PMID- 28496314 OWN - NLM STAT- MEDLINE DCOM- 20180319 LR - 20220330 IS - 1178-2005 (Electronic) IS - 1176-9106 (Print) IS - 1176-9106 (Linking) VI - 12 DP - 2017 TI - Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review. PG - 1295-1308 LID - 10.2147/COPD.S130440 [doi] AB - 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. FAU - Edgar, Ross G AU - Edgar RG AD - Therapy Services, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. AD - Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK. FAU - Patel, Mitesh AU - Patel M AD - Division of Primary Care, University of Nottingham, Nottingham, UK. FAU - Bayliss, Susan AU - Bayliss S AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. FAU - Crossley, Diana AU - Crossley D AD - Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK. AD - Department of Respiratory Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. FAU - Sapey, Elizabeth AU - Sapey E AD - Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK. AD - Department of Respiratory Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. FAU - Turner, Alice M AU - Turner AM AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. AD - Department of Respiratory Medicine, Heart of England NHS Foundation Trust, Birmingham, UK. LA - eng GR - CDRF-2014-05-044/DH_/Department of Health/United Kingdom GR - MR/L008335/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20170502 PL - New Zealand TA - Int J Chron Obstruct Pulmon Dis JT - International journal of chronic obstructive pulmonary disease JID - 101273481 RN - 0 (SERPINA1 protein, human) RN - 0 (alpha 1-Antitrypsin) SB - IM MH - Chi-Square Distribution MH - Disease Progression MH - *Enzyme Replacement Therapy/adverse effects MH - Humans MH - *Lung/drug effects/physiopathology/surgery MH - *Lung Transplantation/adverse effects MH - Observational Studies as Topic MH - *Pneumonectomy/adverse effects MH - Pulmonary Disease, Chronic Obstructive/diagnosis/etiology/physiopathology/*therapy MH - Pulmonary Emphysema/diagnosis/etiology/physiopathology/*therapy MH - Randomized Controlled Trials as Topic MH - Recovery of Function MH - Treatment Outcome MH - alpha 1-Antitrypsin/adverse effects/*therapeutic use MH - alpha 1-Antitrypsin Deficiency/complications/diagnosis/*drug therapy/physiopathology PMC - PMC5422329 OTO - NOTNLM OT - alpha-1 antitrypsin deficiency OT - emphysema OT - transplantation OT - treatment COIS- 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. EDAT- 2017/05/13 06:00 MHDA- 2018/03/20 06:00 PMCR- 2017/05/02 CRDT- 2017/05/13 06:00 PHST- 2017/05/13 06:00 [entrez] PHST- 2017/05/13 06:00 [pubmed] PHST- 2018/03/20 06:00 [medline] PHST- 2017/05/02 00:00 [pmc-release] AID - copd-12-1295 [pii] AID - 10.2147/COPD.S130440 [doi] PST - epublish SO - Int J Chron Obstruct Pulmon Dis. 2017 May 2;12:1295-1308. doi: 10.2147/COPD.S130440. eCollection 2017.