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BACKGROUND: Pulmonary Hypertension (PH) is a common form of high blood pressure in the lungs. It affects the pulmonary arteries, which normally allow blood to flow from the right heart to the lungs. Nitric Oxide (NO) is a potential mediator for establishing PH and decreasing its availability is implicated in the pathogenesis of PH. HYPOTHESIS: We tested the hypothesis that Fractional Exhaled Nitric Oxide (FeNO) is a good indicator to assess disease severity that may add to understanding the disease. METHODS: The aim of the study was to measure FeNO levels in consecutive PH patients and seek correlations with the 6 Minute walk distance (6MWD) within different World Health Organization (WHO) groups and New York Health Association Function Class (NYHA FC). Assignment to groups I or IV was done respecting the current guidelines. All values were taken at Tufts Medical Center PAH clinic visits. FeNO levels were measured utilizing the NIOX device. RESULTS: FeNO levels were highest in WHO Group 1 and lowest in WHO Group 5 patients. There was a strong inverse correlation between FeNO and 6MWD for each NYHA FC. (Pearson correlation of -0.986, p = 0.014). Within WHO Groups, we found significantly inverse correlations between FeNO and 6MWD in PH Group 4 (p= 0.012) and PH Group 5 (p=0.001). NYHA FC correlated with 6MWD across all WHO Groups (P=0.001). CONCLUSION: We report for the first time FeNO levels in all WHO Groups of PH. FeNO levels are low in early disease. FeNO levels correlate inversely with the severity of PH in WHO Group 4 and 5 patients. The increase in FeNO in more severe patients may reflect the degree of oxidative stress and inflammation in severe PH. Further studies to determine whether FeNO may be a biomarker in early disease, especially in PH Group 4 and 5 warrants further investigation.

This study examined pulmonary function, ventilation, exercise tolerance and the fractional concentration of exhaled nitric oxide (FeNO) in healthy controls (CON; n=7) and asthmatics (ASTH; n=7) following two-weeks of high intensity interval training (HIIT). An increase in FeNO above basal levels is associated with lung inflammation and is gaining popularity as a reliable diagnostic tool for the treatment of asthma. PURPOSE: The extent that HIIT decreases FeNO and thus, exercise tolerance in asthmatic subjects has not been previously investigated. METHODS: Pulmonary function was assessed using peak expiratory flow [PEF], forced vital capacity [FVC], and the ratio of forced expiratory volume in one second to FVC [FEV1/FVC]. FeNO was measured noninvasively using a NIOX portable device. Both groups performed a progressive exercise test (20 W/min) on a cycle ergometer to determine peak values of O2 uptake (VO2peak), CO2 output (VCO2peak), ventilation (VE) and time to exhaustion (TTE). Each subject completed six sessions of HIIT, which included 8 minutes of loadless cycling warm-up, 10 x 60 s bouts of exercise interspersed with 60 s periods of recovery at a low intensity of cycling. The intensity of the HIIT protocol was set at a target equivalent to 75% peak WR for ASTH and 80% peak WR for CON. Each training session was followed by 5 minutes of loadless cycling cool down. Following completion of all HIIT sessions, each subject repeated the pulmonary and exercise tests that were performed prior to training. A two-way analysis of variance with repeated measures (ANOVA-RM) was used to examine main effects, group (CON vs. ASTH) and time (Pre- vs. Post-HIIT) and significant interactions (Group x Time). A Student Newman Kuels post hoc test was used to determine specific differences as appropriate. Statistical significance was set at p < 0.05 RESULTS: Significant differences were found between the groups in FeNO, VO2peak, TTE, and peak WR. No differences were found between or within the groups in the pulmonary function measures. The pre-HIIT mean ± SEM of FeNO was 28 ± 2 ppb in ASTH versus 18 ± 1 ppb in CON and post-HIIT 28 ± 2 ppb versus 16 ± 3 ppb. The pre-HIIT mean ± SEM of TTE in ASTH was 691 ± 40 s and in CON was 998 ± 23 s, while post-HIIT TTEs were 781 ± 41 s and 1033 ± 36 s respectively. Pre-HIIT peak WR in ASTH was 175 ± 13 W and in CON 290 ± 10 W, while post-HIIT was 203 ± 14 W in ASTH versus 302 ± 13 W in CON. CONCLUSIONS: The HIIT was well tolerated by the ASTH subjects, and they were able to achieve a higher VE, VCO2, TTE, and peak WR following 6 sessions on HIIT.