The Clinical Course of Severe Alpha-1-Antitrypsin Deficiency in Patients Identified by Screening

Background: Severe alpha-1-antitrypsin deficiency (AATD) is a genetic condition predisposing to chronic obstructive pulmonary disease (COPD) and liver disease. Its natural course is not well known. Our aim was to study the natural course of AATD by analyzing the clinical course in individuals with severe AATD identified by screening.Materials and Methods: Of the 1585 individuals included in the Swedish AATD register, 377 (24%) were identified by screening and included in this retrospective study. The follow-up time was from the date of inclusion in the register to the first lung transplantation, death or the termination of the study on June 1st, 2016. The risk factors for having a diagnosis of COPD were investigated through a proportional hazards model, adjusted for sex, diagnosis before the age of 14 years, smoking habits, occupational exposure to airway irritants and respiratory symptoms or diseases.Results: At inclusion, 71% of the individuals were asymptomatic, ie, without any respiratory symptoms. Compared to the 156 (41%) ever-smokers, the 221 (59%) never-smokers had better lung function (mean FEV1 98 (SD 18) vs 85 (SD 28) % predicted; p < 0.001), and fewer of them were symptomatic, ie, with respiratory symptoms, at inclusion (20% vs 42%; p < 0.001). They also had a lower annual decline in FEV1 (mean 42 (95% CI 36-47) vs 53 (95% CI 47-60) mL·yr-1; p = 0.011) and better survival than the ever-smokers. The risk factors for having a diagnosis of COPD were the identification of severe AATD at an age of ≥14 years and the presence of respiratory symptoms or diseases.Conclusion: Never-smoking individuals with severe AATD identified by screening have better lung function, fewer symptoms, and better survival compared with the ever-smokers. Screening for AATD at an early age may improve the prognosis of AATD