Long-Term Continuous Positive Airway Pressure Therapy Normalizes High Exhaled Nitric Oxide Levels in Obstructive Sleep Apnea

Study Objectives: Upper airway inflammation and oxidative stress have been implicated in the pathogenesis of obstructive sleep apnea (OSA) and may be linked to cardiovascular consequences. We prospectively examined fraction of exhaled nitric oxide (FENO), a surrogate marker of upper airway inflammation using a portable nitric oxide analyzer (NIOX MINO). Design: In consecutive adult nonsmokers with suspected OSA, FENO was measured immediately before and after poly-somnographic studies, and within 1-3 months following continuous positive airway pressure (CPAP) therapy. Measurement and Results: FENO levels were increased in the 75 patients with OSA compared to the 29 controls, both before sleep (13.4 +/- 6.5 ppb vs. 6.5 +/- 3.5; p < 0.001) and after sleep (19.0 +/- 7.7 ppb vs. 6.9 +/- 3.7; p < 0.001). Furthermore, in patients with OSA, FENO levels were significantly higher post-sleep than pre-sleep (19.0 +/- 7.7 ppb vs. 13.4 +/- 6.5; p < 0.001), while there was no significant overnight change in patients without OSA. The rise in FENO correlated with the apnea-hypopnea index (r = 0.65, p < 0.001), nadir oxygen saturation (r = 0.54, p < 0.001), and arousal index (r = 0.52, p < 0.001). Thirty-seven of these patients underwent CPAP titration and treatment. Successful titration was associated with a lower overnight increase in FENO (7.2 +/- 3.3 vs. 11.0 +/- 4.3, p = 0.02). FENO levels declined after 1-3 months of CPAP therapy (11.7 +/- 4.4 ppb, p < 0.001). Conclusions: FENO levels are elevated in OSA, correlate with severity, and decrease after positive pressure therapy. This study supports the role of upper airway inflammation in OSA pathogenesis and a possible role for FENO in monitoring CPAP therapy.