where the stimulation of lung growth becomes diminished over time by the retardation of rib cage growth. Extreme altitudes illustrate the other end of the spectrum, as severe hypoxia stunts rib cage growth, which prevents absolute increases in lung volume. The effect of hypoxia may also be dependent upon time. Exposure too early blunts lung development, whereas exposure during early and later stages of maturation cause alveolar hyperplasia and hypertrophy, respectively (109). Thus, for hypoxia-induced accentuated lung growth to occur in swimmers, there must be a chronic hypoxic stimulus of appropriate dose during development. Whether this occurs in swimmers likely depends on stressors unique to swimming. First, swimming is performed in the supine or prone position while partially or fully submerged in water. Second, a swimmer’s breathing pattern is not only a result of physiological need, but also of stroke rate and biomechanics (i.e., entrainment). Third, swim training often involves breath control drills, including “hypoxic training”, and sprint swimming where breathing frequency is reduced. Lastly, intense swim training often begins at a very young age, as early as 5 years old. Immersion and the supine and prone positions. Increased hydrostatic pressure and decreased gravitational pull during upright immersion causes the redistribution of ~700 mL of blood into the intrathoracic vascular bed (141) and elevates the diaphragm (142). These alterations lead to major changes in ventilatory mechanics and hemodynamics. Central vascular engorgement (CVE) contributes to increased lung recoil at high lung volumes and decreased lung recoil at low lung volumes (143), shifting the transpulmonary pressure-volume curve to the right by ~16 cm H2O (144). Moreover, hydrostatic forces oppose the action of the inspiratory muscles, thereby 96  decreasing the maximum static transpulmonary pressure that can be generated (143). The increased lung recoil and decreased static pressure generated cause a decreased TLC while immersed (143). At RV, the decreased lung recoil but increased hydrostatic pressure assisting expiration may oppose each other and cause no change (145, 146), although some have suggested that CVE leading to increased lung stiffness may increase RV (147). Since VC is the difference between TLC and RV, a decreased TLC and relatively unchanged RV would cause VC to decrease (146) by approximately 10% (148, 149). Furthermore, elevation of the diaphragm to near-resting EELV decreases ERV and therefore FRC (142). Since tidal volume is unchanged (144), lower operating lung volumes decrease airway diameter, increase airway resistance (142, 150), and thereby increases the elastic and overall WOB by 60% (144). Moreover, ERV does not change with increases in VT, so increasing VT occurs solely by utilizing IRV (148). Hemodynamically, 25% of the blood displaced from the legs to the thorax upon immersion is located in the heart, increasing stroke volume (SV) and thus cardiac output (Q̇) by 20-40% (151). The mean pulmonary artery pressure also increases (141), leading to a greater pulmonary capillary blood volume (Vc) and diffusion capacity (152). Moreover, the increased Q̇ and pulmonary artery pressure may create a more homogenous distribution of pulmonary perfusion and therefore ventilation-perfusion ratios (V̇A/Q̇) throughout the lung (153). Cumulatively, these effects may reduce the alveolar-arterial difference (A-aDO2) and increase arterial oxygen tension (PaO2) (153). Many of the studies on immersion were conducted in the seated, upright position, whereas swimming provides the additional stimulus of being performed while either supine (backstroke) or prone (all other strokes). However, evidence of changes in ventilatory mechanics and hemodynamics due to the supine or prone position suggests the changes are similar to those due to immersion. Like immersion, the supine position is also associated with a redistribution of blood 97  to the thorax that increases SV and Q̇ and decreases A-aDO2 (154). The greater amount of blood in the lungs may encroach upon pulmonary air space to decrease TLC, and therefore VC, while FRC and ERV are reduced due to the effects of gravity and diaphragm elevation (129, 155). Diffusion capacity increases because of greater Vc and improved distribution of pulmonary perfusion (156). These effects are nearly identical in the prone position (155-158), where V̇A/Q̇ matching is even better (159). Thus, both immersion and the transition to the supine or prone position are associated with changes in blood volume and diaphragm level; therefore, combining the two conditions may not be additive (151). Deroanne et al. measured compliance and conductance in three subjects while out of the water, immersed in three body positions (standing, supine, and prone), and swimming breaststroke and backstroke (149). Compared to measurements out of water, they found compliance to be lower while supine, standing, and during backstroke swimming. They also observed an increased airway resistance in all body positions and swimming strokes. They associated the mechanical changes with both immersion and changes in body position, clearly illustrating that the two combine to constrain the respiratory system while swimming. Breathing pattern and the ventilatory response to swimming. Unlike other forms of endurance exercise, the ventilatory pattern while swimming is not solely dictated by physiological need. The “obligatory, controlled frequency” breathing of swimmers is influenced by the stroke rhythm and its associated biomechanical events (36). As a result, rapid inspiration occurs above water while a slow, controlled expiration occurs below the surface (160). The interpretation of how these breathing patterns affect the ventilatory and metabolic responses while swimming is affected by the conditions in which swim testing occurs. First, the necessary use of a breathing valve connected to a snorkel to measure metabolic and ventilatory variables enables free 98  respiration and inherently alters the respiratory pattern (160). The impact may be dependent on swimming intensity, as it was reported that swimmers adhere to swimming stroke breathing patterns at low intensities but breathe more freely at high intensities (161). Second, maximal tests may be performed in a flume, using a tethered pulley-weight system, or while free swimming. Differences in V̇O2MAX but not ventilatory parameters have been noted between free and tethered swimming in highly trained swimmers; however, this may have been due to training-induced improvements in V̇O2MAX between measurements (162). Others have found identical values in V̇O2MAX (163) and Q̇ (164) between the modalities in elite swimmers and all respiratory variables in well-trained swimmers (165), Lastly, tests can be performed during breaststroke, backstroke, or front crawl swimming. However, all appear to attain a similar V̇O2MAX (166). Thus, these suggest that the different modes of testing (167) and types of swimming strokes (166) produce similar physiological responses. Highly trained swimmers performing maximal running and swimming tests have been shown to utilize similar (161, 162) or even increased fB (168) while swimming. Conversely, VT is lower, potentially due to the aforementioned effects of hydrostatic pressure and increased flow resistance as well as movement of the chest and involvement of the respiratory muscles in the arm stroke (162, 168). Therefore, at maximal swimming, elite swimmers have a similar (168) or lower V̇E (162, 163). During both submaximal and maximal swimming and running, elite swimmers have been shown to relatively hypoventilate, as evidenced by high estimated arterial and venous CO2 contents and very low ventilatory equivalents (168). In other words, swimmers may ventilate normally, instead of the hyperventilatory response often seen with other athletes, by having a higher alveolar ventilation per breath (169). This does not appear to have a major effect on the V̇O2MAX of elite swimmers, as similar (162, 168) or only slightly lower (163) values have been 99  reported. Moreover, despite a lower maximum HR (162, 163, 168), a greater SV maintains the same Q̇ and A-aDO2 during swimming and running, likely a result of improved venous return and more effective muscle pump action in the arms, shoulders, and chest (168). Arterial oxygen saturation (SaO2) is also maintained above 95% (170). In non-elite or recreational swimmers the cardiorespiratory responses may be attenuated due to a lower training status (171), as studies have shown a decreased VT (171), fB (171), V̇E (168), V̇O2MAX (162, 168, 171, 172), Q̇ (168, 171), and SV (168) during maximal swimming compared to running. However, PaO2, arterial carbon dioxide tension (PaCO2), and SaO2 were similar between maximal swimming and running (171), potentially due to the improved extraction of alveolar O2 as demonstrated by a decreased A-aDO2 (168, 171). Thus, if immersion, body position, and the obligatory breathing pattern of swimming impose restrictions on the respiratory response to maximal swimming, the cardiovascular system appears to be able to compensate by maintaining Q̇ and, more importantly, SaO2 (167, 169). Slight decrements in V̇O2MAX can be explained by less muscle mass being involved, primarily a result of minimal muscular work being necessary to support the body in the water (171). Since hypoxemia is avoided, it appears unlikely that the stressors of normal swimming create a hypoxic stimulus for postnatal lung growth.  Controlled frequency breathing drills and sprint swimming. However, controlled frequency breathing (CFB) drills, also know as “hypoxic training,” performed as part of an intense swim training program were proposed to create an intermittent hypoxic stimulus (173). The theory was that swimmers could become hypoxemic, increase the oxygen deficit, and enhance the anaerobic response by increasing the number of arm strokes between breaths (e.g., breathing every 5th, 6th, etc., arm stroke instead of every 2nd or 3rd), (173). Traditionally, this voluntary 100  hypoventilation is performed using the “inhale-hold” technique whereby a rapid, large inhalation (to near-TLC) is followed by a short breath-hold (5 (174) to ~8 (175) seconds) and rapid expiration (174). However, there is no evidence to suggest this form of CFB improves maximal aerobic or anaerobic power output (169), as investigations of CFB during submaximal (175-179) and maximal (180) swimming have observed blood lactate concentrations to be similar (175, 177-180) or reduced (178). Moreover, the decreased V̇E (175-178, 180) and lower alveolar PO2 (176-178) caused by the lower breathing frequency is compensated for by a significantly increased VT (175-177, 180) and lower FEO2 (175, 176, 178, 180), the latter elucidating that a higher O2 extraction at the alveolar-arterial membrane compensates for the hypoventilation (175, 176, 178). Thus, this traditional “inhale-hold” method of CFB was shown to have minimal effects on arterial oxygen saturation (174, 176) and is again unlikely to cause hypoxemia. A recently proposed “exhale-hold” form of CFB while swimming also appears possible for stimulating intermittent hypoxia (174). Whereas the traditional “inhale-hold” breath is held at a high lung volume near TLC, the proposed “exhale-hold” breath is held at a low lung volume at or below FRC (174). This is accomplished by a quick inspiration to near-TLC and expiration back down to near-FRC, a breath-hold for 4-5 s, followed by a complete exhalation to near-RV before the next rapid inspiration (174). Woorons et al. compared the two techniques with normal breathing by continuously measuring SaO2 via pulse oximetry at the forehead and breath-by-breath metabolics during 10 consecutive 50 m intervals at near-maximal swimming speeds (174). While SaO2 during normal breathing averaged 98% and was ≥94% for most of the “inhale-hold” intervals, SaO2 averaged 89% during the “exhale-hold” intervals and 87% at the end. The authors suggested that the severe hypoxemia observed during “exhale-hold” but not “inhale-hold” was partly due to worsened pulmonary gas exchange, previously demonstrated by an increased A-aDO2 during 101  “exhale-hold” exercise (181, 182). This is likely related to lung volume, which has been stated to be the most important determinant of hypoxemia during apnea (183). During apnea at high lung volumes, V̇A/Q̇ homogeneity may minimize arterial desaturation; conversely, apnea at low lung volumes is associated with airway closure and a heterogeneous distribution of V̇A/Q̇, increasing A-aDO2 and arterial desaturation (183). Toubekis et al. also observed a decreased SaO2 compared to normal breathing during “exhale-hold” CFB intervals of 75-400 m at submaximal intensities (184). However, even though SaO2 decreased to as low as 78%, on average, at the end of some of the intervals, SaO2 recovered to baseline values within 60 s for all distances. Regardless of whether the “inhale-hold” or “exhale-hold” form of CFB is performed, alveolar CO2 tension is also increased (176-178, 184). This creates such a strong stimulus to breathe that numerous authors mentioned that some subjects were unable to complete trials when breathing rate was most restricted (e.g., breathing every 8-10th arm stroke) (177, 180). Therefore, CFB may provide a form of “hypercapnic training” (185) that can improve tolerance to hypercapnia (176). This is important because swimming during both “inhale-hold” and “exhale-hold” CFB was also shown to decrease V̇O2 and V̇CO2 at a given intensity compared to normal breathing (174, 175, 177, 178, 180). The reduced level of metabolism may be related to the decreased V̇E, as the WOB and therefore respiratory muscle V̇O2 may be lower (174). Alternatively, it may indicate a beneficial biomechanical effect with reduced breathing whereby drag is decreased due to less head movement or better body position in the water (167). Therefore, increased hypercapnic tolerance could be advantageous during sprint swimming, as the ability to increase the apneic period would allow some swimmers to breathe minimally and improve movement economy. For example, some swimmers may breathe only 1-2 times during a 50-m race (180). These longer apneic periods may cause intermittent hypoxemia similar to that observed by 102  Matheson and McKenzie (186). Using arterial lines, they directly measured a significant drop in PaO2 and SaO2 with repeated 15-s breath-holds during very intense cycling exercise. Miyasaka et al. observed a 6-14% drop in SaO2 in three male swimmers performing 100 m sprints (187). In both reports, however, SaO2 recovered quickly upon exercise cessation when normal breathing was resumed. Taken altogether, the traditional “inhale-hold” form of CFB has not been shown to decrease SaO2, as the apneic period may not be long enough to cause hypoxemia. While the “exhale-hold” technique was demonstrated to alter SaO2, it is not clear if this is a commonly performed drill. Both techniques may improve hypercapnic tolerance, which may be beneficial during sprint swimming when a drastically reduced breathing frequency causing hypoxemia may also have biomechanical advantages. However, any resultant hypoxemia from “exhale-hold” CFB or sprint swimming is only short-lasting, as SaO2 quickly recovers once the drill or sprint is finished. Therefore, this hypoxemic exposure is so short that it appears unlikely to provide the chronic hypoxic stimulus necessary for lung growth. Age of onset of training. Another unique aspect of competitive swimming is the very young age at which some athletes start training. Coaches of elite swimmers have suggested that intensive swim training programs should begin as early as 5 years old (17). This means that young, competitive swimmers are exposed to the stresses of immersion, the prone and supine positions, and the obligatory breathing pattern at an age when the lung is rapidly developing. Between 1 month and 7 y there is a 13-fold increase in lung volume (37) and an additional 3-fold increase in lung volumes from age 7 to the cessation of lung growth (37, 38). If the growing respiratory system is sensitive to swimming, then swimming during these critical periods of maximal growth are likely to elicit the greatest effects. Such an age-dependent adaptation of the growing lung has been 103  reported in rats (188). At the end of a one-month training period when 2-month-old rats were exposed to swimming five days per week, they had significantly greater alveolar densities and surface area-to-lung volume ratios than the non-exercised rats, suggesting alveolar proliferation. Conversely, the author reported that these differences were not found when 3-month-old rats underwent the same swimming protocol. However, as discussed earlier, immersion, the prone and supine positions, and the obligatory breathing pattern have not been associated with hypoxemia during swimming. Moreover, it is unlikely that young swimmers spend extensive amounts of time performing CFB drills or sprinting with reduced breathing frequencies during the primary years of lung growth. Since extended breath-holds during “hypoxic training” are documented to nearly cause drowning (189), concerns of improper technique leading to shallow water blackout in youth swimmers may limit the amount of time coaches choose to spend on CFB drills. In this thesis, the time spent performing breath-control drills was quantified. These consisted of underwater (dolphin or breast) kick, CFB or freestyle breathing pattern, snorkel sets, or sprints performed with minimal breathing. Of the total weekly swimming time (9.1 ± 3.6 h), breath control drills were only a small portion of this (1.3 ± 1.1 h). Underwater kick was the most common, whereas only three out of 11 swimmers performed FSB and one reported sprints with minimal breathing. Comparisons of the %-predicted TLC and time spent per week performing breath-control drills elucidated no qualitative relationships between them. The four swimmers with the largest %-predicted TLC performed 2 h (117%-predicted TLC), 1 h (122%), 2 h (117%), and 0.25 h (113%), whereas the swimmer who spent the most time doing breath-control drills had the lowest %-predicted TLC (100%). This raises further doubts about the possible connection between intermittent hypoxia and enhanced lung growth in young swimmers. 