Breath Analysis in Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a progressive and devastating condition characterized by vascular cell proliferation and is associated with several metabolic derangements. We hypothesized that metabolic derangements in PAH can be detected by measuring metabolic by-products in exhaled breath. Methods: We collected breath and blood samples from patients with PAH at the time of right-sided heart catheterization (n = 31) and from healthy control subjects (n =34). Breath was analyzed by selected ion flow tube-mass spectrometry in predetermined training and validation cohorts. Results: Patients with PAH were 51.5 +/- 14 years old, and 27 were women (85%). Control subjects were 38 +/- 13 years old, and 22 were women (65%). Discriminant analysis in the training set identifi ed three ion peaks ( H-3 O + 29 +, NO + 56 +, and O (2) + 98 +) and the variable age that correctly classifi ed 88.9% of the individuals. In an independent validation cohort, 82.8% of the individuals were classifi ed correctly. The concentrations of the volatile organic compounds 2-propanol, acetaldehyde, ammonia, ethanol, pentane, 1-decene, 1-octene, and 2-nonene were different in patients with PAH compared with control subjects. Exhaled ammonia was higher in patients with PAH (median [interquartile range]: 94.7 parts per billion (ppb) [70- 129 ppb] vs 60.9 ppb [46- 77 ppb], P,< .001) and was associated with right atrial pressure ( rho = 0.57, P < .001), mean pulmonary artery pressure ( rho = - 0.43, P < .015), cardiac index by thermodilution (rho = - 0.39, P < .03), pulmonary vascular resistance (rho = 0.40, P = .04), mixed venous oxygen (rho = - 0.59, P < .001), and right ventricular dilation (rho = 0.42, P = .03). Conclusions: Breathprint is different between patients with PAH and healthy control subjects. Several specific compounds, including ammonia, were elevated in the breath of patients with PAH. Exhaled ammonia levels correlated with severity of disease.