Exhaled breath markers in patients with obstructive sleep apnoea.
Petrosyan Marina,Perraki Eleni,Simoes Davina,Koutsourelakis Ioannis,Vagiakis Emmanouil,Roussos Charis,Gratziou Christina
Sleep & breathing = Schlaf & Atmung
The objectives of the present study were to assess the level of exhaled breath markers indicating airway inflammation and oxidative stress in patients with obstructive sleep apnoea syndrome (OSAS) in comparison with non-apnoeic (obese and non-obese) subjects and investigate whether therapy with continuous positive airway pressure (CPAP) can modify them. The design was a retrospective observational study, set in Evgeneidio Hospital. Twenty-six OSAS patients and nine obese and 10 non-obese non-apnoeic subjects participated in this study. We measured nasal nitric oxide (nNO), exhaled nitric oxide (eNO), exhaled carbon monoxide (eCO) in exhaled breath, and 8-isoprostane, leukotriene B(4) (LTB(4)), nitrates, hydrogen peroxide (H(2)O(2)), and pH in exhaled breath condensate (EBC) before and after 1 month of CPAP therapy. The levels of eNO and eCO were higher in OSAS patients than in control subjects (p < 0.05). Nasal NO was higher in OSAS patients than in obese controls (p < 0.01). The level of H(2)O(2), 8-isoprostane, LTB(4), and nitrates were elevated in OSAS patients in comparison with obese subjects (p < 0.01). Conversely, pH was lower in OSAS patients than in non-apnoeic controls (p < 0.01). One month of CPAP therapy increased pH (p < 0.05) and reduced eNO (p < 0.001) and nNO (p < 0.05). Apnea/hypopnoea index was positively correlated with 8-isoprostane (r = 0.42; p < 0.05), LTB(4) (r = 0.35; p < 0.05), nitrates (r = 0.54; p < 0.001), and H(2)O(2) (r = 0.42; p < 0.05). Airway inflammation and oxidative stress are present in the airway of OSAS patients in contrast to non-apnoeic subjects. Exhaled breath markers are positively correlated with the severity of OSAS. One-month administration of CPAP improved airway inflammation and oxidative stress.
10.1007/s11325-007-0160-8
Clinical and functional prediction of moderate to severe obstructive sleep apnoea.
Bucca Caterina,Brussino Luisa,Maule Milena Maria,Baldi Ileana,Guida Giuseppe,Culla Beatrice,Merletti Franco,Foresi Antonio,Rolla Giovanni,Mutani Roberto,Cicolin Alessandro
The clinical respiratory journal
INTRODUCTION:Upper airway inflammation and narrowing are characteristics of obstructive sleep apnoea (OSA). Inflammatory markers have been found to be increased in exhaled breath and induced sputum of patients with OSA. OBJECTIVES:The aim of this study was to investigate if the measurement of exhaled nitric oxide (F(ENO) ), as marker of airway inflammation, together with the forced mid-expiratory/mid-inspiratory airflow ratio (FEF(50) /FIF(50) ), as marker of upper airway narrowing, may help to predict OSA. METHODS:Two hundred one consecutive outpatients with suspected OSA were prospectively studied between January 2004 and December 2005. All patients underwent clinical examination, spirometry with measurement of FEF(50) /FIF(50) , maximum inspiratory pressure, arterial blood gas analysis, exhaled nitric oxide (F(ENO) ) and overnight polysomnography. Linear regression models were used to evaluate the effect of measured variables on the apnoea-hypopnoea index (AHI). Models were cross-validated by bootstrapping. RESULTS:Most of the patients were obese and had severe OSA. FEF(50) /FIF(50) , F(ENO) and an interaction term between smoking and F(ENO) contributed significantly to the predictive model for AHI, in addition to age, neck circumference, body mass index and carboxyhaemoglobin saturation. A nomogram to predict AHI was obtained, which converted the effect of each covariate in the model to a 0-100 scale. The nomogram showed a good predictive ability for AHI values between 25 and 64. CONCLUSIONS:The measurement of F(ENO) and of FEF(50) /FIF(50) improves the ability to predict OSA and may be used to identify patients who require a sleep study.
10.1111/j.1752-699X.2010.00223.x
Sleep apnea is associated with bronchial inflammation and continuous positive airway pressure-induced airway hyperresponsiveness.
Devouassoux Gilles,Lévy Patrick,Rossini Eliane,Pin Isabelle,Fior-Gozlan Michèle,Henry Mireille,Seigneurin Daniel,Pépin Jean-Louis
The Journal of allergy and clinical immunology
BACKGROUND:Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated. OBJECTIVE:The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa. METHODS:The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP. RESULTS:Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% +/- 20% vs 43% +/- 12%, P < .05; and 25.02 +/- 9.43 ng/mL vs 8.6 +/- 3.7 ng/mL, P < .001, respectively). IL-8 in sputum supernatant was correlated to apnea hypopnea index (P < .01; r = 0.81). After 1 month of CPAP, this inflammatory pattern remained unchanged, and an increase in airway hyperresponsiveness (AHR) was observed (P < .001). CONCLUSION:Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use. CLINICAL IMPLICATIONS:Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction.
10.1016/j.jaci.2006.11.638
Exhaled nitric oxide from the central airway and alveoli in OSAHS patients: the potential correlations and clinical implications.
