Feasibility of early detection of acute pulmonary exacerbations by breathomics

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

Phoenix

Conferencia; 29th Annual North American Cystic Fibrosis Conference; 2015

Progressive lung function decline in cystic fibrosis (CF) often does not proceed in a linear fashion, but rather is punctuated by acute pulmonary exacerbations (APEs). Inpatient care may be necessary to restore function but even with aggressive treatment, up to 25% of patients fail to recover to baseline function. The frequency of APEs severe enough to require hospitalization is one of the most significant risk factors for death in CF. APE diagnosis remains challenging due to changes in patient symptoms over time, and often is at the discretion of the clinicians. Hence, it is important to develop reliable objective measurements to diagnose an APE, and perhaps even predict oncoming APEs, allowing early intervention to potentially prevent lung function loss. The objective of this study is to evaluate the feasibility of predicting an APE onset by metabolic profiling of exhaled breath condensate (EBC). Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry and supervised classification models were used to profile and identify metabolites in EBC samples, thereby facilitating discrimination of 4 pre-APE patient samples (CF patients 1 to 3 months before an APE) from 19 stable CF patient samples (EBC samples from CF subjects who are clinically stable without an APE for ≥3 months). A panel containing 8 metabolic discriminant features distinguished the 4 pre-APE EBC samples from the 19 stable EBC samples with excellent accuracy, specificity and sensitivity using the orthogonal partial least square discriminant analysis (oPLS-DA) model. Three of the key differentiating metabolites were identified as lactic acid, eicosapentaenoic acid, and hydroxyacetone. Lactic acid was elevated in pre-APE compared to stable CF patient EBC samples. Interestingly, lactic acid has been reported to be elevated in the bronchoalveolar lavage fluid (BALF) of CF patients, relative to control subjects.