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

Alice M Turner,1 Priscilla Wittkopf,2 Caroline von Wilamowitz-Moellendorff,2 Kyle Fahrbach,3 Mariana Farraia,4 May Hagiwara,5 Ed G Marins,5 Anne E Wyman,5 Lisi Wang,5 Suna Park5 1School of Health Sciences, University of Birmingham, Birmingham, UK; 2Evidence Synthesis, Health Economics and Market Access, Evidera, London, UK; 3Evidence Synthesis, Health Economics and Market Access, Evidera, Waltham, MA, USA; 4Evidence Synthesis, Health Economics and Market Access, Evidera, Ede, Netherlands; 5Takeda Development Center Americas, Inc., Cambridge, MA, USACorrespondence: Alice M Turner, School of Health Sciences, University of Birmingham, Birmingham, UK, Tel +44 (0)121 371 3885, Email a.m.turner@bham.ac.ukBackground: 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.Keywords: alpha-1 antitrypsin deficiency, chronic obstructive pulmonary disease, emphysema, meta-analysis, respiratory function test, quality of life