Liu Jie,Li Zheng,Liu Zilong,Zhu Fen,Li Wenjing,Jiang Hong,Wu Xiaodan,Song Yuanlin,Li Shanqun,Bai Chunxue
Sleep & breathing = Schlaf & Atmung
BACKGROUND:The aim of the study was to evaluate exhaled nitric oxide (eNO) derived from different areas of airway in obstructive sleep apnea hypopnea syndrome (OSAHS) patients with NO exchange model and investigate the potential application and interpretation of eNO in clinical setting. METHODS:This study was divided into two parts. Firstly, we performed a case control study in 32 OSAHS patients and 27 non-OSAHS participants. Fractional eNO (FeNO) and eNO from the central airway (J'awNO) and from alveoli (CANO) were compared in OSAHS and control groups. Also, correlation of eNO to severity of OSAHS was analyzed. Secondly, a prospective study was conducted in 30 severe OSAHS patients who received a short-term nasal continuous positive airway pressure (nCPAP) treatment. We evaluated eNO, plasma ET-1 concentration, and echocardiography during the treatment process and explored the potential relationship among them. RESULTS:FeNO and J'awNO were higher in OSAHS and associated with disease severity, while CANO was relatively lower. After nCPAP treatment in severe OSAHS patients, FeNO and J'awNO decreased and CANO increased significantly. Substantial agreement was shown between the elevation of CANO and the decrease of plasma ET-1 concentration after nCPAP by Kappa analysis for consistency. Tei index, which is considered indicative of global right ventricular function, might be predicted by plasma ET-1 levels in severe OSAHS patients. CONCLUSIONS:NO exchange model provides us with more information of eNO derived from different areas. eNO is not only confirmed to be an effective method for airway inflammation evaluation in the follow-up of OSAHS, CANO may also serve as a useful marker in monitoring endothelial function, resistance of pulmonary circulation, and right ventricular function for clinical implication.
10.1007/s11325-015-1198-7
Effect of Continuous Positive Airway Pressure on Airway Inflammation and Oxidative Stress in Patients with Obstructive Sleep Apnea.
Tichanon Promsrisuk,Wilaiwan Khrisanapant,Sopida Santamit,Orapin Pasurivong,Watchara Boonsawat,Banjamas Intarapoka
Canadian respiratory journal
Background. Airway inflammation and oxidative stress may be linked in obstructive sleep apnea (OSA) patients. We determined the effectiveness of continuous positive airway pressure (CPAP) therapy in reducing fractional exhaled nitric oxide (FeNO) and malondialdehyde (MDA) levels in OSA patients. Methods. Thirteen patients with OSA and 13 normal controls were recruited. FeNO and MDA levels were measured in the controls and in OSA patients before and after three months of CPAP therapy. Results. FeNO and MDA levels were higher in the patients compared to the age and gender matched controls (FeNO: 25.9 ± 5.0 versus 17.5 ± 5.9 ppb, P < 0.001; MDA: 14.6 ± 7.8 versus 2.1 ± 0.3 μmol/L, P < 0.001). FeNO and MDA levels were lower post-CPAP compared to pre-CPAP (FeNO: 25.9 ± 5.0 versus 17.0 ± 2.3 ppb, P < 0.001; MDA: 14.6 ± 7.8 versus 10.0 ± 6.4 μmol/L, P < 0.01). Apnea-hypopnea index (15.9 ± 6.6 versus 4.1 ± 2.1/h, P < 0.001) and mean arterial pressure (P < 0.01) decreased following CPAP treatment. Daytime mean SpO2 (P < 0.05) increased. Conclusion. Our study demonstrates that CPAP therapy yields clinical benefits by reducing upper airway inflammation and oxidative stress in OSA patients.
10.1155/2016/3107324
Exhaled nitric oxide in patients with sleep apnea.
Agustí A G,Barbé F,Togores B
Sleep
Cardiovascular diseases are frequent in patients with obstructive sleep apnea syndrome (OSAS), but the mechanisms underlying this association are largely unknown. Nitric oxide (NO) is a key regulatory element of vascular physiology. The concentration of NO in the exhaled air ([NOexh]) appears to be reduced in patients with systemic and pulmonary hypertension. This study sought to investigate whether [NOexh] is abnormal in patients with OSAS, and to explore potential relationships between [NOexh] and the severity of OSAS. We measured [NOexh] in 24 patients with OSAS (apnea-hypopnea index (AHI), 55 +/- 4 hour-1) (x +/- SEM), and in 7 healthy volunteers in whom OSAS was excluded clinically. [NOexh] was measured on line by a chemiluminescence analyzer (Dasibi Environmental Corporation, Glendale, Calif). Seven patients with OSAS (29%) had a positive history of cardiovascular disease. Mean [NOexh] was 19.7 +/- 3.2 ppb in healthy subjects, and 22.2 +/- 3.0 ppb in patients with OSAS (p = ns). [Noexh] was not significantly different in those patients with or without cardiovascular disease. [NOexh] was not significantly related to the AHI, the body mass index, or the arterial O2 saturation at night. These results show that [NOexh] is not abnormal in patients with OSAS, and that it does not relate to the presence of cardiovascular disease or to any of various common indices of disease severity.
Exhaled breath analysis, a simple tool to study the pathophysiology of obstructive sleep apnoea.
