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Craniofacial morphology and sleep disordered breathing in children Aran, Reza 2013

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CRANIOFACIAL MORPHOLOGY AND SLEEP DISORDERED BREATHING IN CHILDREN  by Reza Aran  DMD, The University of British Columbia, 2007  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF  MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES (Craniofacial Science)  THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver)  April 2013  © Reza Aran, 2013  Abstract  Objective: The aim of this study is to understand how craniofacial morphology and the severity of a malocclusion can contribute to sleep disordered breathing (SDB) symptoms in children when controlled for age, gender and body mass index (BMI).  Methods: A total of 301 subjects with complete records were included in this study. Two hundred and thirty-seven were preadolescents, of which 97 were male and 140 were female (mean age 9.9±1.6); 64 were adolescents, of which 24 were male and 40 were female (mean age 13.8±0.9). All the subjects’ parents were asked to complete a SDB questionnaire. Lateral cephalometric images were analyzed to assess the position of the hyoid bone, length of the soft palate, and the maxillary and mandibular dental and skeletal relationship. A clinical examination was performed to determine the Angle classification, Mallampati score, tonsil size (Brodesky), and BMI.  Results: Data from 301 children that completed the questionnaires and underwent a cephalometric analysis were evaluated. Subjects were divided into two groups based on their age and each group was further divided based on gender. By comparing preadolescents with adolescents we found that preadolescents presented a significantly higher incidence of hyperactivity, morning headaches, more frequent snoring, and bedwetting. Adolescents exhibited significantly higher daytime sleepiness, difficulty getting up, and impaired daytime function. When comparing female and male subjects, we found that frequent snoring, and morning headaches were more prevalent among females, while daytime sleepiness, and hyperactivity were more common among males.  	
    ii	
    Craniofacial features that have a significant relationship with SDB symptoms are, a lower position of the hyoid bone, retruded mandible, steeper mandibular plane angle, and retroclined lower incisors. There was no statistically significant relationship between Angle classifications, tonsil size, Mallampati score, and BMI with SDB symptoms in this sample.  Conclusion: This study suggests that craniofacial morphology, but not severity of malocclusions, could be a potential contributing factor to SDB symptom severity.  	
    iii	
    Preface  The research topic of this project was suggested by Dr. Alan Lowe and the research question was identified and the project designed by Reza Aran under the guidance of Drs. Alan Lowe and Fernanda Almeida. The data was collected and analyzed by Reza Aran. Reza Aran prepared the Manuscript with content editing by Drs. Alan Lowe and Fernanda Almeida, and copy editing by Clare Davies.  The study was approved by the University of British Columbia office of Research Services, Humans Research Ethics Board (Certificate Number: H12-00024).  	
    iv	
    Table of Contents 	
   Abstract.............................................................................................................................. ii	
   Preface ............................................................................................................................... iv	
   Table of Contents .............................................................................................................. v	
   List of Tables ................................................................................................................... vii	
   List of Figures................................................................................................................... ix	
   List of Abbreviations ........................................................................................................ x	
   Acknowledgements .......................................................................................................... xi	
   Dedication ....................................................................................................................... xiii	
   Chapter 1: Introduction .................................................................................................. 1	
   1.1	
  	
  	
  Sleep	
  Disordered	
  Breathing	
  (SDB)	
  .....................................................................................	
  1	
   1.2	
  	
  	
  SDB	
  Prevalence	
  .........................................................................................................................	
  1	
   1.3	
  	
  	
  Pathophysiology	
  .......................................................................................................................	
  2	
   1.3.1	
  	
  	
  Three	
  Major	
  Contributing	
  Factors	
  to	
  SDB	
  ...............................................................................	
  2	
   1.4	
  	
  	
  Cephalometric	
  Characteristics	
  of	
  Patients	
  with	
  SDB	
  ...................................................	
  4	
   1.5	
  	
  	
  Diagnosis	
  .....................................................................................................................................	
  8	
   1.6	
  	
  	
  Treatment	
  of	
  SDB	
  .....................................................................................................................	
  9	
   1.6.1	
  	
  	
  Continuous	
  Positive	
  Airway	
  Pressure	
  (CPAP)	
  and	
  Positive	
  Airway	
  Pressure	
   (PAP)	
  .....................................................................................................................................................................	
  9	
   1.6.2	
  	
  	
  Adenotonsilectomy	
  .........................................................................................................................	
  10	
   1.6.3	
  	
  	
  Orthodontic	
  Treatment	
  ................................................................................................................	
  11	
   1.7	
  	
  	
  Age	
  and	
  Gender	
  Differences	
  in	
  SDB	
  ................................................................................	
  15	
   1.8	
  	
  	
  Objectives	
  .................................................................................................................................	
  16	
   1.9	
  	
  	
  Hypothesis	
  ...............................................................................................................................	
  16	
    Chapter 2: Materials and Methods ............................................................................... 18	
   2.1	
  	
  	
  Subjects	
  .....................................................................................................................................	
  18	
   2.2	
  	
  	
  Clinical	
  Findings	
  ....................................................................................................................	
  19	
   2.2.1	
  	
  	
  Mallampati	
  Scores	
  and	
  Tonsil	
  Size	
  ..........................................................................................	
  19	
   2.2.2	
  	
  	
  Angle	
  Classification	
  ........................................................................................................................	
  22	
   2.3	
  	
  	
  Questionnaires	
  .......................................................................................................................	
  24	
   2.4	
  	
  	
  Cephalometric	
  Analysis	
  .......................................................................................................	
  26	
   2.5	
  	
  	
  Method	
  Error	
  ..........................................................................................................................	
  28	
   2.6	
  	
  	
  Statistical	
  Analysis	
  ................................................................................................................	
  28	
   Chapter 3: Results........................................................................................................... 30	
   3.1	
  	
  	
  Subjects	
  .....................................................................................................................................	
  30	
   3.2	
  	
  	
  Clinical	
  Findings	
  ....................................................................................................................	
  31	
   3.2.1	
  	
  	
  Mallampati	
  Scores	
  and	
  Tonsils	
  Size	
  ........................................................................................	
  31	
   3.2.2	
  	
  	
  Body	
  Mass	
  Index	
  ..............................................................................................................................	
  33	
   3.2.3	
  	
  	
  Angle	
  Classification	
  ........................................................................................................................	
  34	
   3.3	
  	
  	
  Questionnaires	
  .......................................................................................................................	
  34	
   3.3.1	
  	
  	
  OSA-­‐18	
  Questionnaire	
  ...................................................................................................................	
  38	
   3.3.2	
  	
  	
  PSQ-­‐22	
  Questionnaire	
  ...................................................................................................................	
  40	
   3.4	
  	
  	
  Cephalometric	
  Analysis	
  .......................................................................................................	
  43	
   3.5	
  	
  	
  Correlation	
  Between	
  Cephalometric	
  Variables	
  and	
  SDB	
  Symptoms	
  ...................	
  45	
   Chapter 4: Discussion ..................................................................................................... 49	
   Chapter 5: Conclusion .................................................................................................... 60	
    	
    v	
    References ........................................................................................................................ 61	
   Appendix .......................................................................................................................... 68	
   Appendix	
  A	
  .......................................................................................................................................	
  68	
   A.1	
  	
  	
  OSA-­‐18	
  Questionnaire	
  ......................................................................................................................	
  69	
   A.	
  2	
  	
  PSQ-­‐22	
  Questionnaire	
  ......................................................................................................................	
  70	
   	
   	
    	
    	
    vi	
    List of Tables 	
   Table 1 Demographic data and questionnaire scores (mean)	
  ..................................................	
  30	
   Table 2 Significant differences between age and gender in Mallampati scores	
  ................	
  32	
   Table 3 Body mass index distribution among the four groups based on age and gender 	
  ...............................................................................................................................................................	
  33	
   Table 4 Angle classification	
  ................................................................................................................	
  34	
   Table 5 OSA-18 Percentages of individual item responses	
  .....................................................	
  35	
   Table 6 PSQ-22 Percentages of individual item responses	
  ......................................................	
  37	
   Table 7 Most common SDB symptoms among the children in our sample according to responses given to the OSA-18 and PSQ-22 questionnaires	
  ............................................	
  38	
   Table 8 Difference between PreAd and Ad in percentages	
  ......................................................	
  39	
   Table 9 Differences between PreAd males and Ad males in percentages	
  ...........................	
  39	
   Table 10 Differences between PreAd females and Ad females in percentages	
  .................	
  39	
   Table 11 Percentage of subjects who chose answered "YES" to the SDB Symptoms and the differences between preadolescents and adolescents	
  ...................................................	
  40	
   Table 12 The percentage of male, female and total sample who answered "YES" to the following SDB symptoms in the PS22 questionnaire and significant P-Value	
  .........	
  41	
   Table 13 A summary of differences between two age groups according to the OSA-18 and PSQ-22 questionnaire	
  ............................................................................................................	
  42	
   Table 14 Cephalometric analyses with mean and standard deviation for the whole sample and both PreAd and Ad	
  ..................................................................................................	
  44	
   Table 15 Corrections between domains and cephalometric variables	
  ..................................	
  45	
    	
    vii	
    Table 16 A summary of important craniofacial features that have significant correlation with SDB symptoms	
  ......................................................................................................................	
  46	
   Table 17 A summary of SDB symptoms which are correlated with each individual cephalometric variable	
  ...................................................................................................................	
  47	
   Table 18 Comparison between males and females of aged 13-16	
  .........................................	
  48	
    	
    viii	
    List of Figures 	
   Figure 1 A summary of important craniofacial features and the supporting literature	
  ......	
  7	
   Figure 2 Mallapati Airway Classification (I-V Scores).	
  ............................................................	
  20	
   Figure 3 Brodsky Classification (0-4 Grades)	
  ..............................................................................	
  21	
   Figure 4 Orhtodontic models and intraoral photos were used to determine Angle classification	
  .....................................................................................................................................	
  23	
   Figure 5 Cephalometric landmarks, and linear and angular cephalometric variables.	
  ....	
  27	
   Figure 6 Percentage of children with different Mallampati scores and the differences between PreAd and Ad groups	
  ...................................................................................................	
  31	
   Figure 7 Percentage of female patients with different Mallampati scores and the differences between PreAd females and Ad females	
  ..........................................................	
  32	
   Figure 8 Classification of patients according to their age and gender who had SDB symptoms according to responses given to the PSQ-22	
  ....................................................	
  42	
    	
    ix	
    List of Abbreviations Ad: adolescent AHI: apnea hypopnea index BMI: body mass index CPAP: continuous positive air pressure MPAP: mean pulmonary artery pressure OA: oral appliances OSA: obstructive sleep apnea OSAS: obstructive sleep apnea PAP: positive air pressure PreAd: preadolescent PSQ: pediatric sleep questionnaire RME: rapid maxillary expansion SDB: sleep disordered breathing	
    	
