Inflammatory mediators in exhaled breath condensate of children with obstructive sleep apnea syndrome. Validation of exhaled volatile organic compounds analysis using electronic nose as index of COPD severity Exhaled nitric oxide from the central airway and alveoli in OSAHS patients: the potential correlations and clinical implications Effects of CPAP therapy withdrawal on exhaled breath pattern in obstructive sleep apnoea Exhaled NO and iNOS expression in sputum cells of healthy, obese and OSA subjects. Long-term continuous positive airway pressure therapy normalizes high exhaled nitric oxide levels in obstructive sleep apnea. Exhaled breath condensate cytokine level as a diagnostic tool for obstructive sleep apnea syndrome. Airway inflammation in obstructive sleep apnea: is leptin the missing link? Editor’s Highlight: Prospective Analyses of Volatile Organic Compounds in Obstructive Sleep Apnea Patients Snoring as a Determinant Factor of Oxidative Stress in the Airway of Patients with Obstructive Sleep Apnea Increased alveolar nitric oxide concentration is related to nocturnal oxygen desaturation in obstructive sleep apnoea.
BACKGROUND Upper airway inflammation is now recognized in adults with obstructive sleep apnea ( OSA ) syndrome . However , the role played by eicosanoids such as leukotrienes and prostagl and ins is unclear . OBJECTIVE To investigate whether eicosanoids are measurable in exhaled breath condensate ( EBC ) , and to determine whether differences in these inflammatory mediators emerge among children with and without sleep-disordered breathing ( SDB ) . METHODS EBC was collected from 50 consecutive snoring children undergoing overnight polysomnography for suspected SDB , and from 12 nonsnoring control subjects .  Prostagl and in E2 ( PGE2 ) , leukotriene B4 ( LTB4 ) , and cysteinyl leukotrienes ( cys-LTs : leukotriene C4 [LTC4]/leukotriene D4 [LTD4]/leukotriene E4 [ LTE4 ] ) EBC levels were analyzed using enzyme-linked immunosorbent assay . RESULTS LTB4 levels were elevated in children with an apnea-hypopnea index ( AHI ) > 5/h ( SDB ; 97.6 + /- 6.3 pg/mL ) compared to children with an AHI < 5/h ( mild SDB ; 66.4 + /- 19.1 pg/mL ; p < 0.01 ) and control subjects ( 27.8 + /- 3.7 pg/mL ; p < 0.01 ) . Similarly , cys-LT ( LTC4/LTD4/LTE4 ) concentrations were also increased in SDB ( 45.1 + /- 10.6 pg/mL in SDB vs 27.6 + /- 8.3 pg/mL in mild SDB , and 15.7 + /- 7.6 pg/mL in control subjects ; p < 0.01 ) . In contrast , PGE2 concentrations were similar among the three groups . CONCLUSIONS Inflammatory mediators such as leukotrienes and prostagl and ins can be readily quantified in EBC collected from the upper airway of children . Disease severity-dependent increases in leukotriene concentrations ( LTB4 and LTC4/LTD4/LTE4 ) emerge among children and may serve as a noninvasive tool in the clinical assessment of these children Aim Six-minute walking test distance ( 6MWD ) and body mass index , obstruction , dyspnea and exercise ( BODE ) index are measures of functional status in COPD patients , but require space , time and patient ’s compliance . Exhaled volatile organic compounds ( VOCs ) analysis via electronic nose is a quick and easy method that has already been used to discriminate COPD phenotypes . The aim of this study is to evaluate whether VOCs analysis can predict functional status and its variation over time in COPD patients . Methods A monocentric prospect i ve study with 1 year of follow-up was carried out . All patients underwent pulmonary function tests , arterial gas analysis , bioimpedance analysis , 6-minute walking test , and VOCs collection .  Exhaled breath was collected with Pneumopipe ® and analyzed using BIONOTE electronic nose . Outcomes prediction was performed by k-fold cross-vali date d partial least square discriminant analysis : accuracy , sensitivity and specificity as well as Cohen ’s kappa for agreement were calculated . Results We enrolled 63 patients , 60.3 % men , with a mean age of 71 ( SD : 8) years , median BODE index of 1 ( interquartile range : 0–3 ) and mean 6MWD normalized by squared height ( n6MWD ) of 133.5 ( SD : 42 ) m/m2 . The BIONOTE predicted baseline BODE score ( dichotomized as BODE score <3 or ≥3 ) with an accuracy of 86 % and quartiles of n6MWD with an accuracy of 79 % . n6MWD decline more than the median value after 1 year was predicted with an accuracy of 86 % by BIONOTE , 52 % by Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) class and 78 % by combined BIONOTE and GOLD class . Conclusion Exhaled VOCs analysis identifies classes of BODE and n6MWD quartiles , and outperforms GOLD classification in predicting n6MWD variation 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 prospect i ve 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 Background Obstructive sleep apnoea ( OSA ) is highly prevalent and associated with cardiovascular and metabolic changes . OSA is usually diagnosed by polysomnography which is time-consuming and provides little information on the patient 's phenotype thus limiting a personalised treatment approach . Exhaled breath contains information on metabolism which can be analysed by mass spectrometry