Controlled Diesel Exhaust Exposure Induces a Concentration-Dependent Increase in Airway Inflammation.

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 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-blinded crossover study with 17 healthy non-smokers exposed to filtered air (FA) and DE standardized to 20, 50 and 150 µg/m3 of particulate matter <2.5µm (PM2.5) for 4h. Before, during and up to 24h from the exposure start, we measured lung function, airway responsiveness and airway inflammation using spirometry, methacholine challenge and fractional exhaled nitric oxide (FeNO) respectively. Additionally, we measured nasal airway inflammation using differential cell counts and cytokines in nasal lavage and epithelial lining fluid at 24h. 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 % ΔFeNO at 4h (β=0.16±0.06). Compared to FA, % ΔFeNO trended towards 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). Additionally, DE exposure induced a trend towards increased nasal IL-6 at 24h (% difference = 0.88 (95% CI: 0.08, 1.70)). There were no effects of DE exposure on FeNO at 24h, lung function, airway responsiveness, or nasal cell counts.

CONCLUSIONS: DE induces a concentration-dependent increase in FeNO, 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 document PM2.5 concentration-response estimates at exposure levels routinely experienced in the community and occupational settings. Clinical trial registered with ClinicalTrials.gov (NCT03234790).