title: The Relationship of the Fibrinogen Cleavage Biomarker Aα-Val360 With Disease Severity and Activity in α1-Antitrypsin Deficiency.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Royal Wolverhampton Hospitals NHS Trust, West Midlands, England.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Carter
authors.affiliation: Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, England.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ungurs
authors.affiliation: Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, England.
authors.forename: Anilkumar
authors.initials: A
authors.lastname: Pillai
authors.affiliation: Mumford Pharma Consulting, LLC, Red Bank, NJ.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Mumford
authors.affiliation: Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, England; ADAPT Project, Lung Function and Sleep, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, England. Electronic address: rob.stockley@uhb.nhs.uk.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stockley
mesh_terms: D000328:Adult; D015415:Biomarkers; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005541:Forced Expiratory Volume; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008137:Longitudinal Studies; D008168:Lung / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011653:Pulmonary Diffusing Capacity; D011859:Radiography; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D019896:alpha 1-Antitrypsin Deficiency / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C464794:fibrinogen Aalpha; D005340:Fibrinogen; D019272:Leukocyte Elastase