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

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.