The Long-term Effects of Nedocromil Sodium and Beclomethasone Dipropionate on Bronchial Responsiveness to Methacholine in Nonatopic Asthmatic Subjects

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Abstract
We investigated the effects of long-term treatment with two anti-inflammatory drugs, nedocromil sodium and beclomethasone dipropionate, on airway hyperresponsiveness to methacholine (PC20), on baseline FEV1 and on the bronchodilating effect of a deep breath in 25 nonsterold-dependent nonatopic asthmatic adults. In all subjects the prestudy PC20 was < 8 mg/ml, the postbron-chodilator FEV1 was > 75% predicted, and skin prick tests and RAST to 13 common allergens were negative. After 2 months run-in, the subjects were randomly allocated into 3 parallel treatment groups to inhale double-blind either 4 mg nedocromil (n = 9) or 100 µg beclomethasone (n = 8) or placebo (n = 8) 4 times daily for 4 months. PC20 was measured using the 2-min tidal breathing method. The effect of a deep breath was measured during methacholine-induced bronchoconstriction by standardized maximal and partial expiratory flow-volume curves and was expressed as a flow ratio (M/P ratio). Pretreatment values of FEV1, PC20, and M/P ratio were not different between the 3 groups. PC20 did not change in the placebo group, but increased significantly by a factor of 3 after 8 wk of treatment with beclomethasone or nedocromil (p < 0.001). FEV1 did not change after treatment with placebo or nedocromil (p > 0.2), but increased (mean change 0.2 L, SD 0.2) after 4 wk of treatment with beclomethasone (p < 0.05). Geometric mean M/P ratio increased from 1.98 to 2.66 after 4 wk of beclomethasone (p < 0.01), but not after nedocromil or placebo. We conclude that prolonged administration of nedocromil as well as beclomethasone attenuates airway hyperresponsiveness to methacholine, but only beclomethasone improves FEVi and enhances deep breath-induced bronchodilation. This suggests that airway hyperresponsiveness in nonatopic asthma is associated with airway inflammation, and that nedocromil and beclomethasone attenuate responsiveness by distinct mechanisms.