Characteristics and outcomes of chronic obstructive pulmonary disease in never smokers in Denmark: a prospective population study

Background A substantial proportion of patients with chronic obstructive pulmonary disease (COPD) have never smoked. We tested the hypothesis that, in individuals with COPD, never smokers have different characteristics and less severe outcomes of the disease than smokers do. Methods We included individuals from the Copenhagen General Population Study, a prospective population study. We identified individuals with COPD spirometrically; that is, as the ratio between forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) under the lower limit of normal (LLN), excluding individuals with self-reported asthma. We examined general characteristics, symptoms, disease severity, and levels of inflammatory biomarkers and alpha 1-antitrypsin at baseline. We assessed risk of lung-related hospital admissions, cardiovascular comorbidities, and all-cause mortality during a median follow-up of 4 years (IQR 2.5-5.6). Findings Between Nov 26, 2003, and July 29, 2010, 68 501 participants from the Copenhagen General Population Study had lung function measurements and complete information on smoking habits available. Of those, we identified 6623 with COPD and no asthma. Of these, 1476 (22%) were never smokers, 2696 (41%) former smokers, and 2451 (37%) current smokers. For comparison we included 24 529 never smokers without COPD. Never smokers with COPD had different clinical characteristics, fewer symptoms, milder disease, and lower levels of inflammatory biomarkers than did current and former smokers with COPD. During follow-up, HRs for hospital admission due to COPD were 8.6 (95% CI 5.3-14) in never smokers, 30 (22-41) in former smokers, and 43 (32-59) in current smokers compared with never smokers without COPD. HRs for hospital admission due to pneumonia were 1.9 (1.4-2.6) in never smokers, 2.8 (2.3-3.4) in former smokers, and 3.4 (2.9-4.2) in current smokers. For hospital admission due to lung cancer, HRs were 11 (5.7-23) in former smokers and 18 (9.2-35) in current smokers, whereas no cases were noted in never smokers. Furthermore, risk of cardiovascular comorbidities and all-cause mortality was increased in former and current smokers but not in never smokers with COPD. Interpretation Compared with current and former smokers, never smokers with COPD had different characteristics and milder disease, limited to the lungs. However, morbidity due to lung-related hospital admissions was nonetheless substantial in never smokers with COPD.