    x	
    Acknowledgements  I would like to acknowledge Dr. Edwin Yen, Dr. Alan Lowe, Dr. David Kennedy and the other members of the Graduate Admission Committee for accepting me into the UBC Graduate Orthodontic Program. I am so grateful to be a part of such an incredible diverse program with such great mentors. Specializing in orthodontics has been a dream and long-term goal for me and I am extremely thankful for the opportunity that I was given. Dr. Yen, your guidance, continued support and wisdom have been a source of inspiration. Research was something undiscovered for me until I started my Master’s project. This was the time that I received research training and I have learned new things and experienced more enthusiasm for research over time. These could not happen without supervision of wonderful, erudite mentors such as Drs. Alan Lowe and Fernanda Almeida. I would like to express my deepest gratitude to Dr. Alan Lowe for supervising my project and giving me such a great insight into the research world of Sleep Disordered Breathing. I am so thankful to Dr. Fernanda Almeida in her co-supervisor role for my project and for her kindness, patience and encouragement, and for teaching me how to be a good researcher. Every time that I meet with you for your feedback, you have been so welcoming and gave me a wonderful energy and a desire to learn and achieve a great improvement. Also, I want to thank Dr. Benjamin Pliska for his participation in my committee, as well as his outstanding clinical knowledge and skills that he generously shared with me in my everyday learning and orthodontic clinics. I want to thank Dr. Hui Chen for her participation in my committee, and for being so positive and encouraging every time I saw her in clinics or seminars.  	
    xi	
    I want to thank Dr. Kazutomo Yagi for his great help through out this project. I have learned a lot from you. You are an exceptional and incredible scholar. And, of course, two wonderful people that I would never forget for their great help and kindness are Mary Wong for the data base and statistical analyses and Sandy Harrison for patient data collection. Thank you to Gail Furlong and Mitchel Wong for helping me to collect the data for my project. I would like to thank Clare Davies, for helping me with copy editing and without whose help I would not have been able to complete the task in a timely way.  Lastly, my fellow residents or so called “Dream Team”, I will miss every moment that we have spent together, from literature reviews to the clinic sessions and to the social events. We have had a wonderful and unforgettable three years together and I wish you the most beautiful, successful and peaceful years ahead.  	
    xii	
    Dedication  There is only one person that I can truly dedicate this to and that is my incredible wife, Katayoun, for her unconditional love and support not only within these past three years, but also throughout all the years of our being together. There have been many others who have helped and guided me along the journey of my life and career, and I am forever grateful for to all of those who have been there to support me. However, I would not be the person who I am today, nor would I be at this place today, without the persistent support, incredible caring, friendship, kindness, constancy, and deep true love that you, Katayoun have given me. I dedicate this to you as a symbol of my deep gratitude and love and look forward to spending the rest of my life making every moment with you and our lovely children as happy and exciting as possible, as that is what you really deserve.  	
    xiii	
    Chapter 1: Introduction  1.1 Sleep Disordered Breathing (SDB) Sleep disordered breathing (SDB) is a general term for several chronic conditions such as habitual snoring, hypopnea, and the more severe condition known as obstructive sleep apnea (OSA).1, 2 Over 20% of children have some signs of SDB such as loud snoring, mouth breathing, difficulty wakening, excessive daytime sleepiness and behavioral changes such as hyperactivity.3, 4 SDB is also known to be an important contributing factor to the problematic behaviors observed in children who suffer from sleep deprivation.5, 6 Other clinical symptoms include failure to thrive,7, 8 hypertension,9 cardiovascular failure,10 and frequent upper airway infections.3, 11, 12 Additionally, Ross et al found that children with SDB have about a 3.6 times higher chance of having severe asthma.13 In summary, SDB children are at a higher risk of metabolic, cardiovascular, and neurobehavioral morbidity.5, 14-19  1.2 SDB Prevalence Schechter found the prevalence of snoring and OSA among children to be 3.2%-12.1% and 0.7%-10.3% respectively.14 Bixler et al, 2009 investigated the prevalence and risk factors of SDB in a general population. They found that the prevalence of moderate SDB was 1.2% and the two main risk factors were BMI and nasal abnormalities.11 In a technical report by Marcus et al, the prevalence of habitual snoring was reported to be 1.5% to 27.6 % and the prevalence of OSA was reported to be 1.2% to 5.7%.20 An adult  	
    1	
    with an apnea hypopnea index (AHI) of more than five events per hour is considered to have OSA, however a child with an AHI of 1 to 2 is considered to have OSA.20, 21 Metabolic and inflammatory factors may play an important role in whether a child develops SDB in adulthood.11 Li et al studied 20,152 children with habitual snoring and found a prevalence of 12% with 14.5% for males and 9.5% for females. Children with SDB had three times more behavioral problems and neurocognitive abnormalities than those without.14 The prevalence of hyperactivity behaviors is higher in younger children with SDB.22  1.3 Pathophysiology For a better understanding, proper diagnosis and accurate treatment, one needs to know the pathophysiology and contributing factors of SDB. The etiology of OSA syndrome is different in adults compared with children. In adults, obesity is the main etiological factor, while in children, adenotonsilar hypertrophy appears to be the main factor.20 In addition to adenotonsilar hypertrophy, two other main contributing factors to OSA syndrome in children are obesity and alterations of the craniofacial morphology.3, 12, 23-25  1.3.1 Three Major Contributing Factors to SDB Approximately 80% of SDB in young children is associated with adenotonsilar hypertrophy26, which is more prevalent among young children (2-8 years).27 Adenotonsilar hypertrophy increases upper airway obstruction27 and this can negatively influence craniofacial development.28 Children with large tonsils may have retrognathic, posteriorly and inferiorly rotated mandibles.23, 29, 30 Children with snoring symptoms at 	
    2	
    age four showed a more constricted maxilla with a greater amount of anterior open bite and posterior crossbite.31 Richards et al reported that in patients who had dysphagia, choking and vomiting experiences, a complete cessation of these symptoms occurred after removal of the adenoid and tonsilar tissues.32 In patients with habitual mouth breathing and asthma, removal of the adenoid and tonsils also brought about significant improvement. It has been suggested that the morbidity of OSA may be increased if diagnosis and treatment of adenotonsilar hypertrophy is delayed.32  While large tonsil size is associated with SDB in young children, in children over six years of age, obesity may contribute to disease severity.33 Larger pharyngeal tonsils in obese SDB children have a greater effect on airway obstruction than they do in normal weight SDB children.34 The severity of SDB is significantly higher in obese children compared to normal weight children35-37 and the risk of SDB in children has been shown to increases by 12% for every 1 kg/m2 BMI increment above the mean BMI.27 In adult obese SDB patients, soft tissue in conjunction with adipose tissue increases the risk of airway obstruction while in non-obese SDB adults, the bony structures of the craniofacial complex may be the main contributing factors to SDB.38 To what extent this could be true in SDB children is unknown. In both obese and non-obese SDB children, skeletal changes are evident but obese children tend to have a larger anterior facial height.36  In addition to adenotonsilar hypertrophy and obesity, craniofacial morphology is another major contributing factor to SDB in young children.3, 12 As previously described, many changes in craniofacial features are closely related to adenotonsilar hypertrophy and  	
    3	
    obesity.28, 36 A steeper mandibular plane angle, larger anterior facial height and tendency to a vertical growth pattern are all characteristics of children who breathe through their mouth.39 A retruded mandible, steep mandibular plane, and longer anterior lower facial height are the main craniofacial characteristics of individuals with SDB symptoms.40-42 Some other craniofacial features related to SDB include a short nasal floor and retroclined lower incisors,23 an increased interincisal angle,42 and a long soft palate.3, 23 Several studies have concluded that a lower position of the hyoid bone is an important craniofacial feature contributing to SDB symptoms.23, 40, 43-45 A higher palatal vault,3, 28 narrow maxilla and posterior crossbite29, 46 have also been reported as important craniofacial characteristics of OSA children.  1.4 Cephalometric Characteristics of Patients with SDB Several studies based on cephalometric variables have suggested that some craniofacial morphometric features are associated with SDB symptoms.28, 29, 41, 46, 47 There is a significant correlation between cephalometric data and AHI scores in that patients with higher AHI scores showed an increased mandibular plane angle, and a decreased length of the mandibular plane (Go-Gn).48 Kawashima et al found that preschool children with enlarged tonsils had retrusive mandibles with a downward and backward rotation.23 SDB children had more hyperdivergent facial types compared with normal subjects.29, 48 Kulnis et al looked at two groups of children, snoring and non-snoring, between the ages of 7-14 years. The snoring children had a different craniofacial morphology when compared with non-snoring children; they had a significantly narrower anteroposterior  	
    4	
    dimension of the pharynx and also a lower hyoid bone compared to the mandibular plane.44 Parkkinen et al compared normal children with subjects who showed SDB symptoms. Children with OSA had an increased anteroposterior jaw relationship, a mandibular plane inclination, total lower anterior facial height, a longer and thicker soft palate, and a lower hyoid bone position relative to the inferior border of the mandible.45, 49  Children who breathe through their mouth tend to have certain cephalometric craniofacial features such as a steeper mandibular plane angle, larger anterior facial height, and a tendency to a vertical growth pattern.39 Juliano et al analyzed cephalometric radiographs of 52 mouth breathing and 90 nose breathing children. They found that mouth breathing children have cephalometric patterns similar to those of adult OSA patients. The common craniofacial features of a mouth breather were a retruded mandible, steep mandibular and occlusal plane angles, and more proclined upper incisors. They found no significant difference between the groups in the position of the hyoid bone relative to the mandibular plane but the hyoid bone was located more anteriorly to the vertebrae in mouth breathers.30  Ozdemir et al looked at eleven measurements of bony structures in lateral cephalometric images. They also looked at other confounding factors such as size of the airway and the adenotonsilar hypertrophy. Patients with higher AHI scores showed increased cranial base angles, a decreased length of the body of the mandible and decreased posterior airway space. They did not find any correlation between protrusion of the maxilla or  	
    5	
    mandible and SDB, but they did find a significant correlation between cephalometric data and adenotonsilar hypertrophy in addition to higher AHI scores.48  Kawashima et al completed a study of preschool children and found that cephalometric craniofacial features of SDB children included a short nasal floor, retrusive mandible, increased interincisal angle, increased posterior facial height, retroclined lower incisors, narrow pharyngeal airway space, anterior tongue base position and long soft palate. They did not find any significant relationship between the hyoid bone position and SDB symptoms.23  Figure 1 provides a summary of the craniofacial features that are correlated with SDB in children and the publications that support these findings.  	
    6	
    Craniofacial features  Literature  Narrow maxilla and posterior crossbite  Agren, 1998; Zucconi, 1999; LofstrandTidstrom, 1999  Steep mandibular plane angle  Zucconi, 1999; Ozdmir, 2004; ZettergrenWijik, 2006; Juliano, 2009; Kawashima, 2000;  Increased lower anterior face height  Zucconi, 1999; Zettergren-Wijik, 2006; Juliano, 2009; Marino, 2009; Kawashima, 2000; Lofstrand-Tidstrom, 1999  Retruded/smaller mandible  Jamieson, 1986; Zucconi, 1999; Ozdmir, 2004; Zettergren-Wijik, 2006; Juliano, 2009; Marino, 2009; Kawashima, 2000; Lofstrand-Tidstrom, 1999; Kim, 2011  Lower hyoid bone Retroclined lower incisors  Jamieson, 1986; Kawashima 2002; Cuccia, 2007; Ozdmir, 2004; Kawashima, 2002; Zettergren-Wijk et al, 2006  Proclined upper incisors  Juliano et al, 2009; Tsuda, 2010  Long soft palate  Jamieson, 1086; Kawashima, 2002; Tsuda, 2010  High palatal height  Lofstrand-Tidstrom, 1999; Tsuda, 2010; Kim, 2011  Figure 1 A summary of important craniofacial features and the supporting literature  	
    7	
    1.5 Diagnosis 	
   SDB has an effect on the growth of children and therefore it is important that it be diagnosed as early as preschool.3, 16, 23 Clinical signs and symptoms that are good predictors of SDB include enlarged pharyngeal tonsils, apnea during sleep, nocturnal snoring, daytime sleepiness, and mouth breathing.50 In addition to these clinical signs and symptoms, there are important radiographic features associated with pediatric SDB such as a retruded or small mandible, increased mandibular plane inclination, increased total and lower anterior facial height, a longer and thicker soft palate, retroclined lower incisors, and a lower hyoid bone position.3, 25, 41, 45  Huynh et al investigated the relationship between responses to a sleep-disordered breathing questionnaire and a clinical orthodontic examination of a subject’s facial and dentoalveolar morphology. A sample of 604 children less than 18 years old underwent a clinical assessment to determine their dental, skeletal, facial and esthetic conditions. Children who suffered from SDB were characterized by hypertrophic adenoids and tonsils, a long and narrow face (dolichocephalic), a high mandibular plane angle, narrow palate, severe crowding in both the maxilla and mandible, allergies, frequent colds, and habitual mouth breathing. They concluded that children with the signs and symptoms of SDB should be referred to a sleep medicine specialist for diagnosis and to an orthodontist for treatment of any dentoskeletal abnormalities.12 In a recent publication from the American Academy of Sleep Medicine (AASM) regarding the indications of polysomnography in children with SDB, it was suggested that clinical evaluation alone is not sufficient to establish a diagnosis of OSA in children. Integration of  	
    8	
    polysomnographic findings with a clinical evaluation is the best way to achieve an accurate diagnosis of SBD in pediatric populations.51  1.6 Treatment of SDB 	
   Marcus et al published a recent technical report on the diagnosis and management of childhood OSA. According to this report, adenotonsilectomy is considered the first line of treatment to improve SDB in both obese and non-obese children. However, there is still a 13%-29% chance for persistent OSA symptoms after adenotonsilectomy. The majority of obese children need continuous positive airway pressure (CPAP) even after removal of the tonsil and adenoid tissues. CPAP is not considered as first-line therapy for children with OSA when adenotonsilectomy is an option. However, for obese individuals who have had an adenotonsilectomy and for those whom surgery is contraindicated, CPAP should still be used. In addition, exercise and weight loss can reduce the severity of OSA in obese children. Orthodontic treatments such as rapid maxillary expansion (RME) or the use of mandibular advancement appliances have been reported as effective for obese and non-obese SDB children.20  1.6.1 Continuous Positive Airway Pressure (CPAP) and Positive Airway Pressure (PAP) 	
