Mihaela Teodorescu1, Ailiang Xie2, Christine A Sorkness3, Joanne Robbins4, Scott Reeder5, Yuanshen Gong2, Jessica E Fedie2, Ann Sexton6, Barb Miller6, Tiffany Huard6, Jaqueline Hind4, Nora Bioty7, Emily Peterson7, Susan J Kunselman7, Vernon M Chinchilli7, Xavier Soler8, Joe Ramsdell8, Jose Loredo8, Elliott Israel9, Danny J Eckert10, Atul Malhotra11. 1. James B. Skatrud Pulmonary/Sleep Research Laboratory, Medical Service, William S. Middleton Memorial Veteran's Hospital, Madison, WI ; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Center for Sleep Medicine and Sleep Research/Wisconsin Sleep, University of Wisconsin School of Medicine and Public Health, Madison, WI. 2. Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI. 3. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI ; University of Wisconsin School of Pharmacy, Madison, WI. 4. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI ; William S. Middleton Memorial Veterans Hospital, Geriatric Research, Education and Clinical Center (GRECC). 5. Departments of Radiology, Medical Physics and Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI. 6. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI. 7. Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, PA. 8. Department of Medicine, University of California at San Diego, San Diego, CA. 9. Department of Medicine, Brigham and Womens Hospital, Harvard University, Boston, MA. 10. Department of Medicine, Brigham and Womens Hospital, Harvard University, Boston, MA ; Neuroscience Research Australia, Sydney, Australia. 11. Department of Medicine, University of California at San Diego, San Diego, CA ; Department of Medicine, Brigham and Womens Hospital, Harvard University, Boston, MA.
Abstract
STUDY OBJECTIVE: Obstructive sleep apnea is prevalent among people with asthma, but underlying mechanisms remain unknown. Inhaled corticosteroids may contribute. We tested the effects of orally inhaled fluticasone propionate (FP) on upper airway (UAW) during sleep and wakefulness. STUDY DESIGN: 16-week single-arm study. PARTICIPANTS: 18 (14 females, mean [ ± SD] age 26 ± 6 years) corticosteroid-naïve subjects with mild asthma (FEV1 89 ± 8% predicted). INTERVENTIONS: High dose (1,760 mcg/day) inhaled FP. MEASUREMENTS: (1) UAW collapsibility (passive critical closing pressure [Pcrit]); (2) tongue strength (maximum isometric pressure-Pmax, in KPa) and endurance-time (in seconds) able to maintain 50% Pmax across 3 trials (Ttot)-at anterior and posterior locations; (3) fat fraction and volume around UAW, measured by magnetic resonance imaging in three subjects. RESULTS: Pcrit overall improved (became more negative) (mean ± SE) (-8.2 ± 1.1 vs. -12.2 ± 2.2 cm H2O, p = 0.04); the response was dependent upon baseline characteristics, with older, male gender, and worse asthma control predicting Pcrit deterioration (less negative). Overall, Pmax increased (anterior p = 0.02; posterior p = 0.002), but Ttot generally subsided (anterior p = 0.0007; posterior p = 0.06), unrelated to Pcrit response. In subjects studied with MRI, fat fraction and volume increased by 20.6% and 15.4%, respectively, without Pcrit changes, while asthma control appeared improved. CONCLUSIONS: In this study of young, predominantly female, otherwise healthy subjects with well-controlled asthma and stiff upper airways, 16-week high dose FP treatment elicited Pcrit changes which may be dependent upon baseline characteristics, and determined by synchronous and reciprocally counteracting local and lower airway effects. The long-term implications of these changes on sleep disordered breathing severity remain to be determined.
STUDY OBJECTIVE: Obstructive sleep apnea is prevalent among people with asthma, but underlying mechanisms remain unknown. Inhaled corticosteroids may contribute. We tested the effects of orally inhaled fluticasone propionate (FP) on upper airway (UAW) during sleep and wakefulness. STUDY DESIGN: 16-week single-arm study. PARTICIPANTS: 18 (14 females, mean [ ± SD] age 26 ± 6 years) corticosteroid-naïve subjects with mild asthma (FEV1 89 ± 8% predicted). INTERVENTIONS: High dose (1,760 mcg/day) inhaled FP. MEASUREMENTS: (1) UAW collapsibility (passive critical closing pressure [Pcrit]); (2) tongue strength (maximum isometric pressure-Pmax, in KPa) and endurance-time (in seconds) able to maintain 50% Pmax across 3 trials (Ttot)-at anterior and posterior locations; (3) fat fraction and volume around UAW, measured by magnetic resonance imaging in three subjects. RESULTS: Pcrit overall improved (became more negative) (mean ± SE) (-8.2 ± 1.1 vs. -12.2 ± 2.2 cm H2O, p = 0.04); the response was dependent upon baseline characteristics, with older, male gender, and worse asthma control predicting Pcrit deterioration (less negative). Overall, Pmax increased (anterior p = 0.02; posterior p = 0.002), but Ttot generally subsided (anterior p = 0.0007; posterior p = 0.06), unrelated to Pcrit response. In subjects studied with MRI, fat fraction and volume increased by 20.6% and 15.4%, respectively, without Pcrit changes, while asthma control appeared improved. CONCLUSIONS: In this study of young, predominantly female, otherwise healthy subjects with well-controlled asthma and stiff upper airways, 16-week high dose FP treatment elicited Pcrit changes which may be dependent upon baseline characteristics, and determined by synchronous and reciprocally counteracting local and lower airway effects. The long-term implications of these changes on sleep disordered breathing severity remain to be determined.
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