Aishah, A.Tong, B.K.Y.Osman, A.M.Pitcher, G.Donegan, M.Kwan, B.C.H.Brown, E.Altree, T.J.Adams, R.Mukherjee, S.Eckert, D.J.2023-10-272023-10-272023Annals of the American Thoracic Society, 2023; 20(9):1316-13252329-69332325-6621https://hdl.handle.net/2440/139805Rationale: Oral appliance therapy (OAT) is an effective treatment for many people with obstructive sleep apnea (OSA). However, OSA pathogenesis is heterogeneous, and, in ∼50% of cases, OAT does not fully control OSA. Objectives: This study aimed to control OSA in individuals with an incomplete response to OAT alone by using additional targeted therapies informed by OSA endotype characterization. Methods: Twenty-three people with OSA (apnea–hypopnea index [AHI], 41 ± 19 events/h) not fully resolved (AHI, >10 events/h) with OAT alone were prospectively recruited. OSA endotypes were characterized pretherapy during a detailed physiology study night. Initially, an expiratory positive airway pressure (EPAP) valve and supine avoidance device therapy were added to target the impaired anatomical endotype. Those with residual OSA (AHI, >10 events/h) then received one or more nonanatomical interventions based on endotype characterization. This included O2 (4 L/min) to reduce high loop gain (unstable respiratory control) and 80/5 mg atomoxetine-oxybutynin to increase pharyngeal muscle activity. Finally, if required, OAT was combined with EPAP and continuous positive airway pressure (CPAP) therapy. Results: Twenty participants completed the study. OSA was successfully controlled (AHI, <10 events/h) with combination therapy in all but one participant (17 of 20 without CPAP). OAT plus EPAP and supine avoidance therapy treated OSA in 10 (50%) participants. OSA was controlled in five (25%) participants with the addition of O2 therapy, one with atomoxetine-oxybutynin, and one required O2 plus atomoxetine-oxybutynin. Two participants required CPAP for their OSA, and another was CPAP intolerant. Conclusions: These novel prospective findings highlight the potential of precision medicine to inform targeted combination therapy to treat OSA.enCopyright status unknownpharmacotherapy; phenotypes; precision medicine; respiratory physiology; sleep-disordered breathingHumansSleep Apnea, ObstructiveProspective StudiesAustraliaAtomoxetine HydrochlorideJournal article10.1513/AnnalsATS.202210-892OC2023-10-27644487Altree, T.J. [0000-0003-1979-8975]Adams, R. [0000-0002-7572-0796]