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https://hdl.handle.net/2440/139805
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Type: | Journal article |
Title: | Stepwise Add-on and Endotype-informed Targeted Combination Therapy to Treat Obstructive Sleep Apnea: A Proof-of-Concept Study |
Author: | 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. |
Citation: | Annals of the American Thoracic Society, 2023; 20(9):1316-1325 |
Publisher: | American Thoracic Society |
Issue Date: | 2023 |
ISSN: | 2329-6933 2325-6621 |
Statement of Responsibility: | Atqiya Aishah, Benjamin K. Y. Tong, Amal M. Osman, Geoffrey Pitcher, Michelle Donegan, Benjamin C. H. Kwan, Elizabeth Brown, Thomas J. Altree, Robert Adams, Sutapa Mukherjee, and Danny J. Eckert |
Abstract: | Rationale: 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. |
Keywords: | pharmacotherapy; phenotypes; precision medicine; respiratory physiology; sleep-disordered breathing |
Rights: | Copyright status unknown |
DOI: | 10.1513/AnnalsATS.202210-892OC |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1196261 |
Published version: | http://dx.doi.org/10.1513/annalsats.202210-892oc |
Appears in Collections: | Medicine publications |
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