Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review

Abstract

Background

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition predisposing individuals to chronic obstructive pulmonary disease (COPD). The treatment is generally extrapolated from COPD unrelated to AATD; however, most COPD trials exclude AATD patients; thus, this study sought to systematically review AATD-specific literature to assist evidence-based patient management.

Methods

Standard review methodology was used with meta-analysis and narrative synthesis (PROSPERO-CRD42015019354). Eligible studies were those of any treatment used in severe AATD. Randomized controlled trials (RCTs) were the primary focus; however, case series and uncontrolled studies were eligible. All studies had ≥10 participants receiving treatment or usual care, with baseline and follow-up data (>3 months). Risk of bias was assessed appropriately according to study methodology.

Results

In all, 7,296 studies were retrieved from searches; 52 trials with 5,632 participants met the inclusion criteria, of which 26 studies involved alpha-1 antitrypsin augmentation and 17 concerned surgical treatments (largely transplantation). Studies were grouped into four management themes: COPD medical, COPD surgical, AATD specific, and other treatments. Computed tomography (CT) density, forced expiratory volume in 1 s, diffusing capacity of the lungs for carbon monoxide, health status, and exacerbation rates were frequently used as outcomes. Meta-analyses were only possible for RCTs of intravenous augmentation, which slowed progression of emphysema measured by CT density change, 0.79 g/L/year versus placebo (P=0.002), and associated with a small increase in exacerbations 0.29/year (P=0.02). Mortality following lung transplant was comparable between AATD- and non-AATD-related COPD. Surgical reduction of lung volume demonstrated inferior outcomes compared with non-AATD-related emphysema.

Conclusion

Intravenous augmentation remains the only disease-specific therapy in AATD and there is evidence that this slows decline in emphysema determined by CT density. There is paucity of data around other treatments in AATD. Treatments for usual COPD may not be as efficacious in AATD, and further studies may be required for this disease group.

Keywords:

• alpha-1 antitrypsin deficiency
• treatment
• emphysema
• transplantation

Acknowledgments

This report is an independent research arising from a Clinical Doctoral Research Fellowship (Ross Edgar), CDRF-2014-05-044, supported by the National Institute for Health Research (NIHR) and Health Education England (HEE). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, Health Education England, or the Department of Health. The review team would like to thank Professor RA Stockley for his collaboration on this review.

Author contributions

All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

Mr Edgar reports grants from HEE and NIHR, during the conduct of the study. This article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, HEE, or the Department of Health.

Dr Patel, Mrs Bayliss, and Dr Crossley have nothing to disclose.

Dr Sapey reports grants from NIHR, during the conduct of the study, and grants from Medical Research Council, Alpha-1 Foundation, and British Lung Foundation, outside the submitted work.

Dr Turner reports grants from Grifols Biotherapeutics, Alpha-1 Foundation, outside the submitted work, and The Birmingham AATD Registry has received past funds from CSL Behring for work in AATD, although this was not held by any of the authors.

The authors report no other conflicts of interest in this work.