within minutes . The objective of this study was to identify a breath profile in OSA recurrence by use of secondary -electrospray-ionization-mass spectrometry ( SESI-MS ) . Methods Patients with OSA effectively treated with CPAP were r and omised to either withdraw treatment ( subtherapeutic CPAP ) or continue therapeutic CPAP for 2 weeks . Exhaled breath analysis by untargeted SESI-MS was performed at baseline and 2 weeks after r and omisation . The primary outcome was the change in exhaled molecular breath pattern . Results 30 patients with OSA were r and omised and 26 completed the trial according to the protocol . CPAP withdrawal led to a recurrence of OSA ( mean difference in change of oxygen desaturation index between groups + 30.3/h ; 95 % CI 19.8/h,40.7/h , p<0.001 ) which was accompanied by a significant change in 62 exhaled features ( 16 metabolites identified ) . The panel of discriminating mass-spectral features allowed differentiation between treated and untreated OSA with a sensitivity of 92.9 % and a specificity of 84.6 % . Conclusion Exhaled breath analysis by SESI-MS allows rapid and accurate detection of OSA recurrence . The technique has the potential to characterise an individual 's metabolic response to OSA and thus makes a comprehensible phenotyping of OSA possible . Trial registration number NCT02050425 ( registered at Clinical Trials.gov ) BACKGROUND Obstructive sleep apnoea ( OSA ) is associated with airways inflammation ; a key role in this regard seems to be played by nitric oxide ( NO ) . The aim of this study was to measure exhaled NO and expression of its enzyme , the inducible nitric oxide synthase ( iNOS ) in cells of induced sputum in OSA patients and in obese subjects without sleep apnoea and to correlate these inflammatory markers with severity of OSA . METHODS We enrolled 18 obese patients with OSA ( 10 men , age 48.2 + /- 8.4 years ) , 15 obese patients without OSA ( eight men , age 52.8 + /- 11 years ) and 10 healthy subjects ( five men , age 42 + /- 4 years ) .  Exhaled NO  was measured using a chemiluminescence analyser ; iNOS expression was measured in the sputum cells by immunocytochemistry . RESULTS Exhaled NO result ed significantly increased in OSA and in obese patients ( 23.1 + /- 2.1 and 17.9 + /- 2.1 p.p.b . ) than in healthy subjects ( 7.2 + /- 0.6 p.p.b . ; P < 0.001 ) . OSA and obese patients showed a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum compared to healthy subjects . In addition , OSA and obese patients showed higher iNOS expression in neutrophils and in macrophages with respect to healthy subjects . A positive correlation between exhaled NO , iNOS expression and AHI was observed . CONCLUSIONS These data confirm the presence of airway inflammation  in OSA and in obese patients , and suggest the possible role for NO and iNOS expression in neutrophils of the induced sputum as noninvasive markers to identify and monitor the airway inflammation in these subjects 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 prospect ively 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 BACKGROUND Relationships between exhaled breath condensate ( EBC ) and serum cytokines and apnea-hypopnea index ( AHI ) in patients with excessive daytime sleepiness and loud snoring were evaluated for their potential to predict the severity of obstructive sleep apnea syndrome ( OSAS ) . METHODS Non-smoking patients with suspected OSAS who had undergone polysomnography ( PSG ) were selected until 22 non-OSAS , and 22 mild , 22 moderate and 24 severe OSAS cases based on AHI were achieved . Ten healthy smokers served as a smoker control group .  Interleukin-6 ( IL-6 ) , interleukin-10 ( IL-10 ) , tumor necrosis factor-alpha ( TNF-alpha ) , and 8-isoprostane  were measured in EBC and serum on the morning after PSG and related to OSAS severity using linear discriminant analysis ( LDA ) and logistic regression ( LR ) . RESULTS Biomarker levels , in both EBC and serum , differed significantly across the four groups . Classification by LDA using IL-10 in EBC showed the highest agreement with AHI classification ( kappa=0.88 ) . LR distinguished moderate and severe OSAS from mild OSAS and non-OSAS perfectly using IL-6 in EBC and almost perfectly using IL-10 in EBC ( area under the ROC curve=0.997 ) . The levels of biomarkers among smokers overlapped with mild to severe OSAS patients . CONCLUSIONS Among non-smoker OSAS suspects , EBC IL-6 and IL-10 have potential to predict severity of OSAS BACKGROUND Local and systemic inflammation is implicated in the pathophysiology of Obstructive Sleep Apnea ( OSA ) .  