Smoking Cessation as a Possible Risk Factor for the Development of Aspirin-Exacerbated Respiratory Disease in Smokers

Abstract

Background: The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is characterized by the low expression of cyclooxygenase-2 (COX-2) in airway epithelia, which decreases the production of prostaglandin E₂ (PGE₂). Conversely, cigarette smoke stimulates COX-2 expression in airway epithelia. Therefore, it was hypothesized that the development of AERD would be suppressed by elevated PGE₂ levels in smokers, and smoking cessation might increase susceptibility to AERD.

Objective: The objective of this study was to evaluate the relationship between smoking and the risk of AERD development.

Methods: The smoking status of patients with AERD (n = 114) was compared with 2 control groups with aspirin-tolerant asthma (ATA), patients diagnosed by a systemic aspirin provocation test (ATA-1, n = 83) and outpatients randomly selected from a large-scale dataset (ATA-2, n = 914), as well as a healthy control group (HC, n = 2313).

Results: At the age of asthma onset, there was a low frequency of current smokers (9.7%), but a high frequency of past smokers (20.2%) in the AERD group compared with the ATA-1 (20.5% and 12.0% for current and past smokers, respectively), ATA-2 (24.5% and 10.3%, respectively), and HC group (26.2% and 12.6%, respectively). After adjustment for confounding variables, AERD was positively associated with smoking cessation between 1 and 4 years before disease onset compared with the ATA-2 group (adjusted odds ratio [aOR] 4.63, 95% confidence interval [CI]: 2.16-9.93) and the HC group (aOR 4.09, 95% CI: 2.07-8.05), implying that smoking cessation was followed by the development of AERD.

Conclusion: Smoking cessation may be a risk factor for the development of AERD.

Keywords: Aspirin-exacerbated respiratory disease; Cyclooxygenase-2; Prostaglandin E(2); Smoking; Smoking cessation.