American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2023
Observational StudyAugmentation Therapy for Severe Alpha-1 Antitrypsin Deficiency Improves Survival and Is Decoupled from Spirometric Decline - A Multi-National Registry Analysis.
Rationale: Intravenous plasma-purified alpha-1 antitrypsin (IV-AAT) has been used as therapy for alpha-1 antitrypsin deficiency (AATD) since 1987. Previous trials (RAPID and RAPID-OLE) demonstrated efficacy in preserving computed tomography of lung density but no effect on FEV1. This observational study evaluated 615 people with severe AATD from three countries with socialized health care (Ireland, Switzerland, and Austria), where access to standard medical care was equal but access to IV-AAT was not. ⋯ The observation that patients with severe AATD fall into two major phenotypes has implications for clinical trial design where FEV1 is a primary endpoint. Recruits into trials are typically older lung indexes entering the plateau phase and, therefore, unlikely to show spirometric benefits. IV-AAT attenuates spirometric decline in lung indexes in GOLD stage 2, a spirometric group commonly outside current IV-AAT commencement recommendations.