Intermittent Hypoxia-Induced Inflammation and the Formation of Exhaled Volatile Organic Compound Profiles in Obstructive Sleep Apnea-Hypopnea Syndrome: A Narrative Review.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by recurrent upper airway obstruction during sleep, intermittent hypoxia (IH), and sleep fragmentation, and is associated with oxidative stress, chronic low-grade inflammation, metabolic dysregulation, and upper airway remodeling. These pathophysiological disturbances may alter the generation and release of volatile metabolites, thereby providing a rationale for investigating exhaled volatile organic compound (VOC) profiles as noninvasive indicators of OSAHS-related redox imbalance, inflammatory activity, and metabolic abnormalities. Focusing on IH-induced inflammatory responses as a central mechanistic link, this review examines the potential mechanisms through which inflammation contributes to changes in exhaled VOC profiles in OSAHS. Repeated hypoxia-reoxygenation and upper airway mechanical stress may activate inflammatory signaling pathways, including nuclear factor κB, hypoxia-inducible factor-1α, and NOD-like receptor family pyrin domain-containing 3, and may influence the generation and release of volatile metabolites such as aldehydes, alkanes, acetone, alcohols, and isoprene through amplified oxidative stress, lipid peroxidation, metabolic reprogramming, and alterations in the local airway microenvironment. Available clinical studies suggest that exhaled VOC profiles in patients with OSAHS may be associated with disease severity, nocturnal hypoxic burden, metabolic abnormalities, and treatment response. However, the specificity and reproducibility of candidate VOCs remain limited by individual metabolic profiles, exogenous exposures, and methodological heterogeneity. Future studies should integrate standardized breath sampling, high-confidence compound identification, longitudinal validation, and concurrent assessment of inflammatory, oxidative stress, and metabolic markers. Inflammation-related VOC profiling may offer mechanistic insight into the pathophysiological heterogeneity of OSAHS and support the development of noninvasive assessment tools and more personalized management strategies.