Women with mild chronic obstructive pulmonary disease (COPD) who seasonally experience short-term exposure to ambient nitrogen dioxide (NO2) and particulate matter 2.5 microns or less in diameter (PM2.5) have an elevated risk for COPD exacerbations, according to a study in Thorax.

Researchers in Canada sought to estimate the relationship between short-term exposures to NO2, PM2.5, and ground-level ozone (O3) and COPD exacerbations during the warm and cool seasons among men and women with mild to moderate disease. The study, conducted from July 1, 2012, to December 31, 2019, involved a subgroup of 449 participants from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study, a prospective, longitudinal, case-crossover study of individuals with and without COPD participants (at least 40 years of age, half women) from 9 study sites. In CanCOLD, researchers gathered information on exacerbation events via telephone interviews every 3 months.

Participants in the current study all had spirometry-diagnosed COPD with at least 1 exacerbation after diagnosis. The researchers divided exacerbations into subgroups, depending upon whether they were symptom-based (characterized by increased dyspnea or sputum volume or purulence for 48 hours or more) or event-based (ie, the exacerbation required the patient to take antibiotics or corticosteroids or to have an unscheduled doctor/emergency room visit or hospitalization).

The researchers further divided exacerbation data based on whether they occurred during a warm (May-October) or cool (November-April) time of year, analyzing data separately to establish temperature directionality. Models were fitted for each Lag (Lag0 to Lag-6) with use of generalized estimating equations.

These results show that seasonal short-term air pollutant exposure is a risk for COPD exacerbations among milder disease individuals and females in settings with relatively low annual average air pollutant concentrations…

Among the 449 total study participants (mean [SD] age, 69.8 [10.2] years; 54% male), there were 1400 symptom-based and 841 event-based exacerbations, with 2156.75 person-years of follow-up.

The researchers found that short-term exposure to ambient NO2 during the warm season and to PM2.5 during the cool season were associated with increased odds of exacerbations. In the warm season analysis, an interquartile range (IQR) NO2 increment was associated with increased odds of symptom-based events (1.14 [1.01-1.29]) on Lag-3; in the cool season analysis, an IQR PM2.5 increment was associated with a statistically significant increased odds of symptom-based exacerbations (1.11 [1.03 to 1.20]) on Lag-1.

Notably, the association between NO2, PM2.5, and exacerbations was found in women but not in men, and in those with mild disease but not in those with predominantly moderate disease.  “[G]ender and disease severity were both observed to be effect modifiers on the association between air pollutant exposure and exacerbations,” said the study authors.

With respect to ozone, the researchers found that during the warm season, an IQR O3 increment on Lag-3 was somewhat associated with reduced odds of event-based exacerbations (0.73 [0.52-1.00]). No significant association was found regarding the composite of NO2 and O3 exposure and exacerbation odds in the warm or cool seasons. Similar associations and magnitude were observed in the NO2-PM2.5 and PM2.5-O3 2-pollutant models compared with those in the single-pollutant models.

Among several limitations, the case-crossover method did not control for time-varying confounders such as daily medication use/adherence and daily activity/time spent outdoors. Also, events recalled further from the time of telephone questionnaires are a potential source of error. Furthermore, it was assumed that participants inhabited the study site city during exacerbations, and the study did not include rural areas. 

These results show that seasonal short-term air pollutant exposure is a risk for COPD exacerbations among milder disease individuals and females in settings with relatively low annual average air pollutant concentrations, which may inform targeted public health interventions and clinical management strategies,” the study authors concluded.

Disclosure: The CanCOLD study is currently funded by the Canadian Respiratory Research Network and the industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline (GSK) Canada Ltd, and Novartis. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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