Clinical Application Of Exhaled Nitric Oxide In Obstructive Sleep Apnea

Section 1:Measurement of exhaled nitric oxide concentration in patients with obstructive sleep apnea:a meta-analysisBackground:Exhaled nitric oxide(eNO)has been proposed as a non-invasive measure of airway inflammation.However,its value in patients with obstructive sleep apnea(OSA)is still controversial.We aim to assess the difference in eNO levels between patients with OSA and controls by a meta-analysis.Methods:A systematic search was performed in the Pubmed,EMBASE,the Cochrane Library,and Medline databases to collect relevant studies published from 1996 to 2016.Eligible studies that reported eNO levels in patients with OSA were included.STATA(version 12.0)was used for data analysis.Results:Two hundred and eighty-four studies were reviewed for inclusion,with 16 studies pooled for analysis[16 studies for fractional exhaled nitric oxide(FENO),five for alveolar nitric oxide(CANO),and four for the maximum airway wall flux of nitric oxide(J'awNO)].The FENO levels were significantly higher in patients with OSA compared with that in the control groups(6.32 ppb,95%confidence interval(CI)4.46-8.33,P<0.001).Furthermore,FENO was significantly increased(4.00 ppb,95%CI 1.74-6.27,P = 0.001)after overnight sleep in patients with OSA,but not in healthy controls.Additionally,long-term continuous positive airway pressure(CPAP)therapy reduced FENO levels(-5.82 ppb,95%CI-9.6 to-2.01,P<0.001).However,the CANO(-0.01 ppb,95%Cl-1.66-1.64,P = 0.989)and J'awNO levels(220.32 pL/s,95%CI-49.31-489.94,P = 0.109)were not significantly different between the OSA groups and non-OSA groups.Conclusion:The results of the meta-analysis suggest that OSA is significantly associated with airway inflammation and elevated FENO levels can be modified by long-term CPAP therapy.J'awNO and CANO levels were not significantly different between the OSA groups and control groups.Section 2:Measurement of fractional exhaled nitric oxide and nasal nitric oxide in male adults with obstructive sleep apneaObjective: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 OSA.Methods:Seventy-five consecutive patients of sleep laboratory and thirty health controls were enrolled in this study.Standard overnight polysomnography(PSG)were carried out in all the participants to diagnose or preclude sleep disorders.FENO and nNO were measured before sleep(9-10 p.m.)and after sleep(6-7 a.m.)in all subjects.Results:Apnea-hypopnea index(AHI)was 28.1(13.80,57.0)/h in OSA patients and 0.85(0.20,1.70)/h in health controls.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 nonsmoking OSA,nNO levels were positively correlated with AHI,oxygen desaturation index(ODI)and average decrease of oxygen saturation;after sleep nNO was also positively associated to recording time with pulse arterial oxygen saturation(SpO2)<90%and negatively associated to minimum SpO2.While FENO had no statistically significant correlation with sleep parameters.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 correlated with OSA severity.Section 3:Relationship between nasal nitric oxide and nasal inflammation in patients with obstructive sleep apneaObjective:Nasal inflammation presents in obstructive sleep apnea(OSA)patients,the purpose of this study was to evaluate the relationship between nasal nitric oxide(nNO)and nasal inflammation in patients with OSA.Methods:Both health controls and nonsmoking patients with OSA undertook polysomnography,measured fractional exhaled nitric oxide(FENO)and nNO before and after sleep.Nasal lavage was performed in all individuals immediately after NO measurement in the morning.The sample of nasal lavage was taken for cell counting and analyzing interleukin 6(IL-6),interleukin 8(IL-8)and interleukin 10(IL-10)by chemiluminescent immunoassay.Results:The concentrations of IL-6,IL-8 and percentage of neutrophils,lymphocytes and eosinophils were significantly higher in 21 patients with OSA than in 10 matched controls.Both before sleep nNO levels and after sleep nNO levels were positive correlated with the percentage of neutrophils(r = 0.528,P = 0.014;r = 0.702,P<0.001,respectively).In addition,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 in nasal lavage.Conclusion:This study confirmed the presence of nasal inflammation in nonsmoking OSA patients,and nNO is a potential bio-marker of nasal inflammation in these patients.