104  Other stimulants inducing postnatal lung growth. Other stimulants of postnatal lung growth include increased parenchymal or vascular mechanical strain and hormonal mediators (109), but these are poorly understood and therefore interactions with the stressors of swimming are purely speculative. One can speculate that the ventilatory demand of thousands of hours spent intensely swim training during growth may provide additional mechanical stress on the feedback loop, accelerating or increasing thoracic and lung growths, or affect the remodelling and expansion of elastin during lung growth, altering the elastic recoil of the lungs. However, there is no convincing evidence that intense exercise affects lung structure (3). If intense exercise influences lung growth, elite athletes from land-based endurance sports would have increased pulmonary function as well. Moreover, without measurements of operating lung volumes or estimations of WOB during swimming, it is impossible to determine if the ventilatory demand differs in young swimmers versus other endurance athletes. In terms of vascular mechanical strain, since immersion and the prone position increase blood volume in the thorax and pulmonary artery perfusion pressure while swimming, and Q̇ is maintained, one can speculate that these may increase chronic capillary distension and shear forces that could stimulate lung growth or affect protein distribution. Lastly, it has been suggested that increased release of exercise-induced growth hormone (GH), due to transient hypoxia and greater arm exercise while swimming, may stimulate lung growth (29). Two arguments counter this possibility. First, GH may not directly induce lung growth, but instead modulate the response to mechanical strain or hypoxia (109). As thoroughly discussed, it has not been shown if either of these responses occurs. Second, greater circulating GH increases whole body growth homogenously until epiphyseal closure (190); therefore, one would expect swimmers to have enhanced growth of height and weight as well, which does not appear to be the case (8). 105  Summary. In conclusion, there is a dose- and time-dependency of chronic hypoxia as a stimulus for induced postnatal lung growth. While swimming provides a unique environment where immersion, the prone and supine positions, and an obligatory breathing pattern all stress the respiratory system, there is no unequivocal evidence that they cause hypoxemia. Certain forms of controlled frequency breathing drills and sprint swimming likely cause hypoxemia, but exposure is acute and recovery to normal values occurs rapidly. Moreover, the prevalence of these drills in a young swimmer’s training program varies depending on the coach, and some swimmers who spent minimal time performing breath-control drills still have large lungs for their age and size. Therefore, young swimmers do not appear to be exposed to either the dose of or time spent in hypoxemia necessary for hypoxia-induced lung growth. Lastly, no other form of induced postnatal lung growth appears likely to induce substantial lung growth in young swimmers. Thus, given the present evidence, intermittent hypoxia or any other form of induced postnatal lung growth stimulus are unlikely to explain the larger TLC of swimmers in this study.  4.1.2.4 Total lung capacity and respiratory musculature. Stronger inspiratory muscles may have also contributed to the larger TLC. Maximal static pressures provide an indirect index of respiratory muscle strength (191), and both PIMAX and PEMAX were greater in swimmers in this study. However, Leith and Bradley measured a 55% increase in maximal static pressures but only 4-5% increase in TLC and VC after 5 weeks of respiratory muscle training in 4 subjects (192). While the increases in TLC and VC were statistically significant, they concluded that increasing respiratory muscle strength only had a limited, ceiling effect on TLC because respiratory system compliance is low at TLC and inspiratory muscle force-length relationships become even more strained with modest increases in 106  volume above TLC. Fanta et al. also observed a slight increase in TLC and VC in 8 subjects performing 6 weeks of inspiratory muscle training by inspiring to TLC, breath-holding at TLC for 10 seconds, then exhaling back to FRC (193). However, PIMAX and PEMAX were unchanged in their subjects. Instead, subjects generated an additional 27 ± 8 cm H2O of inspiratory pressure at their initial TLC (compared to zero before training). Because there were no changes in FRC or RV, and therefore lung elasticity, the authors suggested that greater maximal shortening of the inspiratory muscles may have occurred. This could have resulted from either the force-length relationship of the respiratory muscles shifting to the left due to a decrease in the number of sarcomeres in series, or the inspiratory muscles becoming stronger and producing greater forces at shorter sarcomere lengths near TLC. These findings may translate to swimmers because, as mentioned earlier, immersion and the prone position constrain lung volumes and increase airway resistance, providing a potential inspiratory muscle conditioning stimulus. The hypothesized respiratory muscle adaptations may explain the small (<10%) but statistically significant increases in TLC and FVC despite large increases in PIMAX (20-50%) after 12 weeks of either swim training or swim and inspiratory muscle training in collegiate swimmers (14, 19). However, swimmers reportedly have a similar maximal static inspiratory mouth pressure compared to controls (14, 27-29), and Zinman and Gaultier observed no change in PIMAX despite a significantly increased TLC after one year of training in 17 7-12 y old swimmers (15). Estimates of respiratory muscle force, which reflect the larger chest surface area over which swimmers must dissipate pressures, were shown to be greater in 7-10 y old female swimmers (27) but not collegiate male swimmers (29). Measurements of operating lung volumes and WOB while swimming are needed to confirm an inspiratory muscle conditioning stimulus, and at present there is no evidence that swimmers routinely inspire to TLC while 107  immersed in water. Improvements in quantifying respiratory muscle strength may also provide a better understanding of changes in respiratory musculature with swim training. Ultimately, while respiratory muscle changes may have contributed to the larger lungs of the swimmers in the present study, the contribution is likely to be small and could not account for the entire 20% difference in TLC between the swimmers and controls.  4.1.2.5 Summary on total lung capacity All published studies assessing TLC in competitive young swimmers have measured greater capacities compared to controls (11, 12, 14, 15, 18, 19, 22, 27-29) or predicted values (9, 21, 23, 24, 31). Only the unpublished thesis by Gibbins found a similar TLC between swimmers and controls, and it is important to note the low training stimulus (1000 yards per session, 3-4 sessions per week) and short time period (6 months) of his investigation (42). As stated earlier, lung size, inspiratory muscle force generation, and the inwards elastic recoils of the lungs and chest wall interact to determine TLC. Any contributions from changes in respiratory musculature are likely to be small and could not account for the entire 20% difference in TLC between the swimmers and controls. Given the evidence, an intermittent hypoxic stimulus or alternative form of induced postnatal lung growth is unlikely to contribute to a larger lung size that explains the greater TLC. Moreover, at present, there is no clear indication that the lungs of swimmers have different mechanical properties compared to healthy controls. Therefore, given the tight coupling between chest wall and lung sizes, and that increases in TLC during childhood are due primarily to somatic growth of the chest wall, it is likely that the greater TLC of the swimmers in this thesis were related to larger chests. The facts that greater chest dimensions were observed in swimmers as young as 7-8 y old, persist into young adulthood, and are correlated with larger TLC also provide 108  further evidence that children with larger chests and lungs likely self-select into swimming. Lastly, the tight coupling between chest wall and lung growths could explain the conclusion by Armour et al. that an increased alveolar number, not alveolar distensibility, may have been associated with the physically larger chests of swimmers and could explain the greater TLC (29). It is possible that the larger chests of swimmers stimulated an increased rate of alveolar hyperplasia, as per the aforementioned feedback loop, leading to a greater number of alveoli.  4.1.2.6 Functional residual capacity. Functional residual capacity is the volume remaining in the lungs at the end of a normal, resting expiration. In infants it is determined dynamically; during development, FRC becomes the static passive balance of lung recoil forces inward and chest wall recoil forces outward, potentially a result of the stiffening chest wall (130). Since all lung volumes increase during development due to the growth in lung size, the ratios of lung volumes relative to TLC are useful for assessing the relative contributions of the other determinants. The ratio of FRC to TLC (FRC/TLC) is commonly reported to be independent of height and age, with most reference values ranging from 0.405 to 0.50 (194). However, it was suggested that FRC/TLC may increase slightly during development due to a greater increase in chest wall recoil outwards than lung elastic recoil inwards at FRC (37).  This is indicated by some studies reporting a slight but significant increase in FRC/TLC with increasing age (124, 195). Thus, FRC increases during development primarily due to the growing lungs; any additional increases are marginal, due to a slightly greater change in chest wall recoil outwards. In this study, FRC was similar between the two groups, although only the swimmers increased significantly from PRE to POST (the difference in mean FRC between the groups was 109  only 190 ml at the follow-up). This result is somewhat surprising, as the swimmers had a significantly larger TLC and therefore one would expect a larger FRC as well. Moreover, previous studies of growing and young adult swimmers reported a larger FRC compared to controls (14, 22, 23, 27-29) and predicted values (9, 10, 12, 24, 31). Conversely, Andrew et al. did not observe a distinct difference in FRC compared to controls, but they noted that there was considerable variability in FRC amongst swimmers (11). While Courteix et al. observed no initial differences between 5 9-10 y old female swimmers and 11 matched controls, FRC was larger in swimmers after 1 year (18). As mentioned earlier, the control group had an abnormally small increase in TLC despite growing, on average, 6 cm in height. This may also explain the difference in FRC at their follow-up measurement, as FRC did not change in the control group. A similar explanation may underlie the surprising result in this study. The mean FRC/TLC for the swimmers was 0.46 ± 0.05 (PRE) and 0.47 ± 0.06 (POST). These are comparable to the 0.48 ± 0.07, 0.46 ± 0.05, and 0.49 ± 0.03 reported by Zinman and Gaultier in 7-8, 9-10, and 11-13 y old female swimmers (27), and 0.47 ± 0.02 and 0.49 ± 0.04 observed by Courteix et al. in 9-10 y old female swimmers before and after 1 year of intense training (18). Therefore, the mean FRC/TLC for the swimmers is comparable to previous reports and within the range of previously stated reference values. Whereas others found no differences between swimmers and controls for FRC/TLC (18, 27), in this study the controls had a larger FRC/TLC at both time points. Their initial mean FRC/TLC of 0.56 ± 0.04 appears remarkably high, and it is unusual that their FRC did not change from PRE to POST despite both somatic and lung growth. Thus, the significant interactions for FRC and FRC/TLC were likely due to abnormalities in the control group and not an effect of swimming. 110  If the difference in FRC/TLC was due to swimmers having a smaller FRC relative to TLC, and assuming the greater TLC was primarily due to larger lungs (i.e., a greater number of alveoli) and not a greater ability to distend the existing alveoli, then this would necessitate that the swimmers had either an increased lung recoil inwards or decreased chest wall recoil outwards at FRC. However, Armour et al. found no difference in pressure-volume curves between male collegiate swimmers, runners, and controls when lung elastic static recoil pressures were expressed relative to % TLC (29). Moreover, at present there is nothing to indicate that swimming alters the elastin and collagen distribution in the lung. In terms of chest wall mechanics, as discussed earlier the key contributors to increasing outward recoil during development are changes in chest wall shape, increased respiratory muscle strength, and rib mineralization. Zinman and Gaultier measured larger chest wall dimensions in 7-13 y old competitive female swimmers compared to healthy controls; however, growth in each dimension was proportional and the overall configuration was similar between the groups (27). One can speculate that a greater respiratory muscle mass may decrease chest wall recoil outwards at FRC; however, increased respiratory muscle strength and resting tone would have the opposite effect on chest wall recoil. Hypothetically, these opposing effects would cancel each other out. Lastly, bone mass and size increase with weight-bearing exercise due to increasing muscle size and other loading factors (196, 197). This is particularly important during puberty, when augmented bone mineralization is favourable and physical activity, specifically weight-bearing exercise, can have a critical effect (198). Even though swimming is non-weight-bearing, a recent systematic analysis suggested that children and adolescent swimmers have a similar bone mineral density as sedentary controls (199). Thus, the conclusion that differences in FRC were not the result of swimming is further supported 111  by the lack of evidence supporting the idea that long-term, intense swim training affects the static mechanical properties of the respiratory system.  4.1.2.7 Residual volume. Residual volume is the volume of air remaining in the lungs after a maximal expiration. In young subjects, RV is determined by the balance between expiratory muscle strength and opposing chest and lung elastic recoil forces (200), antagonist muscle contraction (129), and the occurrence of airway closure (102). In children, although the chest wall is more compliant, lower lung elastic recoil and weak expiratory musculature (relative to adulthood) limit their ability to maximally exhale. During adolescence the chest wall stiffens, and despite greater lung elastic recoil (37) and more developed expiratory musculature, expiration becomes limited by the ability to compress the chest wall (91). Closing volume (CV), the volume of air remaining in the lungs once the small dependent airways have closed and remaining expiration is from the upper open airways (201), is high in children (approaching supine FRC) due to earlier airway closure resulting from less elastic recoil of the lungs (201). However, as lung elastic recoil and airway elasticity increase during growth, airway closure decreases. Therefore, CV decreases and converges with RV, reaching a minimum around 16 years where it can be undetectable (37). Thus, while RV increases primarily due to the growing lungs, these mechanical changes may underline secondary increases as evidenced by a marginal increase in the ratio of RV to TLC (RV/TLC) during development (57, 124, 135, 202).  