Fluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects
- *Corresponding Author:
- Delbert R. Dorscheid
Centre for Heart Lung Innovation
St. Paul's Hospital, Rm. 166
1081 Burrard Street, Vancouver
B.C. V6Z 1Y6, Canada
Tel: (604) 806 2746
Fax: (604) 806 8351
E-mail: [email protected]
Received date: February 27, 2014; Accepted date: June 04, 2014; Published date: June 11, 2014
Citation: MacRedmond R E, Singhera GK, Wadsworth SJ, Attridge S, Bahzad M, et al. (2014) Fluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects. J Steroids Hormon Sci 5:134. doi:10.4172/2157-7536.1000134
Copyright: © 2014 MacRedmond R E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Conclusion: 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.