Pulmonary Function Decline in Alpha-1 Antitrypsin Deficiency: A Systematic Review and Meta-Analysis

Background: Limited data exist on pulmonary function decline in patients with alpha-1 antitrypsin deficiency (AATD)-associated lung and/or liver disease. This study aimed to conduct a systematic literature review (SLR) and meta-analysis of pulmonary function decline and associated risk factors, clinical outcomes, and health-related quality of life (HRQoL) in patients with AATD-associated lung and/or liver disease. Methods: Following PRISMA guidelines, studies were identified from MEDLINE/Embase (2003-2023) using Population, Intervention, Comparison, Outcomes, and Study criteria; key congresses were hand-searched (2021-2023). For each publication, two independent reviewers determined eligibility for inclusion and quality was assessed using relevant JBI tools. Meta-analyses were conducted on select outcomes that were deemed appropriate. Results: Overall, 77 publications were included in the SLR and 32 reported pulmonary function decline in patients with AATD-associated lung and/or liver disease. Eight publications that evaluated forced expiratory volume in 1 second (FEV1) in mL, five that evaluated FEV1% predicted and four that evaluated HRQoL (as measured by St. George's Respiratory Questionnaire [SGRQ]) were deemed eligible for meta-analysis. In patients with AATD-associated lung disease, based on the random effects model, annualized change (95% confidence interval) in FEV1 was -39.1 (-45.2, -32.9) mL/year and -1.1 (-1.2, -0.9) %/year, and there was a slight worsening in SGRQ score (1.3 [0.6, 1.9] points/year). Data in patients with AATD-associated liver disease with or without comorbid lung disease were too limited to calculate an annualized rate of decline in pulmonary function or SGRQ. Conclusion: This comprehensive SLR and meta-analysis provides an estimate for annual pulmonary function decline in patients with AATD-associated lung disease and highlights an evidence gap in patients with AATD-associated liver disease with or without comorbid lung disease. Further insights into risk factors or potential biomarkers of pulmonary function decline may support clinical strategies for optimizing treatment.