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Volume 10 No. 02
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Scientific Investigations

Effects of Inhaled Fluticasone on Upper Airway during Sleep and Wakefulness in Asthma: A Pilot Study

http://dx.doi.org/10.5664/jcsm.3450

Mihaela Teodorescu, M.D., F.A.A.S.M.1,2,3; Ailiang Xie, Ph.D.4; Christine A. Sorkness, Pharm.D.2,5; JoAnne Robbins, Ph.D.2,6; Scott Reeder, M.D., Ph.D.7; Yuanshen Gong, Ph.D.4; Jessica E. Fedie, B.S.4; Ann Sexton, M.P.H.2; Barb Miller2; Tiffany Huard, B.S.2; Jaqueline Hind, M.S.2,6; Nora Bioty, M.S.8; Emily Peterson, M.S.8; Susan J. Kunselman, M.A.8; Vernon M. Chinchilli, Ph.D.8; Xavier Soler, M.D., Ph.D.9; Joe Ramsdell, M.D.9; Jose Loredo, M.D., F.A.A.S.M.9; Elliott Israel, M.D.10; Danny J. Eckert, Ph.D.10,11; Atul Malhotra, M.D., F.A.A.S.M.9,10
1James B. Skatrud Pulmonary/Sleep Research Laboratory, Medical Service, William S. Middleton Memorial Veteran's Hospital, Madison, WI; 2Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI; 3Center for Sleep Medicine and Sleep Research/Wisconsin Sleep, University of Wisconsin School of Medicine and Public Health, Madison, WI; 4Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI; 5University of Wisconsin School of Pharmacy, Madison, WI; 6William S. Middleton Memorial Veterans Hospital, Geriatric Research, Education and Clinical Center (GRECC); 7Departments of Radiology, Medical Physics and Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI; 8Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, PA; 9Department of Medicine, University of California at San Diego, San Diego, CA; 10Department of Medicine, Brigham and Womens Hospital, Harvard University, Boston, MA; 11Neuroscience Research Australia, Sydney, Australia

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.

Citation:

Teodorescu M; Xie A; A. Sorkness CA; Robbins J; Reeder S; Gong Y; Fedie JE; Sexton A; Miller B; Huard T; Hind J; Bioty N; Peterson E; Kunselman SJ; Chinchilli VM; Soler X; Ramsdell J; Loredo J; Israel E; Eckert DJ; Malhotra A. Effects of inhaled fluticasone on upper airway during sleep and wakefulness in asthma: a pilot study. J Clin Sleep Med 2014;10(2):183-193.




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