OSA Endotypes and Phenotypes: Toward Personalized OSA Care

3 A new concept is emerging whereby endotypes of OSA may actually predict differing OSA phenotypes. In theory, loop gain-driven OSA may have different consequences from OSA driven by compromise of pharyngeal anatomy. To this point, data suggest that OSA in the elderly may not have as many consequences as OSA in younger people matched on severity of illness. OSA in the elderly has lower loop gain than OSA in younger people and is associated with less negative intrathoracic pressure at the time of arousal as compared with younger individuals with OSA (Kobayashi et al. Chest. 2010; 137[6]:1310). As such, the endotype of OSA in the elderly may explain why the clinical consequences are fewer than in the younger OSA counterparts.

4 The mechanism underlying OSA may be important in determining response to clinical interventions, such as nasal CPAP. Patients with a low arousal threshold may be prone to insomnia when placed on CPAP and could theoretically be poorly tolerant of therapy based on disrupted sleep architecture. Such patients may benefit from non-myorelaxant hypnotic therapy to consolidate sleep and improve CPAP adherence. In addition, patients with high loop gain (unstable ventilatory control) may be prone to develop central apneas when placed on CPAP therapy (Stanchina et al. Ann Am Thorac Soc. 2015;12[9]:1351). These patients may benefit from newer technologies, eg, auto or adaptive servo ventilation - ASV. High loop gain has also been shown to predict failure of upper airway surgery as a treatment for OSA by several groups (Li et al. JCSM. 2017;13[9]:1029). Such patients should, perhaps, undergo nonsurgical therapies for OSA.

We emphasize that some of the points being made are somewhat speculative and, thus, encourage further basic and clinical research to test our assumptions. Robust, multicenter clinical trials assessing hard outcomes will ultimately be required to change the current standard of care. Nonetheless, we believe that a more thorough understanding of OSA pathogenesis can help guide clinical care today and will be critical to the optimal treatment of afflicted individuals tomorrow.

Dr. Owens is Assistant Clinical Professor of Medicine; Dr. Deacon is a Post-Doctoral Research Scholar; and Dr. Malhotra is Kenneth M. Moser Professor of Medicine and Chief, Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego.