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Vascular Component of Airway Remodeling in Asthma Is Reduced by High Dose of Fluticasone

Department of Clinical Sciences, Section of Respiratory Diseases, University of Parma, Parma; Division of Pneumology, Salvatore Maugeri Foundation, IRCCS, Rehabilitation Institute of Tradate, Tradate; Respiratory Pathophysiology Laboratory, Sesto S. Giovanni Hospital, Sesto San Giovanni; Department of Clinical and Experimental Medicine, Section of Respiratory Diseases, University of Padua, Padua; and GSK, Research & Development Unit, Verona, Italy

Correspondence and requests for reprints should be addressed to Alfredo Chetta, M.D., U.O. Clinica Pneumologica, Azienda Ospedaliera e Università di Parma, Viale G. Rasori 10, 43100, Parma, Italy. E-mail: chetta{at}unipr.it

We conducted a randomized, double-blind, parallel-group study to assess the effect of 6 weeks treatment with low-dose (100 µg twice a day) or high-dose (500 µg twice a day) inhaled fluticasone propionate (FP) on the vascular component of airway remodeling in 30 patients with mild to moderate asthma. We also studied the effect on the inflammatory cells and the basement membrane thickness, and we compared findings from bronchial biopsies taken in patients with asthma with those in eight control subjects. 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, patients with asthma showed an increase in the number of vessels and in vascular area as compared with control subjects. In the subjects with asthma, 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 both low- and high-dose FP (p < 0.05). However, the number of vessels, the vascular area, and the basement membrane thickness decreased only after high-dose FP (p < 0.05). In conclusion, this study shows that in patients with mild to moderate asthma, 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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