Distinct risks of exacerbation and lung function decline between never-smokers and ever-smokers with COPD

Background: Chronic obstructive pulmonary disease (COPD) can occur in patients without a history of smoking, which is a strong risk factor for COPD. However, few studies have focused on the prognosis of never-smokers with COPD. We investigated the difference of the longitudinal clinical outcomes between never-smokers and ever-smokers with COPD. Methods: We retrospectively analyzed patients with COPD who underwent chest computed tomography and longitudinal lung function tests from January 2013 to December 2020. We classified patients according to smoking status and examined their histories of acute exacerbation and long-term changes in lung function. Results: Among 583 patients with COPD, 75 (12.9%) had no smoking history. These never-smokers with COPD were predominantly women; they had a lower forced vital capacity and a higher prevalence of asthma, history of tuberculosis, tuberculosis-destroyed lung, and bronchiectasis, but a lower prevalence of emphysema, relative to ever-smokers with COPD. Never-smokers with COPD had significantly lower risks of subsequent moderate to severe exacerbation (β ± standard error, − 0.4 ± 0.12; P = 0.001), any exacerbation (adjusted odds ratio, 0.46; 95% confidence interval, 0.26 − 0.8; P = 0.006), and frequent exacerbation (adjusted odds ratio, 0.28; 95% confidence interval, 0.09 − 0.89; P = 0.03) than ever-smokers with COPD. Never-smokers with COPD also showed significantly slower annual decline of forced expiratory volume in 1 s than ever-smokers with COPD (− 15.7 ± 4.7 vs. −30.4 ± 2.9 mL, respectively; P = 0.03). Conclusions: Never-smokers with COPD had significantly fewer acute exacerbations and slower decline of lung function than ever-smokers with COPD during longitudinal follow-up.