Endotype-informed targeted therapies reduce OSA severity
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Key takeaways:
- Adding expiratory positive airway pressure and supine avoidance therapy to oral appliance therapy lowered apnea-hypopnea index.
- Reductions also occurred with added O2 therapy, atomoxetine-oxybutynin and CPAP.
Adding on endotype-informed targeted combination therapies to oral appliance therapy helped reduce obstructive sleep apnea severity, according to results published in Annals of the American Thoracic Society.
“These novel prospective findings highlight the clinical potential to use endotype-guided combination therapy to provide targeted therapeutic solutions for most patients who do not fully respond to [oral appliance therapy] monotherapy,” Atqiya Aishah, BSc, PhD, of the University of New South Wales in Australia, and colleagues wrote.
In a proof-of-concept study, Aishah and colleagues analyzed 20 patients with OSA who used oral appliance therapy but did not have their condition fully resolved (apnea-hypopnea index [AHI], > 10 events per hour) to find out if OSA endotype-informed targeted therapies plus oral appliance therapy can lower AHI.
Researchers captured patients’ endotypes prior to therapy.
Of the total cohort, 19 patients achieved an AHI of less than 10 events per hour with combination therapy; however, some patients had fewer interventions to get to this point.
The first combination therapy given to patients targeted the impaired anatomical endotype and came in the form of oral appliance therapy plus expiratory positive airway pressure and supine avoidance therapy. Half of the total cohort (n = 10) reached an AHI of less than 10 events per hour with this treatment combination (5 events per hour vs. oral appliance therapy alone, 17 events per hour).
Through pulse oximetry, researchers also found that this combination vs. sole oral appliance therapy contributed to better nadir oxygen saturation.
Researchers further added a targeted nonanatomical intervention to the above combination therapy for the remaining patients with an AHI higher than 10.
To lower high loop gain observed in some patients, which signals unstable respiratory control, researchers added 4 L per minute of oxygen (O2), and this helped five patients achieve an AHI of less than 10 events per hour (7 events per hour vs. first combination therapy, 16 events per hour).
Receiving a combination of 80 mg atomoxetine and 5 mg oxybutynin — designed to raise pharyngeal muscle activity — in addition to the first outlined combination therapy helped one patient with this characteristic reach the AHI milestone (5 events per hour vs. first combination therapy, 16 events per hour).
One additional patient had controlled OSA after receiving the first combination therapy and both O2 and atomoxetine-oxybutynin (7 events per hour vs. first combination therapy, 30 events per hour).
After all these combinations, three patients still had an AHI over 10 events per hour, so researchers treated them with oral appliance therapy, expiratory positive airway pressure and CPAP therapy.
Following receipt of this combination, two patients reached an AHI under 10 events per hour, whereas the last patient could not tolerate CPAP.
For one of the two patients, the road to controlled OSA involved trying the first combination therapy (43 events per hour) plus O2 therapy (32 events per hour) and plus atomoxetine-oxybutynin (28 events per hour) before reaching an AHI of 2 events per hour with the last combination (oral appliance therapy, expiratory positive airway pressure and CPAP). Notably, this patient had high loop gain and inadequate muscle activity, according to researchers.
The second patient underwent the first combination therapy (50 events per hour) plus O2 for high loop gain (34 events per hour) before reaching an AHI of 8.5 events per hour with the last combination.
“These findings provide support for the development of physiology-based precision medicine to treat OSA,” Aishah and colleagues wrote.
Perspective
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OSA is a common sleep disorder affecting nearly 30 million adults in the U.S. Effective treatment options include CPAP therapy and oral appliance therapy. As the authors of this study describe, the physiological causes of sleep apnea are complex, and there isn’t one treatment that provides optimal results for everyone.
A patient who is diagnosed with sleep apnea is encouraged to consult a board-certified sleep medicine physician and the team of clinicians at an American Academy of Sleep Medicine-accredited sleep center. Together, through collaborative decision-making, they can develop a personalized treatment plan that takes into consideration the individual circumstances of the patient.
Although it was only a small, proof-of-concept study, this research produced promising results. There is a great need for more decision-making tools and strategies that promote precision medicine in the sleep field. Most sleep apnea therapies currently are used in isolation. The authors’ exploration of various combination therapies targeting the underlying cause of sleep apnea is an innovative approach.
While supplemental oxygen and atomoxetine-oxybutynin currently are not standard forms of care for typical cases of sleep apnea, this study adds new evidence to the literature supporting their use for selected patients. I look forward to seeing additional studies that build on this methodology in larger and more diverse patient populations.
I anticipate that the use of precision medicine for the treatment of sleep apnea will increase in the years ahead as new therapeutic innovations and treatment methodologies continue to be developed. These innovations will be beneficial for patients who have sleep apnea.
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