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, JARING S. van der ZEE
1999 American Journal of Respiratory and Critical Care Medicine  
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 g twice a day) or salbutamol (Sb; 400 g 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
more » ... bronchial responsiveness to histamine (PC 20 histamine). 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 ϭ ([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 PC 20 histamine increased significantly (mean increase, 2.4 doubling doses), whereas PC 20 histamine decreased in the Sb group. Differences between groups were significant except for the decrease in eosinophils. We conclude that 12 wk of FP (250 g twice a day) decreased the permeability of the blood-airway lumen barrier, in particular for high molecular weight proteins. Nocker RET, Weller FR, Out TA, de Riemer MJ, Jansen HM, van der Zee JS. A double-blind study on the effect of inhaled corticosteroids on plasma protein exudation in asthma. AM J RESPIR CRIT CARE MED 1999;159:1499-1505. Plasma protein exudation is one of the aspects of airway inflammation in asthma (1, 2). In previous studies, we have reported that in patients with asthma the degree of nonspecific bronchial hyperresponsiveness correlated significantly with the degree of plasma protein exudation, assessed either in bronchoalveolar lavage (BAL) fluid or in sputum (3, 4). Corticosteroids are effective in controlling asthma symptoms and in reducing airway obstruction and bronchial hyperresponsiveness (5). These beneficial effects of inhaled corticosteroids are attributed to their antiinflammatory action on the bronchial mucosa (6, 7). Corticosteroids have been reported to inhibit vascular permeability (8). Fluticasone propionate (FP) is a relatively new inhaled synthetic corticosteroid, and has been reported to have a higher topical antiinflammatory effect than other inhaled steroids (9). No information is available on the effects of FP on the blood-to-air space permeability for plasma proteins in patients with asthma. In the present double-blind, parallel-group study we compared the effect of FP and salbutamol (Sb) on inflammatory indices in BAL fluid, and on clinical parameters in patients with asthma. The primary outcomes that were monitored included plasma protein leakage into the airway lumen, cell differentials in BAL fluid, and bronchial hyperresponsiveness to histamine. Significant clinical changes in the primary outcomes were defined as a у 50% decrease in blood-to-air space permeability and percentage of eosinophils in BAL fluid, and more than one doubling dose increase in PC 20 histamine (the concentration of histamine that causes a fall in FEV 1 of 20% of the baseline value). The sample size of the study was based on the results of previous studies (3) and a power of 0.80 to detect the predetermined changes. Secondary outcomes included daily symptoms, morning and evening peak expiratory flow (PEF), and frequency of rescue medication used (salbutamol, 400 g). In addition, correlations between primary outcomes were analyzed. METHODS Patients Thirty-three patients (19 men and 14 women) with mild to moderate asthma were recruited from patients attending the outpatient clinic of pulmonology of the Academic Medical Center (University of Amsterdam, The Netherlands). Asthma was diagnosed according to the American Thoracic Society (ATS) criteria and included a history of recurrent episodes of wheezing, chest tightness, and dyspnea and a
doi:10.1164/ajrccm.159.5.9806116 pmid:10228117 fatcat:k5l7rxsj5zgntamcfzoeo7xr3i