Exhaled breath condensate in pulmonary arterial hypertension

Abstract

Over the last decade, several new agents have been developed for the treatment of pulmonary arterial hypertension (PAH), and blood biomarkers have been developed which aim to monitor such treatment, and which correlate well with physiological parameters, symptoms and mortality. However, little is known regarding biomarkers collected using non-invasive methods such as exhaled breath condensate (EBC). EBC biomarkers show potential as a rapid, repeatable and easy method of sampling the pulmonary vasculature in severely ill patients. The current study aimed to investigate EBC biomarkers in patients with PAH of different aetiologies. We studied 89 patients in four groups: pulmonary arterial hypertension (PAH, n = 30), PAH associated with COPD (COPD/PAH, n = 14), COPD but no PAH (n = 16) and healthy controls (n = 29). Levels of the following EBC markers were measured: amino-terminal pro-brain natriuretic peptide (NT-proBNP), endothelin-1 (ET-1), 6-keto prostaglandin (PG)F1α, hydrogen peroxide (H2O2), total oxides of nitrogen (NOx), total protein and pH. ET-1 and NT-proBNP were measured in plasma concurrently. Data were analysed with ANOVA or Kruskal Wallis tests where appropriate. Correlations were performed using Pearson's correlation coefficient. NT-proBNP was detectable in EBC and was highest in the PAH group, significantly higher than the COPD/PAH group (194.1 ± 23.3 versus 80.8 ± 22.2 fmol ml−1, p < 0.05). EBC ET-1 was significantly higher in subjects with PAH (1.53 ± 0.32 fmol ml−1) compared to those with COPD/PAH (0.25 ± 0.03 fmol ml−1, p < 0.05) and controls (0.66 ± 0.18 fmol ml−1, p < 0.05). 6-keto PGF1α was low in the PAH group, significantly lower than the COPD/PAH group (4027 ± 445 versus 8381 ± 1024 pg ml−1, p < 0.01). EBC biomarkers are measurable in PAH. EBC ET-1 was raised in PAH compared with controls and patients with PAH secondary to COPD, whereas 6-keto PGF1α was low. EBC biomarkers may be useful in detection and monitoring of PAH.