Phenotypic Subtypes of OSA: A Challenge and Opportunity for Precision Medicine.

Current strategies for the management of OSA reflect a one-size-fits-all approach. Diagnosis and severity of OSA are based on the apnea-hypopnea index and treatment initiated with CPAP, followed by trials of alternatives (eg, oral appliances) if CPAP "fails." This approach does not consider the 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 subtypes of patients with unique characteristics, that may enable more personalized approaches to prognostication and treatment. Examples include symptom-based subtypes such as "excessively sleepy" and "disturbed sleep" with differing impact of CPAP on symptoms and health-related quality of life. Polysomnographic subtypes, 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 subtypes 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 subtypes, 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 the heterogeneity of OSA to improve patient lives.