Decline in FEV₁ and hospitalized exacerbations in individuals with severe alpha-1 antitrypsin deficiency

Background and aim: The value of the forced expiratory volume in one second (FEV₁) is useful in the diagnosis and prognosis of chronic obstructive pulmonary disease (COPD). Previous studies on lung function in individuals with severe alpha-1 antitrypsin deficiency (AATD) have shown a variable annual decline in FEV₁ (∆FEV₁). The aim of this study was to analyze ∆FEV₁ and to identify risk factors for ∆FEV₁ in individuals with severe AATD. Material and methods: Data on smoking habits, symptoms, results of lung function tests and exacerbations were obtained from the Swedish AATD Register and the Swedish National Patient Register (SNPR). The ∆FEV₁ was analyzed by random-effects modeling and adjusted for age and FEV₁ at baseline. Results: One hundred and four (9%) current smokers, 539 (48%) ex-smokers and 489 (43%) never-smokers were included in the study and followed-up from 1991 to 2016. A total of 584 (52%) individuals with severe AATD had COPD at inclusion. The median (IQR) annual severe exacerbation rate was 0.66 (1.4). The adjusted mean ∆FEV₁ was significantly higher in the current smokers compared with the ex-smokers and never-smokers (70 [95% CI 56-83] vs 42 [95% CI 36-48] and 32 [95% CI 25-38) mL·yr^-1], in the middle-aged individuals compared with the young individuals (48 [95% CI 41-55] vs 32 [95% CI 18-45] mL·yr^-1), in the individuals with respiratory symptoms at inclusion compared with the asymptomatic individuals (46 [95% CI 40-52] vs 30 [95% CI 22-38]mL·yr^-1), and in the individuals with frequent exacerbations compared with those with infrequent exacerbations (57 [95% CI 47-68] vs 27 [95% CI 17-37] mL·yr^-1). Conclusion: Active smoking, age, respiratory symptoms at baseline and repeated severe exacerbations of COPD are factors associated with an accelerated decline of lung function in individuals with severe AATD.