Bikov Andras,Hull James H,Kunos Laszlo
Sleep medicine reviews
Accelerated airway inflammation may play a crucial role in the pathophysiology of obstructive sleep apnoea (OSA); however this phenomenon has been investigated only in a limited number of studies. The analysis of exhaled breath represents a promising, non-invasive tool to evaluate airway inflammation in this context. The knowledge on exhaled biomarkers in OSA has been growing with an emerging number of methodological studies which help to interpret exhaled breath data. This article not only summarises the results of studies on exhaled breath condensate (EBC) biomarkers, exhaled volatile compounds and exhaled monoxides in OSA, but also aims to critically review methodological limitations and provide some guideline for further research.
10.1016/j.smrv.2015.07.005
[Exhaled nitric oxide in patients with obstructive sleep apnea syndrome].
Przybyłowski Tadeusz,Bielicki Piotr,Kumor Marta,Hildebrand Katarzyna,Maskey-Warzechowska Marta,Fangrat Adam,Górska Katarzyna,Korczyński Piotr,Chazan Ryszarda
Pneumonologia i alergologia polska
UNLABELLED:Exhaled nitric oxide has been extensively investigated as a non-invasive marker of airway inflammation. Some authors have suggested that morning FE(NO) in obstructive sleep apnea syndrome (OSAS) patients is elevated due to inflammation of upper airways, while others have not found any differences between patients and healthy subjects. The purpose of this study was to analyze concentration of exhaled nitric oxide (FE(NO)) in OSAS patients. METHODS:119 (99 M, 20 F) consecutive patients of sleep laboratory participated in this study. Standard overnight sleep studies with polysomnography or portable screening device were carried out in the whole group: OSAS was diagnosed in 66 patients and 53 no-OSAS served as controls. FE(NO) was measured on-line with a flow rate kept at 0.045 - 0.055 l/s, according to the recommendations of ATS using a chemiluminescence analyzer twice: before the sleep study (8-10 p.m.) and after termination of data collection (6 - 8 a.m.). There were no differences in age between patients and controls. Respiratory disturbance index (RDI) was 40.3+/-24.9 in patients and 3.7+/-2.8 in controls (p<0.001). In OSAS patients both evening and morning FE(NO) was significantly higher compared to controls (23.1+/-14.8 ppb vs. 16.8+/-9.8 ppb and 22.4+/-13.2 ppb vs. 15.3+/-8.1 ppb respectively, p<0.05). Weak but statistically significant correlations for the whole group between morning FE(NO) and mean and minimum arterial oxygen saturation (SaO2) during sleep and number of study minutes with SaO2<90% were observed. Lower evening FE(NO) in OSAS patients with coexisting arterial hypertension when compared to normotensive OSAS patients was also noticed (19.1+/-10.8 ppb vs. 27.1+/-19.1 ppb; p<0.05). CONCLUSIONS:The increase in FE(NO) in OSAS patents may be caused by repetitive apneas and hypoxemia during sleep.
The Ventilatory and Diffusion Dysfunctions in Obese Patients with and without Obstructive Sleep Apnea-Hypopnea Syndrome.
Rouatbi Sonia,Ghannouchi Ines,Kammoun Rim,Ben Saad Helmi
Journal of obesity
Objective:To analyze the ventilatory and alveolar-capillary diffusion dysfunctions in case of obesity with or without an OSAS. Methods:It is a cross-sectional study of 48 obese adults (23 OSAS and 25 controls). Anthropometric data (height, weight, and body mass index (BMI)) were collected. All adults responded to a medical questionnaire and underwent polysomnography or sleep polygraphy for apnea-hypopnea index (AHI) and percentage of desaturation measurements. The following lung function data were collected: pulmonary flows and volumes, lung transfer factor for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FNO). Results:Obesity was confirmed for the two groups with a total sample mean value of BMI = 35.06 ± 4.68 kg/m. A significant decrease in lung function was noted in patients with OSAS compared with controls. Indeed, when compared with the control group, the OSAS one had a severe restrictive ventilatory defect (total lung capacity: 93 ± 14 vs. 79 ± 12%), an abnormal DLCO (112 ± 20 vs. 93 ± 22%), and higher bronchial inflammation (18.40 ± 9.20 vs. 31.30 ± 13.60 ppb) ( < 0.05). Conclusion:Obesity when associated with OSAS increases the severity of pulmonary function and alveolar-capillary diffusion alteration. This can be explained in part by the alveolar inflammation.
10.1155/2020/8075482
Airway inflammation in patients affected by obstructive sleep apnea.
Sabato R,Guido P,Salerno F G,Resta O,Spanevello A,Barbaro M P Foschino
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace
Obstructive sleep apnea (OSA) is characterised by repetitive episodes of upper airway occlusion during sleep. OSA has been shown to be associated with a variable degree of nasal inflammation, uvula mucosal congestion and airway hyperreactivity. The upper airway inflammation, whose clinical importance is uncertain, is characterised by leukocytes infiltration and interstitial oedema. In addition, recent data has shown the presence of neutrophilic inflammation in the lower airways. The current opinion is that airway inflammation is caused by the local, repeated mechanical trauma related to the intermittent airway occlusion typical of the disease. Another potential mechanism involves the intermittent nocturnal hypoxemia that through the phenomenon of the ischemia-reperfusion injury may induce the production of oxygen free radicals and therefore cause local and systemic inflammation. Finally, a state of low-grade systemic inflammation may be related to obesity per se with the pro-inflammatory mediators synthesised in the visceral adipose cells. Several authors stress the role of circulating and local inflammatory mediators, such as pro-inflammatory cytokines, exhaled nitric oxide, pentane and 8-isoprostane as the determinants of inflammation in OSA.
