More Than the Sum of the Respiratory Events: Personalized Medicine Approaches for Obstructive Sleep Apnea

Abstract

Traditionally, the presence and severity of obstructive sleep apnea (OSA) have been defined by the apnea-hypopnea index (AHI). Continuous positive airway pressure is generally first-line therapy despite low adherence, because it reliably reduces the AHI when used, and the response to other therapies is variable. However, there is growing appreciation that the underlying etiology (i.e., endotype) and clinical manifestation (i.e., phenotype) of OSA in an individual are not well described by the AHI. We define and review the important progress made in understanding and measuring physiological mechanisms (or endotypes) that help define subtypes of OSA and identify the potential use of genetics to further refine disease classification. This more detailed understanding of OSA pathogenesis should influence clinical treatment decisions as well as help inform research priorities and clinical study design. In short, treatments could be individualized on the basis of the underlying cause of OSA; patients could better understand which symptoms and outcomes will respond to OSA treatment and by how much; and researchers could select populations most likely to benefit from specific treatment approaches for OSA.

Keywords: endotype; genotype; obstructive sleep apnea; phenotype.

Figure 1.

Definitions and examples of how the genotype drives the endotype, which clinically presents as a phenotype that will respond best to a specific treatment intervention. This has been shown in other areas of medicine, such as the treatment of diabetes, in which knowledge of the underlying endotype can impact therapy. For example, metformin (an insulin-sensitizing drug) would not treat hyperglycemia in type 1 diabetes. Bottom panel describes hypothetical pathways that suggest the same may be true for obstructive sleep apnea (OSA). CPAP = continuous positive airway pressure; CVD = cardiovascular disease.