Biomarkers of Idiopathic Pulmonary Arterial Hypertension (iPAH): Volatile Constituents of Expired Breath Condensates (EBC) as Markers of Disease Severity Using Gas Chromatography/Mass Spectroscopy (GC/MS)

Purpose A challenge to pulmonary hypertension diagnosis and treatment is the early detection of occult pulmonary vascular pathology. At our current state of knowledge patients often, despite recognized risk factors for disease, present only after a prolonged interval of symptoms. These symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression of disease. There is significant need to develop new markers for disease detection and management. Nitric oxide (NO) in expired air has been shown to be lower in patients with iPAH. However, due to a lack of specificity for pulmonary hypertension this particular biomarker has not been clinically useful. In the current study the efficacy of volatile constituents of EBC as markers of iPAH was examined. Methods and Materials EBC samples collected from 30 age-matched healthy individuals (CON) and 30 New York Heart functional class 3 and 4 iPAH patients were analyzed using GC/MS. Results One hundred thirty peaks were identified within the GC/MS chromatograms. Of these peaks 19 were identified in the chromatograms of both the CON and iPAH groups, while 62 peaks were unique to the CON group and 49 peaks were unique to the iPAH group. Multivariate ANOVA indicates significant differences between CON and iPAH groups for nitric oxide at an expiratory flow of 50 ml∕sec (NO50) and 5 of the 19 peaks present in both the CON and iPAH groups. Of the 68 peaks present in the iPAH group 38 were significantly correlated with NO50 (4 peaks), DLCO (6 peaks), 6 minute walk distance (8 peaks), brain natriuretic peptide (5 peaks), and pulmonary hemodynamic variables (12 peaks). Volatile constituents of EBC can be used to distinguish healthy individuals from those with iPAH and are correlated with disease severity. Conclusions Volatile constituents of EBC can be used to distinguish healthy individuals from those with iPAH and are correlated with disease severity.Purpose: A challenge to pulmonary hypertension diagnosis and treatment is the early detection of occult pulmonary vascular pathology. At our current state of knowledge patients often, despite recognized risk factors for disease, present only after a prolonged interval of symptoms. These symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression of disease. There is significant need to develop new markers for disease detection and management. Nitric oxide (NO) in expired air has been shown to be lower in patients with iPAH. However, due to a lack of specificity for pulmonary hypertension this particular biomarker has not been clinically useful. In the current study the efficacy of volatile constituents of EBC as markers of iPAH was examined. Methods and Materials: EBC samples collected from 30 age-matched healthy individuals (CON) and 30 New York Heart functional class 3 and 4 iPAH patients were analyzed using GC/MS. Results: One hundred thirty peaks were identified within the GC/MS chromatograms. Of these peaks 19 were identified in the chromatograms of both the CON and iPAH groups, while 62 peaks were unique to the CON group and 49 peaks were unique to the iPAH group. Multivariate ANOVA indicates significant differences between CON and iPAH groups for nitric oxide at an expiratory flow of 50 mlsec (NO50) and 5 of the 19 peaks present in both the CON and iPAH groups. Of the 68 peaks present in the iPAH group 38 were significantly correlated with NO50 (4 peaks), DLCO (6 peaks), 6 minute walk distance (8 peaks), brain natriuretic peptide (5 peaks), and pulmonary hemodynamic variables (12 peaks). Volatile constituents of EBC can be used to distinguish healthy individuals from those with iPAH and are correlated with disease severity. Conclusions: Volatile constituents of EBC can be used to distinguish healthy individuals from those with iPAH and are correlated with disease severity.