Feasibility of Early Detection of Acute Pulmonary Exacerbations by Exhaled Breath Condensate Metabolomics

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

Atlanta

Conferencia; Pittcon 2016 Conference & Expo; 2016

Progressive lung function decline in cystic fibrosis (CF) patients often does not proceed in a linear fashion, rather is punctuated by acute pulmonary exacerbations (APEs). The frequency of APEs severe enough to require hospitalization is a crucial factor of death in CF patients and the diagnosis remains challenging. The objective of this research is to develop reliable methods to predict oncoming APEs in order to prevent associated lung function loss, mortality and morbidity. In this study, untargeted metabolomics profiling of exhaled breath condensate (EBC) samples from 4 pre-APE (CF patients 1 to 3 months before an APE) and 19 stable CF patients (CF subjects who are clinically stable without an APE for ≥3 months) was performed using ultra performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry. A supervised classification model, orthogonal partial least squares discriminant analysis (OPLS-DA), distinguished pre-APE from stable CF samples with good accuracy, sensitivity and specificity. Tentatively identified discriminant metabolites include lactic acid and hydroxyacetone. Elevated lactic acid in pre-APE compared to stable CF EBC samples was found in this study, in agreement with a previous work reporting an increased level of lactate in bronchoalveolar lavage fluid from CF patients with higher inflammation [1]. Hydroxyacetone is an intermediate in the metabolism of glycine, serine and threonine. There is evidence in literature about higher amino acid content in sputum extracts from CF patients compared to non-CF patients [2]. However, direct relationship between hydroxyacetone and CF or other respiratory diseases remains to be elucidated.