title: Elevated airway purines in COPD.
abstract: BACKGROUND
  Adenosine and related purines have established roles in inflammation, and elevated airway concentrations are predicted in patients with COPD. However, accurate airway surface purine measurements can be confounded by stimulation of purine release during collection of typical respiratory samples.
  
  
  METHODS
  Airway samples were collected noninvasively as exhaled breath condensate (EBC) from 36 healthy nonsmokers (NS group), 28 healthy smokers (S group), and 89 subjects with COPD (29 with GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage II, 29 with GOLD stage III, and 31 with GOLD stage IV) and analyzed with mass spectrometry for adenosine, adenosine monophosphate (AMP), and phenylalanine, plus urea as a dilution marker. Variable dilution of airway secretions in EBC was controlled using ratios to urea, and airway surface concentrations were calculated using EBC to serum urea-based dilution factors.
  
  
  RESULTS
  EBC adenosine to urea ratios were similar in NS (0.20 ± 0.21) and S (0.22 ± 0.20) groups but elevated in those with COPD (0.32 ± 0.30, P < .01 vs NS). Adenosine to urea ratios were highest in the most severely affected cohort (GOLD IV, 0.35 ± 0.34, P < .01 vs NS) and negatively correlated with FEV(1) (r = -0.27, P < .01). Elevated AMP to urea ratios were also observed in the COPD group (0.58 ± 0.97 COPD, 0.29 ± 0.35 NS, P < .02), but phenylalanine to urea ratios were similar in all groups. Airway surface adenosine concentrations calculated in a subset of subjects were 3.2 ± 2.7 μM in those with COPD (n = 28) relative to 1.7 ± 1.5 μM in the NS group (n = 16, P < .05).
  
  
  CONCLUSIONS
  Airway purines are present on airway surfaces at physiologically significant concentrations, are elevated in COPD, and correlate with markers of COPD severity. Purinergic signaling pathways are potential therapeutic targets in COPD, and EBC purines are potential noninvasive biomarkers.
authors: Department of Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, NC. Electronic address: Charles_Esther@med.unc.edu.
authors: Charles R
authors: CR
authors: Esther
authors: COPD Discovery Medicine, Respiratory Therapy Area, GlaxoSmithKline, King of Prussia, PA.
authors: Aili L
authors: AL
authors: Lazaar
authors: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors: Elena
authors: E
authors: Bordonali
authors: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors: Bahjat
authors: B
authors: Qaqish
authors: CF/Pulmonary Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors: Richard C
authors: RC
authors: Boucher
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests; D016022:Case-Control Studies; D045853:Exhalation / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology; D011687:Purines / Q000378:metabolism*; D012137:Respiratory System / Q000378:metabolism* / Q000503:physiopathology; D012720:Severity of Illness Index; D012907:Smoking / Q000378:metabolism; D014508:Urea / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011687:Purines; D000249:Adenosine Monophosphate; D010649:Phenylalanine; D014508:Urea; D000241:Adenosine