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

Abstract

Background and Objectives: 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. Materials and Methods: 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. Results: 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. Conclusions: 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.

Risk factors and fraction of exhaled nitric oxide in obstructive sleep apnea in adults

“…Previous studies have reported that F ENO levels in patients with OSA and inflammatory metabolites were increased compared with those of healthy subjects. 20 , 21 Our study also showed that markers, such as age, male sex, BMI, the narrowest transverse diameter of the upper airway, normal tonsil size, and the level of F ENO , were positively related to the severity of OSA. Elevated F ENO levels in patients with OSA indicate the presence of inflammation in the bronchial and upper airway.…”

Metabolomics in Sleep, Insomnia and Sleep Apnea

“…Studies show enhanced levels of inflammatory markers related to oxidative stress in the exhaled breath of OSA patients. 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].…”

A New Perspective towards Diagnosis of Sleep Apnea: Isoprene Detection Using PSSA-g-PANI based SAW Sensor

“…Therefore, monitoring isoprene levels in exhaled breath under normal conditions may provide a non-invasive method to detect, monitor, and control disorders of sleep. In the literature, there are very few studies on the development of sensors for the diagnosis of OSAS (Carpagnano 2011, Bikov et al 2016, Finamore et al 2019, Gouma et al 2011, Gouma 2018. There has been increasing interest in the investigation of lungs by non-invasive means measuring the exhaled breath volatile mediators, such as nitric oxide (NO), carbon monoxide (CO), ethane and pentane and finally the non-volatile substances in the liquid phase of exhalate, termed breath condensate.…”

“…Bikov et al summarized the results of studies on exhaled breath condensate biomarkers, exhaled volatile compounds and exhaled monoxides in OSA, and critically reviewed methodological limitations (Bikov et al 2016). Furthermore, Finamore et al reported that exhaled breath analysis 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 (Finamore et al 2019). After these inspiring studies, Gouma et al described a new concept of a microsystem with three-nanosensor array which potentially serving as a coarse diagnostic tool handheld breath analyzer to provide a first detection device.…”