10.4081/monaldi.2006.572
Increased alveolar nitric oxide concentration is related to nocturnal oxygen desaturation in obstructive sleep apnoea.
Hua-Huy Thong,Le-Dong Nhat-Nam,Duong-Quy Sy,Luchon Laurent,Rouhani Saïd,Dinh-Xuan Anh Tuan
Nitric oxide : biology and chemistry
PURPOSE:To assess distal/alveolar inflammation in patients with suggestive symptoms of obstructive sleep apnoea (OSA) using exhaled nitric oxide (NO) measured by two-compartment model (2-CM) after correction for axial NO back-diffusion (trumpet model). METHODS:Ninety five patients suspected for OSA prospectively underwent pulmonary function test, overnight polysomnography (PSG), and exhaled NO measurement. Patients with apnoea-hypopnoea index (AHI) < 5/hour were included in non-OSA group. Exhaled NO was repeatedly measured after PSG in 21 OSA patients and 8 non-OSA subjects. RESULTS:Alveolar NO concentration (C(ANO)) was significantly higher in OSA patients (n = 71; 4.07 ± 1.7 ppb) as compared with non-OSA subjects (n = 24; 2.24 ± 1.06 ppb; p < 0.0001) whilst maximal bronchial NO flux (J'awNO) and fractional exhaled NO (F(ENO)) did not differ between the two groups. C(ANO) was strongly associated to AHI (r = 0.701; p < 0.0001) and to recording time with SaO2 < 90% (ST-90%; r = 0.659; p < 0.0001) in OSA patients but not in non-OSA persons. The area under ROC curve for screening patients with OSA and significant nocturnal oxygen desaturation (ST-90% > 1%) was 0.865 ± 0.036 (95% IC, 0.793-0.937; p < 0.0001). C(ANO) at 4.5 ppb could detect these patients with specificity of 94% and sensitivity of 46%. Increase of C(ANO) measured after PSG was significantly related to oxygen desaturation index (ST-90%) in OSA patients. CONCLUSIONS:Increased alveolar NO concentration was related to the severity of nocturnal oxygen desaturation in patients with OSA, linking the distal airway inflammation to intermittent hypoxia. (250 words).
10.1016/j.niox.2015.01.008
Exhaled Breath Analysis in Obstructive Sleep Apnea Syndrome: A Review of the Literature.
Medicina (Kaunas, Lithuania)
Obstructive sleep apnea syndrome (OSAS) represents an independent risk factor for cardiovascular, metabolic and neurological events. Polysomnography is the gold-standard for the diagnosis, however is expensive and time-consuming and not suitable for widespread use. Breath analysis is an innovative, non-invasive technique, able to provide clinically relevant information about OSAS. This systematic review was aimed to outline available evidence on the role of exhaled breath analysis in OSAS, taking into account the techniques' level of adherence to the recently proposed technical standards. Articles reporting original data on exhaled breath analysis in OSAS were identified through a computerized and manual literature search and screened. Duplicate publications, case reports, case series, conference papers, expert opinions, comments, reviews and meta-analysis were excluded. : Fractional exhaled Nitric Oxide (FeNO) is higher in OSAS patients than controls, however its absolute value is within reported normal ranges. FeNO association with AHI is controversial, as well as its change after continuous positive airway pressure (C-PAP) therapy. Exhaled breath condensate (EBC) is acid in OSAS, cytokines and oxidative stress markers are elevated, they positively correlate with AHI and normalize after treatment. The analysis of volatile organic compounds (VOCs) by spectrometry or electronic nose is able to discriminate OSAS from healthy controls. The main technical issues regards the dilution of EBC and the lack of external validation in VOCs studies. Exhaled breath analysis has a promising role in the understanding of mechanisms underpinning OSAS and has demonstrated a clinical relevance in identifying individuals affected by the disease, in assessing the response to treatment and, potentially, to monitor patient's adherence to mechanical ventilation. Albeit the majority of the technical standards proposed by the ERS committee have been followed by existing papers, further work is needed to uniform the methodology.
10.3390/medicina55090538
Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese patients with obstructive sleep apnea syndrome.
Carpagnano Giovanna E,Spanevello Antonio,Sabato Roberto,Depalo Annarita,Turchiarelli Viviana,Foschino Barbaro Maria Pia
Translational research : the journal of laboratory and clinical medicine
Airway inflammation plays an important role in obstructive sleep apnea syndrome as well as in obesity. Increasingly, researchers are studying airway inflammation noninvasively and are studying the new markers of airways inflammation. The aim of this study was to measure pH in the exhaled breath condensate (EBC), the exhaled nitric oxide (NO), and the inflammatory cell profile in the induced sputum of obese patients with and without obstructive sleep apnea syndrome (OSAS). The pH in EBC, the exhaled NO, and the induced sputum cells were measured in 30 obese patients with OSAS (OOs), in 20 obese patients without OSAS (ONOs), and in 10 healthy patients (HPs). Levels of pH in EBC were lower in OOs and in ONOs than in HPs. Furthermore, the concentrations of exhaled NO and the percentages of neutrophils in the induced sputum were greater in OOs and in ONOs than in HPs. No significant differences were found between OO and ONO for other measurements of airway inflammation. This study shows the presence of airway's inflammation in obese patients with and without OSAS and indicates that the "exhaled acidopnea" as well as exhaled NO and sputum neutrophils are good tools to measure airway inflammation in these subjects.