Exhaled breath condensate ( EBC ) is a non-invasive sampling method for the lower airways . However , it is important to consider the potential effect of the systemic origin whereas systemic inflammation is significantly elevated . This prospect i ve study was design ed to investigate whether airway inflammation is significantly related to plasma leptin levels in OSA patients . Simultaneously , it was design ed to investigate whether inflammatory variables predict parameters expressing disease severity and finally whether smoking habit affect the above measurements . PATIENTS & METHODS About 45 OSA patients ( mean AHI 40+/-25 , 28 smokers ) and 25 healthy controls ( AHI<5 , 15 smokers ) were studied and underwent overnight diagnostic polysomnography . We measured  pH , 8-isoprostane , TNF-alpha and IL-6 in EBC and leptin in plasma . Plausible associations between leptin and inflammatory parameters were analyzed after adjustment for proper variables . Similar associations between inflammatory variables and parameters of disease severity were also performed . RESULTS An increased level of leptin and respective increase of inflammatory variables was found . No significant association was observed between parameters of EBC and plasma leptin levels . A part of the parameters of disease severity is significantly associated with pH and 8-isoprostane . Smoking did not seem to be a critical confounding factor for evaluation of the above measurements . CONCLUSIONS Increased levels of leptin were not associated with the observed airway  inflammation in OSA . The observed airway inflammation seemed to be independent of smoking habit with limited association with disease severity Various volatile organic compounds ( VOCs ) are known to be toxic . Although exhaled VOC patterns change in obstructive sleep apnea ( OSA ) patients , individual VOC profiles are not fully determined . The primary outcome was VOC characterizations ; secondary outcomes included their relationships with sleep and clinical parameters in OSA patients . We prospect ively examined 32 OSA patients with an apnea-hypopnea index ( AHI ) ≥ 15 by full polysomnography , and 33 age- and sex-matched controls without obvious OSA symptoms . Nine severe OSA patients were examined before and after continuous positive airway pressure ( CPAP ) treatment .  By applying a method which eliminates environmental VOC influences , exhaled VOCs were identified by gas chromatography (GC)-mass spectrometry , and their concentrations were determined by GC . Exhaled aromatic hydrocarbon concentrations ( toluene , ethylbenzene , p-xylene , and phenylacetic acid ) in the severe OSA groups ( AHI ≥ 30 ) and exhaled saturated hydrocarbon concentrations ( hexane , heptane , octane , nonane , and decane ) in the most severe OSA group ( AHI ≥ 60 ) were higher than those in the control group . Exhaled isoprene concentrations were increased in all OSA groups ( AHI ≥ 15 ) ; acetone concentration was increased in the most severe OSA group . Ethylbenzene , p-xylene , phenylacetic acid , and nonane concentrations were increased according to OSA severity , and correlated with AHI , arousal index , and duration of percutaneous oxygen saturation ( SpO2 ) ≤ 90 % . Multiple regression analyses revealed these 4 VOC levels were associated with the duration of SpO2 ≤ 90 % . Isoprene and acetone decreased after CPAP treatment . OSA increased some toxic VOCs , and some correlated with OSA severity . CPAP treatment possibly ameliorates these productions Abstract Purpose In obstructive sleep apnea – hypopnea syndrome ( OSAS ) , airway collapses and vibrations cause local and systemic inflammatory response and oxidative stress ( OS ) . Our objective was to determine the presence of OS in the airway of patients with OSAS compared with controls without OSAS and determine its relation to treatment with CPAP and other clinical variables . Method We performed a prospect i ve observational case – control study with repeated measures . We recruited consecutive patients with SAHS diagnosed using complete polysomnography , and a parallel control group . We collected a sample of exhaled breath condensate ( EBC ) prior to nasal continuous positive airway pressure ( CPAP ) treatment and again after 4 months . The marker of OS used was 8-isoprostane  ( 8-IPN ) . The variables analyzed were age , sex , anthropometric variables , apnea – hypopnea index ( AHI ) , snoring , oxygenation , and polysomnographic variables . Results The study included 20 patients and 10 controls . In cases , the initial value of 8-IPN was 6.8 ( 1.9 ) , and after nasal CPAP , it was 5.3 ( 1.2 ) pg/ml ( p = 0.02 ) . In controls , the value of 8-IPN was 5.6 ( 1.1 ) pg/ml ( p = 0.04 compared to initial values ) . 8-IPN showed significant correlation with snoring , AHI , BMI , nocturnal desaturation index , and non-REM sleep . On multivariate analysis , only snoring was a significant predictor of 8-IPN . Conclusions Snoring , and not OSAS severity , could be the phenomenon underlying the presence of local OS measured in the airway of patients with OSAS 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 prospect ively 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 )
Background and Objectives : Obstructive sleep apnea syndrome ( OSAS ) represents an independent risk factor for cardiovascular , metabolic and neurological events .
Polysomnography is the gold-st and ard 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 clinical ly relevant information about OSAS .
This systematic review was aim ed 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 st and ards .
FeNO association with AHI is controversial , as well as its change after continuous positive airway pressure ( C-PAP ) therapy .