Nedocroinil sodium in bronchial antigen challenge

Sir, Bronchial challenge studies have shown thai nedocromil sodium., a pyranoquinolinc dicarboxylie acid derivative used for ihe treatment of reversible obstructive airways disease [i], inhibits exercise, antigen and cold air induced bronehoconstriction in asthmatic patients [2-5]. A doubie-blind, randomized, cross-over trial comparing the efTects of placebo, and 2 mg and 4 mg nedocromil sodium delivered via pressurized aerosol on the antigeninduced immediate bronchial reaction was conducted in 12 aduit (19-49 yr), allergic, moderately severe asthmatic patients whose FEV| was not less than 75% of predicted normal values. Positive RAST and skin-prick tests to relevant allergens, and antigen PD20FEV1 (provocation dose required to produce a 20"/> fall in FEVi) and methaehoiine PD2n were assessed pre-trial. Methacholine reactivity was high to moderate (PD20 0-015 2-0 mg/ml). Prior to challenge, patients stopped using sodium eromoglycate (1 patient) for 1 week and inhaled ^2 bronchodilators {6 patients) for 8 hr. Thirty minutes after two inhalations of placebo, i mg or 2 mg nedocromil sodium, a 2-min tida! volume inhalation of nebulized antigen solution was given. Doses were doubled at 15 min intervals until FEV| had fallen by . Mean pre-treatment and prc-challenge baseline values were determined from measurements 5 and 10 min before, and 20 and 25 min after treatment. FEV| was measured 5, 10 and 15 min after each challenge. Within patients, challenges were performed on separate days at least 1 week apart (with one 5 day exception). This interval is sufficient for good reproducibility with no influence on subsequent challenges [6]. PD20 was determined by linear interpolation on a log scale between the final two doses of antigen. Patients gave their informed consent and the protoeol was approved by the local ethical committee. Neither nedocromii sodium nor plaeebo exerted any direct effect on EEV, when pre-and post-treatment values were compared. The effect of treatments on antigen PD20FEV1 are shown inTable I. Nedocromil sodium was significantly different (4 mg, P < 0 0 0 1 ; 2 mg, P<0-^\) from placebo. PD20 values with 2 mg and 4 mg nedocromil sodium were approximately 3 and 5 times greater than placebo, respectively. The active treatments were not significantly different ( P > 0-05). Three patients reported unusual symptoms: blisters on the lips after challenge (placebo and control days). headache following placebo, and sneezing and coughing after challenge (4 mg nedocromil sodium day). In these experiments, despite no direct efTeci on bronchial smooth muscle tone, nedocromil sodium gave significant protection against bronchial antigen challenge, with up to 5 times more antigen required to produce a 20% tall in FEV| after inhalation of nedocromil sodium than after inhalation of placebo. The results are in agreement with similar studies which found that 0'5 mg, 1 mg and 2 mg nedocromil sodium given 3 hr [3] and 4 mg given 30 min [4] prior lo antigen chalienge were significantly more effective than placebo in inhibiting the immediate reaction to antigen. Significant, although not complete, inhibition of the late reaction has also been observed [4]. The efficacy of nedocromil sodium is thought to result, in part, from stabilization of connective tissue and mucosal mast cells [I]. In models involving adult patients with atopic asthma it appears to have a potency greater than sodium cromoglycate [7]. Nedocromil sodium is more potent than sodium cromoglycate in attenuating bronchoconstriction in monkeys infected with Ascaris suuin and, unlike sodium cromoglycate. significantly