Am. J. Respir. Crit. Care Med., Volume 159, Number 5, May 1999, 1499-1505

A Double-blind Study on the Effect of Inhaled Corticosteroids on Plasma Protein Exudation in Asthma

ROB E. T. NOCKER, FRANK R. WELLER, THEO A. OUT, MARIËLLE J. de RIEMER, HENK M. JANSEN, and JARING S. van der ZEE

Department of Pulmonology and Clinical and Laboratory Immunology Unit, Academic Medical Center, University of Amsterdam, Amsterdam; and Laboratory for Experimental and Clinical Immunology, Amsterdam, The Netherlands

Plasma protein exudation into the airways is an important pathophysiological event in asthma. The effect of 12 wk of treatment with inhaled fluticasone propionate (FP; 250 µg twice a day) or salbutamol (Sb; 400 µg twice a day) on plasma protein leakage was compared in a double-blind, randomized parallel-group study of 30 patients with asthma. Primary outcomes were plasma protein leakage and size selectivity of the blood-airway lumen barrier, cell differentials in BAL fluid, and bronchial responsiveness to histamine (PC₂₀histamine). Two independent procedures to account for the effect of variable dilution of BAL on the levels of albumin (Alb) and ₂-macroglobulin (A2M) in BAL fluid consisted of correction based on urea levels and on the application of the relative coefficient of excretion [RCE = ([A2M] in BAL fluid/[A2M] in serum)/([Alb] in BAL fluid/[Alb] in serum)]. In the FP group a significant decrease was found in the A2M level and the RCE, and in the percentage of eosinophils in BAL fluid. The PC₂₀histamine increased significantly (mean increase, 2.4 doubling doses), whereas PC₂₀histamine decreased in the Sb group. Differences between groups were significant except for the decrease in eosinophils. We conclude that 12 wk of FP (250 µg twice a day) decreased the permeability of the blood-airway lumen barrier, in particular for high molecular weight proteins.

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