Controlled human exposure study of diesel exhaust on older volunteers with and without COPD

Rationale: While observations suggest a role for air pollution in exacerbation and hospitalization of patients with chronic obstructive pulmonary disease (COPD), it is important to directly investigate whether those with COPD, and/or susceptible individuals without COPD, experience decreased airflow following acute exposure to diesel exhaust (DE; a standard model of traffic-related air pollution). Methods: 19 research participants (7 mild-moderate COPD, 5 ex-smokers without COPD [>10 pack years, quit > 6 months], and 7 never-smokers) aged 40 – 80 consented to participate in this controlled exposure study. Each participant was exposed to diluted DE (PM2.5 @ 300 µg/m3) and filtered air (FA) for two hours, in randomly assigned order, with four weeks washout period between the two conditions. Spirometry was performed before and 24h after each exposure. Bronchoalveolar lavage was collected 24h post-exposure. Linear mixed effects modeling (R package: nlme) was used for statistical analysis. Results: At 24h, COPD participants had a 3.6% decrease in FEV1 from baseline when attributable to DE relative to FA (p=0.038). There was no significant % change in FEV1 in ex-smokers (p=0.17) or never smokers (p=0.28) at 24h; accordingly, COPD status significantly (p=0.021) modified the effect of DE on % change in FEV1 at 24h, in spite of no significant increase in cell numbers in BAL. Conclusion: Airflow in individuals with COPD appears to be impacted acutely by air pollution more than those without COPD. In next steps, we will investigate changes in mucins and inflammatory cytokines that may be responsible for changes in airflow dynamics.