- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Theses and Dissertations /
- Concentration-dependent effects of diesel exhaust exposure...
Open Collections
UBC Theses and Dissertations
UBC Theses and Dissertations
Concentration-dependent effects of diesel exhaust exposure on the human proteome and airways : a double-blinded, crossover study Orach, Juma
Abstract
Air pollution, to which diesel exhaust (DE) is a salient contributor in urban and occupational environments, is a leading contributor to premature mortality and morbidity worldwide. Concentration-responses (C-Rs) are a useful way to assess the magnitude and impact of air pollution exposure using external exposure surrogates and internal response markers. However, concentration-dependent health effects, which are potential markers of the response to DE exposure, are relatively unexplored in controlled human exposures where environmental confounders are limited. To investigate the C-R for DE across a broad range of exposure levels, we conducted a double-blinded crossover controlled human exposure study. Healthy non-smokers aged 19 – 49 were exposed to filtered air (FA) and DE standardized to 20, 50, and 150 µg/m³ PM₂.₅ in randomized order for 4h at the Air Pollution Exposure Laboratory. Before and up to 24h post-exposure, we measured lung function and airway responsiveness to methacholine using spirometry, airway inflammation using fractional exhaled nitric oxide (FeNO) and nasal epithelial lining fluid, symptoms using visual analog score questionnaires, and circulating proteins in blood using proteomics and immunoassays. Linear mixed effects models, repeated measures correlations and sparse partial least squares discriminant analyses were applied for statistical analysis. We identified concentration-dependent alterations in the proteome, which were enriched in complement activation and regulation pathways. Complement factor I was confirmed as significantly decreased by DE, with a potential threshold between 50-150 µg/m³ PM₂.₅. Complement factor I was correlated with changes in airway responsiveness, lung function and nasal cytokines. Although DE had no significant effect on lung function and airway responsiveness, it induced a concentration-dependent increase in FeNO, with a potential threshold between 50-150 µg/m³ PM₂.₅. DE induced a significant increase in symptoms, driven by eye and constitutional symptoms, with a potential threshold below 150 µg/m³ PM₂.₅. Symptoms were correlated with airway inflammation. Taken together, these findings are consistent with concentration-dependent inflammation in the airways and blood that is associated with clinically relevant endpoints, with potential effects thresholds as low as 50 µg/m³ PM₂.₅. My research corroborates known mechanisms of air pollution effects, while advancing novel concentration-dependent endpoints that may be useful markers for biomonitoring.
Item Metadata
Title |
Concentration-dependent effects of diesel exhaust exposure on the human proteome and airways : a double-blinded, crossover study
|
Creator | |
Supervisor | |
Publisher |
University of British Columbia
|
Date Issued |
2023
|
Description |
Air pollution, to which diesel exhaust (DE) is a salient contributor in urban and occupational environments, is a leading contributor to premature mortality and morbidity worldwide. Concentration-responses (C-Rs) are a useful way to assess the magnitude and impact of air pollution exposure using external exposure surrogates and internal response markers. However, concentration-dependent health effects, which are potential markers of the response to DE exposure, are relatively unexplored in controlled human exposures where environmental confounders are limited. To investigate the C-R for DE across a broad range of exposure levels, we conducted a double-blinded crossover controlled human exposure study. Healthy non-smokers aged 19 – 49 were exposed to filtered air (FA) and DE standardized to 20, 50, and 150 µg/m³ PM₂.₅ in randomized order for 4h at the Air Pollution Exposure Laboratory. Before and up to 24h post-exposure, we measured lung function and airway responsiveness to methacholine using spirometry, airway inflammation using fractional exhaled nitric oxide (FeNO) and nasal epithelial lining fluid, symptoms using visual analog score questionnaires, and circulating proteins in blood using proteomics and immunoassays. Linear mixed effects models, repeated measures correlations and sparse partial least squares discriminant analyses were applied for statistical analysis. We identified concentration-dependent alterations in the proteome, which were enriched in complement activation and regulation pathways. Complement factor I was confirmed as significantly decreased by DE, with a potential threshold between 50-150 µg/m³ PM₂.₅. Complement factor I was correlated with changes in airway responsiveness, lung function and nasal cytokines. Although DE had no significant effect on lung function and airway responsiveness, it induced a concentration-dependent increase in FeNO, with a potential threshold between 50-150 µg/m³ PM₂.₅. DE induced a significant increase in symptoms, driven by eye and constitutional symptoms, with a potential threshold below 150 µg/m³ PM₂.₅. Symptoms were correlated with airway inflammation. Taken together, these findings are consistent with concentration-dependent inflammation in the airways and blood that is associated with clinically relevant endpoints, with potential effects thresholds as low as 50 µg/m³ PM₂.₅. My research corroborates known mechanisms of air pollution effects, while advancing novel concentration-dependent endpoints that may be useful markers for biomonitoring.
|
Genre | |
Type | |
Language |
eng
|
Date Available |
2024-01-08
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
|
DOI |
10.14288/1.0438577
|
URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
|
Graduation Date |
2024-05
|
Campus | |
Scholarly Level |
Graduate
|
Rights URI | |
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International