The large, longitudinal Australian study by Hibbert et al. reported average values ranging from 0.23-0.26 in early pubescent females (age 8-13 y old) to 0.30-0.31 in older adolescent females (age 17-20 y old) (57). The ratio was slightly lower in males, ranging from 0.22-0.26 in early pubescent males (age 8-13 y old) to 0.25-0.29 in 112  older adolescent males (age 16-20 y old). They suggested that this might have been related to differences in expiratory muscle strength, chest wall shape, or airway compliance. Conversely, others have reported RV/TLC to be constant throughout development (86) and similar between males and females (86, 195), with most reference values ranging from 0.171 to 0.240 (194). In this thesis, RV was similar between the groups (p=0.70) and therefore RV/TLC was smaller in swimmers (p=0.07). The former agrees with previous reports that found no difference in RV despite a larger TLC in developing and young adult competitive swimmers compared to controls (18, 22, 27) and predicted values (21). However, others observed a greater RV in swimmers compared to controls (14, 27-29) and predicted values (23, 24, 31). Interestingly, swimmers and controls were reported to have a similar RV/TLC (18, 21, 27-29) regardless of whether or not there was a difference in RV. Only Zinman and Gaultier’s oldest cohort had a significantly different RV/TLC, for which swimmers were larger (27). Therefore, the finding that RV/TLC was smaller for the swimmers in this thesis is notable. The average of 0.21 ± 0.03 is comparable to calculations of RV/TLC from previous studies, including 0.186 ± 0.035 in 12-16 y old female swimmers (21); 0.22 ± 0.05 in 9-10 y old female swimmers (18); 0.24 ± 0.05, 0.20 ± 0.07, and 0.25 ± 0.06 in 7-8, 9-10, and 11-13 y old female swimmers, respectively (27); and 0.232 ± 0.06 (28) and 0.213 ± 0.026 (29) in female and male collegiate swimmers, respectively. Moreover, the controls had an RV/TLC (0.24 ± 0.05) within the range of earlier stated reference values. Since RV is determined by lung size, lung elastic recoil, chest wall recoil, and the expiratory muscle’s ability to compress the chest wall, it seems likely that the opposing effects of larger lungs and stronger expiratory musculature interact to determine whether RV is greater than expected. In cases where RV was similar despite swimmers possessing a greater TLC, it is possible 113  that the muscularity effect underlying slight differences in RV/TLC between males and females may also apply to swimmers versus controls. Stronger expiratory musculature may not be captured by PEMAX, as PEMAX is measured at TLC and was observed to be larger in swimmers in some (20), including here, but not all (27-29) studies. On the other hand, in cases where RV was larger than expected, it is possible that the lungs of swimmers are of such size, that even with the muscularity effect, RV is still often observed to be greater than controls. Thus, the similar RV but lower RV/TLC of swimmers in this thesis was likely due to their relatively greater ability to compress their chest wall during maximal expiration.  4.1.2.8 Vital capacity Vital capacity is the difference between TLC and RV; therefore, VC is dictated by the determinants of both TLC and RV. These include lung size, lung and chest wall recoils at RV and TLC, the respiratory musculature’s ability to compress and expand the chest wall, and antagonistic muscle activity. Regardless of whether it is determined using spirometry (i.e., FVC) or as the difference between TLC and RV, vital capacity was consistently observed to be greater in swimmers compared to controls (7, 11, 12, 14, 16-18, 22, 26-30, 40, 41) or predicted values (9, 13, 21, 23-25, 31, 41). Only a couple of studies found no differences with controls (33, 42, 43). Thus, it is likely that a greater lung size, increased TLC, the muscularity effect, and decreasing RV, all contribute to the increased vital capacity of the swimmers in this study.  4.1.2.9 Spirometry Peak expiratory flow (PEF) and peak inspiratory flow near TLC are effort-dependent because they are limited by the rate of muscle shortening and therefore the muscle’s ability to 114  generate force (67, 203). At lower lung volumes, expiratory flow becomes an effort-independent function of airway conductance (which is a function of the interaction between the forces across and intrinsic properties of the airway wall (204)) and lung and chest wall recoil, not of muscular effort (67). Maximum expiratory flow-volume curves provide a great tool for analysis of flows and how they change over time. During development, the MEFV geometrically enlarges primarily due to an increasing TLC, leading to a proportionally larger PEF (205). However, changes in lung mechanics lead to changes in curvature of the MEFV as well. Children have higher airway resistance, lower elastic lung recoil, and nonhomogenous emptying of the alveoli; therefore, peak expiratory flows are lower and they are unable to sustain high flows throughout expiration, causing the curve to be convex to the volume axis (46). During adolescence, larger lungs and an increased Pst(L) lead to a concave curve with greater PEF and forced expiratory flows that can be sustained for more of the expiratory maneuver. However, adolescents can abruptly “fall off” the curve because greater chest wall stiffness limits the expiratory muscles’ ability to compress the chest wall at low lung volumes (91). The curve becomes convex once again with increasing age throughout adulthood as airways become flow-limited and lung elastic recoil decreases. Given that the swimmers in this study had a significantly larger TLC, it is not surprising that they had a greater PEF and other indices of spirometry including FVC, FEV1, and forced expiratory flows (FEF25-75%, FEF25%, FEF50%, and FEF75%). A greater TLC and PEF were also observed in previous reports compared to controls (14, 18, 29) or predicted values (31). Moreover, most studies measuring FEV1 as a surrogate of flow found FEV1 to be greater in swimmers compared to controls (14, 16, 18, 20, 22, 28-30, 40, 41) and predicted values (24, 25, 31, 41). The ratio FEV1/FVC was nearly identical between the groups and did not change over time, with all swimmers having a ratio greater than or equal to 0.80. While swimmers had larger forced 115  expiratory flows, this was likely due to the flows occurring at a higher absolute lung volume. This is highlighted by the average MEFV (Figure 1), which also shows that swimmers and controls generated the same flow for a given volume. Furthermore, the quantitative characteristics of the MEFV were the same. The similar instantaneous and average SR implied similar emptying properties of the lung, while curvature of the MEFV was similar as indicated by comparable β° and FR. Thus, despite having larger lungs and higher peak expiratory flows, swimmers were subject to the same mechanical constraints at low lung volumes as were controls. This result is not surprising when considering that the MEFV was geometrically larger, likely due to a greater TLC, and curvature was the same, likely because there is no evidence of differences in mechanical properties between the groups. Clanton et al. compared 16 collegiate female swimmers and 8 sex-matched controls, finding that the swimmers had a leftward shifted MEFV due to a significantly larger RV and especially TLC (14). Therefore, swimmers produced lower expiratory flows for a given absolute lung volume. However, the swimmers and controls had an identical MEFV when plotted against %-TLC, suggesting that the time constant for lung emptying was the same for swimmers and controls. Thus, the difference between the observations of Clanton et al. and this thesis could be explained by differences in RV. In younger swimmers, when RV is likely to be closer to that of controls, the MEFV is geometrically larger due to a larger TLC but flows are the same for a given absolute lung volume. With continued development, TLC becomes so substantially increased, that despite the muscularity effect, RV may become higher in swimmers. While the MEFV is still a geometrically similar shape in swimmers and non-swimmers (because mechanical lung properties are similar), it is shifted to the left due to the higher RV. 116  These findings appear to contrast those of Courteix et al., who reported that their swimmers had an MEFV shifted rightward and increased forced expiratory flows such that swimming “improved” the flow-volume relationship (18). Moreover, they stated that Raw increased in the control group but not the swimmers, and therefore swimming alters dysanaptic development of the respiratory system. However, there are multiple criticisms of how they reached their conclusions. First, they plotted the MEFV with all groups having their TLC start at the same point along the volume axis. However, TLC was significantly larger at the follow-up measurement in swimmers, hence causing their MEFV to look larger and peak and mid-expiratory flows to look higher. If plotted from RV, which was the same at both time points for both groups, then the MEFV would mirror those reported in this thesis. Second, the difference in changes in forced expiratory flows is confounded by the lack of growth in TLC reported in the control group. Courteix et al. argued that the increased forced expiratory flows over 1 year in swimmers, but not controls, implied that swimming improved conductive properties of the small airways. Yet, given that their control group only increased an average of 90 ml in TLC, one would not expect to measure changes in expiratory flows if minimal changes in TLC were observed. Had the control group experienced normal amounts of lung growth, no differences may have been found. Lastly, Courteix et al. stated that Raw increased only in the control group but there were no statistically significant differences between swimmers and controls at either time point for Raw. Instead, their conclusion was based on a statistically significant difference between the groups in %-change from initial to follow-up. No details of statistical analyses were provided for changes from initial to follow-up in absolute Raw. Thus, critical interpretation of their analysis questions the validity of their statements about the effect of swimming on dysanaptic growth.   117  4.1.2.10 Dysanapsis ratio As stated earlier, the DR can be calculated to estimate differences in airway size relative to lung volume and lung static elastic recoil pressure (60). Longitudinal analysis in children and adolescents showed that DR, using the regression equation from Zapletal et al. based on height to estimate Pst(L)50 (90), range from 0.10-0.20 and steadily decrease with increasing age (57). However, two considerations must be made when interpreting DR. First, because DR is a function of lung size, and airway length is dependent on lung size, DR can be confounded by larger lungs which have longer airways and thus increased airway resistance, causing decreased flows. Therefore, DR must be compared at equal lung volumes to control for airway length. Second, when comparing DR across different lung volumes, interpretation of the growth pattern observed (i.e., isotropic vs. dysanaptic) depends on the exponential function best fitting the theoretical relationship between DR and lung volume. A relationship of VC-2/7 suggests isotropic growth with turbulent flow during the MEFV; VC-1 suggests dysanaptic growth whereby airway and lung sizes are independent; lastly, VC-4/3 suggests dysanaptic growth where airway diameters are independent of lung size but airway length varies according to lung volume (46, 89). Smith et al. used these functions to determine that a relationship of VC-4/3 described dysanaptic growth patterns during prepubescence and VC-1 during postpubescence (128). Their DR were slightly higher (0.37 ± 0.09 to 0.21 ± 0.06 at pre- and post-pubescence, respectively) because they estimated Pst(L)50 using the regression equations calculated by De Troyer et al. based on age (112). Thus, dysanaptic growth occurs throughout development, with different dysanaptic patterns during pre- versus post-pubescence. In this thesis, DR was similar between the two groups. However, DR could not be compared at similar lung volumes because the average TLC for the swimming group was much 118  larger than the control group. Moreover, Figure 9 shows the considerable variability in DR that made individual comparisons at a given lung volume and estimation of the exponential relationship between DR and lung volume difficult. Therefore, interpretation of the effect of swimming on airway diameter from this thesis is limited. Nevertheless, future work should investigate dysanaptic growth patterns in swimmers throughout development for multiple reasons. First, dysanapsis has recently become an increasingly relevant clinical phenomenon (206, 207). Second, as initially suggested by Zinman and Gaultier, assessing dysanaptic growth patterns in swimmers could hold the key to understanding whether competitive swimming affects lung development (27). No single agent can induce lung growth that replicates the coordinated dysanapsis of the normal lung (109). Instead, induced postnatal lung growth exaggerates dysanaptic growth patterns because accelerated alveolar growth occurs without a correspondingly enhanced airway growth (109). The larger airspaces without compensatory larger airways leads to limitations in airway conductance that diminishes the functional benefits of enhanced alveolar growth (109). This is demonstrated by the hypoxia-induced lung growth of high altitude residents (208). Peruvian natives to 3850 m (highlanders) had significantly greater FVC than and similar lung elastic recoil to Peruvian natives to 800 m (lowlanders), but had lower flows and airway conductance at low lung volumes and at all volumes when corrected for lung size. Therefore, if swimming induces postnatal lung growth, then exaggerated dysanaptic growth patterns and increased airway resistance (especially at low lung volumes) would be expected.  4.1.2.11 Maximal static pressures and respiratory muscle force  Maximal static mouth pressures. Maximal pressures measured at the mouth are indicative of the maximum pressures developed by the respiratory muscles, the passive elastic 119  recoil pressure of the respiratory system (lungs and chest wall), and the lung volume at which the pressure is measured (209). They are also influenced by the shape of the chest wall and relaxation of the antagonist muscles (129). Thus, it provides an indirect index of respiratory muscle strength (191). In children and adolescents, maximal static inspiratory and expiratory mouth pressures increase during development (45, 102, 136, 210, 211). This is likely due to respiratory muscle strengthening (i.e., the “muscularity” effect (212)); increasing chest wall outward recoil at RV and increasing elastic lung recoil at TLC may also contribute to improvements in PIMAX and PEMAX, respectively. Moreover, maximal pressures may be relatively higher in children as compared to adults because of mechanical advantages due to the smaller radius of the costal diaphragm and chest wall (213). Pressures are higher in boys than girls (45, 102, 136, 210, 211); while girls reach adult values by puberty (102, 136), boys continue to increase after the growth spurt due to the muscularity effect (102). As mentioned earlier, maximal static mouth pressures were seldom measured in young swimmers. Maximal expiratory pressure was observed to be larger in swimmers compared to controls in only one study (20); others found no difference (27-29). Moreover, only similar measures of PIMAX between swimmers and controls were reported (14, 27-29). In fact, Zinman and Gaultier reported a significantly smaller PIMAX in their 11-13 y old swimming cohort compared to controls (27). Therefore, the findings of greater PEMAX and PIMAX in the swimmers in this thesis are somewhat surprising. Swimmers increased, on average, 16 cm H2O in PIMAX and 13% in %-predicted PIMAX whereas the controls only 8 cm H2O and 5%. Although the interaction effect was not significant, it is possible that inspiratory muscle conditioning due to swimming may explain some of the difference in PIMAX given that swimming was reported to improve inspiratory muscle strength and endurance (14, 19). It seems more likely that differences in both PIMAX and PEMAX 120  may be explained by relatively lower values in the control group. The controls had an average %-predicted PIMAX of 82 ± 30 cm H2O and 87 ± 30 % and %-predicted PEMAX of 77 ± 19 cm H2O and 84 ± 19 % at PRE and POST, respectively. Whereas only one swimmer had a slight decrease in PIMAX (-4%) and PEMAX (-4%), three controls decreased PIMAX (by 10, 10, and 22%) and PEMAX (by 6, 11, and 15%). Moreover, all swimmers had a %-predicted PIMAX greater than 80% at follow-up, while four controls were <70% of predicted values. One control subject struggled with the maneuver and had a %-predicted PIMAX of 26% at the initial measurement. Thus, differences in maximal static mouth pressures reported in thesis may be due to a combination of respiratory muscle conditioning due to swim training and relatively lower values by the control group. Respiratory muscle force. Respiratory muscle force cannot be directly measured in vivo, and the best estimation is pleural pressure (67). However, multiple studies have estimated respiratory muscle force production at different lung volumes (RV, FRC, and TLC) from the product of maximal static pressures and estimations of chest wall surface area (102, 136). Inspiratory and expiratory forces increase with age in both 7-13 y old (136) and 12-20 y old (102) children and adolescents. This occurs to a greater extent than corresponding increases in static pressures (136), reflecting the increasing chest surface area. Therefore, changes in respiratory muscle forces may capture differences between swimmers and controls that maximal static pressures alone cannot. Zinman and Gaultier observed a greater inspiratory muscle force in 7-10 y old swimmers despite a similar PIMAX, suggesting that pressure alone did not account for the larger chest wall surface area over which swimmers must dissipate pressure (27). Conversely, no differences in inspiratory or expiratory muscle force were found between collegiate male swimmers, runners, and controls (29). Although not measured in this study, this suggests that respiratory muscle force (i.e., pleural pressure) and other surrogate measures of respiratory muscle 121  strength (e.g., transdiaphragmatic pressure or diaphragm thickness) may elucidate respiratory muscle training effects of swimming not captured by maximal static mouth pressures.  