Precision Medicine for Obstructive Sleep Apnea

Abstract

Increasingly, obstructive sleep apnea treatment is being recognized as amenable to a precision medicine approach. Many pathophysiologic mechanisms (endotypes) beyond anatomic compromise have now been identified and are readily determined during polysomnography, although randomized controlled trials of endotype-specific therapies are needed. Research indicates that endotypes may also be important in predicting both adherence to therapy and disease consequences (phenotypes). Biomarker discovery and Big Data approaches derived from wearable technology are areas of active investigation and may allow more robust conclusions to be drawn over time, such that patients may soon fully realize the benefits from fresh insights into sleep science.

Keywords: Arousal threshold; Loop gain; OSA Treatment; Obstructive sleep apnea; Precision medicine.

Fig. 1.

Personalized medicine approach in clinical practice based on endotypes. Determination of an individual’s endotype could be used for risk stratification to help decide whether (aggressive) treatment is indicated. In highrisk patients who are CPAP intolerant, this information could further be used to tailor therapy toward the individual’s underlying sleep apnea causes. Note that in a given individual sleep apnea may potentially be due to multiple traits, thus requiring combination therapy; for example, a patient may have sleep apnea due to both high loop gain and low arousal threshold and may thus require both oxygen and a sedative in order to achieve stable breathing at night.

Fig. 2.

Personalized medicine approach in clinical trial design based on endotypes. As discussed in the text, the authors speculate that an individual’s sleep apnea endotype may predict which adverse health outcomes this person is at risk for; it certainly is predictive of which interventions other than CPAP may be efficacious. In this para-digm, a trial seeking to improve hypertension would maximize its power (ie, chance of success) by enrolling primarily patients with OSA due to high loop gain using CPAP (or potentially oxygen) as the intervention. Note that in a given individual sleep apnea may be due to more than one trait, thus increasing the risk of several adverse health outcomes; for example, a patient with OSA from high loop gain and low arousal threshold may be at risk of both hypertension and impaired memory and thus be a good candidate for trials focusing on either outcome.