Taking a daily aspirin was linked to reduced COPD exacerbations, less shortness of breath, and better quality of life, an analysis of the ongoing SPIROMICS study found.
At 3 years follow-up, aspirin users were less likely to have acute COPD exacerbations (adjusted incidence rate ratio [IRR] 0.78, 95% CI 0.65-0.94) compared with non-users, with a similar effect seen for moderate acute COPD exacerbations (IRR 0.86, 95% CI 0.63-1.18), according to Ashraf Fawzy, MD, of Johns Hopkins University in Baltimore, and colleagues.
The association was strongest among study participants reporting symptoms of chronic bronchitis at enrollment, as reported in the journal CHEST.
Aspirin use has been associated with reduced mortality in previous studies, but the newly published investigation is among the first to examine the impact of daily aspirin therapy on respiratory morbidity in COPD.
Preliminary data from this study were presented earlier this year at the American Thoracic Society annual conference.
“The reduced incidence of total and moderate acute COPD exacerbations among aspirin users was independent of concurrent respiratory or cardiovascular medication use and robust when analyzing the entire follow-up period, limiting the analysis to the first year of follow-up, and across all sensitivity analyses,” the authors wrote.
Aspirin use was also associated with lower total scores on the St. George Respiratory Questionnaire (β -2.2, 95% CI -4.1 to -0.4); reduced odds of moderate-to-severe dyspnea, score ≥2 on the modified Medical Research Council Questionnaire (adjusted OR 0.69, 95% CI 0.51-0.93); and lower COPD Assessment Test scores (β -1.1, 95% CI -1.9 to -0.2).
No difference was observed between groups in 6-minute walk distance (β 0.7 meters, 95% CI -14.3 to 15.6).
The analysis included COPD patients in SPIROMICS who self-reported daily aspirin use at study entry, 45% of the 1,698 study participants. Acute exacerbations of COPD were prospectively determined through quarterly structured telephone questionnaires for up to 3 years and categorized as moderate (symptoms treated with antibiotics or oral corticosteroids) or severe (requiring an emergency department visit or hospitalization).
Aspirin users were matched 1:1 with non-users based on propensity score, which resulted in 503 participant-pairs. The association of aspirin use with total, moderate, and severe acute COPD exacerbation was investigated using zero-inflated negative binomial models. Linear or logistic regression were used to investigate the association with baseline respiratory symptoms, quality of life, and exercise tolerance.
The researchers noted that aspirin has several systemic and local pulmonary mechanisms of action that could explain the findings, including “inactivation of platelets and reduced inflammation,” among them.
“A urinary metabolite of thromboxane A2, which is secreted by activated platelets, has been shown to be elevated among patients with COPD and represents the pathway irreversibly blocked by aspirin. Persistent systemic elevation of inflammatory markers interleukin-6 and CRP may represent a systemic inflammatory phenotype of COPD which are attenuated by aspirin in other patient populations,” the researchers wrote.
They further noted that in a 2017 study, treatment with aspirin was found to reduce pro-inflammatory cytokines in bronchoalveolar lavage samples of 33 healthy volunteers.
Study limitations cited by the researchers included the study participants’ self-reporting of daily aspirin use, without dosing information. Information on duration of aspirin use and adherence to therapy before and during the study was also unavailable. COPD exacerbations were not confirmed with medical records, which may have led to misclassification of events.
And despite propensity score matching and other efforts to avoid confounding, the researchers acknowledged that they may not have controlled for all factors that could have impacted their outcomes.
They concluded that a randomized study is needed to determine whether daily aspirin use is protective against COPD exacerbations. “Prospective randomized clinical trials of aspirin use are warranted to explore its potential effect in reducing COPD morbidity,” they wrote.
Funding for this research was provided by the National Heart, Lung, and Blood Institute, the National Institute for Environmental Health Sciences, and by the drugmakers AstraZeneca/Medimmune, GlaxoSmithKline, and others through the Foundation for the NIH and the COPD Foundation.