4.1.2.12 Diffusion capacity of the lungs Diffusion capacity of the lungs for carbon monoxide is anatomically determined by lung volume, alveolar-capillary surface area, alveolar-capillary membrane thickness, and pulmonary capillary blood volume (109). During growth, increases in alveolar surface area, vascular density, and capillary bed size (107) lead to progressive increases in DL,CO with height and lung size (47, 214). The ratio of diffusing capacity of the alveolar membrane to pulmonary capillary blood volume is similar to that in adults, suggesting that the relationship between alveolar capillary diameter and wall thickness is not affected by growth (214). However, DL,CO standardized for alveolar VA (also known as the transfer factor (KCO)) progressively decreases with height (214). This may be due to greater growth in alveolar volume compared to the gas-exchanging portion of the membrane (i.e., basement epithelial membrane of type I cells) (214). While DL,CO is higher in males, KCO is similar between the sexes because the greater DL,CO in males is proportional to their larger lungs (214). In this thesis, resting DL,CO was significantly greater in swimmers compared to controls, even when corrected for hemoglobin (which was similar between the groups). The swimmers also had an average %-predicted DL,CO of 121% at PRE and 122% at POST. These are in accordance with previous studies that measured a greater DL,CO in swimmers than controls (11, 22, 29, 34, 39) and predicted values (24, 29, 31-33, 35). However, differences in DL,COc between swimmers and controls in this thesis were abolished when expressed relative to VA, confirming previous findings (11, 22, 29). Moreover, %-predicted DL,COc/VA averaged 101 and 97% for swimmers at PRE and 122  POST, respectively. Thus, it is likely that DL,CO was greater due to a greater TLC, but it is unknown if any changes in alveolar-capillary membrane or pulmonary capillary blood volume occurred.  4.1.2.13 Summary Development of the respiratory system is characterized by dysanaptic growth of the alveoli and airways, changes in chest wall mechanics, and a tight coupling between chest wall and lung growths. Currently, there is no evidence to suggest that these characteristics are altered by any of the unique challenges imposed by competitive swimming on the developing respiratory system. Therefore, it seems likely that the greater TLC of the swimmers in this thesis and other studies were related to larger chests, with an additional, but limited, contribution by stronger respiratory musculature. The larger TLC can explain why other measures of pulmonary function are greater, including FVC, PEF, mid-expiratory flows, the MEFV, and DL,CO (Table 19). It can also explain the greater FRC in other studies, whereas in this thesis the lack of difference in FRC may have been related to an initially high mean FRC in the controls. This initially high mean FRC in controls may underlie the smaller FRC/TLC found in the swimmers in this thesis, whilst values for FRC/TLC paralleled other reports of swimmers. Conversely, FRC/TLC has been similar between swimmers and controls in other studies because there are no known differences in lung mechanics to suggest otherwise. Greater PEMAX and PIMAX indicate stronger respiratory musculature, leading to a “muscularity effect” underlying a similar RV and lower RV/TLC. Thus, an effect of competitive swimming is not definitively associated with any of the differences in pulmonary function (beyond differences in respiratory musculature) or structure between swimmers and controls. To confirm this conjecture, future work should focus on quantifying and comparing dysanapsis between swimmers and controls.   123  Table 19 – Summary of changes in pulmonary function Measure Determinants Changes with growth Finding here Findings in previous reports on swimmers Mechanism of change Comments TLC Lung size, inspiratory muscle force generation, inwards elastic recoils of lungs and chest wall (139) ↑ with height primarily due to chest wall growth (140) ↑ ↑ compared to controls (11, 12, 14, 15, 18, 19, 22, 27-29) or predicted values (9, 21, 23, 24, 31) ↔ compared to controls (42) -Larger chests -Greater ability of respiratory muscles to distend chest wall  FRC Lung size, static passive balance of lung recoil inwards and chest wall recoil outwards ↑ primarily due to growing lungs ↔ ↑ compared to controls (14, 22, 23, 27-29) or predicted values (9, 10, 12, 24, 31) ↔ compared to controls (11) (in other studies) Larger TLC ↔ FRC potentially due to control group having large FRC at PRE FRC/TLC Mechanical properties of lungs at FRC and TLC Either ↔ or ↑ slightly ↓ ↔ compared to controls (18, 27) (in other studies) Similar mechanical properties of lung ↓ FRC/TLC potentially due to control group having large FRC at PRE RV Lung size, expiratory muscle strength, opposing chest and lung elastic recoil forces (200), antagonist muscles (129), occurrence of airway closure (102) ↑ primarily due to growing lungs ↔ ↑ compared to controls (14, 27-29) or predicted values (23, 24, 31) ↔ compared to controls (18, 22, 27) or predicted values (21) Balance between larger TLC (↑ RV) and muscularity effect (↔ RV)  RV/TLC Mechanical properties of the lungs at RV and TLC Either ↔ or ↑ slightly ↓ (p=0.07) ↑ compared to controls (27) ↔ compared to controls (18, 21, 27-29) -Balance between larger TLC (causing ↔ RV/TLC) and muscularity effect (causing ↓ RV/TLC)  PEF Lung size, effort, expiratory muscle force generation, lung elastic recoil ↑ due to ↑ TLC, ↑ Pst(L) ↑ ↑ compared to controls (14, 18, 29) or predicted values (31) No difference [refs] Larger TLC  FVC or VC Lung size, RV ↑ primarily due to growing lungs ↑ ↑ compared to controls (7, 11, 12, 14, 16-18, 22, 26-30, 40, 41) or predicted values (9, 13, 21, 23-25, 31, 41) ↔ compared to controls (33, 42, 43) Larger TLC, muscularity effect  FEF Lung size, airway conductance, lung and chest wall recoil ↑ due to ↑ TLC, ↑ Pst(L) ↑  Larger TLC (FEF occurs at ↑ volume)  MEFV Lung size, lung mechanics Geometrically enlarges due to ↑ TLC, some changes in curvature Larger Leftward shifted (14) Rightward shifted, larger (18) Larger TLC, similar RV Quantitative characteristics (β°, SR, FR) all similar DL,CO Lung size, alveolar-capillary surface area and membrane thickness, pulmonary capillary blood volume (109) ↑ due to ↑ alveolar surface area, vascular density, capillary bed size (107) ↑ ↑ compared to controls (11, 22, 29, 34, 39) or predicted values (24, 29, 31-33, 35) Larger TLC  DL,CO/VA DL,CO and alveolar volume ↓ with height (214) ↔ ↔ controls (11, 22, 29) -  PEMAX Respiratory muscle pressure generation, passive elastic recoil pressure of respiratory system, lung volume at measurement (209), chest wall shape and antagonist muscles (129) ↑ likely due to muscularity effect (212), some mechanical and chest wall shape changes ↑ ↑ compared to controls (20) ↔ compared to controls (27-29) Muscularity effect Values slightly lower in controls may exaggerate difference PIMAX Same as PEMAX Same as PEMAX ↑ (p=0.06) ↔ compared to controls (14, 27-29) ↓ compared to controls (27) Same as PEMAX Same as PEMAX 124  TLC, total lung capacity; FRC, functional residual capacity; RV, residual volume; PEF, peak expiratory flow; Pst(L), static lung elastic recoil pressure; FVC, forced vital capacity; VC, vital capacity; FEF, forced expiratory flow; MEFV, maximum expiratory flow-volume curve; β°, β-angle; SR, slope ratio; FR, flow ratio; DL,CO, diffusion capacity of the lungs for carbon monoxide; VA, alveolar volume; PEMAX, maximal static expiratory mouth pressure; PIMAX, maximal static inspiratory mouth pressure.   125  4.1.3 Metabolic and ventilatory responses during cycling exercise The secondary finding of this study was that the competitive swimmers, despite having larger lungs and enhanced pulmonary function, experienced similar ventilatory constraints as healthy controls of similar age, size, and sexual maturity while cycling. This was demonstrated by similar EELV, prevalence and severity of EFL, and utilization of V̇ECAP. One season (seven months) of competitive swimming during puberty did not affect the occurrence of these constraints.  4.1.3.1 Metabolic and ventilatory responses during cycling One season of competitive swimming during puberty did not affect the metabolic response to exercise, as there were no two- or three-way statistically significant interactions involving group and time. Differences in absolute work rate and V̇O2 were due to the swimmers being slightly, albeit not significantly, larger in body size. This likely explains the greater V̇CO2 in SWIM, which led to an increased V̇E achieved by a larger VT. However, the absence of any significant interactions between relative work rate and group for V̇E, fB and VT suggested that SWIM and CON had similar relative changes in their ventilatory response as exercise intensity increased. Moreover, nearly identical ventilatory equivalents for oxygen consumption (V̇E/V̇O2) (p=0.76) and carbon dioxide (V̇E/V̇CO2) (p=0.95) reinforce that the groups had similar ventilatory responses to increasing metabolic demands during exercise. Significant two-way interactions between time and relative work rate reflect similar metabolic data at baseline during PRE and POST, but increased values throughout exercise in accordance with higher absolute work rates at POST. The swimmers had similar maximal metabolic responses to cycling exercise as other adolescent female swimmers (Table 20), including relative V̇O2MAX (12, 21, 215-218). However, 126  contrary to previous reports that male (215, 219) and female (215, 217, 219) swimmers had a higher V̇O2MAX compared to untrained controls (215, 217) or other athletes (219), in this thesis there was no difference in relative V̇O2MAX between the groups. This was likely due to the excellent exercise capacity of the control group. Both groups had, on average, a V̇O2MAX that was 115-131% predicted. Moreover, the similar peak aerobic capacity is not surprising when considering that both groups reported similar physical activity levels and nearly doubled the Canadian guideline of at least 60 minutes of daily moderate-vigorous intensity physical activity. Absolute V̇O2MAX increased from PRE to POST in both groups, which is in agreement with previous reports of female swimmers (219) and with absolute V̇O2MAX tending to increase from 8 to 13 y old in healthy, untrained girls (220). Conversely, relative V̇O2MAX did not significantly increase over time. This has been observed in other longitudinal studies of 10-16 y old (217) and 8-16 y old (219) female swimmers, whereas others found it to increase over 3 consecutive years in 13-17 y old female swimmers (13). Robinson et al. had 12 10-16 y old competitive female swimmers perform maximal cycling exercise tests before and after one season of competitive swim training (swimming up to 12-14 km per day as often as 6 days per week) (217). Their relative V̇O2MAX barely changed after one season (47.7 ± 5.2 and 48.9 ± 3.4 ml·kg-1·min-1 before and after, respectively), and they attributed any slight increases to somatic growth. A similar difference between PRE and POST (42.9 ± 6.8 versus 44.4 ± 8.1 ml·kg-1·min-1) was measured here. It is also important to note that V̇O2MAX expressed relative to body weight was shown to decrease with sexual maturity (221) and chronological age (220) in healthy, untrained growing girls, most likely due to increasing subcutaneous fat accumulation post-pubescence (221). Therefore, the maintenance of an elevated relative V̇O2MAX throughout pubescence in female swimmers (219) 127  suggests that intense swim training during adolescence prevents age-related declines in relative V̇O2MAX.   128  Table 20 – Metabolic responses at maximal cycling exercise in adolescent female swimmers Study Age (y) N Height (cm) Mass (kg) HR (bpm) V̇E (l·min-1) V̇O2 (l·min-1) VO2 (ml·kg-1·min-1) Cunningham and Eynon, 1973 (216) 12.2 ± 0.4 8 154.8 ± 10.0 43.3 ± 6.7 191 ± 2 60.9 ± 14.9 1.97 ± 0.31 46.2 ± 7.8 This thesis (PRE)* 12.4 ± 0.8 11 161.3 ± 7.9 52.4 ± 10.8 192 ± 10 85.5 ± 20.8 2.20 ± 0.35 42.9 ± 6.8 Wirth et al., 1978# (218) 12.4 8 155 44.8 186 - 1.94 40.3 Robinson et al. 1978 (PRE)* (217) 12.9 ± 1.9 12 152.9 ± 8.7 45.5 ± 9.9 199 ± 6 64.9 ± 17.6 2.16 ± 0.41 47.7 ± 5.2 Astrand et al. 1963 (21) 12.9 30 164.8 ± 6.5 54.2 ± 7.3 199 ± 8 99.9 ± 16.5 2.80 ± 0.44 51.5 ± 4.4 This thesis (POST)** 13.0 ± 0.8 11 163.4 ± 6.9 55.8 ± 9.8 195 ± 8 100.4 ± 17.6 2.42 ± 0.23 44.4 ± 8.1 Cunningham and Eynon, 1973 13.2 ± 0.1 6 160.0 ± 4.54 52.1 ± 8.1 189 ± 7 63.6 ± 12.0 2.24 ± 0.34 43.4 ± 6.5 Robinson et al., 1978 (POST)** - 12 - - 199 ± 6 63.7 ± 13.4 2.30 ± 0.40 48.9 ± 3.4 Kramer and Lurie, 1964 (215) 14.7 ± 0.8 6 165.9 ± 2.1 61.1± 2.3 197 ± 3 84.1 ± 2.1 3.01 ± 0.09 49.5 ± 2.4 Cunningham and Eynon, 1973 14.9 ± 0.6 5 164.8 ± 7.4 53.7 ± 5.4 189 ± 8 70.0 ± 13.5 2.19 ± 0.34 40.5 ± 2.1 Wirth et al., 1978# 15.9 6 166 53.8 178 - 2.40 44.4 Eriksson et al., 1978 (12) 17.0 9 170.0 ± 3.7 62.5 ± 8.1 201 ± 6 105.6 ± 5.4 3.14 ± 0.22 51.1 ± 5.9 *before one season of swim training. **after one season of swim training. #Standard deviations not provided. HR, heart rate; V̇E, minute ventilation; V̇O2, oxygen consumption.   129  4.1.3.2 Ventilatory mechanics during cycling exercise As mentioned earlier, ventilatory capacity is primarily determined by anatomical features (i.e., lung size, airway size and geometry) (69). Therefore, this thesis explored whether the larger lung volumes and expiratory flows of swimmers lead to larger ventilatory capacities and alleviate ventilatory mechanical constraints during exercise. It was previously suggested that the increased ventilatory capacity could facilitate increased metabolic and ventilatory demands within similar ventilatory constraints. Alternatively, alleviation of ventilatory constraints could be possible by generating higher flows at similar absolute lung volumes, decreasing the susceptibility to EFL and allowing swimmers to operate at lower relative lung volumes that may lower their WOB. In terms of group differences in quantitative measures of ventilatory mechanics, there were no statistically significant differences between swimmers and controls for absolute or relative EELV, prevalence or severity of EFL, V̇ECAP, or utilization of V̇ECAP. As shown in Figure 14C and Figure 14D, swimmers utilized a similar absolute EELV (p=0.18) and attained a larger VT (p=0.02) by tending towards a greater absolute EILV (p=0.05). This was possible because of a larger IC (p<0.001) in swimmers (Figure 16C). In fact, IC was so much larger that swimmers still had a larger IRV (p<0.01), even with a greater EILV (Figure 16A). Given that EILV/FVC was slightly smaller (Figure 15C and Figure 15D, p=0.08), IRV/FVC was slightly larger (Figure 16B, p=0.08), and EELV/FVC was the same (Figure 15C and Figure 15D, p=0.46), these suggest that swimmers utilized a smaller relative amount of their greater inspiratory capacity. This is depicted in Figure 16D, where differences in IRV/IC favoured swimmers but did not reach statistical significance (p=0.10). Despite the significantly greater IC in swimmers, ventilatory mechanics were still similar between the groups. This was because of the similar absolute EELV combined with a MEFV that 130  was only geometrically larger and had similar quantitative characteristics. Recalling Figure 1, swimmers and controls produced similar flows for a given absolute volume on the MEFV. Therefore, the swimmers and controls were subjected to identical flow constraints when operating at a similar EELV. This may explain why, contrary to our secondary hypothesis, they did not operate at a lower relative EELV, they were equally susceptible to EFL, and there were no significant differences in V̇ECAP and V̇E/V̇ECAP. The qualitative differences in ventilatory constraints can also be seen in the composite MEFV and superimposed FVL (Figure 19). Hypothetically, in order to alleviate ventilatory constraints by increasing ventilatory capacity or avoiding EFL, the swimmers would have to operate at a higher EELV. However, this would come at the cost of a greater WOB due to breathing along a less compliant segment of the P-V curve. The similar V̇ECAP also negates the possibility of increased metabolic and ventilatory demands within similar ventilatory constraints. Instead, any increase in demand would necessitate greater susceptibility to ventilatory