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Extracellular purines are biomarkers of neutrophilic airway inflammation

¹ Pediatric Pulmonology, ² Center for Environmental Medicine, Asthma and Lung Biology (CEMALB), ³ Cystic Fibrosis (CF) Research Center, and ⁴ Division of General Medicine and Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

CORRESPONDENCE: C. R. Esther Jr, Pediatric Pulmonology, 5^th Floor Bioinformatics, CB#7220, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7220, USA. Fax: 1 9199666179. E-mail: Charles_Esther{at}med.unc.edu

Keywords: Biomarker, bronchoalveolar lavage fluid, cystic fibrosis, exhaled breath condensate, inflammation, purinergic signalling

Received: July 16, 2007
Accepted January 20, 2008

Purinergic signalling regulates airway defence mechanisms, suggesting that extracellular purines could serve as airway inflammation biomarkers in cystic fibrosis (CF).

The purines adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine were measured in sputum from 21 adults (spontaneously expectorated from seven CF patients, induced from 14 healthy controls) to assess normal values and CF-associated changes. Subsequently, purine levels were measured in bronchoalveolar lavage fluid (BALF) from 37 children (25 CF patients, 12 disease controls) and compared with neutrophil counts, presence of airway infection and lung function. To noninvasively assess airway purines, ATP levels were measured using luminometry in exhaled breath condensate (EBC) from 14 children with CF and 14 healthy controls, then 14 CF children during a pulmonary exacerbation.

Both ATP and AMP were elevated in sputum and BALF from CF subjects compared with controls. In BALF, ATP and AMP levels were inversely related to lung function and strongly correlated with neutrophil counts. In EBC, ATP levels were increased in CF relative to controls and decreased after treatment of CF pulmonary exacerbation.

The purines adenosine triphosphate and adenosine monophosphate are candidate biomarkers of neutrophilic airways inflammation. Measurement of purines in sputum or exhaled breath condensate may provide a relatively simple and noninvasive method to track this inflammation.