Acute air pollution exposure alters neutrophils in never-smokers and at-risk humans

Abstract

Outdoor air pollution exposure increases chronic obstructive pulmonary disease (COPD) hospitalisations, and may contribute to COPD development. The mechanisms of harm, and the extent to which at-risk populations are more susceptible are not fully understood. Neutrophils are recruited to the lung following diesel exhaust exposure, a model of traffic-related air pollution (TRAP), but their functional role in this response is unknown. The purpose of this controlled human-exposure crossover study was to assess the effects of acute diesel exhaust exposure on neutrophil function in never-smokers and at-risk populations, with support from additional in vitro studies.18 participants, including never-smokers (n=7), ex-smokers (n=4) and mild-moderate COPD patients (n=7), were exposed to diesel exhaust and filtered air for 2 h on separate occasions, and neutrophil function in blood (0 h and 24 h post-exposure) and bronchoalveolar lavage (24 h post-exposure) was assessed.Compared to filtered air, diesel exhaust exposure reduced the proportion of circulating band cells at 0 h, which was exaggerated in COPD patients. Diesel exhaust exposure increased the amount of neutrophil extracellular traps (NETs) in the lung across participants. COPD patients had increased peripheral neutrophil activation following diesel exhaust exposure. In vitro, suspended diesel exhaust particles increased the amount of NETs measured in isolated neutrophils. We propose NET formation as a possible mechanism through which TRAP exposure affects airway pathophysiology. In addition, COPD patients may be more prone to an activated inflammatory state following exposure.This is the first controlled human TRAP exposure study directly comparing at-risk phenotypes (COPD and ex-smokers) with lower-risk (never-smokers) participants, elucidating the human susceptibility spectrum.

Trial registration: ClinicalTrials.gov NCT02236039.

Conflict of interest statement

Conflict of interest: D.J. Wooding reports grants from WorkSafeBC and the Canadian Institutes of Health Research, during the conduct of the study. Conflict of interest: M.H. Ryu reports grants from Canadian Respiratory Research Network, WorkSafeBC and Natural Sciences and Engineering Research Council of Canada, during the conduct of the study. Conflict of interest: H. Li reports grants from Sun Yat-sen University International Program Fund and the Chinese Government (scholarship), during the conduct of the study. Conflict of interest: N.E. Alexis has nothing to disclose. Conflict of interest: O. Pena has nothing to disclose. Conflict of interest: C. Carlsten reports grants from Canadian Respiratory Research Network and the Canada Research Chairs Program, during the conduct of the study.

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