10.1016/j.trsl.2007.09.004
Increased oral nitric oxide in obstructive sleep apnoea.
Culla Beatrice,Guida Giuseppe,Brussino Luisa,Tribolo Antonella,Cicolin Alessandro,Sciascia Savino,Badiu Iuliana,Mietta Sabrina,Bucca Caterina
Respiratory medicine
BACKGROUND:Hypoxia and snoring-related mechanical trauma contribute to airway inflammation in obstructive sleep apnoea (OSA). Increased exhaled nitric oxide (FENO), an airway inflammation marker, has been reported in OSA patients. We propose the measure of NO in the oral cavity (oNO) as marker of oropharyngeal inflammation in OSA. METHODS:We compared oNO and FENO of 39 OSA patients with those of 26 mild asthmatics (ASTHMA), 15 patients with chronic rhinitis or rhinosinusitis (CRS) and 24 healthy subjects. A special device was used for oNO measurement. Apnoea/hypopnoea index (AHI), oxygen desaturation index, mean and nadir SaO2 were calculated from the polysomnography. RESULTS:oNO was significantly increased in OSA (104.2 95%CI 80.2-135.5ppb) as compared to ASTHMA (71.9 95%CI 56.3-91.9ppb; p=0.015), CRS (54.4 95%CI 40.2-73.7ppb; p=0.009) and healthy subjects (63.6 95%CI 59-73ppb; p<0.001). oNO was directly related to AHI (r=0.466, p=0.003) and to minutes slept with SaO2 <90% (r=0.471, p=0.011) and it was inversely related to nadirSaO2 (r=-0.393, p=0.018). FENO was highest in asthmatics (40.3 95%CI 32.5-50.1ppb) and only slightly elevated in OSA (23.1 95%CI 19,8-28.3ppb) and CRS (22.8 95%CI 16.8-32.5ppb). CONCLUSIONS:The finding that oral NO is increased in OSA and is related to upper airway obstructive episodes and to hypoxemia severity, strengthens the clinical and pathogenic role of oral inflammation in OSA.
10.1016/j.rmed.2009.09.020
Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea.
Olopade C O,Christon J A,Zakkar M,Hua C,Swedler W I,Scheff P A,Rubinstein I
Chest
BACKGROUND:Upper airway inflammation is present in patients with obstructive sleep apnea (OSA). OBJECTIVE:To determine whether exhaled pentane and nitric oxide (NO) levels, two nonspecific markers of inflammation, are increased in patients with OSA. METHODS:Exhaled nasal and oral pentane and NO levels were determined before and after sleep in 20 patients with OSA (apnea-hypopnea index, 48+/-7; mean+/-SEM) and eight healthy control subjects. RESULTS:In patients with OSA, exhaled nasal and oral pentane levels after sleep were significantly higher than presleep values (6.1+/-1.2 nM vs 3.4+/-0.4 nM, and 7.0+/-1.3 nM vs 4.2+/-0.4 nM, respectively; p<0.05). Likewise, exhaled nasal and oral NO levels after sleep were significantly higher than presleep values in patients with OSA (39.7+/-3.8 ppb vs 28.4+/-2.9 ppb and 10.9+/-1.5 ppb vs 6.6+/-0.8 ppb, respectively; p<0.05). By contrast, there were no significant differences in exhaled nasal and oral pentane, and nasal NO levels before and after sleep in control subjects. Exhaled oral NO levels were significantly increased after sleep in comparison to presleep values in control subjects (p<0.05). CONCLUSION:Exhaled nasal pentane and NO levels are increased after sleep in patients with moderate-severe OSA. These data suggest that upper airway inflammation is present in these patients after sleep.
10.1378/chest.111.6.1500
Study of Exhaled Nitric Oxide in Subjects with Suspected Obstructive Sleep Apnea: A Pilot Study in Vietnam.
Duong-Quy Sy,Hua-Huy Thong,Tran-Mai-Thi Huyen-Tran,Le-Dong Nhat-Nam,Craig Timothy J,Dinh-Xuan Anh-Tuan
Pulmonary medicine
BACKGROUND AND OBJECTIVE:The concentration of exhaled nitric oxide (eNO), reflecting the activity of inducible NO synthase in airway epithelium, has been found to increase in patients with obstructive sleep apnea (OSA). This study aimed to measure eNO concentration in patients with suspected OSA and to correlate different eNO parameters with clinical and sleep apnea characteristics. METHODS:In this cross-sectional study, all patients underwent in-lab overnight polysomnography (PSG) and eNO measurement using a method of multiple flow rates before and after PSG (pre- and post-PSG). RESULTS:According to the result of PSG, 82 persons were divided into two groups: control subjects (n = 30; 54 ± 14 years) and patients with OSA defined as apnea-hypopnea index (AHI) ≥ 5/hour (n = 52; 53 ± 12 years). Body mass index (BMI) and neck and abdomen circumferences of OSA patients were significantly higher than those from control subjects. In OSA group, post-PSG alveolar NO concentration (CANO) (5.3 ± 1.9 ppb) was significantly higher than pre-PSG CANO (4.0 ± 1.7 ppb; P < 0.001). Significant correlations have been found between CANO and AHI (P < 0.001) and between CANO and nadir SpO2 (P < 0.05). The daytime CANO value of more than 4.1 ppb can be used to screen symptomatic subjects for the presence of OSA with a high specificity of 93.3%. CONCLUSION:Our findings indicate CANO as a surrogate marker for OSA in persons with suggestive symptoms.
