title: Fluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects.
abstract: OBJECTIVE
  The airway epithelium has a number of roles pivotal to the pathogenesis of asthma, including provision of a physical and immune barrier to the inhaled environment. Dysregulated injury and repair responses in asthma result in loss of airway epithelial integrity. Inhaled corticosteroids are a corner stone of asthma treatment. While effective in controlling asthma symptoms, they fail to prevent airway remodeling. Direct cytopathic effects on the airway epithelium may contribute to this.
  
  
  METHODS
  This study examined the effects of a 4-week treatment regimen of inhaled fluticasone 500 μg twice daily in healthy human subjects. Induced sputum was collected for cell counts and markers of inflammation. Barrier function was examined by diethylenetriaminepentacetic acid (DTPA) clearance measured by nuclear scintillation scan, and albumin concentration in induced sputum.
  
  
  RESULTS
  Steroid exposure resulted in epithelial injury as measured by a significant increase in the number of airway epithelial cells in induced sputum. There was no change in airway inflammation by induced sputum inflammatory cell counts or cytokine levels. Epithelial shedding was associated with an increase in barrier function, as measured by both a decrease in DTPA clearance and decreased albumin in induced sputum. This likely reflects the normal repair response.
  
  
  CONCLUSIONS
  Inhaled corticosteroids cause injury to normal airway epithelium. These effects warrant further evaluation in asthma, where the dysregulated repair response may contribute to airway remodeling.
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: MacRedmond
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Gurpreet K
authors.initials: GK
authors.lastname: Singhera
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Wadsworth
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Attridge
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bahzad
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Kristy
authors.initials: K
authors.lastname: Williams
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Harvey O
authors.initials: HO
authors.lastname: Coxson
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: White
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Delbert R
authors.initials: DR
authors.lastname: Dorscheid
keywords: Airway epithelial cell; Asthma; Asthma-medication; corticosteroids