Am. J. Respir. Crit. Care Med., Volume 164, Number 1, July 2001, 117-121

Effect of a Long-acting ₂-Agonist over Three Months on Airway Wall Vascular Remodeling in Asthma

BERNADETTE E. ORSIDA, CHRIS WARD, XUN LI, ROS BISH, JOHN W. WILSON, FRANK THIEN, and E. HAYDN WALTERS

Departments of Respiratory Medicine and Allergy and Clinical Immunology, The Alfred Hospital and Monash University Medical School, Melbourne, Victoria, Australia

There are few data regarding the potential effects of antiasthma treatment on indices of airway remodeling, such as the increased subepithelial airway vascularity in patients with asthma. We studied 45 symptomatic subjects with asthma who were receiving treatment with low dose inhaled corticosteroids (ICS) (range 200-500 µg twice a day) and 28 normal subjects without asthma as a control population. Subjects underwent bronchoscopy with airway biopsy and subjects with asthma were then randomized to receive supplementary inhaled salmeterol 50 µg twice a day, fluticasone propionate 100 µg twice a day, or placebo for 3 mo in addition to their baseline ICS. Biopsy of the airway was then repeated. The biopsies were analyzed for vascular structures in the subepithelial lamina propria. Sufficient biopsy material was available for analysis of vascularity in 34 of the subjects with asthma and 28 of the normal subjects. We confirmed that airways of subjects with asthma had a significant increase in the number of vessels/mm² of lamina propria compared with airways of normal subjects (524 ± 137 vessels/mm², n = 34 versus 425 ± 130 vessels/mm², n = 28; p = 0.004). There was a decrease in the density of vessels of lamina propria after treatment only in the salmeterol group compared with baseline (before, 535 ± 153 vessels/mm² versus after, 400 ± 142 vessels/mm²; n = 12; p = 0.04). There was no significant change within the fluticasone (n = 11) or placebo (n = 11) treatment groups, but also no significant differences between the groups. Notably, no treatment was associated with increased airway wall vascularity. The demonstrated fall in vessel number within the salmeterol-treated group may suggest an advantageous effect of long-acting ₂-agonists on this manifestation of airway remodeling over the 3-mo time scale of this study, which is complementary to the action of ICS on airway vascularity.

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