constraints. Thus, the significantly larger TLC and PEF of competitive swimmers did not affect the occurrence of ventilatory constraints while cycling. There were no statistically significant three-way interactions or two-way interactions involving group. The lack of differences in the two-way interactions between group and time implies that one season of competitive swim training did not affect ventilatory mechanics during exercise. The interaction effects between group and work rate for EELV/FVC (p=0.07), EILV (p=0.10), and IRV (p=0.10) approached statistical significance, but post hoc testing revealed few differences. For EELV/FVC, the only difference between swimmers and controls was at baseline (p=0.02). Moreover, only at baseline was EILV not significantly greater in swimmers (p=0.09), and swimmers also had a greater IRV at all work rates. Therefore, the pattern of the ventilatory responses was similar between swimmers and controls, with swimmers having a response of 131  greater magnitude for most measures. Lastly, all interactions between time and work rate were either significant (p<0.05) or approached significance (p<0.10). Akin to the metabolic responses, this likely reflects similar ventilatory data at baseline during PRE and POST, but increased differences throughout exercise in accordance with higher absolute work rates and metabolic demands at POST. Taken altogether, these results suggest that one season of competitive swim training did not affect ventilatory mechanics during exercise. Regardless of training status, the prevalence of EFL was much higher in this study than previously reported for postpubescent girls. Emerson et al. observed EFL in only 2 out of 10 (20%) post-pubescent girls (mean age 14.1 ± 1.0 y and Tanner stage 3.7 ± 0.7) (62) compared to 52% (22 out of 42 total tests) here. There are multiple possible explanations for this difference. First, the subjects in this study were slightly younger and prevalence of EFL was more comparable to the high rates of EFL observed during prepubescence (56% (63) to 93% (61)). It is possible that, with further maturational development and continued lung growth upon cessation of somatic growth in height, the ventilatory capacity increases such that the occurrence of EFL in females becomes less frequent. Alternatively, the difference could be explained by differing fitness levels. The subjects in this thesis had an average relative V̇O2MAX >40 ml·kg-1·min-1 compared to only 33.0 ± 6.7 ml·kg-1·min-1 in the 10 girls tested by Emerson et al. (62). The greater metabolic demand could have led to a greater ventilatory response, increasing the susceptibly to EFL. It is interesting to note that the prevalence of EFL was reported to be 45% in healthy young women (60) and 90% in trained young women (58) and occurred in women of all levels of cardiovascular fitness (59, 60). Thus, further investigation of changes in female susceptibility to ventilatory constraints with maturation is clearly needed.  132  4.1.3.3 Individual responses Figure 17 and Figure 18 display the individual MEFV and FVL for each subject. It is interesting to note the different ventilatory mechanics utilized throughout exercise in subjects with the largest lungs and higher cardiovascular fitness levels. Three of the swimmers with the largest %-predicted FVC (S01, 131-132%; S04, 129-130%; and S07, 143%) became dynamically hyperinflated at maximal exercise (i.e., EELV at maximal exercise was greater than baseline). This occurred despite a V̇E/V̇ECAP that was near or well below average (69-77%, 46-44%, and 66-73%, respectively), but none of them experienced EFL at peak exercise. Conversely, S08 (132-136%-predicted FVC) did not dynamically hyperinflate and instead became flow-limited, utilizing all of her ventilatory capacity (94-120%). She was also the swimmer with the highest relative and %-predicted V̇O2MAX (values at POST were 56.0 ml.kg-1.min-1, 162%-predicted). The swimmer with the second-highest values (S12 POST, 55.0 ml.kg-1.min-1, 159%-predicted) had the opposite ventilatory response, avoiding EFL and using a lower proportion of her V̇ECAP (65%) by dynamically hyperinflating. Thus, the high ventilatory demand comes at the cost of either dynamic hyperinflation with a concurrent decrease in V̇E/V̇ECAP, or EFL and an increased V̇E/V̇ECAP. The different individual responses of subjects with large lungs or high fitness levels display no preference for either breathing strategy.  4.1.3.4 Summary of ventilatory and metabolic responses to cycling exercise Taken altogether, the swimmers and controls had similar metabolic and ventilatory responses to cycling exercise. Differences in absolute work rate and therefore V̇O2 and V̇CO2 could be attributed to the swimmers being slightly larger in size. The greater absolute metabolic demand likely caused the increased V̇E, which was achieved in swimmers by increasing VT. To 133  facilitate a greater VT, the swimmers operated at a similar EELV and higher EILV, utilizing a smaller relative portion of their significantly greater IC. However, because swimmers and controls had similar flows for a given absolute FVC on the MEFV, the swimmers were therefore subjected to identical flow constraints when operating at a similar EELV. This likely explains why they were equally susceptible to EFL, and why there were no significant differences in V̇ECAP and V̇E/V̇ECAP despite the swimmers having larger lungs.  4.2 Methodological considerations 4.2.1 Tanner level of maturation When investigating growth in youth, standardizing for maturational age is important because gestational age does not account for differences in the age of onset of puberty (75). Methods of standardization include radiography of the carpal bones (to determine skeletal age), and grouping subjects according to their maturational stage measured by Tanner level of maturation (75). Tanner staging uses the assessment of primary and secondary sex characteristics (penis, testes, and pubic hair for boys; pubic hair and breasts for girls) to classify five stages of maturation (stage 1 to stage 5), and can be self-assessed or done through a physician assessment. However, it must be acknowledged this method has limitations because maturation is a continuous process whereas the assessment of Tanner stages places individuals on an integer scale. Therefore, it is possible for individuals to spend different amounts of time in each Tanner stage. For example,, for two individuals who both reported a SMR of 4, the first individual could have been in stage 4 for many months whereas the second just entered it; in such a case, the two individuals would be documented at the same level of maturity, whereas the first individual is more developed. Thus, in this study it is possible that the reported SMR between swimmers and controls was similar, but the 134  swimmers could have been at a further point of maturation in each given SMR. This could have contributed to the difference in lung volumes. Despite these limitations, self-reported Tanner staging was used because the method has been validated against a physician assessment (74) and allows sexual maturity to be assessed quickly and non-invasively. Once separated into the five stages, growth velocities for each stage can be determined. In a mixed-longitudinal analysis of competitive swimmers versus controls that used Tanner staging, the largest increases in both female swimmers and controls in FVC and FEV1 occurred between Tanner stages 3 (12.2 ± 1.0 y old) and 4 (13.1 ± 0.9 y old) and between Tanner stages 4 and 5 (14.1 ± 1.1 y old) (16). Although the changes between Tanner stages 2 (11.9 ± 0.9 y old) and 3 were smaller in magnitude, they were still greater in swimmers (mean 0.28 l) than controls (mean 0.14 l) (16). A separate longitudinal analysis showed that the PGV for VC in girls occurred between the ages of 11.5-13.5 y (57). Mathematical modelling of longitudinal data determined that the PGV for girls occurred at age 11.25 ± 0.94 y for FVC and 11.75 ± 0.51 y for FEV1 (72), and radiographic analysis showed lung and chest lengths and widths peaked around age 12 y in girls (73). Therefore, the period of PGV for the lungs in girls is during Tanner stages 2-4, or a gestational age of 11-14 y. This thesis focused on Tanner stages 2-4 with the rationale that these stages of maturation would likely elicit the greatest effects if competitive swimming were to affect lung development during puberty. However, because potential subjects were not screened for a Tanner stage between 2 and 4, this thesis recruited girls between the ages of 11-14 y old.  4.2.2 Technique Children can reliably perform FVC maneuvers at ~8 y old (46) (with some as young as 3-6 y old (222)), while measurements of maximal static pressures are reproducible above 8 y of age 135  (45), TLC above 6 y of age (37), and diffusion capacity above 6 y (47). Regardless, given the age of the subjects in this study and that some of the maneuvers are maximal, effort-dependent, and require substantial coordination, some subjects may not have the necessary coordination or motivation to properly perform these maximal maneuvers. This would cause underestimation of their true physiological measurements. Although this could affect all subjects in the study, it was more likely to occur in controls and confound data for maximal maneuvers in favour of swimmers. Competitive swimming requires coordinated maximal inspirations alternating with maximal expirations, therefore swimmers have much more training and experience in performing respiratory maneuvers. It is possible that this could have contributed to the differences in pulmonary function observed in this study. However, the controls appeared to have “normal” function, as evidenced by mean %-predicted values ranging between 90-105% for most measures and averaging 94 ± 7% for TLC. Moreover, Respiratory Therapists experienced with the pediatric population performed the pulmonary function testing to ensure all subjects elicited maximal efforts. Thus, it is unlikely that poor technique explains the difference in lung function between swimmers and controls. Calculations of operational lung volumes, EFL, and V̇ECAP during exercise all depend on proper technique and adequate effort during the FVC, gFVC, and IC maneuvers. Inadequate effort during the FVC maneuvers could lead to a smaller MEFV, which would translate into a false positive determination of EFL, lower V̇ECAP, and higher V̇E/V̇ECAP. Conversely, poor effort during the IC maneuver could have caused an overestimation of EILV and EELV, false negative determination of EFL, higher V̇ECAP, and lower V̇E/V̇ECAP. As stated in the previous paragraph, these were more likely to occur in the control group and confound the outcome measures in favour of the swimmers. However, multiple steps were taken to minimize the likelihood of these errors. 136  First, all subjects practiced and performed FVC and IC maneuvers with visual feedback and verbal coaching from the Respiratory Therapists during the lung function testing, prior to entering the Exercise Physiology Laboratory. Upon entering the laboratory, they received further coaching and practiced the FVC and IC maneuvers while becoming familiarized with the equipment (e.g., breathing through the mask, sitting on the cycle ergometer). Second, multiple FVC and gFVC trials were performed before and after the exercise test, again with extensive coaching. Third, two IC maneuvers were performed during each stage, in case the first maneuver was later deemed to be inadequate (e.g., an inspiration was performed with a closed glottis). Lastly, although esophageal pressure was not measured, inspiratory flow was used as a surrogate for assessing effort during the IC maneuver. Visual inspection of the MEFV and FVL in Figure 17 and Figure 18 suggests that most subjects adequately performed the FVC, gFVC, and IC maneuvers. In most cases, the first and second IC maneuvers during each stage produced similar inspiratory flows and volumes. Moreover, all subjects were motivated, focused, and compliant, especially during exercise. Thus, there is no evidence to support a systematic difference in technique between the swimmers and controls that could have affected the results of this thesis.  4.2.3 Predictive equations When selecting reference equations, it was recommended that the reference subjects have similar anthropometric and ethnic backgrounds and, if possible, all reference equations are taken from the same source (223). The healthy Australian population studied by Hibbert et al. had a similar age (8-18 y old), height, and ethnic background (Caucasian) as most subjects in this thesis (85). Moreover, they published a comprehensive set of reference equations that could be used for all measures of spirometry (including mid-expiratory flows) and lung volumes determined here, 137  unlike those by Cook and Hamann (224) (which were previously recommended for children aged 5-18 y old (86)) which lacked spirometry. Although Hibbert et al. used body plethysmography to measure lung volumes, they found similar values compared to previous studies using helium dilution (85). A recent, large study from The Netherlands involving over 500 2-18 y old children comprehensively measured spirometry, lung volumes, and diffusion calculation using similar techniques to this thesis (225). While this appeared to be an ideal set of predictive equations, calculated %-predicted values were very high for some measures (e.g., average %-predicted RV was 126-129% in all groups) and low for others (e.g., average %-predicted FRC was 75-80% in all groups). Therefore, the equations by Hibbert et al. were preferred for spirometry and lung volumes and those for diffusion capacity came from a large study of American and Australian 5-19 y old Caucasian children with similar heights and measurement techniques to the present investigation (87). Reference values for maximal static mouth pressures were derived from measurements in a Spanish population of 8-17 y old children and adolescents (45). Domenech-Clar et al. stated that their predictive equation for PEMAX in females was not suitable for calculating reference values (45). However, upon calculating %-predicted values from predictive equations for this study and the large cross-sectional study by Wilson et al. (210), the equations of Domenech-Clar et al. provided more reasonable values and were used in analysis. To note, their predictive equations only had a predictive power ranging between 0.21-0.51, despite rigorous methodology (45). They attributed this to high variability of maximal static pressures in the population. Given that height and age are the most important determinants in spirometry reference equations, height was measured on the day of lung function testing to the nearest 1 mm and age was calculated as a decimal (with the date of birth rounded to the 1st or 15th day of the month for 138  subject confidentiality) to avoid prediction bias (226). Moreover, all the reference equations used in this thesis included height and age in their statistical modelling, with most including both in the published equation (45, 85, 87).  4.2.4 Interpretation of changes in lung function In healthy subjects, variation between pulmonary function tests may be technical (e.g., equipment, procedure, calibration, technician expertise, subject, and their interaction) or biological (227). Therefore, it is important to interpret whether differences reflect a change in pulmonary function (signal) or test variability (noise) (223, 227). For example, it was suggested that year-to-year changes of ≥15% in FVC and FEV1 and ≥10% in DL,CO are needed for changes in adults to be considered clinically significant (223). Measurement noise is often assessed using the coefficient of variation, but assessing test reproducibility in children and adolescents is difficult because of their rapidly growing lungs (227). The within-subject coefficient of variation for TLC measured using plethysmography ranged from 3-9% in 61 6-18 y old healthy boys and girls (205). More recently, the large Dutch study of 500 2-18 y old children calculated absolute coefficients of variation for FVC (0.11), FEV1 (0.11), PEF (0.15), FEF25% (0.18), FEF50% (0.23), FEF75% (0.31), FEF25-75% (0.24), TLC (0.10), FRC (changed with height and age), RV (0.24), RV/TLC (0.0023), DL,CO (changed with age and sex), VA (0.11), and DL,CO/VA (0.23) (225). In this thesis, the swimmers had a 20% greater TLC than controls. This far exceeds the 3-9% coefficient of variation and further supports that swimmers had larger lungs at the initial time point. From PRE to POST, the change in TLC averaged 0.35 ± 0.13 l (7.8 ± 3.6%) and 0.26 ± 0.25 l (6.3 ± 5.8%) in swimmers and controls, respectively. Given that these absolute changes in TLC are greater than the 139  coefficient of variation determined by Koopman et al. (225), it suggests that the swimmers and controls both had a measurable amount of growth in TLC. In order to reduce between-measurement variability, the same experienced Respiratory Therapists performed both PRE and POST measurements using the same equipment and protocols at the same location. Given that the testing was performed in the Respiratory Clinic of a large, tertiary children’s hospital, equipment calibration and quality control checks are both performed routinely. These ensured high reproducibility and precision. Lastly, subjects were highly motivated and had extensive coaching and practice before conducting the maneuvers.  