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Original Research: OBSTRUCTIVE LUNG DISEASES |

Elevated Airway Purines in COPDExhaled Breath Condensate Adenosine in COPD

Charles R. Esther, Jr, MD, PhD; Aili L. Lazaar, MD; Elena Bordonali, PhD; Bahjat Qaqish, PhD; Richard C. Boucher, MD
Author and Funding Information

From the Department of Pediatric Pulmonology (Dr Esther), the Department of Biostatistics (Drs Bordonali and Qaqish), and the CF/Pulmonary Research Center (Dr Boucher),University of North Carolina at Chapel Hill, Chapel Hill, NC; and COPD Discovery Medicine (Dr Lazaar), Respiratory Therapy Area, GlaxoSmithKline, King of Prussia, PA.

Correspondence to: Charles R. Esther Jr, MD, PhD, University of North Carolina at Chapel Hill, Pediatric Pulmonology, CB#7217, Chapel Hill, NC 27599; e-mail: Charles_Esther@med.unc.edu


Funding/Support: This study was supported by the National Institutes of Health [Grants 1K23HL089708, SCCOR HL34322 MTCC] and GlaxoSmithKline.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;140(4):954-960. doi:10.1378/chest.10-2471
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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 FEV1 (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.

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