The Relationship of the Fibrinogen Cleavage Biomarker Aα-Val360 With Disease Severity and Activity in α1-Antitrypsin Deficiency.

Abstract

New markers of COPD and emphysema disease activity are urgently required since current measures of disease severity do not reflect the total disease burden nor predict disease progression. A recently described in vivo marker of neutrophil elastase activity (Aα-Val360) may be an effective marker of COPD and emphysema disease activity, and the current study explores its use in patients with α1-antitrypsin deficiency (AATD) across the disease severity spectrum with particular interest in whether it can be used as an early predictor of the need for intervention. Cross-sectional and longitudinal relationships between Aα-Val360 and full lung-function tests, CT scan densitometry, and other biomarkers were explored in this study of a registry of untreated patients with PiZZ AATD. The Aα-Val360 related cross-sectionally to physiologic, radiologic, and symptomatic markers of disease severity though not disease progression. Similar cross-sectional relationships were observed in subjects with mild physiologic abnormalities; however, in this subgroup, baseline Aα-Val360 concentration did relate to subsequent disease progression. In cross-sectional studies, Aα-Val360 reflects disease severity in AATD and may be a useful marker of disease activity in patients with early disease in whom therapeutic intervention may be indicated.