Controlled Diesel Exhaust Exposure Induces a Concentration-dependent Increase in Airway Inflammation: A Clinical...

Rationale: Air pollution exposure is harmful to human airways, and its impacts are best studied using concentration-response relationships. However, most concentration-response research on airway health has investigated chronic exposures, with less being known about acute effects, which can be robustly studied using controlled human exposures. Objectives: To investigate the concentration relationship between airway health measures and diesel exhaust (DE). Methods: We conducted a double-blind crossover study with 17 healthy nonsmokers exposed to filtered air and DE standardized to 20, 50, and 150 μg/m³ of particulate matter ⩽2.5 μm in aerodynamic diameter for 4 hours. Before, during, and up to 24 hours from the exposure start, we measured lung function, airway responsiveness, and airway inflammation using spirometry, methacholine challenge, and fractional exhaled nitric oxide (Fe_NO), respectively. In addition, we measured nasal airway inflammation using differential cell counts and cytokines in nasal lavage and epithelial lining fluid at 24 hours. We assessed DE concentration responses and associations between outcomes using linear mixed effects models and repeated measures correlations, respectively, thereafter adjusting for multiple comparisons. Results: DE exposure increased percentage ΔFe_NO at 4 hours (β = 0.16 ± 0.06). Compared with filtered air, percentage ΔFe_NO trended toward an increase at concentrations of 20 μg/m³ (β = 18.66 ± 8.76) and 50 μg/m³ (β = 19.33 ± 8.92) and increased significantly at 150 μg/m³ (β = 34.43 ± 8.92). In addition, DE exposure induced a trend toward increased nasal IL-6 at 24 hours (percentage difference, 0.88; 95% confidence interval, 0.08, 1.70). There were no effects of DE exposure on Fe_NO at 24 hours, lung function, airway responsiveness, or nasal cell counts. Conclusions: DE induces a concentration-dependent increase in Fe_NO, indicating that it may be a sensitive marker of an acute inflammatory response in the airways. We report responses at concentrations below those in previous controlled DE exposure studies, and we document particulate matter ⩽2.5 μm in aerodynamic diameter concentration-response estimates at exposure levels routinely experienced in the community and occupational settings. Clinical trial registered with www.clinicaltrials.gov (NCT03234790).