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

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, PGF_2α, 6-keto-PGF_1α, 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.