Measurement of fractional exhaled nitric oxide and nasal nitric oxide in male patients with obstructive sleep apnea

Abstract

Objective Airway inflammation plays an important role in obstructive sleep apnea (OSA); exhaled nitric oxide is regarded as a noninvasive marker of airway inflammation. The aim of this study was to evaluate fractional exhaled nitric oxide (FeNO) and nasal nitric oxide (nNO) in patients with OSA. Methods Seventy-five patients with OSA and 30 health controls were enrolled in this study. FeNO and nNO were measured before and after sleep. Nasal lavage was performed in 31 non-smoking individuals immediately after NO measurement in the morning. The sample of nasal lavage was taken for cell classification and analyzing interleukin 6 (IL-6) and interleukin 8 (IL-8). Results Both FeNO and nNO were significantly higher in OSA (before sleep FeNO 21.08 ± 8.79 ppb vs.16.90 ± 6.86 ppb, p = 0.022; after sleep FeNO 25.57 ± 15.58 ppb vs.18.07 ± 6.25 ppb, p = 0.003; before sleep nNO 487.03 ± 115.83 ppb vs. 413.37 ± 73.10 ppb, p = 0.001; after sleep nNO 550.07 ± 130.24 ppb vs. 460.43 ± 109.77 ppb, p < 0.001). Furthermore, in non-smoking OSA, nNO levels were positively correlated with apnea hypopnea index (AHI) and average decrease of pulse arterial oxygen saturation (SpO 2 ); after sleep, nNO was also positively associated to recording time with SpO 2 < 90% and negatively associated to minimum SpO 2 . Both before and after sleep nNO levels were positively correlated with the percentage of neutrophils in nasal lavage ( r = 0.528, p = 0.014; r = 0.702, p < 0.001, respectively). Additionally, before sleep nNO was also positively associated with IL-6 ( r = 0.586, p = 0.005) and IL-8 ( r = 0.520, p = 0.016) concentration. Conclusion This study sustains the presence of airway inflammation in OSA patients with the increase of FeNO and nNO. The data suggests nNO might have greater value than FeNO since it positively correlated with OSA severity, and nNO is a potential bio-marker of nasal inflammation in non-smoking OSA patients. Electronic supplementary material The online version of this article (10.1007/s11325-018-1760-1) contains supplementary material, which is available to authorized users.

Exhaled Breath Analysis in Obstructive Sleep Apnea Syndrome: A Review of the Literature

“…Even the association of the eNO with the apnea-hypopnea index (AHI) is controversial. Indeed, while some studies found a strong and positive correlation between FeNO and AHI, with a r of 0.8–0.9 [23,33], or oNO and AHI ( r : 0.46) [32] and a negative one between CaNO and AHI, with a r of 0.9 [23], this was not confirmed by other studies [20,21,22,27,28,39,41].…”

“…The study of FeNO in the diagnosis of OSAS has led to contradictory findings. Indeed, while some studies described a raising of FeNO level in OSAS [20,21,22,23,24,25], the majority did not confirm the finding [26,27,28,29,30] or just showed a higher concentration in OSAS patients when compared with non-obese healthy controls [31,32,33]. Besides, even considering only those studies with a positive finding, the FeNO level, albeit statistically higher than healthy controls, did not reach a clinical significance.…”

“…Furthermore, it is still unclear whether an overnight change in the production of eNO exists or not. While some studies reported an overnight increase in FeNO [20,24] and in the concentration of nitric oxide exhaled by the nose (nasal nitric oxide–nNO–) and by the mouth (orale nitrix oxide–oNO–) [39] in OSAS patients [20,39], other studies failed to confirm the evidence [21], or they found an overnight increase limited to subgroups of OSAS, such as obese OSAS patients [29] or children with mild OSAS but not moderate/severe [28], or healthy controls [39].…”

Prevalence and impact of comorbid obstructive sleep apnoea in diffuse parenchymal lung diseases

“…Sputum gene expression analyses have identified a significant increase for IL-6 and IL-8 in IPF patients [30]. Both IL-6 and IL-8 may mediate nasal inflammation in OSA patients, and were positively correlated with AHI [31]. Another possible explanation is that pulmonary function tests in identified studies were performed in an upright position but not in a supine position, which could not accurately reflect pulmonary function changes during sleep [13,23,26].…”

Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review

“…Many studies have investigated eNO behavior in patients with obstructive sleep apnea (OSA), reporting slightly, but still significantly higher levels of FeNO and J’awNO and, conversely, reduced CaNO values than healthy controls [ 94 , 95 , 96 ]. Interestingly, c-PAP therapy led to a normalization of eNO parameters, suggesting its potential role as a biomarker of compliance and response to therapy [ 97 , 98 ].…”