Chest
Volume 153, Issue 3, March 2018, Pages 744-755
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Contemporary Reviews in Sleep Medicine
Personalized Management Approach for OSA

https://doi.org/10.1016/j.chest.2017.06.011Get rights and content

OSA is a heterogeneous disorder. If left untreated, it has major health, safety, and economic consequences. In addition to varying levels of impairment in pharyngeal anatomy (narrow/collapsible airway), nonanatomical “phenotypic traits” are also important contributors to OSA for most patients. However, the majority of existing therapies (eg, CPAP, oral appliances, weight loss, positional therapy, upper airway surgery) target only the anatomical cause. These are typically administered as monotherapy according to a trial and error management approach in which the majority of patients are first prescribed CPAP. Despite its high efficacy, CPAP adherence remains unacceptably low, and second-line therapies have variable and unpredictable efficacies. Recent advances in knowledge regarding the multiple causes of OSA using respiratory phenotyping techniques have identified new targets or “treatable traits” to direct therapy. Identification of the traits and development of therapies that selectively target one or more of the treatable traits has the potential to personalize the management of this chronic health condition to optimize patient outcomes according to precision medicine principles. This brief review highlights the latest developments and emerging therapies for personalized management approaches for OSA.

Section snippets

Upper Airway Anatomy and Collapsibility

Although OSA is a heterogeneous disorder, a prerequisite cause of its development is some level of anatomical compromise/increased upper airway collapsibility. Static imaging during wakefulness shows reduced pharyngeal lumen size in patients with OSA compared with non-OSA control subjects.15 Obesity is a major contributor to pharyngeal narrowing. Increased fat deposition in the soft tissues, tongue, and lateral pharyngeal walls directly reduces the pharyngeal airspace in obese patients with OSA.

Current Treatments That Target Impaired Upper Airway Anatomy

Anatomical treatments for OSA work by altering upper airway structure to prevent pharyngeal collapse during sleep.

Nonanatomical Contributors to OSA and Potential Targeted Therapies

In addition to the importance of impaired upper airway anatomy to the pathogenesis of OSA, recent advances in OSA phenotyping and respiratory neurobiology have identified nonanatomical causes and novel targets for therapy.7, 8 Approximately 70% of patients with OSA have impairment in one or more nonanatomical contributors.7 These are briefly summarized below.

Muscle Control and Function

The pharyngeal muscles play a pivotal role in the maintenance of upper airway patency. They receive complex neural input from respiratory pattern-generator neurons. This action includes synchronized drive with inspiration to stiffen and dilate the airway to oppose inspiratory collapse.49 Upper airway dilator muscles also receive reflex input from pressure-sensitive mechanoreceptors in the airway and from chemoreceptors via changes in CO2 or oxygen. The genioglossus is the largest dilator muscle

Hypoglossal Nerve Stimulation

Stimulation of the hypoglossal nerve, which innervates intrinsic and extrinsic muscles of the tongue, improves upper airway patency during sleep. Sustained reductions in AHI (> 50%) after 6, 12, and 36 months of follow-up, as well as subjective measures of sleepiness and quality of life, have been reported.54, 55, 56, 57 Prediction of successful treatment response may be dependent on an individual’s Pcrit, pharyngeal shape, and site of airway collapse.57, 58

Arousal Threshold

Cortical arousals from sleep during an obstructive event occur when increasing negative intra-thoracic pressure reaches a certain threshold (ie, the arousal threshold).69 Repetitive cycling between wakefulness and sleep can destabilize breathing, prevent deep sleep, and perpetuate OSA severity.69, 70 Evidence indicates that 30% to 50% of all patients with OSA7, 71, 72 (and > 85% of nonobese patients)14 wake up too easily to small changes in intra-thoracic pressure (between zero and –15 cm H2O).

Hypnotic Agents

Standard doses of eszopiclone (3 mg), zopiclone (7.5 mg), and trazodone (100 mg) increase the threshold for arousal to negative pressure71, 73, 74 and can reduce the AHI by approximately 25% to 50%71, 75 without increasing hypoxemia. However, high doses of certain hypnotic agents in severe OSA may prolong apneic events and worsen hypoxemia.73, 76 Other sleep-promoting agents such as nitrazepam (5 mg or 10 mg) and tiagabine (12 mg) do not reduce the AHI77, 78 or arousal threshold77 and are

Loop Gain

During sleep, Paco2 tightly regulates ventilation via afferent feedback from chemoreceptors. The sensitivity of the ventilatory control system involves two principal components: controller (chemoresponsiveness) and plant (excretion of CO2) gain. Overall “loop gain” is quantified as the ventilatory response/ventilatory disturbance ratio. High loop gain indicates unstable ventilatory control. Specifically, an individual with high loop gain has an excessively large ventilatory response to very

Oxygen Therapy

Supplemental oxygen has been used as a treatment for OSA in unselected patients with variable efficacy.83 Oxygen therapy reduces loop gain by approximately 50% and lowers the AHI by approximately 50% in patients with OSA with high loop gain.84

Targeted Therapy for OSA

Figure 3 summarizes some of the existing and experimental targeted therapies to treat OSA.

Conclusions

There has been substantial recent progress toward personalized management for OSA via advances in knowledge on the multiple causes of OSA, identification of new therapeutic targets, promising proof-of-concept data for targeted therapies including combination therapy, and ongoing development of simplified phenotyping tools to be used in the clinic to inform targeted therapies for OSA. This research has the potential to realign treatment and management approaches for this common, chronic health

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: J. C. C. and J. A. are supported by the NeuroSleep National Health and Medical Research Council of Australia Centre of Research Excellence Fellowships (1060992) and do not have any conflicts to declare. D. J. E. is supported by a National Health and Medical Research Council of Australia Senior Research Fellowship (1116942) and has served on an advisory board for Bayer Pharmaceuticals and has received

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