Chest
Volume 140, Issue 4, October 2011, Pages 954-960
Journal home page for Chest

Original Research
Obstructive Lung Diseases
Elevated Airway Purines in COPD

https://doi.org/10.1378/chest.10-2471Get rights and content

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.

Section snippets

Study Subjects

Subjects were participants in one of two observational studies: RES19044 (A Multi-center Cohort Study to Evaluate Radiological, Physiological and Biochemical Biomarkers in Patients with Chronic Obstructive Pulmonary Disease and Age and Gender Matched Controls)18 or ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) (clinicaltrials.gov; Identifier: NCT00292552).19 RES19044 was approved by Institutional Review Boards at St. Elizabeth's Medical Center (00195)

Adenosine and Other Biomarkers Measured in EBC

Airway concentrations of purines and other metabolites were successfully measured in EBC from 153 subjects: 36 healthy nonsmokers (NS group), 28 healthy smokers (S group), and 89 subjects with COPD (GOLD stage II, 29; GOLD stage III, 29; and GOLD stage IV, 31). Age and gender distribution was generally similar among cohorts, whereas FEV1 was decreased significantly in COPD (Table 1). Use of inhaled corticosteroids was common in the COPD cohorts (Table 1), as was use of inhaled long-acting β

Discussion

This study demonstrated that purine concentrations on airway surfaces, as measured through analysis of EBC, are elevated in COPD and correlated with markers of disease severity. These results are consistent with previous human4, 5 and animal studies9, 13 that link adenosine and airway inflammation and suggest that this purine plays a pathophysiologic role in COPD.10, 23, 24 Although indirect evidence of elevated airway adenosine in COPD has previously been reported,11 this study represents the

Acknowledgments

Author contributions: Dr Esther had full access to the data and vouches for the integrity of the manuscript.

Dr Esther: contributed to performing mass spectrometry, data analyses, and wrote and critically reviewed the manuscript.

Dr Lazaar: contributed to providing samples and critically reviewed the manuscript.

Dr Bordonali: contributed to providing biostatistical support and critically reviewed the manuscript.

Dr Qaqish: contributed to providing biostatistical support and critically reviewed the

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  • Cited by (0)

    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).

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