COPD Exacerbations, Air Pollutant Fluctuations, and Individual-Level Factors in the Pandemic Era

Sahar Mikaeeli,1– 3 Dany Doiron,1 Jean Bourbeau,1,4,5 Pei Zhi Li,1 Shawn D Aaron,6 Kenneth R Chapman,7 Paul Hernandez,8 François Maltais,9 Darcy D Marciniuk,10 Denis E O’Donnell,11 Don D Sin,12 Brandie L Walker,13 Wan C Tan,12 Simon Rousseau,3 Bryan A Ross1,4,5 On behalf of the CanCOLD Collaborative Research Group and the Canadian Respiratory Research Network1Respiratory Epidemiology and Clinical Research Unit, Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre (RI-MUHC), Montreal, Quebec, Canada; 2Division of Experimental Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada; 3Meakins-Christie Laboratories, Research Institute at McGill University Health Centre, Montreal, Canada; 4Division of Respiratory Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada; 5Montreal Chest Institute, McGill University Health Centre, Montreal, QC, Canada; 6The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada; 7Toronto General Hospital Research Institute, University of Toronto, Toronto, Ontario, Canada; 8Department of Medicine, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; 9Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada; 10Respiratory Research Centre and Division of Respirology, Critical Care and Sleep Medicine; University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 11Department of Medicine, Queen’s University, Kingston, Ontario, Canada; 12Centre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada; 13Department of Medicine, University of Calgary, Calgary, Alberta, CanadaCorrespondence: Bryan A Ross, Respiratory Epidemiology and Clinical Research Unit (RECRU), Research Institute of the McGill University Health Centre (RI-MUHC), 5252 De Maisonneuve, Room 3D.57, Montreal, QC, H4A 3S5, Canada, Tel +1-514-843-1465, Email bryan.ross@mcgill.caPurpose: Pandemic-era associations between air pollutant exposures and exacerbations of chronic obstructive pulmonary disease (COPD) are under-explored. Given the considerable observed pandemic-era pollutant fluctuations, these associations were investigated along with possible individual-level risk factors.Patients and Methods: Participants with spirometry-confirmed COPD from Canadian Cohort Obstructive Lung Disease (CanCOLD) were included, with data collected before (“pre-pandemic”) and during (“pandemic”) the COVID-19 pandemic. Nitrogen dioxide (NO2), fine particulate matter (PM2.5), ground-level ozone (O3), total oxidant (Ox) and weather data were obtained from national databases. Associations between each air pollutant and “symptom-based” exacerbations (increased dyspnea or sputum volume/purulence ≥ 48hrs) and “event-based” exacerbations (“symptom-based” plus requiring antibiotics, corticosteroids, or unscheduled healthcare use) were estimated in separate models. Generalized estimating equations (GEE) models were reported as rate ratios (RRs) per interquartile range (IQR) increment in pollutant concentration with 95% confidence intervals (95% CIs).Results: NO2, PM2.5, and Ox (NO2+O3) concentrations (but not O3) fell significantly during the pandemic. In the 673 participants with COPD included, both symptom-based and event-based exacerbation rates were likewise significantly higher during the pre-pandemic period. During the pre-pandemic period, Ox was positively associated with symptom-based exacerbations (RR: 1.21 [1.08,1.36]). During the pandemic period, Ox was positively associated with symptom-based (1.46 [1.13,1.89]) and event-based (1.43 [1.00,2.05]) exacerbations. Fewer self-reported pandemic protective behaviors, and higher viral infectious symptoms, were also associated with exacerbations. In stepwise multivariable risk-factor analyses, female gender (1.23 [1.04,1.45] and 1.41 [1.13,1.76]) and co-morbid asthma (1.65 [1.34,2.03] and 1.54 [1.19,2.00]) were associated with symptom-based and event-based exacerbations, respectively, blood eosinophils (1.42 [1.10,1.84]) were associated with event-based exacerbations, and each IQR increment in Ox was associated with symptom-based exacerbations (1.31 [1.06,1.61]).Conclusion: Ox exposure was consistently associated with symptom-based COPD exacerbations, and female gender, co-morbid asthma, and blood eosinophilia were found to be relevant risk factors.Plain language summary: Previous research has identified air pollution as a relevant non-infectious trigger for episodic ‘lung attacks’, referred to as exacerbations, in patients living with chronic obstructive pulmonary disease (COPD). Very few studies, however, have studied this relationship during the COVID-19 pandemic. During that time, there were large fluctuations in key forms of air pollution (air pollutants). The few studies available used population-level approaches and relied on hospital administrative coding of visits to classify the disease and to identify exacerbation events. This approach may lead to potentially missing clinically important non-severe events and may limit individual-level risk factor assessment around this period.This study was conducted in participants with COPD as confirmed by the gold-standard test, spirometry, who were living in 9 Canadian cities across 6 provinces. The results showed that while the air pollutants nitrogen dioxide (NO2), fine particulate matter (PM2.5), and total oxidant (Ox) concentrations were all notably higher before the pandemic (pre-pandemic), only ambient Ox concentration was consistently associated with exacerbations. This relationship was seen across both pre-pandemic and pandemic periods. Female gender, co-morbid asthma, and eosinophilia were identified as notable risk factors for exacerbations and were effect modifiers for the association between Ox exposure and exacerbations. This study adds to a very limited existing literature on the relationship between air pollutant fluctuations and exacerbations of COPD around the pandemic era and highlights important risk factors to guide targeted public health and exposure response interventions.Keywords: Chronic obstructive pulmonary disease, acute exacerbations of chronic obstructive pulmonary disease, ambient air pollution, COVID-19 pandemic, total oxidant concentration

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