   Literature supports the use of nasal CPAP as an effective way of treating the symptoms of OSAS in young children.52-54 However, compliance can sometimes be a barrier for effective use of CPAP. Marcus et al compared CPAP with PAP devices in OSA children 	
    9	
    aged 2-16 years. After three months of PAP use, a significant improvement in neurobehavioral function was observed. The investigators recommended PAP for children with OSAS especially for those for whom compliance might be a barrier to effective use of CPAP.55 In those children where surgery is a contraindication or those who do not respond adequately to surgical removal of the adenoid and tonsils, CPAP or PAP could be a useful aids to reduce OAS symptoms.20  1.6.2 Adenotonsilectomy 	
   Surgical removal of the hypertrophic adenoid and tonsils in children has been found to significantly improve SDB symptoms and consequently quality of life.19, 56, 57 LofstrandTidestrom et al reported improvement in SDB symptoms in children who had an adenotonsilectomy at an early age. However, they have observed significant relapse in terms of both OSA symptoms and dentofacial development during the teen-age years.31 Lipton et al analyzed the published literature on the treatment and morbidity of OSA children and found that adenotonsilectomy remains the first line of treatment.15 However, Kim et al found that over 40% of children with SDB symptoms had persistent presurgical symptoms even after an adenotonsilectomy.4 Nevertheless, in a systemic review and meta-analysis by Bonuck et al, they found that several studies reported a significant improvement in children’s SDB symptoms and the growth after surgical removal of the adenoid and tonsils.58 Ozdmir et al also observed significant improvement in craniofacial features and SDB symptoms after removal of the tonsils and adenoid tissues.48 While surgical removal of hypertrophic adenoid and tonsils is generally recommended, a recent study by Tatlipinar et al suggested that adenotonsilar hypertrophy increases the risk of 	
    10	
    cardiopulmonary complications and may affect a child’s quality of life.19 LofstrandTidestrom et al found that surgical removal of the adenoid and tonsils in snoring children did not change the development of dentofacial features. They recommended collaboration between professionals from all relevant disciplines including orthodontists, otolaryngologists, and speech and language specialists.31  1.6.3 Orthodontic Treatment 	
   Sleep related disorders could induce unfavorable effects on craniofacial and dental development in young children. Early diagnosis and treatment of SDB has a significant impact on the normalization of dentofacial morphology as a child grows.42 O’Brein et al emphasized the need for early diagnosis and treatment of SDB in young children to achieve a better prognosis.16  Orthodontic treatment may be necessary for those children with SDB who have a constricted maxilla, an anterior open bite, and a long lower facial height especially when they do not experience significant improvement in their craniofacial features and SDB symptoms even after removal of the adenoid and tonsils at an early age.31 Normal weight children who do not respond well to the surgical removal of the adenoid and tonsilar tissues often show specific craniofacial features that result in the overall reduction of the upper airway space.4 In cases where craniofacial features and malocclusions are contributing factors to the persistence of symptoms even after removal of the adenoid and tonsilar tissues, a systematic approach is recommended such as an adenotonsilectomy followed by orthodontic treatment.4 	
    11	
    Orthodontic therapy at an early age should be encouraged in OSA children because this treatment may permanently modify these children’s nasal breathing and respiration and consequently prevent obstruction of the upper airway.59 In a recent study by Villa et al it is recommended that orthodontic appliances such as a rapid maxillary expansion (RME), a lower jaw positioner, or a modified monobloc are effective for treating OSA in children with malocclusions.60  1.6.3.1 Palatal Expansion 	
   Orthodontic treatment such as maxillary expansion (RME) in conjunction with adenotonsilectomy may improve symptoms in children with SDB.61 In orthodontic treatment with RME there may be an increase in nasal cavity width and a subsequent decrease in nasal airway resistance. This can improve the patient’s natural function and finally reduce the chance of developing breathing-related issues.61, 62Pirelli et al studied a group of 60 OSA children between the ages of 6-13 years with constricted maxillae. They all received RME and CT scans were used to analyze the children’s craniofacial features before and after expansion. There was great improvement in the size of the upper airway/nasomaxillary complex and consequently an improvement in the symptoms of OSA.63 When Villa et al looked at OSA improvement in children 12 months after RME treatment, they found that there was a significant reduction in SDB symptoms and the effect of treatment remained 24 months after the end of the orthodontic treatment.64  	
    12	
    1.6.3.2 Functional and Mandibular Advancement Appliances 	
   The use of mandibular advancement appliances for sleep disorders is not new. The first report of a device used for sleep disordered breathing problems was by Pierre Robin in 1939.65 Mandibular advancement devices have been an effective way of treating OSA symptoms in adults,66 and are considered a moderately effective treatment for snoring and mild to moderate OSA in adult patients.67  Functional orthopedic appliances and oral appliances may be helpful in the treatment of those children with craniofacial anomalies who are at a higher risk of SDB. With the increasing prevalence of OSA in children, oral appliance therapy is also becoming a promising option for children.68  In their review of oral appliances (OAs) for snoring and obstructive sleep apnea in adults, Ferguson et al believe that the mechanisms of action of oral OAs during sleep are improvement of upper airway muscle tone that in turn improves the upper airway patency and consequently brings about a reduction in upper airway collapsibility.69 To what extent this mechanism is similar in children warrants further investigation.  Both the Herbst and the Twin Block are functional appliances that could be used in patients with retruded mandibles based on patient-specific dentoalveolar conditions and the need for treatment.70 Lawton et al compared the Herbst with the Twin block in a randomized crossover study. They found no significant difference between the efficacy of the two appliances while both appliances in OSA patients.70  	
    13	
    The majority of the literature on OAs is based on studies of adult subjects; most studies done of children are non-randomized and non-controlled. Furthermore, many of the studies done of children are undertaken with only a small sample size and short follow up times, such as the investigations by Villa et al 2002, Rose et al, 2006 and Schutz et al, 2011.  In a randomized controlled study of a small group of children by Villa et al, jawpositioning appliances were used and a significant improvement in OSA symptoms was observed compared with the control group. They concluded that treatment of OSAS with an OA in children with malocclusions is an effective and well-tolerated method. Although their sample was small and the time for follow up was short, the result was nevertheless promising.59  In a case report study, Rose et al used RME followed by Frannkel-II and functional Regulator Type-II appliances in OSA patients with more severe craniofacial anomalies; significant improvement in SDB symptoms was observed in both groups.71 Schutz et al found a significant improvement in SDB symptoms after one year of treatment in OSA patients using a Herbst appliance which included a palatal expansion screw to advance the lower jaw and expand the upper jaw at the same time.72 Further randomized controlled trials on OAs and functional orthodontic/orthopedic appliances are needed.  	
    14	
    1.7 Age and Gender Differences in SDB 	
   Kawashima et al looked at the differences between males and females with SDB. They found that preschool males with SDB have a longer anterior facial height and anteriorly positioned hyoid bone when compared with females of the same age. On the other hand, females had a narrower pharyngeal airway.73 Redline et al studied risk factors for sleepdisordered breathing, including obesity, in young children and found that SDB symptoms were associated with obesity but not age or gender.27 In a recent study by Kim et al, SDB children in different age groups revealed different clinical symptoms. Problems with breathing, sleep terrors, bruxism and delayed growth were more common among preadolescents while impaired daytime function, daytime sleepiness, insomnia, morning headaches, difficulties going to sleep and unrefreshing sleep were more common among adolescents. A smaller mandible and a high and narrow palatal vault were evident among the children with SDB without any significant differences between genders or age groups.4 Kawashima et al looked at gender-dependent differences in craniofacial features. They compared craniofacial morphology and hyoid bone position of preschool children with SDB. The results showed that males had a longer anterior facial height, and a hyoid bone positioned more anteriorly compared with SDB females. On the other hand, SDB females had a narrower pharyngeal airway space. There was no significant difference between the two genders with grade 3+ tonsils in terms of SDB symptoms (when controlled for tonsil size). SDB males compared with normal males had a larger interincisal angle, a longer lower facial height, retroclined lower incisors, a short nasal floor, a narrower pharyngeal space, and a longer soft palate, while SDB females compared with normal females had a narrower pharyngeal space, and longer soft palate.  	
    15	
    It appears that in preschool children, males with SDB have skeletal risk factors and females with SDB have airway risk factors.73  1.8 Objectives 	
   Children with SDB have characteristic craniofacial morphological features that can affect their growth from an early age. Prevention of SDB by altering the morphology and function of the craniofacial complex may be one of the options for young children. However, to what extent the craniofacial morphology of children impacts the upper airway and increases the incidence of sleep apnea is still poorly understood. The goal of this project is to understand how the craniofacial morphology and severity of malocclusion may contribute to SDB symptoms in children according to their age and gender. Such knowledge will facilitate early treatment and reduce the risk of continuing development of the SDB profile.  1.9 Hypothesis 	
   Adenotonsilar hypertrophy, obesity and craniofacial morphology and the degree of their contribution to SDB varies among different age groups and genders. It has been well established that certain craniofacial features are a risk factor for SDB in adults. However, to what extent these craniofacial features could be related to SDB in children remains unclear. We hypothesize that in young children, craniofacial complex dimensions and severity of malocclusion are associated with SDB symptoms. The aim of this study is to  	
    16	
    determine if craniofacial morphology and severity of malocclusion are related to SDB symptoms in children aged 5-16 years when controlled for age, gender, and BMI.  	
    17	
    Chapter 2: Materials and Methods 2.1 Subjects 	
   In this retrospective study, we reviewed 450 patient records from the undergraduate and graduate orthodontic clinics at the University of British Columbia. The study was comprised of subjects from 5-16 years old, of both genders and of different ethnicities including Caucasian, Asian, Spanish, Indian, and some other smaller ethnicities. Exclusion criteria were individuals less than 5 and more than 16 years old, those with significant craniofacial abnormalities, incomplete records, or if their images had been taken on a different cephalostat.  Patients were divided into two groups: those from the undergraduate clinic who were put in the group PreAd (preadolescents, 5-12 years) and those from the graduate clinic who were put in the group Ad (adolescents, 13-16 years old). Patients from the undergraduate clinic generally had less severe malocclusions and were in need of more basic orthodontic treatment, while the patients from the graduate clinic had more severe malocclusions and were in of more extensive orthodontic treatments. We further divided each group into two subgroups for comparison between genders of the same age range: PreAd males, PreAd females, Ad males, and Ad females.  	
    18	
    2.2 Clinical Findings  2.2.1 Mallampati Scores and Tonsil Size 	
   Validated diagnostic diagrams (Mallampati and Brodsky) were used to categorize the visibility of the entrance of the upper airway (Mallampati) and the size of the palatal tonsils in transverse (Brodsky). Mallampati airway classification uses four categories (grades I-IV). Class I: the soft palate and entire uvula are visible, Class II: the soft palate and a portion of the uvula are visible, Class III: the soft palate is visible and the base of the uvula may be visible, Class IV: neither the soft palate nor the uvula are visible (Figure 2). During assessment, each patient was instructed to open his or her mouth wide and protrude his or her tongue forward as far as possible while trying not to emit any sound. The Brodsky classification shows the transverse occupancy of both the right and left pharyngeal tonsils. This classification has five grades (grades 0-4). 0: if the tonsils do not extending beyond the tonsilar pillar, 1: if the tonsils occupy less than 25% of the airway, 2: if the tonsils occupy 25%-50% of the airway, 3: if the tonsils occupy 50%-75% of the airway, 4: if the tonsils occupy more than 75% of the airway (Figure 3).  	
    19	
    Figure 2 Mallapati Airway Classification (I-V Scores). During assessment, the patient is instructed to open his or her mouth as wide as possible, while protruding the tongue as far as possible. Patients are instructed to not emit sounds during the assessment. Class I: soft palate and entire uvula is visible, Class II: soft palate and portion of uvula visible, Class III: soft palate visible (may include base of uvula), Class IV: Soft palpate not visible74  	
    20	
    !  !  ! Figure 3 Brodsky Classification (0-4 Grades) 75  !  0: Tonsils are in fossa 1: If the tonsils occupied less than 25% of the airway 2: If the tonsils occupied 25% to 50% of the airway 3: If the tonsils occupied 50% to 75% of the airway 4: If the tonsils occupied greater than 75% of the airway  	
    21	
    2.2.2 Angle Classification 	
   To determine the Angle classification, orthodontic models and intraoral photos of each individual patient were analyzed by the author. We used both photos and digital orthodontic models for greater accuracy and reliability (Figure 4). Angle Class I: the mesiobuccal cusp of the upper first molar occludes on the buccal grove of the lower first molar, Class II division 1: the mesiobuccal cusp of the upper first molar occludes anterior to the buccal grove of the lower first molar with the proclined upper incisors, Class II division 2: the mesiobuccal cusp of the upper first molar occludes mesial to the buccal grove with retroclined upper incisors, Class III: the mesiobuccal cusp of the upper first molar occludes distal to the buccal grove of the lower first molar.  	
    22	
    ! ! ! ! ! ! ! ! ! ! ! ! !  !!  ! Figure 4 Orthodontic models and intraoral photos were used to determine Angle classification  	
    23	
    2.2.3	
  	
