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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/L987    most recent 90512.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Esther, C. R. Articles by Boucher, R. C. PubMed PubMed Citation Articles by Esther, C. R., Jr. Articles by Boucher, R. C.

Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosis

¹Division of Pediatric Pulmonology, ²Center of Environmental Health and Susceptibility, Department of Environmental Sciences and Engineering, and ³Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill; and ⁴Environmental Protection Agency, Chapel Hill, North Carolina

Submitted 2 October 2008 ; accepted in final form 19 March 2009

Exhaled breath condensate (EBC) analyses promise simple and noninvasive methods to measure airway biomarkers but pose considerable methodological challenges. We utilized mass spectrometry to measure EBC purine biomarkers adenosine and AMP plus urea to control for dilutional variability in two studies: 1) a cross-sectional analysis of 28 healthy, 40 cystic fibrosis (CF), and 11 asthmatic children; and 2) a longitudinal analysis of 26 CF children before and after treatment of a pulmonary exacerbation. EBC adenosine, AMP, and urea were readily detected and quantified by mass spectrometry, and analysis suggested significant dilutional variability. Using biomarker-to-urea ratios to control for dilution, the EBC AMP-to-urea ratio was elevated in CF [median 1.3, interquartile range (IQR) 0.7–2.3] vs. control (median 0.75, IQR 0.3–1.4; P < 0.05), and the adenosine-to-urea ratio was elevated in asthma (median 1.5, IQR 0.9–2.9) vs. control (median 0.4, IQR 0.2–1.6; P < 0.05). Changes in EBC purine-to-urea ratios correlated with changes in percent predicted forced expiratory volume in 1 s (FEV₁) (r = –0.53 AMP/urea, r = –0.55 adenosine/urea; P < 0.01 for both) after CF exacerbation treatment. Similar results were observed using dilution factors calculated from serum-to-EBC urea ratios or EBC electrolytes, and the comparable ratios of EBC electrolytes to urea in CF and control (median 3.2, IQR 1.6–6.0 CF; median 5.5, IQR 1.4–7.7 control) validated use of airway urea as an EBC dilution marker. These results show that mass spectrometric analyses can be applied to measurement of purines in EBC and demonstrate that EBC adenosine-to-urea and AMP-to-urea ratios are potential noninvasive biomarkers of airways disease.

adenosine; adenosine monophosphate; urea