Regular Aspirin Use May Slow COPD Progression

Regular aspirin use was associated with a more than 50% reduction in emphysema/chronic obstructive pulmonary disease (COPD) progression in an elderly cohort over a decade in a longitudinal analysis of data from a large lung study.

The association was seen across aspirin doses and was greatest in older study participants with significant airflow obstruction.

“These findings, along with supportive results in animals, suggest that further study of aspirin and platelet activation in emphysema may be warranted,” Carrie Aaron, MD, of Columbia University, New York City, and colleagues wrote in the journal CHEST.

They noted that platelet activation reduces pulmonary microvascular blood flow and contributes to inflammation, which has been shown to be important in the pathogenesis of COPD/emphysema.

“We hypothesized that regular use of aspirin, a platelet-inhibitor, would be associated with slower progression of emphysema-like lung on computed tomography (CT), and slower decline in lung function,” the researchers wrote.

To test the theory, they examined data from the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which assessed the percentage of emphysema-like lung below-950 Hounsfield units (“percent emphysema”) on cardiac and full-lung CT.

Spirometry was conducted during 2004-2007 and repeated in 2010-2012 in accordance with American Thoracic Society-European Respiratory Society guidelines following the MESA Lung protocol; all exams were reviewed by one investigator.

At the time of the participants’ first spirometry measurement, airflow obstruction was defined as pre-bronchodilator FEV1/FVC <0.70 and restrictive ventilatory defect as FVC<lower limit of normal and FEV1/FVC≥0.7.
Regular aspirin use was defined as 3 or more days per week and mixed effects models adjusted for demographics, anthropometry, smoking, hypertension, ACE-inhibitor use, C-reactive protein, sphingomyelins, and scanner factors.

The analysis included 4,257 participants from the MESA Lung Study. Their mean (±SD) age was 61±10 years, 54% were ever-smokers, and 22% used aspirin regularly.

Among the main findings:
On average percent emphysema increased 0.60 percentage points over 10 years (95% CI 0.35 to 0.94).
Progression of percent emphysema was slower among regular aspirin users compared to non-aspirin users (fully adjusted model: -0.34% per 10 years, 95% CI -0.60 to -0.08; P=0.01).

Results were similar in ever-smokers and for doses of 81 mg and 300-325 mg. A greater magnitude effect was seen among participants with airflow limitations.

No association was found between aspirin use and change in lung function.

Results were similar after propensity score weighting and when the exposure was defined as any aspirin use at baseline, and there was no evidence for effect modification associated with age and race/ethnicity.

Results were also similar after adjustment for inhaler, NSAID, COX-2 inhibitor, ADP-receptor inhibitors, statin, and diuretic use.

“This is the first study of which we are aware to show an association between aspirin use and longitudinal progression of percent emphysema,” the researchers wrote.

“Prior studies have found platelet-receptor related genes serotonin receptor 4 (HTR4), von Willebrand factor (VWF) and its platelet-receptor, GP1BA, to be associated with FEV1 and COPD. Additionally, platelet factor 4 increased emphysema when added to a neutrophil elastase animal model of emphysema, and platelet activation was found to be greater in COPD compared to controls, and during exacerbation.”

Study limitation cited by the researchers included the observational nature of the study, which raised the possibility of residual confounding and the reliance on self-reporting for frequency of aspirin use.

In addition, percent emphysema assessment was limited to the lower two-thirds of the lungs and baseline differences in emphysema were significant among aspirin users and non-users, with users having a greater percent emphysema.

Despite these and other caveats, pulmonary specialist James Donohue, MD, of the University of North Carolina School of Medicine at Chapel Hill agreed with the researchers’ conclusion that the preliminary findings are compelling enough to warrant further study.

“The hypothesis is solid for aspirin having a role in preventing emphysema through anti-inflammatory small blood vessel effects and the case for further research is strong,” Donohue told MedPage Today.

Funding for this research was provided by the U.S. National Institutes of Health and the Alpha1 Foundation.

References:
https://pulmccm.org/copd-review/regular-aspirin-use-may-slow-copd-progression/

Chest: https://www.ncbi.nlm.nih.gov/pubmed/29246770

https://www.medpagetoday.com/pulmonology/smokingcopd/70094
https://www.sciencedirect.com/science/article/pii/S0012369217332105