Early Detection of Cystic Fibrosis Acute Pulmonary Exacerbations by Exhaled Breath Condensate Metabolomics

ZANG, XIAOLING; MONGE, MARÍA EUGENIA; GAUL, DAVID A.; MCCARTY, NAEL A.; STECENKO, ARLENE; FERNÁNDEZ, FACUNDO M.

JOURNAL OF PROTEOME RESEARCH

AMER CHEMICAL SOC

Año: 2020 vol. 19 p. 144 - 152

1535-3893

The most common cause of death in cystic fibrosis (CF) patients is progressive lungfunction decline, which is punctuated by acute pulmonary exacerbations (APEs). A majorchallenge is to discover biomarkers for detecting an oncoming APE and allow for preemptiveclinical interventions. Metabolic profiling of exhaled breath condensate (EBC) samples collectedfrom CF patients before, during and after APEs and under stable conditions (n=210) wasperformed using ultraperformance liquid chromatography (UPLC) coupled to Orbitrap massspectrometry (MS). Negative ion mode MS data showed that classification between metabolicprofiles from ?pre-APE? (pending APE before the CF patient had any signs of illness) and stableCF samples was possible with good sensitivities (85.7% and 89.5%), specificities (88.4% and84.1%), and accuracies (87.7% and 85.7%) for pediatric and adult patients, respectively.Improved classification performance was achieved by combining positive with negative ionmode data. Discriminant metabolites included two potential biomarkers identified in a previouspilot study: lactic acid and 4-hydroxycyclohexylcarboxylic acid. Some of the discriminantmetabolites had microbial origins, indicating a possible role of bacterial metabolism in APEprogression. The results show promise for detecting an oncoming APE using EBC metabolites,thus permitting early intervention to abort such event.