  	
  Body	
  Mass	
  Index	
  (BMI)	
   	
   Each individual’s height and weight were measured in inches and pounds respectively. These measurements were then converted to meters and kilograms and the body mass index (BMI) was calculated. Using growth charts showing BMI for age from the Center of Disease Control, we divided our sample into four groups: 0: underweight, 1: normal, 2: overweight, 3: obese. 76  2.3 Questionnaires 	
   Franco et al developed the OSA-18 questionnaire based on responses from the caregivers of 61 OSA children. This study was comprised of subjects from 6 months to12 years old, of both genders and of different ethnicities including Caucasian (8%), African American (85), and Spanish (7%). The test-retest reliability was done according to Litwin et al, 1995 and the R-value was more than 0.74. The Respiratory Disturbance Index (RDI) was classified as normal to mild OSA if RDI ≤ 5, moderate OSA for RDI = 6-9 and severe OSA for RDI ≥ 10. The impact of OSA on quality of life was large for 36%, moderate for 31%, and small for 33%. The investigators concluded that the OSA-18 is a useful way to determine the quality of life in OSA children.77  Chervin et al developed the PSQ-22 questionnaire based on responses from the parents of 54 SDB children after polysomography and from the parents of 108 children before polysomography as a control group. They applied a simple questionnaire with a “yes/no/don’t know” response format. The SDB subjects and the control group included 	
    24	
    children of both genders aged 2-18 with means of 9.3±4.1 and 7.0±3.8 years respectively. Sensitivity and specificity of the test and correct classification were found to be similar for both groups. The scales showed good internal consistency and in a separate sample (n=21), a good test-retest stability. They recommended the PSQ-22 as a useful way to identify SDB in clinical research where polysomnography is not feasible.6  We used the two validated standardized questionnaires previously described (part one OSA-18 and part two, PSQ-22) to evaluate SDB symptoms. Parents or guardians who were able to monitor their children both during the day and at night while the children were sleeping completed the questionnaires. The OSA questionnaire (OSA-18) comprised 18 questions related to SDB symptoms in children. Each question was scored based on a graded scale of 1 to 7. The higher the grade, the higher the possibility of SDB and so reduced quality of life. Part one was divided into five domains including daytime function, sleep disturbances, physical symptoms, emotional symptoms and parents’/caregivers’ concerns (Appendix A.1). Based on previous reports, those patients who scored over 60 were considered to have a high likelihood of SDB. Part two, the pediatric sleep questionnaire (PSQ-22), consisted of 22 questions to evaluate sleep related breathing disorder symptoms (Chervin et al 2000) (Appendix A.2). Each question could be answered with “yes”, “no”, or “don’t know”. Only “yes” answers were considered as indicative of the presence of SDB symptoms.  	
    25	
    2.4 Cephalometric Analysis 	
   All cephalometric images were obtained from the same cephalostat with subjects holding their heads in a natural position with the Frankfort horizontal plane parallel to the floor. Dolphin imaging software, version 10.2 premium, was used to digitize and analyze the data with the UBC standardized lateral cephalometric analysis for OSA. The reference points and lines were used in the cephalometric analysis are shown in Figure 5 and include 14 linear and 9 angular measurements. The linear measurements were palatal height (PALHT), upper facial height (UFH), lower facial height (LFH), total facial height (TFH), length of soft palate (PNS-P), mandibular body length (Go-Gn), hyoid bone position (MP-H), vertical airway length (PNS-Eb [V]), position of the maxillary central to Nasion-A point line (U1-NA), position of the lower incisor relative to Nasion-B point line (L1-NB), hard tissue chin button prominence (Pog-NB), facial convexity (A-NPog), overjet and overbite. To measure the palatal height, we used a McKee analysis to measured, in millimeters, from the mesiobucal cup tip of the upper first molar to the palatal plane. The angular measurements included the antroposterior position of the maxilla and the mandible relative to the anterior cranial base and to each other (SNA, SNB and ANB respectively), the chin position relative to the anterior cranial base (SNPog), the upper incisor to the anterior cranial base (U1-SN), the lower incisor to the mandibular plane (L1-MP), the interincisal angle (U1-L1), and the mandibular plane angle (MP-SN).  	
    26	
    ! "#  $!"#  %#  $# ).#  -#  /0#  ,#  %!"#  10# 2# $(# )*# '+# '$#  &$#  Figure 5 Cephalometric landmarks, and linear and angular cephalometric variables. Point S sella, N nasion, A point A, B point B, ANS anterior nasal spine, PNS posterior nasal spine, Pg pogonion, Gn gnathion, Me menton, Go gonion, H hyoid bone, Eb base of epiglottis, P tip of soft palate, SN anterior cranial base, MP (Me-Go) mandibular plane, OP occlusal plane (midpoint between maxillary and mandibular incisor edge to midpoint between maxillary and mandibular molar mesial cusps). Linear variables; PALHT (palatal height) mesiobucal cups tip of upper first molar to palatal plane, OB overbite (vertical overlap of upper and lower incisors), OJ (horizontal overlap of upper and lower incisors), UFH (N-ANS) upper anterior face height, LFH (ANS-Me) lower anterior face height, TFH (N-Me) total anterior face height, U1-NA distance from incisal, edge of upper incisor to NA plane, L1-NB distance from incisal edge of lower incisor to NB plane, Pg-NB distance between Pogonion and vertical continues of NB plane, CONV (facial convexity) distance from NPg to A point, Go-Gn mandibular body length, MP-H position of hyoid bone to mandibular plane, PNS-P length of soft palate, VAL (PNS-Eb) vertical airway length. Angular measurements; SNA antroposterior position of maxilla relative to anterior cranial base, SNB antroposterior position of mandible relative to anterior cranial base, ANB anteroposterior relationship of maxilla to mandible relative to anterior cranial base, U1-SN inclination of upper incisor relative to anterior cranial base, L1-MP inclination of lower incisor relative to mandibular plane, U1-L1 interincisal angle, SNPg chin position relative to anterior cranial base, SN-MP mandibular plane angle relative to cranial base, H ANGLE soft tissue facial convexity (based on Tsuda et al, 2010).3  	
    27	
    2.5 Method Error 	
   The author digitized ten randomly selected lateral cephalometric radiographs on three separate occasions to calculate the error of method according to Bland J. & Altman D. Methodology of error measurement.78 The standard deviation of repeated measurements on the same subject enabled us to measure the size of the measurement errors. A method error within 0.94mm was found for the linear measurement variables and within 0.71 degrees was found for the angular measurements.78  2.6 Statistical Analysis 	
   Statistical software (SPSS software, Chicago, II USA) was used to analyze the data. Data were presented as mean and standard deviations. A P value of less than 0.05 was considered significant. We used nonparametric tests to analyse the questionnaires, which were not normally distributed. Spearman’s rho test was used to identify correlations between the cephalometric variables and the questionnaires (questions and domains). The Mann-Whitney Test was used to compare the responses to the questionnaires between the two different age groups and also between genders. A 2-tailed t-test was then used to find the significant differences between all the groups in terms of age and gender. We used the Kruskal-Willias Test to determine the correlation between the Angle classification and the SDB symptoms among all the groups according to genders and age. In addition to these nonparametric tests, we also used parametric tests for the data, which related to the cephalometric variables, age, and BMI and were considered normally distributed. The  	
    28	
    Leven’s Test was used to determine the equality of variances across the samples and to predetermine for the t-test. A paired t-test was also used to identify the mean value of the cephalometric variables between the genders of different age groups. A one-way ANOVA test was used to find the significance of the mean value between and within the four groups. After finding the significant differences between the groups by ANOVA, we used the Tucky HSD to find the mean differences of P value of less than 0.05, between each group with other groups. A Chi-Square test was used to find the significance of the questionnaires in terms of the Mallampati and Tonsil scores.  	
    29	
    Chapter 3: Results 3.1 Subjects 	
   A total of 405 patient records were reviewed. Of these, 79 patient records were excluded because the children were older than 16 years, 67 records were excluded because the child’s height and weight had not been recorded at the time SDB questionnaires were completed, and three cases were excluded because images had been taken on a different cephalostat. We analyzed 301 cases of both genders and different ethnicities including Caucasian, Asian, Spanish, Indian and some other smaller ethnicities. Our sample of 301 was divided into two groups according to age. The group PreAd (preadolescents=5-12 years) included 237 children, 97 male and 140 female with a mean age of 9.9±1.6, and the group Ad (adolescents=13-16) included 64 children, 24 male and 40 female with a mean age of 13.8±0.9. We also divided each group into two subgroups for comparison between genders of the same age range. A mean score for the questionnaire OSA-18 was 29.6±12.5. A summary of these findings is provided in Table 1. Table 1 Demographic data and questionnaire scores (mean) N Age Male/Female Questionnaire score  	
    Total 301 5-16 121/180 29.6±12.5  Group PreAd/5-12 years 237 9.9±1.6 97/140 29.1±11.7  Group Ad/13-16 years 64 13.8±0.9 24/40 31.6±15.2  30	
    3.2 Clinical Findings  3.2.1 Mallampati Scores and Tonsils Size 	
   We assessed the Mallampati scores of all subjects by clinical examination and determined the percentage of each group (PreAd and Ad) with a score of I to IV (Figure 6).  45	
   40	
   35	
   30	
   25	
    Preadolescents	
    20	
    Adolescents	
    15	
   10	
   5	
   0	
   Mallam	
  I	
    Mallam	
  II	
    Mallam	
  III	
    Mallam	
  IV	
    Figure 6 Percentage of children with different Mallampati scores and the differences between PreAd and Ad groups  There was no significant correlation between the Mallampati scores and SDB symptoms for all 301 children, but when comparing the two different age groups (PreAd and Ad) we found that group Ad had higher Mallampati scores (Median=3, P=008) than PreAd (Median=2, P=0.295) (Table 2 and Figure 6). There was no significant difference between PreAd and Ad males. However Ad females had higher Mallampati scores (grade  	
    31	
    III and IV) when compared with PreAd females (Median=3, P=0.009) (Table 2. and Figure 7).  Table 2 Significant differences between age and gender in Mallampati scores Mallampati  Median  2-tailed  PreAd vs Ad  2/3*  0.009**  PreAd Females vs Ad Females  2/3*  0.008*  PreAd Males vs Ad Males  2/2  0.295  *  Median for Mallampati scores P<0.05  **  40	
   35	
   30	
   25	
   Female	
  5-­‐12	
    20	
    Female	
  13-­‐16	
    15	
   10	
   5	
   0	
   Mallam	
  I	
    Mallam	
  II	
    Mallam	
  III	
    Mallam	
  IV	
    Figure 7 Percentage of female patients with different Mallampati scores and the differences between PreAd females and Ad females  	
    32	
    We did not find any significant correlation between tonsil size, SDB symptoms, and cephalometric variables in our sample when we looked at individual groups and when we pooled the groups together as one sample. 3.2.2 Body Mass Index 	
   According to the Body Mass Index (BMI) charts from the Center of Disease Control (CDC), 4.7% of our sample were considered underweight, 71.1% normal/healthy weight, 16.6% overweight and finally 7.6% obese. We also divided the sample into four groups based on age and gender to determine the distribution of BMI (PreAd-M= males 5-12, Ad-M= males 13-16, PreAd-F= females 5-12, and Ad-F= females 13-16). We found that the majority of overweight and obese children were preadolescents of both genders (Table 3).  Table 3 Body mass index distribution among the four groups based on age and gender Gender and  Age Groups  Total (n/%)  BMI groups  PreAd-M  Ad-M  PreAd-F  Ad-F  0: Underweight  6  0  7  1  14/4.7  1: Normal  62  18  104  30  214/71.1  2: Overweight  19  4  19  8  50/16.6  3: Obese  10  2  10  1  23/7.6  Total  97  24  140  40  301/100  There was no significant correlation between BMI and SDB symptoms in our sample when we looked at individual groups and when we pooled the groups together as one  	
    33	
    sample. The only sleep-related symptom listed in the PSQ-22 questionnaire that showed a moderate correlation with BMI was sleepiness during the daytime (P=0.032).  3.2.3 Angle Classification 	
   The Angle classification distribution among the sample was 28.9% Class I, 52.8% Class II division 1, 9.0% Class II division 2, and 8.3% Class III malocclusion (Table 4). There was no statistically significant difference between the Angle classifications with respect to SDB symptoms when controlled for tonsil size, age, gender, and Mallampati scores.  Table 4 Angle classification N/%  Cl. I 87/28.9%  Cl. II Div 1 162/52.8%  Cl. II Div 2 27/9%  Cl. III 25/8.3%  Total 301/100%  3.3 Questionnaires 	
