Concentration-dependent effects of diesel exhaust exposure on the human proteome and airways : a double-blinded, crossover study
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Orach, Juma
issued: 2024-01-08T20:16:01Z
issued: 2023
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
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…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/87156
note: CONCENTRATION-DEPENDENT EFFECTS OF DIESEL EXHAUST EXPOSURE ON THE HUMAN PROTEOME AND AIRWAYS: A DOUBLE-BLINDED, CROSSOVER STUDY by Juma Orach B.Sc., University of British Columbia, 2018 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2023 © Juma Orach, 2023 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Concentration-dependent Effects of Diesel Exhaust Exposure on the Human Proteome and Airways: A Double-blinded, Crossover Study Submitted by __Juma Orach__ in partial fulfilment of the requirements for the degree of __Doctor of Philosophy__ in __Experimental Medicine__ Examining Committee: Dr. Christopher Carlsten, Professor, Department of Medicine, UBC Supervisor Dr. Scott Tebbutt, Professor, Department of Medicine, UBC Supervisory Committee Member Dr. Sarah Henderson, Associate Professor, School of Population and Public Health, UBC Supervisory Committee Member Dr. Stephanus F Van Eeden, Professor Emeritus, Department of Medicine, UBC University Examiner Dr. Karen Bartlett, Professor, School of Population and Public Health, UBC University Examiner Dr. James G. Martin, Professor, Department of Medicine, McGill University External Examiner iii 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 wher…
has type: Thesis/Dissertation
date issued: 2024-05
is shown at: 10.14288/1.0438577
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Carlsten, Christopher Russell
type: Text
identifier URI: http://hdl.handle.net/2429/87156