4.2.5 Exposure to chlorine and FEV1/FVC The relationship between swimming, chlorine, and asthma has been reviewed elsewhere (228) and will only be briefly discussed here. Chronic exposure to chlorine derivatives has been suggested to cause exercise-induced bronchial epithelial damage (6) that may underlie the increase in respiratory symptoms, airway inflammation, and airway hyperresponsiveness (AHR) observed in adult elite swimmers (229). However, evidence in young swimmers is inconclusive. Swimming was not shown to increase the risk of asthma in children longitudinally followed from birth until age 10 years (230). In a cross-sectional analysis of male and female swimmers aged 8-20, no significant relationship was found between duration of exposure to chlorination products and methacholine (MCh) challenge response or asthma-like symptoms score (231). Chlorine exposure was not found to affect airway inflammation in elite adolescent swimmers (232), and no differences were found in the prevalence of AHR to a bronchial provocation test (either eupcanic voluntary hyperpnea (EVH) or MCh challenge) in elite adolescent swimmers, recreational adolescents, and adolescents with asthma, all aged 12-16 y (229). Moreover, there were no 140  differences in the prevalence of respiratory symptoms between the swimmers and recreational controls, leading the authors to conclude that elite swimmers do not develop respiratory symptoms, airway inflammation, and AHR until later in their swimming careers (229). Analysis of elite swimmers aged 15-25 y may support this notion, as both male and female swimmers had a very high prevalence of lower respiratory symptoms and AHR in response to both MCh and EVH challenges (71) that exceeded the prevalence in winter sport athletes and recreational controls (233). Longitudinal analysis of swimmers from childhood to young adulthood is needed to determine if this later-onset of AHR is indeed the case. In this thesis, only those with no history of asthma, reactive airway disease, other lung problems, or use of an inhaler were included. Over the study period, no swimmers were diagnosed with asthma or prescribed an inhaler due to exercise-induced bronchoconstriction. Moreover, the ratio FEV1/FVC was nearly identical between the groups and did not change over time, with all swimmers having a ratio greater than or equal to 0.80. This suggests that any exposure to chlorine during the study period for the swimmers did not affect their spirometry. Because EVH tests were not performed, it is unclear if there were any changes in clinical indicators of asthma or exercise-induced bronchoconstriction. It is also unknown if the findings of this thesis would be different if young swimmers with a history of asthma, reactive airway disease, or use of an inhaler were included.  4.3 Methodological improvements 4.3.1 Sample size and study duration Prior to recruitment, a sample size of 16 subjects per group was determined to be necessary to detect an effect size of 0.92 using a significance level of α=0.05 and power of β=0.80 (G*Power 141  3.1.9.2; http://www.gpower.hhu.de). The effect size was estimated from the average change in TLC after one year in young, competitive female swimmers aged 10.8 years (15) compared to similarly-aged, healthy, normal children from a separate study (57). Moreover, in anticipation of a 25% dropout rate, 20 subjects per group was proposed to be required to appropriately power this semi-longitudinal analysis. Because only 21 subjects total were used in the final analysis, it is possible that this thesis was underpowered to detect the estimated effect size. Furthermore, the effect size used in the sample size estimate was extracted from one-year longitudinal studies; however, this thesis only lasted 7-8 months. Therefore, the magnitude of the effect size between the groups in this thesis was even smaller and a sample size greater than 16 subjects per group would have been necessary. This further highlights the possibility that the study was underpowered. While increasing the number of subjects and the duration of time between visits (i.e., at least one year) are two definitive methodological improvements, it is interesting to speculate how these would have affected the results of this thesis. The initial differences in pulmonary function between the swimmers and controls were so great (e.g., TLC was, on average, ~800 ml larger in the swimmers) that they were unlikely to be affected by a larger sample size. On the other hand, the changes from PRE to POST were similar between the groups. It is unknown if a larger sample size would have caused the changes to be larger in swimmers or only reduce the variability such that the same difference in means became statistically significant. In terms of duration, a longer period between visits would have facilitated more time for the effect to take place; however, it is again not clear if this would have led to a disproportionately greater amount of lung growth in swimmers. It is also important to recall that the measured changes in TLC were similar to expected amounts of growth for both swimmers and controls. Lastly, larger and longer studies by Andrew 142  et al. (11), Baxter-Jones and Helms (17), and Engstrom et al. (9), have observed similar results to this thesis. Conversely, smaller (Courteix et al. (18)) or similarly-sized (Zinman and Gaultier (15)) studies have observed differences between swimmers and controls over the course of 1 year of intense swim training. Thus, whether these two methodological improvements would have affected the first major finding of this thesis is unknown. The secondary purpose of this thesis was to characterize and compare their ventilatory mechanics during cycling exercise. Given its exploratory nature, effect and sample sizes were not estimated beforehand and it is not possible to determine if this thesis was appropriately powered to detect differences in the exercise responses. However, once again one can speculate if the results would have been different with a larger sample size or longer duration. Given that most of the p-values for the interaction and main effects were >0.30 for the metabolic variables, these responses are unlikely to be affected by more subjects or time between visits. However, for the operational lung volumes many p-values ranged from 0.03 to 0.18 for the two-way interactions as well as the main effect for group. Thus, it is possible that a larger sample size or time between visits may have affected the statistical significance and therefore the interpretation of the operating lung volumes throughout exercise.   4.3.2 Sex-based differences Given the extensive literature on female swimmers, as well as time and cost constraints, this thesis only assessed female swimmers during the pubertal growth spurt. It is unknown if the same results would be observed in a male cohort. While a variety of sex-based differences in lung growth underlie normal dysanaptic development of the alveoli and airways (48, 49), it is not clear if mechanisms of induced postnatal lung growth differ between males and females. Thus, the 143  inclusion of male swimmers and controls may have elucidated if the effect of competitive swimming during puberty differed in males. However, considering that no unequivocal evidence connected the respiratory challenges imposed by swimming and induced postnatal lung growth, one can speculate that competitive swimming during puberty would not affect lung development in males.  4.3.3 Control group Comparing different exercise modalities, such as running and cross-country skiing, may elucidate if lung development is comparable between swimmers and other endurance-trained athletes. Given that this thesis found no effect of competitive swimming during puberty despite the numerous stressors that are unique to intensive swim training (i.e., submersion, the prone and supine positions, an obligatory breathing pattern, breath control drills, and the young starting age of intense training), it is difficult to hypothesize mechanisms by which land-based endurance sports could cause beneficial adaptations within the lungs. Specifically, it is not clear how intensive, land-based endurance training may cause induced postnatal lung growth through a chronic hypoxic stimulus, increased parenchymal or vascular mechanical strain, or altered hormonal mediators. Previous studies assessed lung function in land-based, endurance-trained athletes and found: absolute and %-predicted TLC, VC, and DL,CO were similar between 8 collegiate male runners and controls of similar age and height (29); lung volumes were comparable between 11 Division I cross-country female runners and 10 controls matched for height and age (28), and DL,CO during exercise was not different between collegiate male runners and similarly-aged male students (34). Thus, while adding land-based endurance athletes may control for the effect of chronic endurance training, it is not clear if the results of this thesis would be any different. 144   4.3.4 Additional measures of pulmonary structure and function Although differences in lung structure and function were observed, it is only possible to speculate on the underlying physiological mechanisms. Further investigations measuring esophageal and gastric pressures (using an esophageal balloon), airway resistance (using full body plethysmography or the forced oscillation technique), and lung elastic static recoil could provide further insight on the mechanical (e.g., compliance, resistance, WOB) differences between swimmers and controls. This may highlight if the greater lung capacities of swimmers are related to alveolar hyperplasia, alveolar hypertrophy, increased distensibility, or another related mechanism. It could also facilitate quantification of the dysanapsis ratio without estimating Pst(L)50. Measurements of chest wall dimensions would have confirmed if the larger lungs of swimmers correlated with a larger chest wall surface area. As discussed earlier, chest wall dimensions were observed to be larger in multiple cohorts of competitive swimmers (16, 27, 29), and larger chests were correlated with a greater TLC (29). Partitioning diffusion capacity can elucidate whether the increased diffusion capacity in swimmers was solely due to larger alveolar volumes, or if there were other differences in alveolar membrane thickness, pulmonary capillary blood volume, or other structural or functional determinants of gas exchange. Lastly, measuring arterial saturation may provide insight on exercise-induced arterial hypoxemia during exercise and any possible correlation with the occurrence of ventilatory constraints.  4.4 Unresolved questions and future directions Moving forward, three primary unresolved questions can guide future research questioning whether competitive swimming affects lung development. The first future direction is to 145  longitudinally quantify dysanapsis (using the dysanapsis ratio, imaging, or other) in a large sample of male and female swimmers, land-based endurance athletes, and controls starting in prepubescence (e.g., 7-8 y old) and continuing into postpubescence. This will address the unresolved question: does competitive swimming exaggerate dysanaptic growth patterns? As mentioned earlier, altered dysanaptic growth patterns may highlight an effect of competitive swimming on lung development by accelerating alveolar growth without corresponding enhanced airway growth. The second future direction is to compare mechanical properties of the lungs between swimmers, land-based athletes, and controls during development, including airway resistance and conductance, lung compliance, and elastance. This will address the unresolved question: do competitive swimmers have mechanically different lungs? Lastly, the third future direction is to measure work of breathing and operating lung volumes in competitive swimmers while swimming. This will address the unresolved question: do the unique stressors of swimming affect the work of breathing and create a stimulus for respiratory muscle conditioning?  Beyond these three questions, another direction not addressed in this thesis is why competitive swimmers have larger lungs. This posits several interesting questions, including: Is enhanced pulmonary function beneficial to swimmers? The second paragraph of this thesis stated that larger lungs may be beneficial to swimmers because of increased FRC (which may act as a reservoir for gas exchange, thereby attenuating oscillations in arterial blood gases between breaths), improved ventilatory capacity, and greater buoyancy in the water to decrease drag. First, it was mentioned earlier that the cardiovascular system appears to be able to maintain Q̇ and SaO2 and compensate for any respiratory limitations while swimming. Therefore, it is not clear to what extent an increased FRC is beneficial to swimmers. Second, in this thesis, V̇ECAP was similar between swimmers and controls because of the same EELV. It is not clear how the MEFV 146  and operating lung volumes differ when in the water. Lastly, the energetics of swimming are complicated (234). Yet, it has been suggested that arm position may be of more importance to buoyancy characteristics (specifically the distance between the centres of mass and buoyancy) than lung volume (235). Future work is necessary to clarify how larger lungs contribute to improved swimming performance. If self-selection occurs, do children self-select into swimming because of favourable genetic endowments beyond pulmonary function such as chest size, shoulder girth, or alternative anthropometric characteristics? It is possible that benefits relating to larger chests or alternative anthropometric advantages, specifically with regards to buoyancy or drag, may be the favourable endowments that lead to self-selection into swimming. In this case, since chest wall and lung growths are tightly coupled, by necessity swimmers with larger chests would also have larger lungs. In other words, the direction of causality can be questioned: is it that children with larger lungs become swimmers, or that children who became swimmers also happen to have larger lungs? If swimmers have larger lungs because of genetic endowment, at what point are these favourable genetic endowments important? Miller et al. measured DL,CO in 22 collegiate swimmers  and found that most successful swimmers have an above-average DL,CO (35). However, the authors observed no difference in performance between those with lower (<100%) and higher (≥110%) %-predicted DL,CO, nor did they find a relationship between performance DL,CO or VC. It is possible that, while large lungs may be a prerequisite for becoming a top swimmer (12), they do not differentiate performance between top swimmers. Thus, it is possible that the favourable genetic endowments may be more important at a young age when entering the sport and relatively less important at an older age when one is already a top swimmer. This highlights the Matthew effect whereby the favourable genetic endowments, which may have originally led to self-selection into 147  swimming, may also lead to early success and therefore subsequent opportunities and affordances that lead to further success (236). This may be particularly important in swimming where the relative age effect has a limited effect on age-group swimming performance (237, 238), and other factors such as swimming technique and race distance are more predictive of performance (237).   148  CONCLUSION By the time they reach puberty, competitive swimmers already have enhanced lung function compared to healthy controls regardless of the age they started swimming or number of years of experience. One season of training did not further accentuate this enhanced function, and no associations between changes in lung function and swim training volume were found. 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J Sports Sci. 2016;34(12):1124-31.    163  APPENDICES Appendix A: Individual subject data – group tables Table 21 – Individual anthropometric data for SWIM Participant  Age (y) Height (cm) Mass (kg) BMI (kg/m2) BSA (m2) SMR pubic hair SMR breasts Hemoglobin (g/dL) S01 Pre 13.8 163.1 61.3 23.0 1.67 5 4 16.6  Post 14.4 164.4 59.7 22.1 1.65 5 4 15.6 S02 Pre 12.5 160.9 44.7 17.3 1.41 3 4 12.9  Post 13.2 164.6 51.1 18.9 1.53 4 4 12.8 S04 Pre 13.7 177.9 71.2 22.5 1.88 4 4 14.4  Post 14.3 177.9 70.8 22.4 1.87 4 4 14.4 S05 Pre 12.3 166.5 59.3 21.4 1.66 4 4 13.3  Post 12.9 168.4 65.8 23.2 1.75 5 5 14.2 S06 Pre 12.2 157.9 43.5 17.4 1.38 4 4 13.4  Post 12.8 161.2 50.2 19.3 1.50 4 4 13.8 S07 Pre 12.7 167.0 67.5 24.2 1.77 4 4 13.4  Post 13.3 168.0 71.8 25.4 1.83 5 4 14.6 S08 Pre 11.6 153.3 46 19.6 1.40 3 2 13.6  Post 12.3 156.3 48.1 19.7 1.45 4 3 14.4 S09 Pre 11.3 147.3 39.2 18.1 1.27 2 2 11.5  Post 11.9 151.2 44.5 19.5 1.37 2 4 12 S10 Pre 12.1 157.0 45.3 18.4 1.41 1 3 11.5  Post 12.6 160.0 48.9 19.1 1.47 3 4 13.7 S11 Pre 12.3 162.5 52.4 19.8 1.54 4 4 14.1  Post 12.8 163.1 56.4 21.2 1.60 4 4 13.2 S12 Pre 12.3 161.2 45.7 17.6 1.43 4 4 11.4  Post 12.9 162.7 46.6 17.6 1.45 4 5 12.7 BMI, body mass index; BSA, body surface area; SMR, sexual maturity rating.   