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

  • Alice M Turner*
  • , Priscilla Wittkopf
  • , Caroline von Wilamowitz-Moellendorff
  • , Kyle Fahrbach
  • , Mariana Farraia
  • , May Hagiwara
  • , Ed G Marins
  • , Anne E Wyman
  • , Lisi Wang
  • , Suna Park
  • *Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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.
Original languageEnglish
Number of pages16
JournalInternational Journal of Chronic Obstructive Pulmonary Disease
Volume21
DOIs
Publication statusPublished - 9 Jan 2026

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