Health status decline in α-1 antitrypsin deficiency: a feasible outcome for disease modifying therapies?

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0844-6) contains supplementary material, which is available to authorized users.