Phenotypic sub-types of obstructive sleep apnea: a challenge and opportunity for precision medicine.

Abstract:

Current strategies for management of obstructive sleep apnea (OSA) reflect a one-size-fits-all approach. Diagnosis and severity of OSA are based on the apnea hypopnea index and treatment initiated with continuous positive airway pressure (CPAP), followed by trials of alternatives, such as oral appliances, if CPAP “fails.” This approach does not consider heterogeneity of individuals with OSA, reflected by varying risk factors, pathophysiological causes, clinical manifestations and consequences. Recently, studies using analytic approaches such as cluster analysis have taken advantage of this heterogeneity to identify OSA phenotypes, or sub-types of patients with unique characteristics, that may enable more personalized approaches to prognostication and treatment. Examples include symptom-based sub-types such as “Excessively sleepy” and “Disturbed sleep” with differing impact of CPAP on symptoms and health-related quality of life. Polysomnographic sub-types, distinguished by respiratory event association with hypoxemia, arousals or both, exhibit varying risks of cardiovascular disease and response to therapy. This review summarizes the findings from recent cluster analysis studies in sleep apnea and synthesizes common themes to describe the potential role (and limitations) of phenotypic sub-types in precision medicine for OSA. It also highlights future directions, including linking of phenotypes to clinically relevant outcomes, rigorous and transparent assessment of phenotype reproducibility and need for tools that categorize patients into sub-types, to prospectively validate phenotype-based prognostication and treatment approaches. Finally, we highlight the critical need to include women and more racially/ethnically diverse populations in this area of research, if we are to leverage heterogeneity of OSA to improve patient lives.

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