Quality of Life and Mortality Outcomes for Augmentation Naïve and Augmented Patients with Severe Alpha-1 Antitrypsin Deficiency

Paul R. Ellis, Kristen E. Holm, Radmila Choate, David M. Mannino, Robert A. Stockley, Robert A. Sandhaus, Alice M. Turner

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Intravenous alpha-1 antitrypsin (AAT) augmentation therapy is the only specific treatment available for alpha-1 antitrypsin deficiency (AATD)-related lung disease. It is widely used worldwide but remains unavailable to patients with AATD in the United Kingdom. While randomized trials of augmentation therapy have demonstrated biochemical efficacy and lung tissue preservation using computed tomography (CT) densitometry, these studies were not adequately powered to demonstrate effectiveness in well-accepted clinical endpoints such as quality of life (QOL) or survival. We used large, prospectively followed AATD patient populations in the United States and United Kingdom to explore these important clinical endpoints. Methods: Our inclusion criterion was adults with severe AATD and associated lung disease. The treatment group was U.S. AATD patients receiving augmentation therapy for lung disease. The control group was augmentation therapy naïve AATD patients. Multivariable regression and survival analyses were used to assess QOL and mortality outcomes respectively. Results: Mean annual deterioration of the St George’s Respiratory Questionnaire total score was 1.43 points greater/year in the control group compared to those receiving augmentation therapy (95% confidence interval [CI] 0.47 to 2.39, p=0.003). At 7 years, median survival was 82.7% (95% CI 75.3 to 90.7) for the control group versus 87.8% (95% CI 82.8 to 93.2) in the augmentation group, p=0.66. There was significant heterogeneity between cohorts. Conclusion: A comparison of 2 highly characterized AATD cohorts was not able to reliably determine if AAT augmentation therapy improves QOL or mortality in patients with severe AATD-related lung disease. Alternative surrogate biomarkers of disease progression, such as CT lung density, may be a more pragmatic option.

Original languageEnglish
Pages (from-to)139-147
Number of pages9
JournalChronic Obstructive Pulmonary Diseases
Issue number2
StatePublished - 2023

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  • AAT augmentation therapy
  • alpha-1 antitrypsin deficiency
  • emphysema

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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