164  Table 22 – Individual anthropometric data for CON Participant  Age (y) Height (cm) Mass (kg) BMI (kg/m2) BSA (m2) SMR pubic hair SMR breasts Hemoglobin (g/dL) C01 Pre 11.1 147.0 43.4 20.1 1.33 2 2 13.3  Post 11.7 149.3 46.3 20.8 1.39 2 3 13.4 C02 Pre 12.2 153.7 40.2 17.0 1.31 3 3 13.6  Post 12.8 159.1 45.3 17.9 1.41 4 4 17 C03 Pre 12.8 166.0 47.8 17.3 1.48 3 3 13.4  Post 13.5 168.9 51.4 18.0 1.55 3 4 14.2 C04 Pre 14.2 164.2 49.9 18.5 1.51 3 4 14.6  Post 14.9 166.7 53.8 19.4 1.58 5 4 14 C05 Pre 11.4 145.6 35.9 16.9 1.20 1 1 13.4  Post 12.1 149.3 37.5 16.8 1.25 3 3 13.7 C08 Pre 13.6 164.6 49.5 18.3 1.50 4 4 13.6  Post 14.2 167.6 56.6 20.1 1.62 4 4 13.4 C09 Pre 13.5 158.9 48.9 19.4 1.47 4 4 13.5  Post 141 161.1 51.9 20.0 1.52 4 4 13.5 C10 Pre 14.3 164.9 47.4 17.4 1.47 3 3 13.4  Post 14.8 165.4 48.4 17.7 1.49 3 3 13.4 C11 Pre 14.3 160.8 45.5 17.6 1.43 3 3 12.1  Post 14.8 161.9 47.7 18.2 1.46 3 3 12.2 C12 Pre 14.8 156.9 54.9 22.3 1.55 5 5 13.7  Post 15.5 157.7 54.7 22.0 1.55 5 5 12.3 BMI, body mass index; BSA, body surface area; SMR, sexual maturity rating.   165  Table 23 – Individual physical activity questionnaire data (each question is scored out of 5) Participant #1 #2 #3 #4 #5 #6 #7 #8 #9 Average  All activities PE class Recess Lunch After school Evenings Weekend Typical week Typical week  S01           S02 1.6 3 3 1 3 4 4 5 4.4 3.22 S04 1.9 4 1 1 5 4 2 1 3.0 2.55 S05 1.5 4 1 1 4 1 2 4 2.7 2.36 S06 1.9 5 4 1 5 5 2 5 4.3 3.69 S07 1.6 4 3 4 3 2 2 4 3.6 3.01 S08 2.0 4 3 1 4 3 3 4 3.4 3.04 S09 1.3 4 3 3 5 1 3 4 4.3 3.18 S10 2.0 5 2 3 1 4 2 4 4.3 3.04 S11 1.5 5 2 3 1 4 3 5 5.0 3.28 S12 1.4 4 4 4 2 4 2 4 3.6 3.22 C01 2.6 4 4 4 3 3 3 4 4.0 3.52 C02 2.2 5 2 2 3 1 1 3 2.7 2.43 C03 1.9 5 - 2 4 4 3 4 4.0 3.49 C04 2.3 5 2 3 4 4 4 5 4.1 3.72 C05 2.1 5 5 4 3 3 4 3 4.1 3.69 C08 2.0 4 2 1 3 3 3 4 3.9 2.87 C09 1.2 5 2 2 5 4 3 4 3.9 3.34 C10 1.9 1 1 1 5 4 5 4 4.6 3.05 C11 2.1 1 2 1 5 3 5 4 4.4 3.06 C12 1.2 4 1 1 2 3 3 1 2.4 2.07    166  Table 24 – Individual moderate and vigorous intensity physical activity data Participant Vigorous intensity Moderate intensity per week Total time Guideline met?  Frequency Time per session (min) Frequency Time per session (min) Per week (min) Per day (min)  S01        S02 6.5 150 1.5 75 1088 155 YES S04 5 120 3 100 900 129 YES S05 3 135 5 105 930 133 YES S06 6 150 2 60 1020 146 YES S07 5 90 3 45 585 84 YES S08 6 90 3 60 720 103 YES S09 5 120 2 30 660 94 YES S10 5 120 1 90 690 99 YES S11 6 90 2 150 840 120 YES S12 6 120 5 60 1020 146 YES C01 3 120 2 180 720 103 YES C02 5 40 3 20 260 37 NO C03 5 120 1 150 750 107 YES C04 7 90 7 20 770 110 YES C05 4 105 3.5 34 540 77 YES C08 3 180 1.5 90 675 96 YES C09 3 45 5 180 1035 148 YES C10 3 20 6 180 1140 163 YES C11 2 45 6 240 1530 219 YES C12 5 45 7 10 295 42 NO    167  Table 25 – Individual training data for SWIM Participant Age (y) Training history (y) Swimming sessions per week Weekly swimming Non-swimming training sessions Breath control drills    # Distance (km) Time (h) Distance (km) Time (h) # per week Time per session (h) Time per week (h) Time per week (h) Drills Details S01 8.8 5.7 7 4.5 1.75 25 12 3 1 2 2 UK Go at least 6 m underwater off the wall within sets S02 10.0 3.2 1 3 1.25 3 1 7 2 12 0 None - S04 7.4 6.9 7 3.5 2 24.5 15.5 1 2 2 0.5 Other Sprints (12.5-25m) are always done with minimum breathing, though this was regularly backstroke. S05 6.0 6.9 6 4 1.75 24 11 0 0 0 1 UK Sets of 8x25 working on dolphin kick distance and kicks between breaths S06 10.1 2.8 6 4.8 1.75 30 10.5 3 1 3 4 UK Specific metres off walls within sets S07 10.3 3.0 5 3.5 1.5 18 9 2 1 3 1 UK, FSB, SS  S08 9.5 2.8 6 3 1.75 17 10.5 2 1 2 2 UK Normally go by number of kicks; typically, 5-15m off the walls; average being around 6.5-7m S09 10.2 1.8 5 2.5 1.5 10 8 5 0 1 0.25 UK Performing 4-15 dolphin kicks off the wall depending on set and if she had fins S10 8.6 4.0 5 3.9 1.5 20.8 7.5 5 1 3.5 0.5 UK, FSB  S11 10.1 2.8 5 4 1.5 20 7.5 5 1 2.5 1 UK, FSB  S12 10.1 2.8 5 2.5 1.5 12 7.5 2 1 2 1.5 UK Normally go by number of kicks; go 5-10m off the wall with the average being around 6m FSB, freestyle breathing pattern (“hypoxic training”); UK, underwater (dolphin or breast) kick; SS, snorkel set   168  Table 26 – Individual spirometry data for SWIM Participant  FVC FEV1 FEV1/FVC PEF FEF25-75% FEF25% FEF50% FEF75%   (l) % pred (l) % pred (%) (l·s-1) % pred (l·s-1) % pred (l·s-1) % pred (l·s-1) % pred (l·s-1) % pred S01 Pre 4.35 131* 3.85 129 88 8.04 115 4.26 115 6.65 127 4.77 132 2.30 121  Post 4.54 132* 4.00 129 88 8.06 112 4.36 114 7.17 132 4.93 131 2.33 117 S02 Pre 3.57 114 3.06 109 86 6.65 100 3.96 113 5.97 122 4.52 133 1.77 101  Post 3.72 111 3.39 113 91 7.09 102 4.13 111 6.22 120 4.27 118 2.57 135 S04 Pre 5.31 129* 4.40 119 83 7.95 104 4.35 99 7.46 126 4.67 111 2.39 100  Post 5.43 130* 4.65 124 86 8.02 103 5.22 117 7.86 129 5.73 133 2.88 117 S05 Pre 4.13 122* 3.53 117 85 6.30 91 3.82 103 5.45 107 4.62 129 2.03 108  Post 4.20 119 3.74 118 89 6.36 90 4.12 107 5.56 105 4.71 126 2.67 134 S06 Pre 3.16 106 2.64 99 84 6.32 98 2.47 73 4.82 103 2.67 82 1.36 82  Post 3.68 116 2.94 103 80 6.69 99 2.63 74 5.64 114 2.93 85 1.32 74 S07 Pre 4.92 143* 4.18 136 85 7.01 100 4.31 114 6.11 118 4.90 135 2.40 124  Post 5.03 143* 4.31 136 86 7.90 111 4.49 116 6.70 125 5.35 143 3.07 153 S08 Pre 3.63 132* 3.15 128 87 6.25 102 3.55 113 5.81 133 4.35 144 1.78 117  Post 3.97 136* 3.36 129 85 7.09 111 3.36 101 6.60 143 3.64 114 1.90 117 S09 Pre 3.09 123* 2.55 114 83 4.89 85 2.49 85 4.35 107 2.76 99 1.32 96  Post 3.52 131* 2.87 119 82 5.23 86 2.71 87 4.32 99 2.97 100 1.41 95 S10 Pre 3.42 117 2.79 106 81 6.03 94 2.56 77 5.08 110 2.96 92 1.23 76  Post 3.74 121 3.05 110 82 6.45 97 2.83 81 5.47 113 3.23 96 1.74 100 S11 Pre 4.02 126* 3.49 122 87 5.88 88 3.86 109 5.28 108 4.34 127 2.21 124  Post 4.13 127* 3.44 118 83 6.76 99 3.33 92 5.17 103 3.96 113 1.84 100 S12 Pre 3.50 112 3.10 110 88 5.95 90 3.50 100 5.25 108 3.80 112 2.16 123  Post 3.71 114 3.27 112 88 7.05 103 4.22 116 6.38 127 4.52 129 2.36 129 *Above or **below the limits of abnormality in percent predicted, based on equations for healthy children and adolescents. FVC, forced vital capacity; FEV1, forced expiratory volume in one second; PEF, peak expiratory flow; FEF, forced expiratory flow.   169  Table 27 – Individual spirometry data for CON Participant  FVC FEV1 FEV1/FVC PEF FEF25-75% FEF25% FEF50% FEF75%   (l) % pred (l) % pred (%) (l·s-1) % pred (l·s-1) % pred (l·s-1) % pred (l·s-1) % pred (l·s-1) % pred C01 Pre 2.53 102 2.09 94 83 4.77 84 1.92 66** 3.94 97 2.11 76 1.09 80  Post 2.68 103 2.23 96 83 5.00 85 2.03 67 4.15 98 2.28 79 1.18 82 C02 Pre 2.97 106 2.57 102 86 5.47 88 2.97 92 5.28 117 3.44 111 1.36 88  Post 3.31 108 2.85 103 86 6.43 97 3.24 93 6.11 126 3.82 114 1.53 89 C03 Pre 2.88 85 2.40 79** 83 4.95 71 2.33 62** 3.92 76 2.60 72 1.13 59  Post 2.88 80** 2.43 75** 84 4.98 69 2.48 63** 4.29 79 2.89 76 1.26 61 C04 Pre 3.62 106 2.47 81** 68** 5.16 72** 1.76 46** 3.14 59** 1.92 52** 0.90 46**  Post 3.96 110 2.82 87 71** 5.74 78** 2.08 52** 3.65 65** 2.33 60** 1.10 52** C05 Pre 2.28 93 1.95 89 86 4.49 79 2.08 72 3.59 89 2.38 87 1.03 77  Post 2.31 88 2.00 85 87 5.08 85 2.06 68 3.60 84 2.35 80 1.31 90 C08 Pre 3.29 97 2.87 94 87 6.34 90 3.17 84 4.95 94 3.45 94 1.73 90  Post 3.78 106 3.24 101 86 6.51 89 3.5 89 6.14 111 3.79 98 1.81 87 C09 Pre 3.87 124 3.36 120 87 6.9.0 102 3.8 108 6.08 122 4.22 123 2.00 113  Post 3.86 119 3.33 114 86 6.94 100 3.65 100 6.37 123 3.96 111 1.76 94 C10 Pre 3.46 100 2.62 84 76** 5.93 83 2.14 56** 4.37 81 2.53 67 0.94 47**  Post 3.58 102 2.57 81** 72** 5.87 80 1.81 46** 4.02 72** 2.12 55** 0.81 39** C11 Pre 2.96 91 2.68 92 90 6.2.0 89 3.22 88 6.10 117 3.57 99 1.66 89  Post 3.11 93 2.94 97 94 6.48 91 3.62 96 6.45 120 3.91 106 2.08 107 C12 Pre 3.47 111 3.11 111 90 6.81 99 4.04 113 6.79 132 4.54 130 2.01 112  Post 3.35 105 3.00 104 90 6.92 98 3.99 109 6.78 128 4.41 122 1.97 106 *Above or **below the limits of abnormality in percent predicted, based on equations for healthy children and adolescents. FVC, forced vital capacity; FEV1, forced expiratory volume in one second; PEF, peak expiratory flow; FEF, forced expiratory flow.   170  Table 28 – Individual lung volume data for SWIM Participant  TLC FRC RV VC FRC/TLC RV/TLC   (l) % pred (l) % pred (l) % pred (l) (au) (au) S01 Pre 5.28 116 2.84 123 1.17 103 4.11 0.54 0.22  Post 5.58 117 2.90 119 1.19 99 4.39 0.52 0.21 S02 Pre 4.49 106 2.18 104 1.15 114 3.34 0.49 0.26  Post 4.66 102 2.46 108 1.15 104 3.51 0.53 0.25 S04 Pre 6.22 108 2.98 103 1.25 88 4.97 0.48 0.20  Post 6.55 111 2.83 93 1.28 85 5.27 0.43 0.20 S05 Pre 4.75 104 2.15 97 0.80 75 3.95 0.45 0.17  Post 5.16 107 2.66 112 0.95 83 4.21 0.52 0.18 S06 Pre 4.01 100 1.57 79 0.94 98 3.07 0.39 0.23  Post 4.44 103 2.08 97 0.83 80 3.61 0.47 0.19 S07 Pre 5.71 122* 2.34 102 1.04 94 4.67 0.41 0.18  Post 5.96 123* 2.42 101 1.05 90 4.91 0.41 0.18 S08 Pre 4.34 117 2.07 113 0.87 98 3.47 0.48 0.20  Post 4.86 123* 2.31 118 0.92 97 3.94 0.48 0.19 S09 Pre 3.83 113 1.83 108 0.90 109 2.93 0.48 0.23  Post 4.38 121 1.87 103 0.91 103 3.47 0.43 0.21 S10 Pre 4.37 110 2.25 115 1.01 107 3.36 0.51 0.23  Post 4.72 112 2.63 127 1.13 112 3.59 0.56 0.24 S11 Pre 4.59 107 1.66 79 0.73 72 3.86 0.36 0.16**  Post 4.75 107 1.68 77 0.75 70 4.00 0.35 0.16** S12 Pre 4.39 104 2.09 100 1.03 102 3.36 0.48 0.23  Post 4.81 109 2.53 116 1.33 125 3.48 0.53 0.28 *Above or **below the limits of abnormality in percent predicted, based on equations for healthy children and adolescents. TLC, total lung capacity; FRC, functional residual capacity; RV, residual volume; VC, vital capacity.   171  Table 29 – Individual lung volume data for CON Participant  TLC FRC RV VC FRC/TLC RV/TLC   (l) % pred (l) % pred (l) % pred (l) (au) (au) C01 Pre 3.39 101 1.75 104 0.78 96 2.61 0.52 0.23  Post 3.40 97 1.53 87 0.74 86 2.66 0.45 0.22 C02 Pre 3.67 97 1.94 103 0.74 81 2.93 0.53 0.20  Post 3.92 94 1.83 88 0.69 68 3.23 0.47 0.18 C03 Pre 3.88 84 2.15 94 1.11 100 2.77 0.55 0.29  Post 4.02 81** 2.47 100 1.16 96 2.86 0.61 0.29 C04 Pre 4.46 95 2.56 107 1.17 99 3.29 0.57 0.26  Post 5.09 101 2.58 99 1.31 101 3.78 0.51 0.26 C05 Pre 3.11 94 1.81 108 0.86 105 2.25 0.58 0.28  Post 3.13 88 1.61 90 0.87 99 2.26 0.51 0.28 C08 Pre 4.22 91 2.34 100 1.11 97 3.11 0.55 0.26  Post 4.98 100 2.49 98 1.26 101 3.72 0.50 0.25 C09 Pre 4.48 106 2.25 105 0.71 67 3.77 0.50 0.16**  Post 4.68 105 2.51 110 0.78 69 3.9 0.54 0.17 C10 Pre 4.32 91 2.43 100 0.99 82 3.33 0.56 0.23  Post 4.59 94 2.49 98 1.08 86 3.51 0.54 0.24 C11 Pre 3.78 85 2.47 108 1.26 111 2.52 0.65 0.33  Post 4.04 87 2.43 101 1.37 115 2.67 0.60 0.34 C12 Pre 4.01 94 2.21 99 0.83 75 3.18 0.55 0.21  Post 4.07 92 2.12 91 0.86 74 3.21 0.52 0.21 *Above or **below the limits of abnormality in percent predicted, based on equations for healthy children and adolescents. TLC, total lung capacity; FRC, functional residual capacity; RV, residual volume; VC, vital capacity.    172  Table 30 – Individual diffusion capacity data for SWIM Participant  DL,CO DL,COc VA DL,COc/VA   (mL·min-1·mmHg-1) % pred (mL·min-1·mmHg-1) % pred (l) % pred (mL·min-1·mmHg-1·l-1) % pred S01 Pre 24.89 124 22.91 114 5.15 121 4.45 88  Post 28.37 137 26.72 129 5.44 124 4.91 98 S02 Pre 26.72 140 27.14 142 4.39 110 6.18 121  Post 25.30 125 25.79 127 4.55 106 5.67 113 S04 Pre 27.32 114 26.54 111 6.07 113 4.38 92  Post 24.73 102 24.02 99 6.40 118 3.75 79 S05 Pre 20.40 100 20.47 100 4.62 106 4.43 89  Post 23.49 111 22.94 109 5.02 110 4.57 92 S06 Pre 20.22 110 20.22 110 3.91 103 5.17 100  Post 20.75 107 20.51 106 4.33 107 4.73 93 S07 Pre 26.20 127 26.20 127 5.56 125 4.71 95  Post 26.07 123 25.19 119 5.80 127 4.34 88 S08 Pre 23.43 136 23.29 136 4.24 122 5.49 104  Post 25.82 143 25.08 139 4.75 128 5.28 102 S09 Pre 18.69 118 19.96 126 3.75 119 5.33 99  Post 22.00 130 23.06 137 4.29 126 5.38 101 S10 Pre 21.29 117 22.74 125 4.27 114 5.33 103  Post 22.67 120 22.46 118 4.61 117 4.87 95 S11 Pre 23.52 121 23.04 119 4.48 110 5.14 101  Post 23.22 117 23.36 118 4.63 111 5.05 100 S12 Pre 23.53 123 25.23 132 4.29 107 5.88 115  Post 25.26 128 25.83 131 4.71 113 5.48 108 DL,CO, diffusion capacity of the lung for carbon monoxide; DL,COc, DL,CO corrected for hemoglobin; VA; alveolar volume.   173  Table 31 – Individual diffusion capacity for CON Participant  DL,CO DL,COc VA DL,COc/VA   (mL·min-1·mmHg-1) % pred (mL·min-1·mmHg-1) % pred (l) % pred (mL·min-1·mmHg-1·l-1) % pred C01 Pre 18.31 116 18.37 116 3.29 105 5.58 103  Post 17.09 104 17.09 104 3.29 100 5.19 97 C02 Pre 18.88 108 18.76 108 3.59 101 5.23 100  Post 18.95 101 17.30 92 3.82 98 4.52 88 C03 Pre 22.40 109 22.40 109 3.78 86 5.93 119  Post 22.95 107 22.42 105 3.91 84 5.73 116 C04 Pre 22.16 108 21.41 104 4.35 100 4.92 98  Post 24.45 114 24.02 112 4.97 108 4.84 97 C05 Pre 18.69 120 18.69 120 3.03 99 6.17 114  Post 16.76 101 16.61 100 3.04 92 5.46 102 C08 Pre 22.60 111 22.46 110 4.11 95 5.47 109  Post 25.67 120 25.67 120 4.85 105 5.29 107 C09 Pre 23.88 126 23.80 125 4.37 111 5.44 106  Post 23.90 121 23.83 121 4.57 110 5.22 102 C10 Pre 20.80 100 20.80 100 4.22 96 4.93 98  Post 21.30 101 21.30 101 4.49 100 4.75 95 C11 Pre 20.46 104 21.36 108 3.68 89 5.81 114  Post 20.95 104 21.79 108 3.93 92 5.54 109 C12 Pre 19.43 102 19.25 101 3.89 99 4.95 95  Post 19.25 99 19.95 103 3.95 98 5.05 98 DL,CO, diffusion capacity of the lung for carbon monoxide; DL,COc, DL,CO corrected for hemoglobin; VA; alveolar volume.   174  Table 32 – Individual maximal static pressure data for SWIM Participant  PIMAX PEMAX   (cm H2O) % pred (cm H2O) % pred S01 Pre 71 72 146 125  Post 80 81 158 130 S02 Pre 55 64 106 99  Post 83 91 102 91 S04 Pre 124 113 121 105  Post 150 136 137 114 S05 Pre 68 71 131 124  Post 97 95 135 122 S06 Pre 121 145 117 112  Post 126 141 123 112 S07 Pre 122 120 104 96  Post 118 111 113 100 S08 Pre 75 90 101 100  Post 91 106 119 113 S09 Pre 87 112 92 94  Post 99 120 108 105 S10 Pre 66 78 88 84  Post 82 93 123 114 S11 Pre 101 112 119 113  Post 113 120 151 138 S12 Pre 64 75 104 98  Post 95 108 124 112 PIMAX, maximum inspiratory pressure; PEMAX, maximum expiratory pressure.   175  Table 33 – Individual maximal static pressure data for CON Participant  PIMAX PEMAX   (cm H2O) % pred (cm H2O) % pred C01 Pre 73 92 100 103  Post 66 80 108 107 C02 Pre 105 130 100 95  Post 122 142 94 86 C03 Pre 71 80 87 79  Post 64 69 77 67 C04 Pre 78 84 101 85  Post 101 104 119 95 C05 Pre 79 105 98 98  Post 88 113 117 112 C08 Pre 56 61 51 44  Post 95 97 111 93 C09 Pre 97 108 80 70  Post 98 106 94 79 C10 Pre 76 84 86 72  Post 59 64 109 88 C11 Pre 23 26 68 57  Post 41 45 82 66 C12 Pre 48 50 78 63  Post 53 55 66 51 PIMAX, maximum inspiratory pressure; PEMAX, maximum expiratory pressure176  Table 34 – Individual maximal exercise data for SWIM Participant  Duration (min) Work rate (W) Work rate (W·kg-1) HR (bpm) RPE VT (l) fB V̇E (l·min-1) V̇O2 (l·min-1) V̇O2 (ml·kg-1 ·min-1) V̇O2 (% pred) V̇CO2 (l·min-1) RER EFL (%) EFL? V̇E/V̇ECAP (%) S01 Pre 15.8 180 2.9 202 10 1.30 94 120.4 2.42 39.4 119 2.62 1.09 0 NO 77  Post 18.5 220 3.7 205 10 1.58 88 137.4 2.46 41.2 124 2.97 1.21 0 NO 69 S02 Pre 10.6 140 3.1 194 9 1.39 44 59.7 1.68 37.7 108 1.77 1.05 58 YES 94  Post 15.0 180 3.5 191 10 1.79 49 87.1 2.33 45.6 133 2.53 1.09 37 YES 85 S04 Pre 18.2 200 2.8 182 10 2.21 43 95.3 2.59 36.4 112 2.89 1.12 0 NO 46  Post 18.0 200 2.8 182 10 2.17 38 83.3 2.63 37.1 114 2.82 1.08 0 NO 44 S05 Pre 10.0 120 2.0 181 4 1.48 37 54.4 1.71 28.8 86 1.78 1.04 0 NO 40  Post 14.0 160 2.4 195 10 1.79 45 79.7 2.14 32.6 99 2.39 1.12 0 NO 58 S06 Pre 13.1 160 3.7 182 9.5 1.23 71 86.4 2.16 49.6 141 2.49 1.16 44 YES 91  Post 16.0 180 3.6 185 7 1.62 61 98.2 2.34 46.7 136 2.77 1.18 60 YES 99 S07 Pre 19.3 220 3.3 208 10 2.24 48 106.9 2.70 40.0 122 3.02 1.12 0 NO 66  Post 18.0 200 2.8 208 10 2.30 52 118.3 2.69 37.4 115 3.09 1.15 0 NO 73 S08 Pre 13.4 160 3.5 205 10 1.59 65 101.4 2.25 49.0 141 2.60 1.17 57 YES 94  Post 16.3 200 4.2 201 10 1.69 71 118.3 2.69 56.0 162 3.07 1.14 73 YES 120 S09 Pre 11.5 140 3.6 186 10 1.58 44 70.1 1.79 45.8 128 2.16 1.21 16 YES 71  Post 16.0 180 4.0 194 10 1.85 52 96.3 2.19 49.1 140 2.68 1.23 47 YES 89 S10 Pre 13.8 160 3.5 185 10 1.47 46 68.3 2.19 48.2 138 2.28 1.05 0 NO 66  Post 16.4 200 4.1 191 10 1.55 60 93.2 2.53 51.7 150 2.77 1.11 49 YES 88 S11 Pre 15.8 180 3.4 195 10 1.58 61 96.3 2.54 48.4 142 2.87 1.13 30 YES 90  Post 14.9 180 3.2 195 8 1.52 60 90.4 2.04 36.2 108 2.38 1.17 39 YES 87 S12 Pre 15.8 180 3.9 197 10 1.42 58 81.8 2.21 48.5 139 2.47 1.12 0 NO 70  Post 18.0 200 4.3 201 10 1.61 63 102.0 2.56 55.0 159 2.96 1.16 0 NO 65 HR, heart rate; bpm, beats per minute; RPE, rating of perceived exertion; VT, tidal volume; fB, breathing frequency; V̇E, expired minute ventilation; V̇O2, oxygen consumption; V̇CO2, carbon dioxide production; RER, respiratory exchange ratio; EFL, expiratory flow limitation; V̇ECAP, ventilatory capacity.   