Prospective analyses of volatile organic compounds in obstructive sleep apnea patients

Abstract

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 prospectively 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.

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

“…However, none of the compounds described by Greulich were also identified by Dragonieri and colleagues, who reported a good discriminative capacity between OSAS and obese controls basing on the following compounds: tetrachloroethene, 2,3,5-trimethylhexane, β-pinene, 1,3,5-trimethylbenzene, 9-methylacridine, tetradecane, 6,10-dimethyl-5,9-undecadien-2-one and β-ionone [61]. Besides, Aoki and colleagues found that although almost all the aromatic and satured hydrocarbons are more expressed in the exhaled breath of severe OSAS patients, only isoprene is always elevated in OSAS, regardless the severity of the disease [62].…”

“…Albeit apparently contradictory, it is possible that the association between AHI and breath pattern is mediated by patients’ comorbidities, as suggested by Incalzi and colleagues [67]. Breath-pattern is sensitive to the effects of the C-PAP therapy, indeed concentrations of isoprene and acetone decrease [62] and it is possible to discriminate treated and untreated patients with good accuracy [68]; even a single night treatment is associated with a change in the breath pattern. Interestingly, the breath pattern change does not have the same characteristics in all OSAS patients, with two different types of response being distinguished depending on the comorbidities of those individuals [67].…”

Metabolomics in Sleep, Insomnia and Sleep Apnea

“…Metabolomic approaches have been applied in the study of OSA, whereby they can be categorized into two types of studies, including (1) metabolomic studies of exhaled breath [ 38 , 39 , 40 ], and (2) studies of the blood and/or urine metabolome [ 41 , 42 , 43 , 44 ].…”

“…Markers of chronic inflammation were enhanced, showing an increase in pro-inflammatory cytokines, while anti-inflammatory cytokines decreased [ 47 ]. Furthermore, elevations of toxic volatile organic compounds in patients with OSA were observed [ 38 ]. More specifically, aromatic hydrocarbons (phenylacetic acid, ethylbenzene, toluene and p-xylene), saturated hydrocarbons (hexane, octane, heptane, nonane and decane), acetone and isoprene were elevated, which have been suggested as potential biomarkers.…”

Role of lung volume and airway inflammation in obstructive sleep apnea

“…Because of the nonspecific nature of electronic nose measurements, the individual molecules responsible for the differences in OSA are not known. Elevated levels of exhaled butanol [74], toluene, ethylbenzene, p-xylene, phenylacetic acid, hexane, heptane, octane, nonane, decane, acetone, and isoprene [75] as well as an overnight increase in exhaled pentane [64] were reported in OSA. In addition, CPAP withdrawal resulted in alterations in the concentrations of several volatile organic compounds [76].…”