10.1155/2016/3050918
Nasal nitric oxide improved by continuous positive airway pressure therapy for upper airway inflammation in obstructive sleep apnea.
Hamada Satoshi,Tatsumi Shuji,Kobayashi Yoshiki,Yasuba Hirotaka
Sleep & breathing = Schlaf & Atmung
PURPOSE:In this report, we examined the association between obstructive sleep apnea (OSA) and upper and lower airway inflammation based on nitric oxide (NO) measurements. METHODS:Study subjects included 51 consecutive participants. Sleep-disordered breathing was evaluated by a type 3 portable monitor and quantified by respiratory disturbance index (RDI). Airway inflammation was noninvasively analyzed by the measurement of nasally and orally exhaled NO; nasal value was presented as nasally exhaled NO minus orally exhaled NO. In 15 patients prescribed nasal continuous positive airway pressure (nCPAP) therapy, exhaled NO was re-evaluated in 10.7 ± 6.3 months after nCPAP therapy. RESULTS:Nasal NO was significantly higher in patients with severe OSA (RDI ≥ 30/h) than those with non-OSA (RDI < 10/h) (76.9 ± 26.0 ppb vs. 47.9 ± 22.0 ppb, respectively, p = 0.016) and correlated with RDI (rho = 0.36, p = 0.0099), whereas orally exhaled NO did not differ between non-OSA and OSA patients and was not correlated with RDI. In 15 patients, nasal NO after nCPAP therapy was significantly decreased than that before nCPAP therapy (81.9 ± 31.2 ppb vs. 53.7 ± 27.2 ppb, respectively, p = 0.0046); in 11 patients having good compliance to nCPAP therapy (nCPAP use >4 h per night on more than 70% of nights), this association was more remarkable. CONCLUSIONS:In OSA, upper but not lower airway inflammation can be increased by repetitive collapse of the upper airway. Future studies are required to determine the role of nasal NO in OSA.
10.1007/s11325-016-1431-z
Alveolar-derived exhaled nitric oxide is reduced in obstructive sleep apnea syndrome.
Foresi Antonio,Leone Clementina,Olivieri Dario,Cremona George
Chest
BACKGROUND:Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular diseases, in particular systemic arterial hypertension. We postulated that intermittent nocturnal hypoxia in OSAS may be associated to decreased fractional exhaled nitric oxide (FENO) levels from distal airspaces. METHODS:Multiple flow rate measurements have been used to fractionate nitric oxide (NO) from alveolar and bronchial sources in 34 patients with OSAS, in 29 healthy control subjects, and in 8 hypertensive non-OSAS patients. The effect of 2 days of treatment with nasal continuous positive airway pressure (nCPAP) on FENO was examined in 18 patients with severe OSAS. RESULTS:We found that the mean [+/- SE] concentrations of exhaled NO at a rate of 50 mL/s was 21.8 +/- 1.9 parts per billion (ppb) in patients with OSAS, 25.1 +/- 3.3 ppb in healthy control subjects, and 15.4 +/- 1.7 ppb in hypertensive control patients. The mean fractional alveolar NO concentration (CANO) in OSAS patients was significantly lower than that in control subjects (2.96 +/- 0.48 vs 5.35 +/- 0.83 ppb, respectively; p < 0.05). In addition, CANO values were significantly lower in OSAS patients with systemic hypertension compared to those in normotensive OSAS patients and hypertensive patients without OSAS. The mean values of CANO significantly improved after nCPAP therapy (2.67 +/- 0.41 to 4.69 +/- 0.74 nL/L, respectively; p = 0.01). CONCLUSIONS:These findings suggest that alveolar FENO, and not bronchial FENO, is impaired in patients with OSAS and that this impairment is associated with an increased risk of hypertension. NO production within the alveolar space is modified by treatment with nCPAP.
10.1378/chest.06-3124
The association between exhaled nitric oxide and sleep apnea: the role of BMI.
JalilMirmohammadi Seyyed,Mehrparvar Amir Houshang,Safaei Sara,Samimi Ehsan,Torab Jahromi Mona
Respiratory medicine
BACKGROUND:Obstructive sleep apnea syndrome is associated with airway inflammation. Measurement of exhaled nitric oxide is a non-invasive method for evaluation of airway diseases. It seems that obesity is an exacerbating factor for airway inflammation. We aimed to evaluate the changes of exhaled nitric oxide after sleep in patients suffering from OSA regarding BMI. METHOD:In 54 patients referred for polysomnography, exhaled nitric oxide measurements were performed before and after sleep. Subjects were divided into three categories: normal, obese with sleep apnea and non-obese, based on polysomnographic recordings and BMI. RESULTS:47 subjects had abnormal apnea/hypopnea index (AHI mean = 39.7) and 7 were normal regarding AHI (AHI mean = 3.0). BMI was significantly correlated to AHI, number of desaturations and hypoxia. Among those with apnea, 31 subjects were obese and 16 were non-obese. Exhaled nitric oxide levels in normal and OSA subjects showed no significant change, but a significant increase was found in obese patients with apnea (14.7 pre-sleep mean, 20.0 post-sleep mean). CONCLUSIONS:Obesity is an effective factor in the inflammation of airways in patients with obstructive apnea.
10.1016/j.rmed.2014.05.010
Long-term continuous positive airway pressure therapy normalizes high exhaled nitric oxide levels in obstructive sleep apnea.