177  Table 35 – Individual maximal exercise data for CON Participant  Duration (min) Work rate (W) Work rate (W·kg-1) HR (bpm) RPE VT (l) fB V̇E (l·min-1) V̇O2 (l·min-1) V̇O2 (ml·kg-1 ·min-1) V̇O2 (% pred) V̇CO2 (l·min-1) RER EFL (%) EFL? V̇E/V̇ECAP (%) C01 Pre 9.8 120 2.8 186 10 1.09 57 61.8 1.64 37.7 107 1.59 0.98 0 NO 63  Post 12.0 140 3.0 186 10 1.15 58 67.0 1.68 36.4 105 1.88 1.11 50 YES 83 C02 Pre 11.4 140 3.5 204 9.5 1.26 46 57.4 1.73 42.9 120 1.84 1.07 0 NO 47  Post 14.5 180 4.0 208 9.5 1.65 48 79.1 2.21 48.7 140 2.45 1.12 9 YES 75 C03 Pre 13.7 160 3.3 183 8 1.28 60 76.4 1.98 41.3 120 2.19 1.11 6 YES 84  Post 14.0 160 3.1 185 8 1.27 70 88.2 2.05 39.9 117 2.27 1.11 0 NO 78 C04 Pre 17.9 200 4.0 195 9 1.53 54 81.8 2.23 44.7 130 2.56 1.15 60 YES 101  Post 20.0 220 4.1 197 10 1.69 55 92.0 2.54 47.3 140 3.03 1.19 35 YES 79 C05 Pre 8.9 120 3.3 199 10 1.06 40 42.5 1.45 40.3 110 1.59 1.10 0 NO 58  Post 11.8 140 3.7 198 8 1.15 54 62.3 1.67 44.5 123 2.03 1.22 20 YES 77 C08 Pre 13.2 160 3.2 199 10 1.61 60 95.3 2.03 41.0 120 2.56 1.26 3 NO 82  Post 14.5 180 3.2 197 10 1.59 63 98.8 2.05 36.2 108 2.57 1.27 28 YES 83 C09 Pre 12.7 160 3.3 201 7 1.69 42 70.6 1.87 38.2 111 2.18 1.17 0 NO 49  Post 13.5 160 3.1 203 8 1.80 54 97.6 2.01 38.7 114 2.60 1.30 0 NO 69 C10 Pre 16.0 180 3.8 194 10 1.76 47 82.5 2.17 45.8 133 2.59 1.19 62 YES 108  Post 18.0 200 4.1 202 10 1.90 47 89.7 2.33 48.1 139 2.72 1.17 66 YES 115 C11 Pre 12.5 160 3.5 199 9 1.58 42 65.9 1.70 37.3 107 1.98 1.17 0 NO 55  Post 15.4 180 3.8 202 10 1.65 51 83.2 2.15 45.1 131 2.48 1.15 42 YES 88 C12 Pre 11.6 140 2.6 200 10 1.59 54 86.0 1.71 31.2 93 2.18 1.27 0 NO 49  Post 12.0 140 2.6 203 10 1.62 58 94.9 1.98 36.1 107 2.31 1.17 26 YES 77 HR, heart rate; bpm, beats per minute; RPE, rating of perceived exertion; VT, tidal volume; fB, breathing frequency; V̇E, expired minute ventilation; V̇O2, oxygen consumption; V̇CO2, carbon dioxide production; RER, respiratory exchange ratio; EFL, expiratory flow limitation; V̇ECAP, ventilatory capacity.   178  Table 36 – Individual maximal exercise operational lung volume data for SWIM Participant  EILV (l) EILV/FVC (%) EELV (l) EELV/FVC (%) IRV (l) IRV/FVC (%) IC (l) VT/FVC (%) S01 Pre 2.94 75 1.64 42 1.00 25 2.30 33  Post 3.67 90 2.09 51 0.42 10 2.00 39 S02 Pre 2.14 86 0.75 30 0.36 14 1.75 55  Post 2.68 82 0.89 27 0.60 18 2.39 55 S04 Pre 4.07 84 1.86 39 0.75 16 2.96 46  Post 4.07 83 1.91 39 0.86 17 3.02 44 S05 Pre 2.65 74 1.17 33 0.94 26 2.42 41  Post 2.80 76 1.00 27 0.90 24 2.70 48 S06 Pre 2.16 73 0.93 31 0.81 27 2.04 41  Post 2.65 78 1.02 30 0.75 22 2.38 48 S07 Pre 3.69 86 1.45 34 0.59 14 2.83 52  Post 3.97 86 1.67 36 0.64 14 2.94 50 S08 Pre 2.42 81 0.83 28 0.58 19 2.17 53  Post 2.72 79 1.03 30 0.70 21 2.39 49 S09 Pre 2.38 91 0.81 31 0.25 9 1.82 60  Post 2.86 89 1.01 31 0.35 11 2.20 58 S10 Pre 2.59 89 1.12 39 0.32 11 1.79 50  Post 2.53 73 0.98 28 0.93 27 2.48 45 S11 Pre 2.35 69 0.77 23 1.03 31 2.61 47  Post 2.47 66 0.95 25 1.30 34 2.82 40 S12 Pre 2.39 76 0.96 31 0.75 24 2.18 45  Post 2.76 81 1.15 34 0.67 19 2.28 47 EILV, end-inspiratory lung volume; FVC, forced vital capacity; EELV, end-expiratory lung volume; IRV, inspiratory reserve volume; ERV, expiratory reserve volume; VT, tidal volume.   179  Table 37 – Individual maximal exercise operational lung volume data for CON Participant  EILV (l) EILV/FVC (%) EELV (l) EELV/FVC (%) IRV (l) IRV/FVC (%) IC (l) VT/FVC (%) C01 Pre 1.97 82 0.89 37 0.45 18 1.53 45  Post 1.92 78 0.77 31 0.55 22 1.70 47 C02 Pre 2.08 85 0.82 33 0.38 15 1.64 51  Post 2.52 84 0.87 29 0.48 16 2.13 55 C03 Pre 2.26 90 0.98 39 0.27 10 1.55 51  Post 2.33 90 1.06 41 0.26 10 1.53 49 C04 Pre 2.52 85 0.99 33 0.44 15 1.97 52  Post 3.13 89 1.44 41 0.38 11 2.07 48 C05 Pre 1.62 79 0.57 28 0.42 21 1.47 52  Post 1.80 79 0.65 29 0.48 21 1.63 50 C08 Pre 2.58 85 0.97 32 0.46 15 2.07 53  Post 2.54 76 0.95 29 0.78 24 2.37 48 C09 Pre 3.12 87 1.44 40 0.46 13 2.14 47  Post 2.84 76 1.04 28 0.88 24 2.68 48 C10 Pre 2.45 83 0.69 23 0.50 17 2.26 60  Post 2.72 85 0.82 26 0.47 15 2.37 59 C11 Pre 2.10 83 0.52 20 0.44 17 2.02 62  Post 2.50 89 0.85 30 0.29 11 1.94 59 C12 Pre 2.70 87 1.12 36 0.40 13 1.98 51  Post 2.46 79 0.84 27 0.64 21 2.26 52 EILV, end-inspiratory lung volume; FVC, forced vital capacity; EELV, end-expiratory lung volume; IRV, inspiratory reserve volume; IC, inspiratory capacity; VT, tidal volume.    180  Appendix B: Individual subject data – individual tables and figures This appendix contains the individual subject data for the ventilatory response to exercise. Each subject has two pages. The first page displays selected anthropometric, pulmonary function, and maximal exercise data as well as their MEFV and FVL for all stages of exercise, PRE (top) and POST (bottom). The MEFV, baseline, and maximal exercise stage are bolded, and exercise stages positive for EFL are presented in dashed lines. The second page presents their EFL severity and V̇E/V̇ECAP in tabular form and their ventilatory mechanics; absolute operational lung volumes (top left), relative operational lung volumes (top right), ventilation and ventilatory capacity (bottom left), and breathing frequency and tidal volume (bottom right). On all graphs, PRE is represented with open symbols, POST with closed.   181  Table 38 – S01 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 13.8 5 163.1 61.3 5.28 180 202 120.4 39.4 2.62 1.09 POST 14.4 5 164.4 59.7 5.58 220 205 135.7 41.2 2.97 1.21    Figure 20 – S01 MEFV and FVL for PRE (top) and POST (bottom).   182  Table 39 – S01 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W PRE MAX 200 W 220 W EFL (% VT) PRE 0 0 0 0 0 0 0 0 0 0 - -  POST 0 0 0 0 0 0 0 0 0 - 0 0 V̇E/V̇ECAP (%) PRE 6 15 17 18 25 27 31 44 65 77 - -  POST 6 13 16 20 21 26 29 37 46 - 57 69   Figure 21 – S01 ventilatory mechanics.  183  Table 40 – S02 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 12.5 3 160.9 44.7 4.49 140 194 59.7 37.7 1.77 1.05 POST 13.2 4 164.6 51.1 4.66 180 191 87.1 45.6 2.53 1.09    Figure 22 – S02 MEFV and FVL for PRE (top) and POST (bottom).   184  Table 41 – S02 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W EFL (% VT) PRE 0 0 0 4 0 52 58 - -  POST 0 0 0 0 0 0 0 0 37 V̇E/V̇ECAP (%) PRE 14 50 40 58 68 90 94 - -  POST 9 32 27 35 42 49 66 66 85   Figure 23 – S02 ventilatory mechanics.   185  Table 42 – S04 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 13.7 4 177.9 71.2 6.22 200 182 95.3 36.4 2.89 1.12 POST 14.3 4 177.9 70.8 6.55 200 182 83.3 37.1 2.82 1.08    Figure 24 – S04 MEFV and FVL for PRE (top) and POST (bottom).   186  Table 43 – S04 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W 200 W MAX EFL (% VT) PRE 0 0 0 0 0 0 0 0 0 0 0  POST 0 0 0 0 0 0 0 0 0 0 0 V̇E/V̇ECAP (%) PRE 5 10 13 16 21 20 26 31 38 43 46  POST 6 12 17 19 24 24 29 33 38 43 44   Figure 25 – S04 ventilatory mechanics.   187  Table 44 – S05 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 12.3 5 166.5 59.3 4.75 120 181 54.4 28.8 1.78 1.04 POST 12.9 5 168.4 65.8 5.16 160 195 79.7 32.6 2.39 1.12    Figure 26 – S05 MEFV and FVL for PRE (top) and POST (bottom).   188  Table 45 – S05 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W PRE MAX 140 W 160 W POST MAX EFL (% VT) PRE 0 0 0 0 0 0 0 0 0 0  POST 0 0 0 0 0 0 0 0 0 0 V̇E/V̇ECAP (%) PRE 8 19 27 28 34 36 40 - - -  POST 7 18 20 26 30 37 - 48 56 58   Figure 27 – S05 ventilatory mechanics.   189  Table 46 – S06 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 12.2 4 157.9 43.5 4.01 160 182 86.4 49.6 2.49 1.16 POST 12.8 4 161.2 50.2 4.44 180 185 98.2 46.7 2.77 1.18    Figure 28 – S06 MEFV and FVL for PRE (top) and POST (bottom).   190  Table 47 – S06 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W MAX EFL (% VT) PRE 0 0 0 0 0 0 0 44 - -  POST 0 0 0 0 0 0 0 51 72 60 V̇E/V̇ECAP (%) PRE 12 32 38 45 52 60 67 91 - -  POST 14 35 41 41 47 56 56 92 115 99   Figure 29 – S06 ventilatory mechanics.   191  Table 48 – S07 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 12.7 4 167 67.5 5.71 220 208 106.9 40.0 3.02 1.12 POST 13.3 5 168 71.8 5.96 200 208 118.3 37.4 3.09 1.15    Figure 30 – S07 MEFV and FVL for PRE (top) and POST (bottom).    192  Table 49 – S07 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W 200 W POST MAX 220 W EFL (% VT) PRE 0 0 0 0 0 0 0 0 0 0 - 0  POST 0 0 0 0 0 0 0 0 0 20 0 - V̇E/V̇ECAP (%) PRE 6 18 23 24 26 30 31 35 46 63 - 66  POST 6 21 23 30 33 41 45 58 70 74 73 -   Figure 31 – S07 ventilatory mechanics.  193  Table 50 – S08 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 11.6 3 153.3 46 4.34 160 205 101.4 49.0 2.60 1.17 POST 12.3 4 156.3 48.1 4.86 200 201 118.3 56.0 3.07 1.14    Figure 32 – S08 MEFV and FVL for PRE (top) and POST (bottom).   194  Table 51 – S08 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W 200 W EFL (% VT) PRE 0 0 0 0 0 0 0 57 - -  POST 0 0 0 0 0 0 0 0 59 73 V̇E/V̇ECAP (%) PRE 10 32 32 31 38 47 63 94 - -  POST 13 27 33 33 41 43 49 62 99 120   Figure 33 – S08 ventilatory mechanics.   195  Table 52 – S09 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 11.3 2 147.3 39.2 3.83 140 186 70.1 45.8 2.16 1.21 POST 11.9 2 151.2 44.5 4.38 180 194 96.3 49.1 2.68 1.23    Figure 34 – S09 MEFV and FVL for PRE (top) and POST (bottom).   196  Table 53 – S09 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W MAX EFL (% VT) PRE 0 0 0 0 0 0 16 - - -  POST 0 0 0 0 0 0 0 7 49 47 V̇E/V̇ECAP (%) PRE 7 26 37 38 47 54 71 - - -  POST 6 25 24 26 35 39 46 68 87 89   Figure 35 – S09 ventilatory mechanics.   197  Table 54 – S10 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 12.1 1 157 45.3 4.37 160 185 68.3 48.2 2.28 1.05 POST 12.6 3 160 48.9 4.72 200 191 93.2 51.7 2.77 1.11    Figure 36 – S10 MEFV and FVL for PRE (top) and POST (bottom).   198  Table 55 – S10 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W MAX EFL (% VT) PRE 0 0 0 0 0 0 0 0 - -  POST 0 0 0 0 0 0 0 0 29 49 V̇E/V̇ECAP (%) PRE 8 16 21 33 32 50 58 66 - -  POST 11 20 25 29 36 45 51 61 81 88   Figure 37 – S10 ventilatory mechanics.   199  Table 56 – S11 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 12.3 4 162.5 52.4 4.59 180 195 96.3 48.4 2.87 1.13 POST 12.8 4 163.1 56.4 4.75 180 195 90.4 36.2 2.38 1.17    Figure 38 – S11 MEFV and FVL for PRE (top) and POST (bottom).   200  Table 57 – S11 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W EFL (% VT) PRE 0 0 0 0 0 0 0 0 30  POST 0 0 0 0 0 0 0 0 39 V̇E/V̇ECAP (%) PRE 16 25 20 22 34 38 56 76 90  POST 8 30 31 34 37 50 63 77 87   Figure 39 – S11 ventilatory mechanics.   201  Table 58 – S12 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 12.3 4 161.2 45.6 4.39 180 197 81.8 48.5 2.47 1.12 POST 12.9 4 162.7 46.6 4.81 200 201 102.0 55.0 2.96 1.16    Figure 40 – S12 MEFV and FVL for PRE (top) and POST (bottom).   202  Table 59 – S12 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W 200 W MAX EFL (% VT) PRE 0 0 0 0 0 0 0 0 0 - -  POST 0 0 0 0 0 0 0 0 0 0 0 V̇E/V̇ECAP (%) PRE 8 19 26 30 38 40 48 52 70 - -  POST 7 16 22 21 24 26 35 42 57 63 65   Figure 41 – S12 ventilatory mechanics.   203  Table 60 – C01 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 11.1 2 147 43.4 3.39 120 186 61.8 37.7 1.59 0.98 POST 11.7 2 149.3 46.3 3.4 140 186 67.0 36.4 1.88 1.11    Figure 42 – C01 MEFV and FVL for PRE (top) and POST (bottom).   204  Table 61 – C01 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W PRE MAX 140 W POST MAX EFL (% VT) PRE 0 0 0 0 0 0 0 - -  POST 0 0 0 0 0 5 - 50 50 V̇E/V̇ECAP (%) PRE 9 22 29 33 52 63 63 - -  POST 12 33 43 47 61 74 - 89 83   Figure 43 – C01 ventilatory mechanics.   205  Table 62 – C02 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 12.2 3 153.7 40.2 3.67 140 204 57.4 42.9 1.84 1.07 POST 12.8 4 159.1 45.3 3.92 180 208 79.1 48.7 2.45 1.12    Figure 44 – C02 MEFV and FVL for PRE (top) and POST (bottom).   206  Table 63 – C02 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W EFL (% VT) PRE 0 0 0 0 0 0 0 - -  POST 0 0 0 0 0 0 0 0 9 V̇E/V̇ECAP (%) PRE 7 21 22 24 38 43 47 - -  POST 6 20 29 33 35 45 51 66 75   Figure 45 – C02 ventilatory mechanics.   207  Table 64 – C03 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 12.8 3 166 47.8 3.88 160 183 76.4 41.3 2.19 1.11 POST 13.5 3 168.9 51.4 4.02 160 185 88.2 39.9 2.27 1.11    Figure 46 – C03 MEFV and FVL for PRE (top) and POST (bottom).   208  Table 65 – C03 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W POST MAX EFL (% VT) PRE 0 0 0 0 0 0 0 6 -  POST 0 0 0 0 0 0 0 0 1 V̇E/V̇ECAP (%) PRE 10 24 36 39 49 55 70 84 -  POST 7 20 24 35 36 49 61 78 78   Figure 47 – C03 ventilatory mechanics.   209  Table 66 – C04 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 14.2 3 164.2 49.9 4.46 200 195 81.8 44.7 2.56 1.15 POST 14.9 5 166.7 53.8 5.09 220 197 92.0 47.3 3.03 1.19    Figure 48 – C04 MEFV and FVL for PRE (top) and POST (bottom).   210  Table 67 – C04 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W 200 W 220 W POST MAX EFL (% VT) PRE 0 0 0 0 0 0 0 3 51 60 - -  POST 0 0 0 0 0 0 0 0 0 0 0 35 V̇E/V̇ECAP (%) PRE 14 32 41 49 57 50 68 73 94 101 - -  POST 6 22 26 32 34 30 42 44 55 69 79 65   Figure 49 – C04 ventilatory mechanics.   211  Table 68 – C05 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 11.4 1 145.6 35.9 3.11 120 199 42.5 40.3 1.59 1.10 POST 12.1 3 149.3 37.5 3.13 140 198 62.3 44.5 2.03 1.22    Figure 50 – C05 MEFV and FVL for PRE (top) and POST (bottom).   212  Table 69 – C05 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W EFL (% VT) PRE 0 0 0 0 0 0 -  POST 0 0 0 0 0 0 20 V̇E/V̇ECAP (%) PRE 10 24 34 42 52 58 -  POST 10 19 23 34 41 52 77   Figure 51 – C05 ventilatory mechanics.   213  Table 70 – C08 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 13.6 4 164.6 49.5 4.22 160 199 95.3 41.0 2.56 1.26 POST 14.2 4 167.6 56.6 4.98 180 197 98.8 36.2 2.57 1.27    Figure 52 – C08 MEFV and FVL for PRE (top) and POST (bottom).   214  Table 71 – C08 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W EFL (% VT) PRE 0 0 0 0 0 0 0 3 -  POST 0 0 0 0 0 0 0 36 28 V̇E/V̇ECAP (%) PRE 8 23 28 38 48 54 71 82 -  POST 8 19 21 25 38 46 60 83 83   Figure 53 – C08 ventilatory mechanics.   215  Table 72 – C09 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 13.5 4 158.9 48.9 4.48 160 201 70.6 38.2 2.18 1.17 POST 14.1 4 161.1 51.9 4.68 160 203 97.6 38.7 2.60 1.30    Figure 54 – C09 MEFV and FVL for PRE (top) and POST (bottom).   216  Table 73 – C09 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W EFL (% VT) PRE 0 0 0 0 0 0 0 0  POST 0 0 0 0 0 0 0 0 V̇E/V̇ECAP (%) PRE 4 15 13 15 25 30 43 49  POST 6 10 17 18 18 26 55 69   Figure 55 – C09 ventilatory mechanics.   217  Table 74 – C10 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 14.3 3 164.9 47.4 4.32 180 194 82.5 45.8 2.59 1.19 POST 14.8 3 165.4 48.4 4.59 200 202 89.7 48.1 2.72 1.17    Figure 56 – C10 MEFV and FVL for PRE (top) and POST (bottom).   218  Table 75 – C10 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W PRE MAX 200 W POST MAX EFL (% VT) PRE 0 0 0 0 0 0 17 39 51 62 - -  POST 0 0 0 0 0 0 15 27 44 - 66 66 V̇E/V̇ECAP (%) PRE 11 27 31 37 49 47 66 79 103 108 - -  POST 8 23 32 36 41 44 59 75 83 - 116 115   Figure 57 – C10 ventilatory mechanics.   219  Table 76 – C11 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 14.3 3 160.8 45.5 3.78 160 199 65.9 37.3 1.98 1.17 POST 14.8 3 161.9 47.7 4.04 180 202 83.2 45.1 2.48 1.15    Figure 58 – C11 MEFV and FVL for PRE (top) and POST (bottom).   220  Table 77 – C11 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W 160 W 180 W EFL (% VT) PRE 0 0 0 0 0 0 0 0 -  POST 0 0 0 0 0 0 1 24 42 V̇E/V̇ECAP (%) PRE 6 21 25 36 33 46 48 55 -  POST 10 27 29 37 54 49 56 74 88   Figure 59 – C11 ventilatory mechanics.   221  Table 78 – C12 selected anthropometric, pulmonary function, and maximal exercise data.  Age (y) SMR pubic hair Height (cm) Weight (kg) TLC (l) Work rate (W) HR (bpm) V̇E (l·min-1) V̇O2MAX (ml·kg-1·min-1) V̇CO2 (l·min-1) RER PRE 14.8 5 156.9 54.9 4.01 140 200 86.0 31.2 2.18 1.27 POST 15.5 5 157.7 54.7 4.07 140 203 94.9 36.1 2.31 1.17    Figure 60 – C12 MEFV and FVL for PRE (top) and POST (bottom).   222  Table 79 – C12 EFL severity and V̇E/V̇ECAP.   REST 40 W 60 W 80 W 100 W 120 W 140 W MAX EFL (% VT) PRE 0 0 0 0 0 0 0 0  POST 0 0 0 0 0 0 0 26 V̇E/V̇ECAP (%) PRE 4 16 18 30 34 46 59 49  POST 7 21 28 33 36 49 68 77   Figure 61 – C12 ventilatory mechanics.   223  Appendix C: Questionnaires, forms, and documents    224     225     226     227     228     229    230   231  Appendix D: Predictive equations Table 80 – Predictive equations and the limits of abnormality Measurement Study Equation Limits of abnormality (%) Notes TLC Hibbert et al., 1989 (85) 𝑒0.0075×𝐴𝑔𝑒×𝐻𝑡3+1.1808 ln(𝐻𝑡)+0.4927 <83, >121 Age is in y; Ht is in m FRC  𝑒0.0130×𝐴𝑔𝑒×𝐻𝑡3+0.0606   RV  𝑒0.0153×𝐴𝑔𝑒×𝐻𝑡3−0.4694 ln(𝐻𝑡)−0.5604 <63, >159  FVC  𝑒1.4393×𝐻𝑡+0.0221×𝐴𝑔𝑒−1.4500 <83, >121  FEV1  𝑒1.4267×𝐻𝑡+0.0247×𝐴𝑔𝑒+1.5717 <82  PEF  𝑒−0.0079×𝐴𝑔𝑒×𝐻𝑡2+1.7246 ln(𝐻𝑡)+0.0477×𝐴𝑔𝑒+4.8292 <79  FEF25-75%  𝑒1.1257×𝐻𝑡+0.0259×𝐴𝑔𝑒−0.8787 <67  FEF25%  𝑒1.4917 ln(𝐻𝑡)+0.0377×𝐴𝑔𝑒+0.4041 <73  FEF50%  𝑒1.7560 ln(𝐻𝑡)+0.03305×𝐴𝑔𝑒−0.0269 <64  FEF75%  𝑒0.0143×𝐴𝑔𝑒×𝐻𝑡2+1.4952 ln(𝐻𝑡)−0.6127 <69  RV/TLC   <0.17, >0.38  DL,CO and DL,COc Kim et al., 2012 (87) 𝑒0.796+0.012×𝐻𝑡+0.018×𝐴𝑔𝑒  Age is in months; Ht is in cm VA  𝑒−1.424+0.016×𝐻𝑡+0.019×𝐴𝑔𝑒    DL,COc/VA  8.458 − 0.021×𝐻𝑡   Pst(L)50 Zapletal et al., 1976 (90) 𝑃𝑠𝑡(𝐿)50 = 0.0770×𝐻𝑒𝑖𝑔ℎ𝑡 − 3.3871   PIMAX Domenech-Clar et al., 2003 (45) −33.854 − (1.814×𝐴𝑔𝑒) − (0.004×𝐻𝑡×𝑊𝑡)  Age is in y; Height is in cm PEMAX  17.066 + (7.22×𝐴𝑔𝑒)   V̇O2MAX Cooper et al., 1984 (88) 28.5×𝑊𝑡 + 288.2  In mL/min TLC, total lung capacity; Ht, height; FRC, functional residual capacity; RV, residual volume; FVC, forced vital capacity; FEV1, forced expired volume in one second; PEF, peak expiratory flow; FEF, forced expiratory flow; DL,CO, diffusion capacity of the lungs for carbon monoxide; VA, alveolar volume; PIMAX, maximal inspiratory pressure; Wt, weight; PEMAX, maximal expiratory pressure; VO2MAX, maximal oxygen consumption. 

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