   The data from the OSA-18 and PSQ-22 questionnaires show that some SDB symptoms were reported in more than 15% of individuals in our sample. We categorized the range of answers to questions on the OSA-18 from 1 - 7 into three main categories as follow: Category 1: None of the time (1) and Hardly any of the time (2), Category 2: A little of the time (3) and Some of the time (4), and Category 3: Good bit of the time (5), Most of the time (6), and All of the time (7).  	
    34	
    According to responses given to the OSA-18 questionnaire by all 301 children, the combined symptoms most commonly seen were loud snoring (15%), mouth breathing (16%) and difficulty waking (21.2%)(Table 5).  Table 5 OSA-18 Percentages of individual item responses Domains  Questions  None/hardly  Little/some  D1: Sleep disturbance  Q1 Loud snoring*  85.0  12.0  Good bit/most/all 3.0  Q2 Breath holding/pauses  97.0  2.7  0.3  Q3 Chocking or gasping Q4 Fragmented sleep Q5 Mouth breathing*  97.3 90.0 84.0  2.3 7.3 10.0  0.3 2.3 6.0  Q6 Frequent colds or URIs Q7 Rhinorrhea Q8 Dysphagia Q9 Mood swings or tantrums Q10 Aggression/hyperactivity Q11 Discipline problems Q12 Daytime drowsiness  89.7 86.7 97.3 86.7  9.0 12.0 2.3 11.0  1.3 1.3 0.3 2.3  92.7  6.0  1.3  92.4 92.7  6.6 6.6  1.0 0.7  Q13 Poor attention span Q14 Difficulty waking* Q15 Worried over children’s health Q16 Concerned not enough air Q17 Missed activities Q18 Frustration  88.7 78.7 93.0  9.3 14.6 5.3  2.0 6.6 1.7  97.0  2.0  1.0  96.0 88.7  3.3 8.6  0.7 2.7  D2: Physical symptom  D3: Emotional symptoms  D4: Daytime function  D4: Caregiver concern  * over 15% We analyzed patient responses to the PSQ-22 questionnaire and summarized the findings as provided below in Table 6. This table shows the percentage of children that responded with Yes, No, or Don’t Know to each single SDB symptom. According to the PSQ-22 questionnaire as completed by the entire sample of 301 children, the symptoms most  	
    35	
    commonly seen were mouth breathing during the day (18.9%), dry mouth on waking (28.2%), waking unrefreshed in the morning (20.6), hard to wake up in the morning (2,4.6), not listening when spoken to directly (19.6), and interrupts or intrudes on others (15.9).  	
    36	
    Table 6 PSQ-22 Percentages of individual item responses Questions  Yes  No  Don’t Know  PSQ 1: snores more often  10.3  82.7  7  PSQ 2: always snores  7  89.7  3.3  PSQ 3: snores loudly  10.6  88  1.3  PSQ 4: heavy or loud breathing  12.3  83.7  4  PSQ 5: have trouble breathing  4  92  4  PSQ 6: stop breathing during night  2.7  91.4  6  PSQ 7: mouth breathing during day*  18.9  75.1  6  PSQ 8: dry mouth on waking up  28.2  63.5  8.3  PSQ 9: waking unrefreshed in the morning  20.6  72.4  7  PSQ 10: sleepiness during the day  11.6  84.7  3.7  PSQ 11: sleepiness at school  5.3  93  1.7  PSQ 12: hard to wake up in morning  24.6  75.4  0  PSQ 13: not listening when spoken to directly  19.6  79.1  1.3  PSQ 14: difficulty organizing tasks  14.3  84.1  1.7  PSQ15: easily distracted  21.3  74.4  4.3  PSQ 16: fidgets with hands and feet  18.6  78.1  3.3  PSQ 17: “On the go”/hyperactive  14  80.4  5.6  PSQ 18: interrupts or intrudes on others  15.9  81.7  2.3  PSQ 19: occasionally wetting the bed  4.3  95.3  0.3  PSQ 20: wakes up with headache  7  90.4  2.7  PSQ 21: stops growing  4  94  2  PSQ 22: overweight  6  90.7  3.3  *  	
    Over 15%  37	
    Table 7 shows a summary of the most common SDB symptoms among the children in our sample according to responses given to the OSA-18 and PSQ-22 questionnaires.  Table 7 Most common SDB symptoms among the children in our sample according to responses given to the OSA-18 and PSQ-22 questionnaires OSA-18  PSQ-22  Daytime Sleepiness  Breathing Pauses  Difficulty Getting Up  Bed Wetting  Frequent Colds  Snores More Often  Daytime Function  Hyperactivity Headache in Morning  3.3.1 OSA-18 Questionnaire 	
   The next three tables (Tables 8,9, and10) document the severity of SDB symptoms for each age and gender group according to responses given to the OSA-18.  By comparing PreAd with Ad, we found that the percentage of Ad who had “Some” or “Good Bit” of daytime sleepiness and difficulty getting up was significantly higher than PreAd (Table 8).  	
    38	
    Table 8 Difference between PreAd and Ad in percentages  Hardly Some Good bit * Significant percentage  Daytime Sleepiness Preadolescents Adolescents 94.9 84.4 4.6 14.1* 0.4 1.6*  Difficulty Getting Up Preadolescents Adolescents 81.9 67.2 13.1 20.3* 5.1 6.6*  By comparing PreAd males with Ad males, we found that frequent colds were more common among PreAd males, while daytime sleepiness was more prevalent among Ad males (Table 9). Table 9 Differences between PreAd males and Ad males in percentages  Hardly Some Good bit * Significant percentage  Frequent Colds Male 5-12 Male 13-16 79.2 94.8 * 20.8 5.2 0.0 0.0  Daytime Sleepiness Male 5-12 Male 13-16 92.8 79.2 7.2 16.7* 0.0 4.2*  By comparing PreAd females with Ad females, we found that daytime sleepiness and difficulty getting up were more prevalent among Ad females then PreAd females (Table 10). Table 10 Differences between PreAd females and Ad females in percentages  Hardly Some Good bit * Significant percentage  	
    Daytime sleepiness Female Female 5-12 13-16 96.4 87.5 2.9 12.5* 0.7 0.0  Difficulty Getting up Female Female 5-12 13-16 83.6 62.5 11.4 25.0* 5.0 12.5*  39	
    Overall, based on the OSA-18 questionnaire, several significant differences between age groups and genders were found. There was a higher incidence of daytime sleepiness among adolescents compared to preadolescents of both genders. Adolescents, especially females, showed a greater degree of difficulty getting up in the morning. Frequent colds appeared to be more prevalent among younger males.  3.3.2 PSQ-22 Questionnaire The next two tables (Tables 11 and12) identify the severity of PSQ-22 SDB symptoms based on age and gender. When comparing age groups, we found that the prevalence of breathing pauses and bed wetting among preadolescents was 3.2% and 7.2% respectively, while the prevalence was zero in adolescents for both symptoms (Table 11).  Table 11 Percentage of subjects who chose answered "YES" to the SDB Symptoms and the differences between preadolescents and adolescents Preadolescents  Adolescents  SDB Symptoms  YES  NO  YES  NO  Breathing Pause  3.2  96.8  0.0  100  Bed wetting  7.2  92.8  0.0  100  When comparing different genders, several PSQ-22 SDB symptoms were significant. Snoring more often and morning headaches were more frequent among females than males (13.3% vs 5.8% and 10.6% vs 1.7% respectively), while sleepiness during the day  	
    40	
    and hyperactivity were more prevalent among males (9.1% vs 2.8% and 19% vs 10.6% respectively) (Table 12).  Table 12 The percentage of male, female and total sample who answered "YES" to the following SDB symptoms in the PS22 questionnaire and significant P-Value Male=121  Female=180 Total=301  P*  Snore more often  5.8  13.3  10.3  0.045  Sleepy during day  9.1  2.8  5.3  0.038  “On the go”/Hyperactivity  19  10.6  13.6  0.031  Headache in morning  1.7  10.6  7  0.005  *  P<0.05  Figure 8 shows the number of patients from each group based on age and gender who presented with all four SDB symptoms. There were significant differences between PreAd and Ad for both genders. Snoring and morning headaches were more evident in PreAd females compared with Ad females. Sleepiness during the day and hyperactivity were more common among PreAd males than Ad males. We also found that hyperactivity was more common among preadolescents of both genders when controlled for age (Figure 8).  	
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    20	
   18	
   16	
   14	
   12	
    Male	
  5-­‐12	
    10	
    Male	
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    8	
    Female	
  5-­‐12	
    6	
    Female	
  13-­‐16	
    4	
   2	
   0	
   Snore	
  more	
   Sleepy	
   On	
  the	
  go	
   Headache	
  in	
   often	
   during	
  day	
   morning	
    Figure 8 Classification of patients according to their age and gender who had SDB symptoms according to responses given to the PSQ-22  In summary, when comparing preadolescents with adolescents based on the OSA-18 and PSQ-22 questionnaires, we found that snoring frequency, hyperactivity, morning headache and bedwetting were more prevalent among preadolescents, while difficulty getting up, daytime sleepiness and impaired daytime function were more common among adolescents. (Table13). Table 13 A summary of differences between two age groups according to the OSA-18 and PSQ-22 questionnaire More Common Among Preadolescents  More Common Among Adolescents  Snoring often  Difficulty getting up in the morning  “On the go”/hyperactivity  Impaired daytime function  Morning headaches  Daytime sleepiness  Bed wetting  	
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    3.4 Cephalometric Analysis  Table 14 shows cephalometric variables with mean and standard deviations for normal (according to UBC Sleep Study analysis), the whole sample and the two main groups, PreAd and Ad. We have divided the cephalometric analysis into four categories including the maxilla, mandible, intermaxillary relationship and upper airway. Looking at the maxilla and mandible individually, all variables are within normal limit of mean and standard deviation of norm. But looking at the intermaxillary relationship, four variables (ANB, H-Angel, Convexity and Overjet) showed significant variation from the normal standard. They all showed an increased anteroposterior measurement between the maxilla and mandible. This could be normal in growing children to some extent (Table 14).  	
    43	
    Table 14 Cephalometric analyses with mean and standard deviation for the whole sample and both PreAd and Ad Mean and Standard Deviation Cephalometric Variables Maxilla  PreAd (n=180)  Ad (n=121)  Total (n=301) Normal  U1-SN SNA U1-NA (mm) PALHT (mm)  105.7±8.0 82.4±3.9 3.2±2.4 17.95±2.3  105.9±8.5 83.0±3.6 3.4±2.9 21.0±2.7  105.8±8.1 82.5±3.8 3.2±2.5 18.6±2.7  102.6±2.5 82.0±3.5 4.3±2.7 N/A  Mandible SN-Pg SNB L1-MP LI-NB (mm) Pg-NB GoGn (mm) Mp-H (m)  77.8±3.4 77.4±3.5 93.6±6.1 4.7±2.2 0.7±1.6 69.6±5.8 11.4±4.6  79.1±3.8 78.5±3.7 94.1±7.6 5.1±2.4 1.2±1.4 74.9±5.1 13.1±4.1  78.1±3.5 77.6±3.5 93.7±6.4 4.8±2.2 0.8±1.6 70.7±6.0 11.6±4.5  80.0±3.5 80.9±3.4 95.0±7.0 4.0±1.8 2.1±1.7 72.6±4.4 15.0±2.0  InterMaxillary relationship ANB U1-L1 MP-SN UFH (mm) LFH (mm) TFH (mm) H-Angle Convexity (mm) Overjet (mm) Overbite (mm)  5.0±2.3 126.5±9.9 34.1±5.2 46.3±3.6 60.7±4.9 105.6±6.8 17.2±4.8 4.2±2.4 4.8±2.6 3.0±2.1  4.5±2.0 126.3±11.2 33.6±5.7 49.6±2.9 65.2±7.4 113.5±8.9 15.6±4.8 3.8±2.2 4.5±2.2 2.7±2.1  4.9±2.3 126.4±10.1 34.0±5.3 47.0±3.5 61.7±5.8 107.3±8.0 16.8±4.8 4.1±2.3 4.8±2.6 2.9±2.1  1.6±1.5 130.0±6.0 33.0±6.0 50.0±2.5 65.0±4.5 115.0±5.5 10.0±4.0 1.0±2.0 2.5±2.5 2.5±2.0  Upper airway PNS-P (mm) PNS-V (mm)  29.6±3.1 53.0±5.8  31.6±3.3 59.2±6.2  30.1±3.2 54.3±6.4  N/A N/A  	
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    3.5 Correlation Between Cephalometric Variables and SDB Symptoms 	
   Three main domains from the OSA-18 questionnaire that appeared to have a significant correlation with cephalometric variables in SDB children were sleep disturbances, daytime function and caregiver concern. Cephalometric variables that showed significant correlation with SDB symptoms were a lower position of the hyoid bone in relation to the inferior border of the mandible (MP-P), retroclination of the lower incisor to the mandibular plane (L1-MP), retroposition of the mandible in relation to the cranial base (SN-Pog), and a steeper inclination of the mandibular plane to the cranial base (MP-SN). Children with a lower position of the hyoid bone and retroclined lower incisors had more sleep disturbances during the night. Those with a retruded mandible and a higher mandibular plane angle relative to the anterior cranial base had more impaired daytime function. Individuals with a lower position of the hyoid bone raised caregiver concerns more often (Table 15).  Table 15 Corrections between domains and cephalometric variables Cephalometric  Sleep Disturbance  Domains Daytime Function  Caregiver Concern  Variables  R  P  R  P  R  P  MP-H  0.188  0.001  0.096  0.097  0.177  0.002  L1-MP  -0.152  0.008  0.014  0.804  -0.056  0.306  SN-Pog  0.031  0.583  0.168  0.003  0.060  0.299  MP-SN  0.094  0.105  -0.162  0.005*  0.018  0.753  R- Pearson correlation r * P<0.01  	
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    By looking at the relationship between individual questions and cephalometric variables, we found a significant correlation between seven SDB symptoms and four cephalometric variables (Table 16). A lower position of the hyoid bone was correlated with all of the SDB symptoms in Table 17 except for difficulty organizing tasks. Retroclined lower incisors had a significant correlation with three main symptoms including loud snoring, breath-holding, and the feeling of choking, which could all affect sleep quality. A retruded mandibular position was related to excessive daytime sleepiness. A larger mandibular plane angle relative to the cranial base was correlated with loud snoring and difficulty organizing tasks (Tables 16 and 17).  Table 16 A summary of important craniofacial features that have significant correlation with SDB symptoms (R-value) SDB Loud Holding Choking Cephalometric snoring breath sleep Variables  Symptoms Restless Excessive Parent Difficulty sleep daytime worries/ organizing sleepiness frustration task  MP-H  0.151  0.221  0.178  0.155  L1-MP  - 0.192  - 0.211  - 0.197  SN-Pog MP-SN  0.155  0.167  0.165 0.175  0.182  R – Pearson correlation r P<0.01  	
