Long-term continuous positive airway pressure therapy normalizes high exhaled nitric oxide levels in obstructive sleep apnea

Abstract

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 polysomnographic 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.

Keywords: Sleep disordered breathing; endogenous nitrate vasodilator; positive pressure ventilation.

Figure 1. Flow diagram summarizing study enrollment

Figure 2. Reasons for dropping out of study

Figure 3. FENO levels before and after sleep in OSA and non-OSA subjects

Pre-sleep FENO (prePSGno) and post-sleep FENO (postPSGno) levels during 1 night of diagnostic PSG study in OSA (N = 75) and non-OSA subjects (N = 29). OSA patients had significantly higher prePSG_no and postPSG_no than non-OSA patients. *, mean ± SD.

Figure 4. Relationship between ΔFENOpre-postPSG levels and AHI

Rise in FENO levels following sleep (ΔFENOpre-postPSG) in our study cohort (N = 104) increased with OSA severity, as indicated by AHI. There was a significant positive correlation between ΔFENOpre-postPSG and AHItotal (r = 0.65, p < 0.001).

Figure 5. FENO levels at various study stages in OSA patients on CPAP therapy

This graph shows the trending of FENO values (mean ± 95% confidence intervals) taken before and after sleep during PSG study (prePSG_no and postPSG_no), before and after sleep during CPAP titration night (preCPAP_no and postCPAP_no), and following 1-3 months of CPAP therapy (T_no) in the OSA patients (N = 37) who were started on CPAP therapy and had undergone all 5 sets of NO measurements. Mean FENO levels increased following sleep during both nights of PSG and CPAP titration studies. Mean FENO level, T_no, dropped to a level lower than baseline pre-sleep values after regular long-term use of CPAP therapy.