Translation of obstructive sleep apnea pathophysiology and phenotypes to personalized treatment: a narrative review

Obstructive Sleep Apnea (OSA) arises due to periodic blockage of the upper airway (UA) during sleep, as negative pressure generated during inspiration overcomes the force exerted by the UA dilator muscles to maintain patency. This imbalance is primarily seen in individuals with a narrowed UA, attributable to factors such as inherent craniofacial anatomy, neck fat accumulation, and rostral fluid shifts in the supine posture. Sleep-induced attenuation of UA dilating muscle responsiveness, respiratory instability, and high loop gain further exacerbate UA obstruction. The widespread comorbidity profile of OSA, encompassing cardiovascular, metabolic, and neuropsychiatric domains, suggests complex bidirectional relationships with conditions like heart failure, stroke, and metabolic syndrome. Recent advances have delineated distinct OSA phenotypes beyond mere obstruction frequency, showing links with specific symptomatic manifestations. It is vital to bridge the gap between measurable patient characteristics, phenotypes, and underlying pathophysiological traits to enhance our understanding of OSA and its interplay with related outcomes. This knowledge could stimulate the development of tailored therapies targeting specific phenotypic and pathophysiological endotypes. This review aims to elucidate the multifaceted pathophysiology of OSA, focusing on the relationships between UA anatomy, functional traits, clinical manifestations, and comorbidities. The ultimate objective is to pave the way for a more personalized treatment paradigm in OSA, offering alternatives to continuous positive airway pressure therapy for selected patients and thereby optimizing treatment efficacy and adherence. There is an urgent need for personalized treatment strategies in the ever-evolving field of sleep medicine, as we progress from a ‘one-size-fits-all’ to a ‘tailored-therapy’ approach.