    46	
    Table 17 A summary of SDB symptoms which are correlated with each individual cephalometric variable  By comparing cephalometric variables between PreAd males and PreAd females found no significant difference between the two groups. When evaluating the differences between male and female adolescents (ages 13-16), we found that males presented higher values in palatal height, upper facial height (UFH), lower facial height (LFH), total facial height (TFH), proclination of the lower incisors (L1-NB), and lower facial convexity (HAngle), while females presented higher values of the angle between the upper and lower incisors (U1-L1) and the distance between the posterior nasal spine and the base of the epiglottis (PNS-V) (Table 18). Despite the significant differences between the two groups, there was no significant deviation from the normal mean and standard deviation based on the UBC Sleep Study analysis.  	
    47	
    Table 18 Comparison between males and females of aged 13-16 Palatal Height mm UFH mm LFH mm TFH mm U1-L1° L1-NB° H-ANGLE° PNS-Vmm  Males 13-16 22.2 ± 2.7 51.2 ± 2.9 68.9 ± 7.3 118.7 ± 8.3 122.2 ± 9.1 6.3 ± 2.1 17.2 ± 3.9 61.91 ± 6.3  Females 13-16 20.2 ± 2.4 48.7 ± 2.4 62.9 ± 6.6 110.4 ± 7.7 128.8 ± 11.7 4.4 ± 2.2 14.7 ± 5.0 67.62 ± 5.7  Sig. (2-tailed) P=0.003 P=0.000 P=0.001 P=0.000 P=0.020 P=0.001 P=0.037 P=0.007  In summary, when comparing preadolescents and adolescents, we found that preadolescents presented a significantly higher incidence of hyperactivity, headaches in the morning, snoring and bedwetting. Adolescents showed significantly higher daytime sleepiness, difficulty getting up, and impaired daytime function. By comparing females with males we found that frequent snoring and morning headaches were more prevalent among females, while daytime sleepiness, and hyperactivity were more common among males. Craniofacial features that have a significant relationship with SDB symptoms are a lower position of the hyoid bone, a retruded mandible, a steeper mandibular plane angle and retroclined lower incisors. There was no statistically significant relationship between SDB symptoms and the Angle classification, tonsil size, Mallampati scores or BMI.  	
    48	
    Chapter 4: Discussion  The present study supports the hypothesis that craniofacial morphology is correlated to SDB symptoms in children. The majority of studies on the relationship between SDB symptoms and craniofacial morphology have been of children with SDB symptoms compared to children with no SDB symptoms.12, 23, 39, 43, 45 In the present study, subjects were recruited from both undergraduate and graduate orthodontic clinics at the University of British Columbia. These children were attending the clinics solely to receive orthodontic treatment. In terms of the severity of malocclusion, the children recruited from the undergraduate clinic were considered to have less severe malocclusions and in need of more basic orthodontic treatment; however the children recruited from the graduate clinic were considered to have more severe malocclusions and in need of more extensive orthodontic treatment, such as rapid maxillary expansion, extractions with full edgewise therapy and/or orthognathic surgery.  In a previous study in our laboratory, (Tsuda et al, 2010), we looked at the incidence of SDB symptoms and their correlation with craniofacial features in otherwise healthy preadolescent children. In the present study, in addition to the preadolescents from the undergraduate orthodontic clinic, we included adolescent orthodontic patients from the graduate orthodontic clinic. Supplemental to the incidence of SDB symptoms and their correlation with the craniofacial morphology in both groups, we divided our subjects into different groups based on their age and gender to determine any possible correlation between SDB symptoms and age, gender, BMI, and severity of malocclusion. The most  	
    49	
    common SDB symptoms were snoring, difficulty getting up, daytime sleepiness, morning headaches, hyperactivity and frequent colds. All these symptoms were significantly correlated with several craniofacial features. These craniofacial features included a retruded mandible (greater SN-Pog), a steeper mandibular plane (increased MP-SN angle), a lower position of the hyoid bone (longer MP-H), and retroclined lower incisors (smaller L1-MP) as shown in tables 17 and 18.  Snoring, difficulty waking, and daytime sleepiness were three important symptoms significantly correlated with SDB in this study, which is in accordance with previous reports.3, 4 Corbo et al found that habitual snoring was more common among males than females, and Li et al reported a higher prevalence of habitual snoring among males (14.6%) than females, (9.5%).79, 80 Corbo et al also found that obese males older than 15 were at significantly higher risk of being habitual snorers.79 However, our results showed a higher prevalence of snoring in females (13.3%) compared with males (5.8%). We also found a higher prevalence among younger children and we did not find any correlation between obesity and snoring. In accordance to the findings of Chang et al and Kim et al who found a higher prevalence of daytime sleepiness in older children.4, 81 In our study, difficulty waking was more common among adolescents regardless of their gender, but Laberge et al found that difficulty waking was more common in early adolescent females with possible causes being hormonal changes and higher pubertal status.82 Individual preferences in sleep-wake timing and age-related changes in sleep-wake timing can vary among subjects.83 Changes in reproductive hormones during puberty can affect circadian rhythms and circadian physiology during early adulthood.84 Therefore, in adolescents,  	
    50	
    difficulty waking, and daytime sleepiness could be due in part to circadian rhythms and hormonal changes in addition to the presence of SDB.  Another SDB symptom that related to the quality of sleep in children was the presence of morning headaches.4, 85 In our study, morning headaches were more prevalent among preadolescent females. In contrast, in a study reported by Kim et al, morning headaches and unrefreshing sleep appeared to be more prevalent among adolescents regardless of gender.4 Zwart et al found that the overall frequency of recurrent headaches did not vary significantly with the age of the children, but the frequency of recurrent headaches was significantly higher among females.85 There is hardly any published data about the pathophysiology of morning headaches and OSA in young children.  Poor quality of sleep in SDB children can have an adverse effect on their daytime behavior and school performance.2, 7, 8 Results from the present study as well as from several other studies have shown that hyperactivity was more common among younger SDB children.16, 22, 81, 86 Chervin et al suggested that there was a link between sleepiness and hyperactive behavior in both males and females during childhood and adolescence.22 Our data suggests a higher prevalence of hyperactivity among preadolescent males compared with preadolescent females. In a recent meta-analysis review by Willcutt, the prevalence of attention-deficit/hyperactivity disorder was reported to be higher among young males.87 Further research is needed to determine the etiology of this disorder and investigate its prevalence among children with SDB symptoms.  	
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    Frequent colds or upper airway infections have been reported as a symptom in subjects with SDB.2, 3 Bixler et al reported nasal abnormalities (e.g. chronic sinusitis/rhinitis) as an important risk factor for SDB in children between 5-12 years.11 During the completion of the SDB questionnaires pertaining to younger children, we also found that parents repeatedly reported their children as having frequent colds. The obstruction of the nasal airway forces children to breathe through their mouth during the day and at night during sleep. This might affect their growth pattern leading to a more vertical face pattern.12 A steeper mandibular plane angle, a larger anterior facial height and a tendency to a vertical growth pattern are characteristics of children who breathe through their mouth.39 It seems that obstruction of the nasopharyngeal complex and craniofacial anomalies in growing children are correlated and further study is needed to identify the cause and effect relationship between these two variables.  Gozal et al and Bixler et al reported obesity as an important risk factor for SDB in children.7, 11 However, this was not the case for the group of children in the present study when controlled for age and gender. In our sample, more than 75% of the population was either normal weight or underweight (71.1% and 4.7% respectively) and the percentage of overweight and obese children was significantly less (16.6% and 7.6% respectively). In their review, Cuccia et al, looked at common craniofacial changes in patients suffering from OSA with regards to degree of obesity. They found that in both obese and nonobese OSA children, skeletal changes were evident, but the obese subjects presented with greater intermaxillary divergence and an increased angle between the palatal plane (ANSPNS) and the mandibular plane (Go-Me).36  	
    52	
    Neither Mallampati scores nor tonsilar grades were revealed to be significantly related to SDB symptoms in our sample when we controlled for age, gender and BMI. However, Kim et al found a significant correlation between higher Mallampati scores and the severity of SDB in children.4 The majority of the studies reporting a significant correlation between adenotonsilar hypertrophy and SDB symptoms in children included younger subjects.26, 27, 31, 34, 80 In the present study we did not find any significant correlation between tonsilar size and SDB symptoms. This could be explained by the majority of our sample being older than 6-8 years and having tonsils significantly reduced in size because of growth and developmental changes. In the study by Kawashima et al, no difference was found between either a tonsil size of grade II (25%75% tonsil visible) or a tonsil size of grade III (>75% visible) as contributing to SDB symptoms in preschool children.41 Parkkenin et al reported no association between size of tonsils and increased AHI.45 We measured tonsil grades with a visual scale using a Brodesky chart, which is a 2D method that measures the tonsils in a transverse direction. This may not be as accurate as a 3D method that can measures not only the transverse but also the anteroposterior and vertical dimensions.  According to our data, Angle classification cannot be used to determine SDB patients as confirmed by previous studies.3, 29, 46 However, Parkkinen et al found a class II molar relationship in children with SDB.49 When we controlled for age, gender and BMI, there was no correlation between the Angle classification and cephalometric variables with regards to SDB symptoms. The Angle classification shows the dental relationship  	
    53	
    between the upper and lower first molars but it does not represent the skeletal facial type of children. A child can have a Class I skeletal facial type with a Class II or a Class III dental relationship often because of early loss of primary teeth. We feel that the Angle classification alone without consideration of the mandibular and maxillary skeletal relationship is not a good indicator of a patient’s facial and/or skeletal type.  A retruded or smaller mandible was one of the craniofacial features that had a significant correlation with SDB symptoms in the children in our study and also in several other studies.23, 29, 30, 40, 41, 45, 47, 48, 88 Lofstrand-Tidestrom et al found that a shorter lower dental arch was significantly correlated with SDB in four year-old children.46 Children with smaller mandibles and longer anterior facial heights showed more symptoms of SDB.89 Schiffman et al used magnetic resonance imaging (MRI) to determine the mandible dimensions in both OSA and normal children. The 3D analysis of the mandible size and shape showed no significant differences between the two groups. However, the position of the mandible relative to the cranial base and facial skeleton was not evaluated in this study.90 Kawashima et al reported an anterior displacement of the tongue base in patients having large tonsils and a retruded mandible.23 However, one must always remember that short mandibles in children may simply reflect normal growth and associations with SDB should be interpreted with caution.  In an orthodontic clinic, cephalometric radiographs are routinely taken when patients are awake and have a natural head posture. In this position, patients may position their tongue more anteriorly for better respiration. While a patient is asleep, the muscles that  	
    54	
