Characteristics and Prognosis of Never-Smokers and Smokers with Asthma in the Copenhagen General Population Study. A Prospective Cohort Study

Rationale: Asthma is associated with complications, cardiovascular comorbidities, and higher mortality in some individuals.

Objectives: To test the hypothesis that, among individuals with asthma, never-smokers have different characteristics and a better prognosis than smokers.

Methods: We recruited 94,079 individuals aged 20-100 years from the Copenhagen General Population Study, a prospective cohort study. Among these individuals, 5,691 (6%) had self-reported asthma (2,304 never-smokers, 2,467 former smokers, and 920 current smokers). We examined respiratory symptoms, lung function, and levels of inflammatory and allergic biomarkers in systemic circulation. Furthermore, we assessed prospectively the risk of asthma or chronic obstructive pulmonary disease (COPD) exacerbations, pneumonias, lung cancer, ischemic heart disease, ischemic stroke, and all-cause mortality during 4.5 years of follow-up.

Measurements and main results: Compared with never-smokers without asthma, individuals with asthma had more respiratory symptoms and airflow limitation and higher levels of inflammatory and allergic biomarkers, which were most pronounced in smokers. Among individuals with asthma compared with never-smokers without asthma, multivariable adjusted hazard ratios for asthma exacerbations were 11 (95% confidence interval: 5.8-22) in never-smokers, 13 (6.2-29) in former smokers, and 18 (8.2-39) in current smokers. The corresponding values for other endpoints were, respectively, 8.9 (2.1-38), 23 (8.8-58), and 36 (12-105) for COPD exacerbations; 1.5 (0.9-2.2), 1.6 (1.0-2.4), and 2.4 (1.6-3.7) for pneumonias; 0.6 (0.1-5.1), 4.0 (1.3-12), and 13 (4.3-41) for lung cancer; 1.2 (0.9-1.6), 1.5 (1.2-2.0), and 2.0 (1.4-2.9) for ischemic heart disease; 1.4 (0.9-2.1), 1.2 (0.8-1.9), and 3.0 (1.7-5.3) for ischemic stroke; and 0.9 (0.6-1.3), 1.5 (1.1-2.0), and 2.7 (1.9-3.7) for all-cause mortality.

Conclusions: Never-smokers with asthma had an increased risk of asthma and COPD exacerbations, and possibly pneumonias. Importantly, the risks for lung cancer, cardiovascular comorbidities, and death were restricted to smokers with asthma. Thus, tobacco smoking was the main explanation for poor prognosis in asthma.