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Ryu, Min Hyung

University of British Columbia

Our world is populated with numerous urban and occupational hotspots where air pollution levels exceed acceptable levels. Due to our sustained reliance on fossil fuels, many millions of people around the world are breathing in polluted air daily. There is growing evidence that chronic obstructive pulmonary disease (COPD) can be caused and exacerbated by air pollution exposure, but the mechanisms by which this occurs, specifically in COPD, are poorly understood. To fill this knowledge gap, we conducted a controlled human exposure study of older adults to diesel exhaust (DE)—a model for traffic-related air pollution. We recruited thirty research participants (10 ex-smokers with mild-moderate COPD, 20 healthy (9 ex-smokers, 11 never-smokers)) who completed the double-blinded, crossover, controlled human exposure study. Each participant was exposed to filtered air and DE, each for a two-hour period, in a randomly assigned order. Bronchoscopy was performed post-exposure to collect airway samples. Airway lavage samples were probed for changes in cell composition, acute inflammatory proteins, matrix proteinases, and anti-proteases. This investigation revealed that participants with COPD were uniquely susceptible to an inflammatory response not seen in ex-smokers without COPD or never-smoking healthy controls. Next, we evaluated the impact of DE exposure on airway mucosal transcriptome using RNA-seq. We showed that exposure to DE increased expression of antioxidant genes in the airway epithelium in vivo, and this expression was modified in the COPD epithelium. Last, we investigated the impact of DE exposure on airway microbiome using 16S rRNA sequencing. Although we did not observe a significant impact on alpha diversity of respiratory microbiome by DE exposure, we discovered that the effect of DE exposure on lung function and cytokines were modified by the respiratory microbiome richness, a simple count of the species of bacteria found in airways. Taken together, my research provides unique and novel insights into how air pollution impacts those with COPD. While epidemiological studies clearly demonstrate a relationship between air pollution and COPD morbidity and mortality, this work adds novel experimental human evidence to support this concept, demonstrating that COPD patients are more susceptible to the harmful effects of air pollution.

Text

2022-06-30

Attribution-NonCommercial-ShareAlike 4.0 International

http://hdl.handle.net/2429/78755

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-sa/4.0/