    keep the tongue in a forward and upward position, such as the genioglossus and palatoglossus, may become more relaxed and the subsequent retropositioning of the tongue may contribute to the obstruction of the upper pharyngeal airway.  In addition to a retruded mandible, a steep mandibular plane angle was another important craniofacial feature shown to have a significant correlation with SDB symptoms in our study sample and in several other studies. 23, 29, 30, 40, 45, 47, 48, 88 We found that a steeper mandibular plane angle (greater MP-SN angle) had a significant correlation with some of the SDB symptoms observed in children such as impaired daytime function, loud snoring and difficulty organizing tasks.  A lower position of the hyoid bone also had a significant correlation with SDB symptoms in the present study as well as in many other studies.3, 40, 43, 45, 48, 73, 89 Kawashima et al studied the position of the hyoid bone in males and females with SDB. They found that the hyoid bone was located more anteriorly in relation to the third cervical vertebra in male subjects compared with females.73 Finkelstein et al found a larger distance between the hyoid bone and the mandibular plane of children with increasing severity of SDB.89 On the other hand, Bates et al found that the hyoid bone in OSA adult patients was rotated counterclockwise and the distance from the most anterior superior part to the mandibular plane was consequently decreased.91 Kawashima et al looked at patients with normal faces, high angle faces, and low angle faces, and they found no significant differences in the position of the hyoid bone in relation to the mandibular plane between the three groups.88 Characteristics of a high angle face are a longer anterior facial height,  	
    55	
    steeper mandibular plane, and tendency to an anterior open bite. Several studies have shown that the above features are common among OSA subjects,29, 30, 42, 46 but in the study by Kawashima et al, 2002 on normal subjects with three different facial types, the position of the hyoid bone did not differ in high angle faces compared with the other two groups. Our data showed that a lower position of the hyoid bone in children is significantly correlated with several SDB symptoms, including loud snoring, breathholding during sleep, choking or gasping during sleep, restless sleep, and excessive daytime sleepiness.  Van De Graaff et al studied the suprahyoid muscles of dogs and the musculature relationship with upper airway resistance and concluded that the hyoid bone and muscles could strongly affect upper airway flow resistance.92 The hyoid bone has no direct attachment to the craniofacial bones. It attached to the mandible, cranial base, tongue and pharyngeal cartilages by supra and infra hyoid muscles and tendons. Any change or displacement on the supra or infra hyoid structures can change the position of the hyoid bone. We assume that a retroposition of the mandible as seen in severe Class II skeletal patients, a downward and backward rotation of the mandible as seen in high angle cases, and a lower position of the tongue base may affect the position of the hyoid bone. Further studies with 3D imaging in SDB children may be able to determine the contribution of a lower position of hyoid bone to obstruction of the pharyngeal area.  We support the idea that a steep mandibular plane, and a lower position of the hyoid bone are correlated and are characteristics of SDB children. Further study is needed to  	
    56	
    understand the craniofacial development, airway dimensions and respiratory functions and their correlations in growing OSA children with more varying degrees of SDB.  In accordance with our study, retroclined lower incisors in SDB patients have been reported by a few other investigators to be an important cephalometric finding.41, 42 In the present study, we found that retroclination of the lower incisors was correlated to SDB symptoms to a higher degree in adolescent females compared with adolescent males.  A longer soft palate is another craniofacial feature that was found to be correlated with SDB in children.3, 23, 40 Parkkinen et al compared normal children with children who presented more severe SDB symptoms. They found that a longer and thicker soft plate was correlated with OSA in children.45 However, in our study there was not a significant correlation identified between the length of the soft palate and SDB symptoms.  Increased palatal height in patients with SDB is a craniofacial feature that has been reported by several studies.3, 4, 46 Tsuda et al studied the height of the palatal vault by measuring from orthodontic models and found a significant correlation between a higher palatal vault and SDB symptoms in children.3 Another study by Parkkinen et al, analyzed orthodontic models of three groups of children including OSA children and snoring children compared with normal subjects as a control group. They found that there was no statistically significant difference between all three groups in terms of the height of the palate.49 We used a McKee analysis to measure the palatal height from lateral cephalometrics by measuring the distance from the mesiobuccal cusp tip of the upper first  	
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    molar to the palatal plane (ANS-PNS line) in millimeters. We did not find a significant correlation between palatal height and SDB symptoms in the whole sample or when we controlled for age and gender. The technique we used to measure the palatal height as well as the lower severity of SDB in our sample could be why we did not find a positive relationship.  There are other potential limitations with our study. The sample consisted of a group of children who were enrolled in orthodontic treatment clinics and who had a lower degree of SDB disease severity. Measurement of tonsil size by a visual scale (Brodesky) may have less accuracy than a 3D method even though this technique has been widely used in previous studies. We did not quantify adenoid size because the majority of the children in our sample were older than 6-7 years. Our sample consisted of some ethnicities that may have different cephalometric variables. Even though validity of the OSA-18 and PSQ-22 questionnaire were assessed by Franco et al, 2000 and Chervin et al, 2000 respectively, there potentially could be some bias in the inclusion criteria.  Several studies have suggested early orthodontic intervention for children with craniofacial abnormalities and SDB symptoms.3, 23, 42, 59 The results of this study suggest that SDB in children is a multifactorial disorder and these factors may vary based on a child’s age and gender. We may need a multidisciplinary approach toward the diagnosis and treatment of these cases to achieve better outcomes. According to the review of the literature done by Marcus et al, the first line of treatment for OSAS in young children is still adenotonsilectomy even though there might be some residual symptoms after  	
    58	
    surgery.20 One important difference between SDB children and adults is that children are still growing. Any factor that may interfere with a child’s development may have an impact on their craniofacial features over the course of their lifetime. We recommend an orthodontic examination of SDB children to obtain a proper diagnosis of the craniofacial features and, if necessary, timely orthodontic treatment such as palatal expansion or mandibular advancement appliances. Further studies are needed to find out if combining adenotonsilectomy and orthodontic treatment in young children with craniofacial abnormalities could have a significant impact on reducing SDB symptoms and achieving more permanent results.  To improve our understanding of the causal relationship between craniofacial morphology and SDB, a population-based study is needed with a large sample size including different races, genders and age groups, with diagnosed SDB children and a control group.  	
    59	
    Chapter 5: Conclusion 	
   Snoring, difficulty getting up, daytime sleepiness, morning headaches, hyperactivity and frequent colds were the most common SDB symptoms observed in the SDB children in our sample. The craniofacial features that had a significant relationship with SDB symptoms were a lower position of the hyoid bone, a retruded mandible, steep mandibular plane angle, and retroclined lower incisors. There was no statistically significant relationship between SDB symptoms and the Angle classification, tonsil size, Mallampati scores or BMI. Craniofacial morphology, but not severity of malocclusion, could be an important contributing factor to the severity of SDB symptoms. SDB is a multifactorial disease and warrants a multidisciplinary approach for a better diagnosis and proper treatment. A child may present with some sleep related symptoms and specific craniofacial characteristics that could be suggestive for SDB. The important role of the dental practitioner is to recognize the need for further investigation and possible treatment in the future to improve the quality of life of a child with SDB.  	
    60	
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  Mouth	
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  Children	
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  to	
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  treatment	
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  in	
  relation	
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  as	
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  of	
  severity	
  of	
  sleep	
  apnea	
  in	
   children	
  with	
  snoring.	
  Sleep	
  &	
  breathing	
  =	
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  &	
  Atmung	
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  and	
  craniofacial	
   variables	
  in	
  subjects	
  with	
  obstructive	
  sleep	
  apnea	
  syndrome:	
  comparisons	
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  R,	
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  D.	
  Obesity	
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  obstructive	
  sleep	
  apnea	
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   Lessa	
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  children	
  with	
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  sleep	
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  Changes	
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   45.	
   46.	
   47.	
   48.	
    49.	
   50.	
   51.	
   52.	
   53.	
   54.	
   55.	
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  Breathing	
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   Craniofacial	
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  Pediatric	
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   Aurora	
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   Marcus	
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  Lutz	
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  Adherence	
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  and	
  effectiveness	
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  airway	
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  Pediatrics	
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   Koontz	
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  KJ,	
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  Marcus	
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   Sleep	
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   Waters	
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  Clinical	
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  Two	
  Different	
  Modes	
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   62.	
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   64.	
   65.	
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  apnea	
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  36	
  months	
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   Sleep	
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  nasal	
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  and	
  breathing	
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   Relationship	
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  Atmung	
  2012;16(2):271-­‐3.	
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  official	
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  of	
  the	
  American	
  Association	
  of	
  Orthodontists,	
  its	
  constituent	
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   Clark	
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  for	
  snoring	
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  sleep	
  apnea.	
  Sleep	
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  Atmung	
  2012.	
   Ferguson	
  KA,	
  Cartwright	
  R,	
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  appliances	
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  Sleep	
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  HM,	
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  JM,	
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  mandibular	
  advancement	
  splints	
  in	
  the	
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  Journal	
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  Fortschritte	
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   73.	
   74.	
   75.	
   76.	
   77.	
    78.	
   79.	
   80.	
   81.	
   82.	
   83.	
    84.	
   85.	
    86.	
   87.	
    	
