title: Identification of lipocalin and apolipoprotein A1 as biomarkers of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Much effort is being made to discover noninvasive biomarkers of chronic airway disease that might enable better management, predict prognosis, and provide new therapeutic targets.
  
  
  OBJECTIVE
  To undertake a comprehensive, unbiased proteomic analysis of induced sputum and identify novel noninvasive biomarkers for chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Induced sputum was obtained from patients with COPD with a spectrum of disease severity and from control subjects. Two-dimensional gel electrophoresis and mass spectrometric identification of differentially expressed proteins were first applied to induced sputum from patients with GOLD stage 2 COPD and healthy smoker control subjects. Initial results thus obtained were validated by a combination of immunoassays (Western blotting and ELISA) applied to a large subject cohort. The biomarkers were localized to bronchial mucosa by immunohistochemistry.
  
  
  RESULTS
  Of 1,325 individual protein spots identified, 37 were quantitatively and 3 qualitatively different between the two groups (P < 0.05%). Forty protein spots were subjected to tandem mass spectrometry, which identified 15 separate protein species. Seven of these were further quantified in induced sputum from 97 individuals. Using this sequential approach, two of these potential biomarkers (apolipoprotein A1 and lipocalin-1) were found to be significantly reduced in patients with COPD when compared with healthy smokers. Their levels correlated with FEV(1)/FVC, indicating their relationship to disease severity.
  
  
  CONCLUSIONS
  A potential role for apolipoprotein A1 and lipocalin-1 in innate defense has been postulated previously; our discovery of their reduction in COPD indicates a deficient innate defense system in airway disease that could explain increased susceptibility to infectious exacerbations.
authors.affiliation: Inflammatory Cell Biology Group, Division of Infection, Inflammation, and Immunity, Sir Henry Wellcome Laboratories, South Block, Southampton General Hospital, Southampton, UK. bln1@soton.ac.uk
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Nicholas
authors.forename: Paul
authors.initials: P
authors.lastname: Skipp
authors.forename: Sheila
authors.initials: S
authors.lastname: Barton
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.forename: Dinesh
authors.initials: D
authors.lastname: Bagmane
authors.forename: Richard
authors.initials: R
authors.lastname: Mould
authors.forename: Gilbert
authors.initials: G
authors.lastname: Angco
authors.forename: Jon
authors.initials: J
authors.lastname: Ward
authors.forename: Binita
authors.initials: B
authors.lastname: Guha-Niyogi
authors.forename: Susan
authors.initials: S
authors.lastname: Wilson
authors.forename: Peter
authors.initials: P
authors.lastname: Howarth
authors.forename: Donna E
authors.initials: DE
authors.lastname: Davies
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennard
authors.forename: C David
authors.initials: CD
authors.lastname: O'Connor
authors.forename: Ratko
authors.initials: R
authors.lastname: Djukanovic
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000032:analysis / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015153:Blotting, Western; D029481:Bronchitis, Chronic / Q000378:metabolism; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005540:Forced Expiratory Flow Rates; D006801:Humans; D054834:Lipocalins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000737:chemistry; D012720:Severity of Illness Index; D012907:Smoking / Q000378:metabolism; D013183:Sputum / Q000737:chemistry / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D015415:Biomarkers; D054834:Lipocalins