Mechanism-based Precision Medicine for Oral Appliance Therapy: A Prospective Observational Study
2020 Strategic Research Grant
Scott Sands, PhD
Brigham and Women’s Hospital and Harvard Medical School
Key Project Outcome
The AASM Foundation grant supported initiation of a dental sleep medicine clinical research program at the Brigham and Women’s Hospital; as part of our program, high-quality polysomnography data are collected in participating patients with sleep apnea before and after routine oral appliance treatment. Our major goal is to test our new methods that uses a baseline sleep study to determine why each patient has sleep apnea (underlying causes). Four key causes include: the degree of upper airway collapsibility, the compensatory responses of the upper airway muscle reflexes, the degree of oversensitivity of breathing control reflexes, and the degree of arousability from sleep. Our primary project here aimed to put these measures together to describe each patient as either likely or unlikely to respond to oral appliance therapy in terms of the improvement in sleep apnea severity, plus patient satisfaction. To date, baseline and follow-up data from 59 individuals have been analyzed. In this group, oral appliances improved sleep apnea severity by a greater amount in patients with greater upper airway collapsibility, less oversensitive breathing control reflexes, and lower arousability. The same factors also predicted greater treatment satisfaction, suggesting that the improvements seen on the sleep study were being translated into symptomatic improvements that are meaningful for the patients. When accounting for the multiple traits; treatment responses appeared slightly stronger in those who were more obese and more severe, population groups who are not typically considered for oral appliance care. As we collect the remaining data, we will evaluate this model’s predictive value in the final 50 patients. Overall, oral appliances appear most effective in patient in whom sleep apnea is driven more by anatomical rather than non-anatomical causes. Additional data collection is planned before finalizing and validating a prediction model to be tested in external clinical centers. Beyond the specific project, the AASM Foundation grant facilitated an ancillary study as part of our new program including work by Drs. Daniel Vena and Reza Radmand on oral appliances and 24-hr blood pressure outcomes in sleep apnea, and facilitated an NIH NHLBI R01 award to Drs. Wellman (PI), Sands (Co-I), and Aishah (post-doc) to provide targeted rescue therapies to oral appliance non-responders. The investigators are grateful for the early contribution by the AASM Foundation to our ongoing efforts to better understand which patients benefit most from oral appliances for the treatment of sleep apnea.