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  a	
  sleep-­‐related	
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    67	
    Appendix Appendix A  	
    68	
    A.1 OSA-18 Questionnaire Please circle the number that best describes how often each symptom or problem has occurred during the past four weeks. Sleep Disturbances None of Hardly A little Some of A good Most of During the past 4 weeks how often the time any of the of the the time bit of the the time has your child had…. time time time  All of the time  1….loud snoring? 2. …breath-holding spells or pauses in breathing at night? 3…. choking or made gasping sounds while asleep? 4…. restless sleep or frequent waking from sleep? Physical symptoms During the past four weeks, how often has your child had…. 5… mouth breathing because of nasal obstruction?  1 1  2 2  3 3  4 4  5 5  6 6  7 7  1  2  3  4  5  6  7  1  2  3  4  5  6  7  1  2  3  4  5  6  7  6…frequent colds or upper respiratory infections?  1  2  3  4  5  6  7  7…. nasal discharge or runny nose  1  2  3  4  5  6  7  8…. difficulty in swallowing foods?  1  2  3  4  5  6  7  1  2  3  4  5  6  7  10… aggressive or hyperactive behavior? 11… discipline problems? Daytime functions During the past four weeks, how often has your child had…. 12… excessive daytime sleepiness?  1  2  3  4  5  6  7  1 1  2 2  3 3  4 4  5 5  6 6  7 7  1  2  3  4  5  6  7  13… a poor attention span or concentration? 14…. difficulties getting up in the morning? Caregiver concerns During the past four weeks, how often have the problems described above… 15…caused you to worry about your child’s general health? 16… created concern that your child is not getting enough air? 17… interfered with your ability to perform daily activities? 18… made you frustrated?  1  2  3  4  5  6  7  1  2  3  4  5  6  7  1  2  3  4  5  6  7  1  2  3  4  5  6  7  1  2  3  4  5  6  7  1  2  3  4  5  6  7  1  2  3  4  5  6  7  Emotional symptoms During the last four weeks, how often your child had….. 9…. mood swings or temper tantrums?  	
    69	
    A. 2 PSQ-22 Questionnaire For each of the questions below, please circle the answer that best describes your child’s condition. While sleeping, does your child…. 1. …snore more often than half the time?  Yes  No  Don’t Know  2. …always snore?  Yes  No  Don’t know  3. …snores loudly?  Yes  No  Don’t know  4. … have “heavy” or loud breathing?  Yes  No  Don’t know  5. …have trouble breathing, or struggle to breathe?  Yes  No  Don’t know  6. …have you ever seen your child stop breathing at night?  Yes  No  Don’t know  7. …tend to breathe through the mouth during the day?  Yes  No  Don’t know  8. …have a dry mouth on waking up in the morning?  Yes  No  Don’t know  9. …wake up feeling unrefreshed in the morning?  Yes  No  Don’t know  10. …have a problem with sleepiness during the day?  Yes  No  Don’t know  11. …has a teacher or other supervisor commented that your  Yes  No  Don’t know  Yes  No  Don’t know  13. …does not seem to listen when spoken to directly  Yes  No  Don’t know  14. …has difficulty organizing task and activities  Yes  No  Don’t know  15. …is easily distracted by extraneous stimuli  Yes  No  Don’t know  16. …fidgets with hands or feet or squirms in seat  Yes  No  Don’t know  17. …is ‘on the go’ or often acts as if ‘driven by a motor’  Yes  No  Don’t know  18. …interrupts or intrudes on others  Yes  No  Don’t know  19. …does your child occasionally wet the bed  Yes  No  Don’t know  20. …did your child wake up with morning headaches  Yes  No  Don’t know  21. …did your child stop growing at the normal rate at any  Yes  No  Don’t know  Yes  No  Don’t know  Does your child…  child appears sleepy during the day? 12. …is it hard to wake your child up in the morning? This child often…  time since birth? 22. …is your child overweight?  	
    70	
    

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