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Published ahead of print on December 4, 2002, doi:10.1164/rccm.200207-710OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 5, March 2003, 751-757

A more recent version of this article appeared on March 1, 2003
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Submitted on July 17, 2002
Accepted on November 18, 2002

VASCULAR COMPONENT OF AIRWAY REMODELING IN ASTHMA IS REDUCED BY HIGH DOSE OF FLUTICASONE

Alfredo Chetta1*, Andrea Zanini2, Antonio Foresi3, Mario Del Donno1, Antonio Castagnaro1, Raffaele D'Ippolito1, Simonetta Baraldo4, Renato Testi5, Marina Saetta4, and Dario Olivieri1

1 Department of Clinical Sciences, Section of Respiratory Diseases, University of Parma, Parma, Italy, 2 IRCCS Rehabilitation Institute of Tradate, Division of Pneumology, Salvatore Maugeri Foundation, Tradate, Italy, 3 Respiratory Pathophysiology Laboratory, Sesto San Giovanni Hospital, Sesto San Giovanni, Italy, 4 Department of Clinical and Experimental Medicine, Section of Respiratory Diseases, University of Padua, Padua, Italy, 5 Research and Development Unit, GSK, Verona, Italy

* To whom correspondence should be addressed. E-mail: chetta{at}unipr.it.

We conducted a randomized double-blind, parallel-group study to assess the effect of six weeks treatment with low dose (100 µg, bid) or high dose (500 µg, bid) inhaled fluticasone propionate (FP) on the vascular component of airway remodeling in 30 mild to moderate asthmatics. We also studied the effect on the inflammatory cells and the basement membrane thickness and we compared findings from bronchial biopsy taken in asthmatics to those in 8 controls. Bronchial responsiveness to methacholine and asthma symptom score were measured before and after treatments. Eight patients in the low dose FP group and eight patients in high dose FP group completed the study. At baseline, asthmatics showed an increase in the number of vessels and in vascular area as compared to controls. In asthmatics, number of vessels correlated with vascular area (p<0.01) and with number of mast cells (p<0.01). Bronchial responsiveness to methacholine, asthma symptom score and inflammatory cells decreased significantly after the low and high dose FP (p<0.05). However, the number of vessels, vascular area and the basement membrane thickness decreased only after high dose FP (p<0.05). In conclusion, this study shows that in mild to moderate asthmatic patients, high dose of inhaled FP given over 6 weeks, can significantly affect airway remodeling, by reducing both submucosal vascularity and basement membrane thickness.
Key words: Asthma; Airway Inflammation; Inhaled Steroids; Bronchial Biopsy




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