LEUKOTRIENE ANTAGONIST PREVENTS EXACERBATION OF ASTHMA DURING REDUCTION OF HIGH-DOSE INHALED CORTICOSTEROID

To test whether the leukotriene antagonist ONO-1078 (pranlukast) preve nts asthma exacerbations during reduction of high-dose inhaled cortico steroid, we conducted a randomized, double-blind, placebo-controlled s tudy in 79 asthma patients requiring high doses (1,500 mu g/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (du ration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV(1) percentage of predicted, 80.7 +/- 2.0%). After a 2-wk r un-in period, the doses of BDI were halved, while the patients were as signed to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV(1) decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sus tained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta(2)-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 gr oup. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, r espectively), compared with no change in the ONO-1078 group. Therefore , the leukotriene antagonist ONO-1078 prevents the asthma deterioratio n provoked by a 6-wk reduction of the dose of inhaled BDI into half.