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.
Abstract
Acute human exposure to traffic-related air pollution leads lower airway neutrophils to release neutrophil extracellular traps, linked to COPD severity and airflow limitation. Ex-smokers and COPD patients mount a greater neutrophil response to exposure. http://bit.ly/2DEsYzE
Footnotes
This article has supplementary material available from erj.ersjournals.com
This study is registered at www.clinicaltrials.gov with identifier NCT02236039. Individual participant data will not be made available.
We would like to acknowledge grant funding from the Canadian Respiratory Research Network for this project. D.J. Wooding was supported by a Canada Graduate Scholarship (CIHR-CGSM), and a WorkSafeBC Training Award (RS2017-TG05). M.H. Ryu was supported by a Graduate Student Scholarship from Canadian Respiratory Research Network, WorkSafeBC Research Training Award (RS2016-TG08) and an NSERC Alexander Graham Bell Scholarship (CGS-D). H. Li was supported by International Program Fund for doctoral students from Sun Yat-sen University and the Chinese Government Scholarship. Funding information for this article has been deposited with the Crossref Funder Registry.
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.
- Received July 30, 2019.
- Accepted November 26, 2019.
- Copyright ©ERS 2020