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

Int J Chron Obstruct Pulmon Dis. 2017 May 2:12:1295-1308. doi: 10.2147/COPD.S130440. eCollection 2017.

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; emphysema; transplantation; treatment.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Chi-Square Distribution
  • Disease Progression
  • Enzyme Replacement Therapy* / adverse effects
  • Humans
  • Lung Transplantation* / adverse effects
  • Lung* / drug effects
  • Lung* / physiopathology
  • Lung* / surgery
  • Observational Studies as Topic
  • Pneumonectomy* / adverse effects
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / therapy*
  • Pulmonary Emphysema / diagnosis
  • Pulmonary Emphysema / etiology
  • Pulmonary Emphysema / physiopathology
  • Pulmonary Emphysema / therapy*
  • Randomized Controlled Trials as Topic
  • Recovery of Function
  • Treatment Outcome
  • alpha 1-Antitrypsin / adverse effects
  • alpha 1-Antitrypsin / therapeutic use*
  • alpha 1-Antitrypsin Deficiency / complications
  • alpha 1-Antitrypsin Deficiency / diagnosis
  • alpha 1-Antitrypsin Deficiency / drug therapy*
  • alpha 1-Antitrypsin Deficiency / physiopathology

Substances

  • SERPINA1 protein, human
  • alpha 1-Antitrypsin