Lower leukotriene C4 levels in bronchoalveolar lavage fluid of asthmatic subjects after 2.5 years of inhaled corticosteroid therapy

Y Oosterhoff,S E Overbeek,J A Noordhoek,D S Postma,F J Zijlstra,H C Hoogsteden,R Douma

doi:10.1155/s0962935195000688

Abstract

Long-term treatment with inhaled corticosteroids has been shown to result in improvement of symptoms and lung function in subjects with asthma. Arachidonic acid (AA) metabolites are thought to play a role in the pathophysiology of asthma. It was assessed whether differences could be found in bronchoalveolar lavage (BAL) AA metabolite levels between subjects with asthma who were treated for 2.5 years with inhaled bronchodilators alone or in combination with inhaled corticosteroids. Prostaglandin (PG)D2, PGF2α, 6-keto-PGF1α, thromboxane B2, leukotriene (LT)C4 and LTB4 levels and cell numbers were assessed in BAL fluid from 22 non-smoking asthmatic subjects. They were participating in a randomized, double-blind multicentre drug trial over a period of 2.5 years. Results of the group treated with inhaled corticosteroids (CS+: beclomethasone 200 μg four times daily) were compared with the other group (CS−) which was treated with either ipratropium bromide (40 μg four times daily) or placebo. BAL LTC4 levels of asthmatic subjects were significantly lower after 2.5 years inhaled corticosteroid therapy (CS+, 9(1–17) pg/ml vs. CS−, 16(6-53) pg/ml; p = 0.01). The same trend was observed for the PGD2 levels. The results suggest that inhaled corticosteroids may exert their beneficial effect on lung function via a mechanism in which inhibition of LTC4 synthesis in the airways is involved.

Highlights

Recent long-term studies on the prognosis and morbidity of obstructive airways disease have shown that addition of inhaled corticosteroids to maintenance treatment with a 2-agonist in hyper-responsive patients with obstructive airways disease leads to a significant reduction of respiratory symptoms, exacerbation rates, airway obstruction and airway hyper-responsiveness. 12These findings are thought to be a consequence of suppression of inflammatory processes in the airways.No single cell type or mediator in the inflammatory processes in the airways is responsible for the clinical events in asthma
In order to assess the role of arachidonic acid (AA) metabolites in the effects of long-term treatment of asthmatic subjects with corticosteroids, AA metabolite levels in bronchoalveolar lavage (BAL) fluid were assessed in a subgroup of non-smoking asthmatic patients who participated in a randomized, double-blind multicentre drug trial for 2.5 years
AA metabolite levels are considered as biochemical markers of on-going chronic airway inflammation in the airways of asthmatic subjects.-5 we investigated whether differences in BAL AA metabolite levels could be detected between subjects treated with [2-agonists and inhaled corticosteroids for 2.5 years and those treated with inhaled 2-agonists alone

Summary

Introduction

Recent long-term studies on the prognosis and morbidity of obstructive airways disease have shown that addition of inhaled corticosteroids to maintenance treatment with a 2-agonist in hyper-responsive patients with obstructive airways disease leads to a significant reduction of respiratory symptoms, exacerbation rates, airway obstruction and airway hyper-responsiveness. 12These findings are thought to be a consequence of suppression of inflammatory processes in the airways.No single cell type or mediator in the inflammatory processes in the airways is responsible for the clinical events in asthma. There is substantial evidence that arachidonic acid (AA) metabolites play an important role in the pathophysiology of the disease. They are potent airway constrictors, increase mucus secretion, play a role in chemotaxis and may. One potential mode of action of inhaled corticosteroids involves the modulation of arachidonic acid (AA) metabolite levels in the airways. They may decrease AA metabolite synthesis by their inhibitory effect on phospholipase A2 or by inhibition of synthesis of cytokines that stimulate AA metabolite release. In order to assess the role of AA metabolites in the effects of long-term treatment of asthmatic subjects with corticosteroids, AA metabolite levels in bronchoalveolar lavage (BAL) fluid were assessed in a subgroup of non-smoking asthmatic patients who participated in a randomized, double-blind multicentre drug trial for 2.5 years

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