Beyond the Apnea-Hypopnea Index: A Pathophysiological and Phenotypic Approach to Personalized Treatment in Obstructive Sleep Apnea

Tanriverdi U., Senel G. B.

CURRENT TREATMENT OPTIONS IN NEUROLOGY, vol.28, no.1, 2026 (SCI-Expanded, Scopus)

Abstract

Purpose of review Obstructive sleep apnea (OSA) is a highly prevalent disorder characterized by recurrent upper airway collapse during sleep and associated with substantial cardiovascular, metabolic, and neurocognitive morbidity. This narrative review summarizes the major symptom-based and polysomnographic phenotypes of OSA, examines their association with the underlying physiological traits, and considers the implications for treatment selection.Recent findings Despite its widespread use, the apnea-hypopnea index (AHI) inadequately captures the biological heterogeneity of OSA, treating all respiratory events as equivalent and correlating only modestly with symptom burden and clinical outcomes. This limitation has contributed to a uniform treatment paradigm in which positive airway pressure (PAP) therapy is applied irrespective of the underlying mechanism. PAP remains the therapeutic benchmark for moderate-to-severe OSA, but its real-world effectiveness is constrained by suboptimal adherence. Increasing evidence supports the concept of OSA as a heterogeneous syndrome comprising distinct clinical phenotypes and underlying pathophysiological endotypes. The PALM framework groups the principal physiological contributors into four traits: pharyngeal collapsibility, arousal threshold, loop gain, and upper airway muscle responsiveness. We discuss how these endotypes are associated with disease expression, comorbidity profiles, and treatment responsiveness, including outcomes with PAP, mandibular advancement devices, positional therapy, surgery, hypoglossal nerve stimulation, and pharmacological approaches. Particular emphasis is placed on non-invasive endotyping, especially the Phenotyping Using Polysomnography (PUP) approach, which provides model-derived estimates of these traits from standard polysomnography, and on the limitations that currently constrain its use in individual patients.Summary Integrating phenotypic and endotypic information offers a precision medicine approach to OSA, moving beyond AHI-based classification toward individualized, mechanism-targeted therapy. Such an approach has the potential to improve treatment selection, enhance adherence, and optimize clinical outcomes in this diverse and complex disorder.