title: Urinary desmosine: a biomarker of structural lung injury during CF pulmonary exacerbation.
abstract: BACKGROUND
  Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators.
  
  
  METHODS
  Urine and blood samples plus lung function measurements were collected at up to three points during hospitalization for treatment of a CF pulmonary exacerbation. We used a repeated measures model, adjusted for age and time between measurements, to compare log transformed urine desmosine concentrations across multiple time points and to correlate those concentrations with related clinical variables. Change in UDes concentration was investigated using a statistical model that incorporated normalization factors to account for variations in urinary concentration.
  
  
  RESULTS
  Desmosine was measured by radioimmunoassay (RIA) in 155 spot urine samples from 53 CF patients hospitalized for 63 pulmonary exacerbations (range of results: 0-235 pmol Des/ml). Specific gravity (SG) adjusted UDes concentration decreased significantly during admission for CF pulmonary exacerbation, P < 0.01 (average length of stay = 11 days). No correlation was observed between UDes concentration and lung function or inflammatory markers.
  
  
  CONCLUSIONS
  UDes decreased significantly following treatment for an acute pulmonary exacerbation and may be a useful biomarker of short-term injury to the CF lung. Further investigation is needed to evaluate the utility of UDes concentration in the long-term progression of CF lung disease.
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School and The University of Minnesota Amplatz Children's Hospital, Minneapolis, Minnesota 55455, USA. lagun005@umn.edu
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Laguna
authors.forename: Brandie D
authors.initials: BD
authors.lastname: Wagner
authors.forename: Barry
authors.initials: B
authors.lastname: Starcher
authors.forename: Heidi K
authors.initials: HK
authors.lastname: Luckey Tarro
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Mann
authors.forename: Scott D
authors.initials: SD
authors.lastname: Sagel
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Accurso
mesh_terms: D056151:Airway Remodeling; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000378:metabolism / Q000652:urine*; D003895:Desmosine / Q000378:metabolism / Q000652:urine*; D018450:Disease Progression; D004549:Elastin / Q000378:metabolism*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism / Q000652:urine*; D008297:Male; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism / Q000652:urine*; D011446:Prospective Studies; D012129:Respiratory Function Tests
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; D003895:Desmosine; D002097:C-Reactive Protein; D004549:Elastin