Chua Ai-Ping,Aboussouan Loutfi S,Minai Omar A,Paschke Kelly,Laskowski Daniel,Dweik Raed A
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine
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.
10.5664/jcsm.2740
Airway and alveolar nitric oxide measurements in obstructive sleep apnea syndrome.
Fortuna A M,Miralda R,Calaf N,González M,Casan P,Mayos M
Respiratory medicine
STUDY OBJECTIVES:The process of intermittent hypoxia-reoxygenation produces airway inflammation and endothelial dysfunction that favors the development of cardiovascular disorders in obstructive sleep apnea syndrome (OSAS). Nitric oxide (NO) is an important mediator in airway inflammation and the regulation of endothelium-dependent vasodilation. DESIGN:This study compared airway NO (FE(NO)) and alveolar NO (CA(NO)) measurements in exhaled breath in 30 OSAS patients to those of 30 healthy (non-OSAS) individuals and determined the relationship between NO levels and OSAS severity. Additionally, NO measurements were analyzed after 3 months of CPAP treatment. MEASUREMENTS AND RESULTS:The mean (±SD) FE(NO) level in the OSAS group (27.2 ± 18 ppb) was higher than in the healthy non-OSAS group (p = 0.006). The mean CA(NO) level was 1.65 ± 0.90 ppb, lower than in the non-OSAS group (p = 0.001). A significant correlation was found between FE(NO) and CA(NO) levels and the apnea-hypopnea index (AHI) in the OSAS group (r = 0.8, p < 0.05; r = -0.9, p = 0.01, respectively). FE(NO) levels decreased and CA(NO) levels increased significantly after CPAP treatment. CONCLUSIONS:Severe OSAS patients have higher FE(NO) and lower CA(NO) levels and these are restored to normal after CPAP treatment, reflecting the correction of local upper airway inflammation and endothelial dysfunction present in OSAS patients. Exhaled breath techniques can be useful to identify airway inflammation and endothelial dysfunction in severe OSAS patients.
10.1016/j.rmed.2010.12.004
Measurement of exhaled nitric oxide concentration in patients with obstructive sleep apnea: A meta-analysis.
Zhang Dongmei,Luo Jinmei,Qiao Yixian,Xiao Yi,Huang Rong,Zhong Xu
Medicine
BACKGROUND:Exhaled nitric oxide (eNO) has been proposed as a noninvasive measure of airway inflammation. However, its value in patients with obstructive sleep apnea (OSA) is still controversial. The authors 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 eighty-four studies were reviewed for inclusion, with 16 studies pooled for analysis (16 studies for fractional exhaled nitric oxide [FENO], 5 for alveolar nitric oxide [CANO], and 4 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% CI -1.66 to 1.64, P = 0.989) and J'awNO levels (220.32 pl/s, 95% CI -49.31 to 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.
10.1097/MD.0000000000006429
Measurement of fractional exhaled nitric oxide and nasal nitric oxide in male patients with obstructive sleep apnea.
Sleep & breathing = Schlaf & Atmung
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); after sleep, nNO was also positively associated to recording time with SpO < 90% and negatively associated to minimum SpO. 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.
10.1007/s11325-018-1760-1
Fractional Exhaled Nitric Oxide Measurements and Screening of Obstructive Sleep Apnea in a Sleep-Laboratory Setting: A Cross-Sectional Study.
Duarte Ricardo L M,Rabahi Marcelo F,Oliveira-E-Sá Tiago S,Magalhães-da-Silveira Flavio J,Mello Fernanda C Q,Gozal David
Lung
PURPOSE:Obstructive sleep apnea (OSA) is a common condition characterized by repetitive collapse of the upper airways and intermittent oxygen desaturation, which may lead to airway inflammation. Here, we explored whether fractional exhaled nitric oxide (FeNO) levels provide a non-invasive screening tool of OSA. METHODS:Over a 3-month period, FeNO levels were measured in consecutive non-smoking patients referred for a sleep laboratory. All patients underwent full polysomnography. OSA severity was classified based on the apnea/hypopnea index: ≥ 5.0/h as any OSA, ≥ 15.0/h as moderate/severe OSA, and ≥ 30.0/h as severe OSA. FeNO was measured by a portable device (NIOX-MINO®; Aerocrine AB, Solna, Sweden) and expressed as parts per billion (ppb). Discrimination by area under the curve (AUC) and binary logistic regression were performed. RESULTS:A total of 229 subjects were evaluated. Mean FeNO values were similar among subjects without OSA or with OSA: 16.9 ± 10.6 ppb versus 20.2 ± 14.5 ppb, p = 0.221; respectively. FeNO was not an inclusionary parameter to predict any OSA, moderate/severe OSA, and severe OSA: odds ratio (OR) 1.023 (95% confidence interval [CI]: 0.986-1.062); OR 1.012 (95% CI: 0.991-1.034); and OR 0.999 (95% CI: 0.980-1.018), respectively. The AUC values for FeNO in the diagnosis of any OSA, moderate/severe OSA, and severe OSA showed no discriminatory properties: AUC: 0.567 (95% CI: 0.464-0.670), AUC: 0.541 (95% CI: 0.465-0.618), and AUC: 0.535 (95% CI: 0.459-0.610); respectively. CONCLUSIONS:In a sleep-lab setting, our findings suggest that FeNO measurements are inconsequential in the screening of OSA in adults.
10.1007/s00408-018-0190-y
Risk factors and fraction of exhaled nitric oxide in obstructive sleep apnea in adults.
