Fluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects.

TitleFluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects.
Publication TypeJournal Article
Year of Publication2014
AuthorsMacRedmond, RE, Singhera, GK, Wadsworth, SJ, Attridge, S, Bahzad, M, Williams, K, Coxson, HO, White, SR, Dorscheid, DR
JournalJ Steroids Horm Sci
Date Published2014 Jun 11

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.

Alternate JournalJ Steroids Horm Sci
PubMed ID25324978
PubMed Central IDPMC4196246
Grant ListR01 HL060531 / HL / NHLBI NIH HHS / United States