Metabolomic signatures in nuclear magnetic resonance spectra of exhaled breath condensate identify asthma

Abstract

Exhaled breath condensate (EBC) holds promise as a noninvasive method of collecting airway-lining fluid, although at an unknown dilution [1]. While metabolomic studies of EBC using nuclear magnetic resonance (NMR) spectroscopy have previously shown promise in asthma diagnosis and subtyping [2, 3], a study that was recently published in the European Respiratory Journal that failed to find usable NMR signature in EBC collections from disposable systems [4]. This led the authors to conclude that NMR metabolomics lacks sufficient sensitivity for metabolic fingerprinting of EBC. Interestingly, they were able to obtain high quality results from the same samples with mass spectroscopy, which they recommended for future use. As this is a nascent and technically complex field, we present our very different early experiences, which suggest that reproducible, valid and useful NMR metabolomic fingerprinting of EBC is indeed possible. Specifically, we found that the presence or absence of a trident peak at 7 ppm during NMR spectroscopy reliably distinguished between EBC samples collected from normal and asthmatic subjects, respectively. This peak probably represents ammonium ion, loss of which in asthma is consistent with reduced expression of glutaminase, an enzyme that converts glutamine to glutamate and ammonia [5]. Institutional committees approved all research protocols. The subjects included both adults (>21 yrs) and children (6-15 yrs). Adult asthmatic subjects (n=7) were physician diagnosed, meeting American Thoracic Society/European Respiratory Society criteria [6], and were nonsmokers. Control normal adults were healthy nonsmoking volunteers (n=10). The children were part of an ongoing prospective asthma cohort for which multidimensional genotype and phenotype data is being.