PMID- 30029692 OWN - NLM STAT- MEDLINE DCOM- 20181112 LR - 20210109 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 19 IP - 1 DP - 2018 Jul 20 TI - Health status decline in alpha-1 antitrypsin deficiency: a feasible outcome for disease modifying therapies? PG - 137 LID - 10.1186/s12931-018-0844-6 [doi] LID - 137 AB - BACKGROUND: Trials of disease modifying therapies in Chronic Obstructive Pulmonary Disease (COPD) provide challenges for detecting physiological and patient centred outcomes. The purpose of the current study was to monitor decline in health status in Alpha-1 antitrypsin deficiency (AATD) and determine its' relationship to conventional physiology. METHODS: Patients recruited to the UK-AATD database with a median follow up of 7 years (IQR 5-10) were studied to determine annual change in St George's Respiratory Questionnaire (SGRQ), FEV(1), gas transfer and their feasibility of use in future trials. RESULTS: Annual decline in SGRQ had a wide range, was greater for patients with established COPD and correlated with decline in FEV(1) (p < 0.0001). Total score decline was greater (p < 0.05) for those with accelerated FEV(1) decline (median = 1.07 points/year) compared to those without (median = 0.51). Power calculations indicated effective intervention would not achieve MCID for the SGRQ unless the timeframe was extended for up to 8 years. More than 5000 patients/arm would be required for a statistically significant modest effect over 3 years even in those with rapid FEV(1) decline. CONCLUSION: Despite AATD being a rapidly declining form of COPD, deterioration in SGRQ was slow consistent with ageing and the chronic nature of disease progression. Power calculations indicate the numbers needed to detect a difference with disease modifying therapies would be prohibitive especially in this rare cause of COPD. These data have important implications for future study design of disease modifying therapies even in COPD not associated with AATD. FAU - Stockley, Robert A AU - Stockley RA AD - Lung Investigation Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2GW, UK. Rob.Stockley@uhb.nhs.uk. FAU - Edgar, Ross G AU - Edgar RG AUID- ORCID: 0000-0002-5971-3035 AD - Therapy Services, University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2GW, UK. AD - Institute of Applied Health Research, University of Birmingham, Birmingham, B15 2TT, UK. FAU - Starkey, Sian AU - Starkey S AD - Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2GW, UK. FAU - Turner, Alice M AU - Turner AM AD - Institute of Applied Health Research, University of Birmingham, Birmingham, B15 2TT, UK. AD - Heart of England NHS Foundation Trust, Respiratory Medicine, Bordesley Green East, Birmingham, B9 5SS, UK. LA - eng GR - CDRF-2014-05-044/DH_/Department of Health/United Kingdom GR - CDRF-2014-05-044/National Institute for Health Research/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180720 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cohort Studies MH - Cross-Sectional Studies MH - *Disease Progression MH - Feasibility Studies MH - Female MH - Follow-Up Studies MH - *Health Status MH - Humans MH - Male MH - Middle Aged MH - Pulmonary Disease, Chronic Obstructive/*diagnosis/epidemiology/*therapy MH - Registries MH - Treatment Outcome MH - alpha 1-Antitrypsin Deficiency/*diagnosis/epidemiology/*therapy PMC - PMC6053712 OTO - NOTNLM OT - Alpha-1 antitrypsin deficiency OT - Disease progression OT - Health related quality of life COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All patients gave written informed consent in line with GCP and the study had ethical approval from South Birmingham LREC 3359a. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: RAS had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. RAS has received fees for advisory board activity from CSL Behring, Shire pharmaceuticals, Kamada, Boehringer Ingelheim, Akari, Mereobiopharma and Astra Zeneca. RGE reports grants from Health Education England (HEE) and National Institute for Health Research (NIHR) (CDRF-2014-05-044), 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, the NIHR or the Department of Health. SH declares that she has no competing interests. AMT reports grants from Grifols biotherapeutics, and from Alpha-1 Foundation, outside the submitted work. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/07/22 06:00 MHDA- 2018/11/13 06:00 PMCR- 2018/07/20 CRDT- 2018/07/22 06:00 PHST- 2018/05/17 00:00 [received] PHST- 2018/07/13 00:00 [accepted] PHST- 2018/07/22 06:00 [entrez] PHST- 2018/07/22 06:00 [pubmed] PHST- 2018/11/13 06:00 [medline] PHST- 2018/07/20 00:00 [pmc-release] AID - 10.1186/s12931-018-0844-6 [pii] AID - 844 [pii] AID - 10.1186/s12931-018-0844-6 [doi] PST - epublish SO - Respir Res. 2018 Jul 20;19(1):137. doi: 10.1186/s12931-018-0844-6.