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

MacRedmond RE, Singhera GK, Wadsworth SJ, Attridge S, Bahzad M, Williams K, Coxson HO, White SR, Dorscheid DR - J Steroids Horm Sci (2014)

Bottom Line: Direct cytopathic effects on the airway epithelium may contribute to this.Steroid exposure resulted in epithelial injury as measured by a significant increase in the number of airway epithelial cells in induced sputum.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.

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.

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.

No MeSH data available.


Related in: MedlinePlus

Diethylenetriaminepentacetic acid (DTPA) clearance is reduced after exposure to inhaled fluticasone. Subjects inhaled Technetium-labeled diethylenetriaminepentacetic acid (99mTc-DTPA) at visit 1 and 2 and images were recorded every 30 seconds for a total period of 30 minutes. Analysis done on those scans to calculate T1/2 value at visit 1 and visit 2 (*p<0.05)
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Figure 3: Diethylenetriaminepentacetic acid (DTPA) clearance is reduced after exposure to inhaled fluticasone. Subjects inhaled Technetium-labeled diethylenetriaminepentacetic acid (99mTc-DTPA) at visit 1 and 2 and images were recorded every 30 seconds for a total period of 30 minutes. Analysis done on those scans to calculate T1/2 value at visit 1 and visit 2 (*p<0.05)

Mentions: The mean (SEM) half-life of DTPA in the lungs increased from 90.1 (4.3) seconds to 106 (5.4) seconds following 28 days of inhaled fluticasone. The difference between the means was significant at p<0.05 (Figure 3A), and paired analysis showed a significant increase in T½ between visit 1 and visit 2 at p<0.02 (Figure 3B).


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

MacRedmond RE, Singhera GK, Wadsworth SJ, Attridge S, Bahzad M, Williams K, Coxson HO, White SR, Dorscheid DR - J Steroids Horm Sci (2014)

Diethylenetriaminepentacetic acid (DTPA) clearance is reduced after exposure to inhaled fluticasone. Subjects inhaled Technetium-labeled diethylenetriaminepentacetic acid (99mTc-DTPA) at visit 1 and 2 and images were recorded every 30 seconds for a total period of 30 minutes. Analysis done on those scans to calculate T1/2 value at visit 1 and visit 2 (*p<0.05)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196246&req=5

Figure 3: Diethylenetriaminepentacetic acid (DTPA) clearance is reduced after exposure to inhaled fluticasone. Subjects inhaled Technetium-labeled diethylenetriaminepentacetic acid (99mTc-DTPA) at visit 1 and 2 and images were recorded every 30 seconds for a total period of 30 minutes. Analysis done on those scans to calculate T1/2 value at visit 1 and visit 2 (*p<0.05)
Mentions: The mean (SEM) half-life of DTPA in the lungs increased from 90.1 (4.3) seconds to 106 (5.4) seconds following 28 days of inhaled fluticasone. The difference between the means was significant at p<0.05 (Figure 3A), and paired analysis showed a significant increase in T½ between visit 1 and visit 2 at p<0.02 (Figure 3B).

Bottom Line: Direct cytopathic effects on the airway epithelium may contribute to this.Steroid exposure resulted in epithelial injury as measured by a significant increase in the number of airway epithelial cells in induced sputum.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.

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.

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.

No MeSH data available.


Related in: MedlinePlus