Feng Xiaokai,Guo Xiheng,Lin Junling,Zhao Zhiling,Tong Zhaohui
The Journal of international medical research
OBJECTIVE:This study aimed to evaluate the relationship between obstructive sleep apnea (OSA) and the fraction of exhaled nitric oxide (F), and to assess the effect of risk factors of airway inflammation on OSA. METHODS:Medical records of patients in the Respiratory Sleep Center at Chao-Yang Hospital in Beijing between January 2015 and June 2017 were analyzed. All patients were diagnosed with OSA. Data of the medical history, clinical examinations, F, and upper airway computed tomographic findings were collected. Logistic regression was used to evaluate risk factors of OSA. RESULTS:A total of 181 patients were admitted to the Respiratory Sleep Center during the study and 170 had a diagnosis of OSA and were included in the study. Single factor analysis showed that male sex, age, body mass index, smoking index, alcohol consumption, F, soft palate thickness, soft palate length, the narrowest transverse diameter of the upper airway, tonsil size, and nasal sinusitis were risk factors for sleep-disordered breathing and disease severity. CONCLUSIONS:Male sex, age, body mass index, F, the narrowest transverse diameter of the upper airway, and normal tonsil size are associated with OSA and disease severity. The severity of OSA is associated with F levels.
10.1177/0300060520926010
Exhaled Nitric Oxide as a Surrogate Marker for Obstructive Sleep Apnea Severity Grading: An In-Hospital Population Study.
Nature and science of sleep
PURPOSE:Our study aimed to evaluate the relationship between exhaled nitric oxide (eNO) markers and obstructive sleep apnea (OSA) severity and verify the changes in eNO profiles among mild, moderate, and severe OSA subgroups. METHODS:This study was a cross-sectional and in-hospital population-based study. We investigated 123 OSA patients (17 mild, 23 moderate and, 83 severe OSA) in the department of respiratory diseases. Studied data included anthropometry, respiratory polygraphy, biological markers, spirometry, and multi-flow eNO measurements. Data analysis implied linear correlation, non-parametric ANOVA, and pair-wise comparison. RESULTS:No significant difference could be found among 3 OSA severity subgroups for FENO at - four sampling flow rates (50-350 mL/s). The bronchial production rate of NO (J'awNO) was proportionally increased, with median values of 11.2, 33.9, and 36.2 in mild, moderate, and severe OSA, respectively (p=0.010). The alveolar concentration of NO (CANO) changed with a non-linear pattern; it was increased in moderate (6.49) vs mild (7.79) OSA but decreased in severe OSA (5.20, p = 0.015). The only correction that could be established between OSA severity and exhaled nitric oxide markers is through J'AWNO (rho=0.25, p=0.02) and CANO (rho= 0.18, p=0.04). There was no significant correlation between FENO measured at three different flow rates and the OSA severity. We also found a weak but significant correlation between FENO 100 and averaged SpO2 (rho = 0.07, p= 0.03). CONCLUSION:The present study showed that J'AWNO, which represents eNO derived from the central airway, is proportionally increased in more severe OSA, while eNO from alveolar space, indicated by CANO, was also associated with OSA severity and relatively lower in the most severe OSA patients. In contrast, stand-alone FENO metrics did not show a clear difference among the three severity subgroups.
10.2147/NSS.S307012
Fractional exhaled nitric oxide-a possible biomarker for risk of obstructive sleep apnea in snorers.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine
STUDY OBJECTIVES:Airway inflammation in patients with obstructive sleep apnea (OSA) has been described and can be assessed by measuring the biomarker fractional exhaled nitric oxide (FeNO). In this pilot study, we investigated FeNO measurements in identification of OSA among persons with snoring. METHODS:In this study we aimed to investigate (1) if FeNO could be used in screening for OSA, (2) if daytime sleepiness correlated to FeNO levels, and (3) whether asthma affected FeNO levels. Persons with snoring were prospectively included in three primary care ear, nose, and throat clinics. Patients underwent spirometry, FeNO tests, and partial polygraphy. They filled out questionnaires on sinonasal and asthma symptoms, daytime sleepiness, and quality of life. Current smokers, patients with upper airway inflammatory conditions, and patients treated with steroids were excluded. RESULTS:Forty-nine individuals were included. Median apnea-hypopnea index was 11.4, mean age was 50.9 years, and 29% were females. OSA was diagnosed in 73% of the patients of whom 53% had moderate-severe disease. Patients with moderate-severe OSA had significantly higher FeNO counts than patients with no or mild OSA ( = .024). Patients younger than 50 years with a FeNO below 15 had the lowest prevalence of moderate-severe OSA. No correlation was found between FeNO measurements and daytime sleepiness, and asthma did not affect FeNO levels. CONCLUSIONS:We found a low prevalence of moderate-severe OSA in persons with snoring when FeNO and age were low. This might be considered in a future screening model, though further studies testing the FeNO cutoff level and the diagnostic accuracy are warranted. CLINICAL TRIAL REGISTRATION:Registry: ClinicalTrials.gov; Name: NO Measurements in Screening for Asthma and OSA, in Patients With Severe Snoring; URL: https://clinicaltrials.gov/study/NCT03964324; Identifier: NCT03964324. CITATION:Kiaer E, Ravn A, Jennum P, et al. Fractional exhaled nitric oxide-a possible biomarker for risk of obstructive sleep apnea in snorers. . 2024;20(1):85-92.
10.5664/jcsm.10802