title: Effects of inhaled fluticasone on upper airway during sleep and wakefulness in asthma: a pilot study.
abstract: 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.
  
  
  METHODS
  16-week single-arm study.
  
  
  METHODS
  18 (14 females, mean [ ± SD] age 26 ± 6 years) corticosteroid-naïve subjects with mild asthma (FEV1 89 ± 8% predicted).
  
  
  METHODS
  High dose (1,760 mcg/day) inhaled FP.
  
  
  METHODS
  (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.
authors.affiliation: 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.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Teodorescu
authors.affiliation: Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Ailiang
authors.initials: A
authors.lastname: Xie
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI ; University of Wisconsin School of Pharmacy, Madison, WI.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.affiliation: 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).
authors.forename: Joanne
authors.initials: J
authors.lastname: Robbins
authors.affiliation: Departments of Radiology, Medical Physics and Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Scott
authors.initials: S
authors.lastname: Reeder
authors.affiliation: Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Yuanshen
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Fedie
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Ann
authors.initials: A
authors.lastname: Sexton
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Barb
authors.initials: B
authors.lastname: Miller
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Huard
authors.affiliation: 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).
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Hind
authors.affiliation: Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, PA.
authors.forename: Nora
authors.initials: N
authors.lastname: Bioty
authors.affiliation: Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, PA.
authors.forename: Emily
authors.initials: E
authors.lastname: Peterson
authors.affiliation: Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, PA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kunselman
authors.affiliation: Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, PA.
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.affiliation: Department of Medicine, University of California at San Diego, San Diego, CA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Soler
authors.affiliation: Department of Medicine, University of California at San Diego, San Diego, CA.
authors.forename: Joe
authors.initials: J
authors.lastname: Ramsdell
authors.affiliation: Department of Medicine, University of California at San Diego, San Diego, CA.
authors.forename: Jose
authors.initials: J
authors.lastname: Loredo
authors.affiliation: Department of Medicine, Brigham and Womens Hospital, Harvard University, Boston, MA.
authors.forename: Elliott
authors.initials: E
authors.lastname: Israel
authors.affiliation: Department of Medicine, Brigham and Womens Hospital, Harvard University, Boston, MA ; Neuroscience Research Australia, Sydney, Australia.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eckert
authors.affiliation: Department of Medicine, University of California at San Diego, San Diego, CA ; Department of Medicine, Brigham and Womens Hospital, Harvard University, Boston, MA.
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000367:Age Factors; D000402:Airway Obstruction / Q000150:complications* / Q000188:drug therapy*; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000150:complications* / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D010865:Pilot Projects; D017286:Polysomnography / Q000187:drug effects / Q000379:methods; D012737:Sex Factors; D012890:Sleep / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000150:complications*; D014851:Wakefulness / Q000502:physiology
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D000068298:Fluticasone
keywords: Asthma; genioglossus; inhaled corticosteroid; lung; obstructive; sleep apnea