title: Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency.
abstract: BACKGROUND
  The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors.
  
  
  METHODS
  We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid.
  
  
  RESULTS
  Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines.
  
  
  CONCLUSIONS
  We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. j.stolk.long@lumc.nl
authors.forename: Jan
authors.initials: J
authors.lastname: Stolk
authors.forename: Barbara
authors.initials: B
authors.lastname: Veldhuisen
authors.forename: Laura
authors.initials: L
authors.lastname: Annovazzi
authors.forename: Chiara
authors.initials: C
authors.lastname: Zanone
authors.forename: Elly M
authors.initials: EM
authors.lastname: Versteeg
authors.forename: Toine H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: Jo H M
authors.initials: JH
authors.lastname: Berden
authors.forename: Willem
authors.initials: W
authors.lastname: Nieuwenhuizen
authors.forename: Paolo
authors.initials: P
authors.lastname: Iadarola
authors.forename: Maurizio
authors.initials: M
authors.lastname: Luisetti
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003895:Desmosine / Q000032:analysis*; D004311:Double-Blind Method; D004646:Emphysema / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006497:Heparan Sulfate / Q000032:analysis*; D006801:Humans; D006820:Hyaluronic Acid / Q000627:therapeutic use; D008297:Male; D010447:Peptide Hydrolases / Q000032:analysis*; D015990:Placebo Effect; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D003895:Desmosine; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D010447:Peptide Hydrolases