The long-term effect of nedocromil sodium on the maximal degree of airway narrowing to methacholine in atopic asthmatic subjects


Dr J. K. Sont, Lung Function Laboratory, C2-P, Department of Pulmonology, University Hospital Leiden, PO Box 9600, NL-2300 RC Leiden, The Netherlands.


Airway hyperresponsiveness in asthma is characterized by increased airway sensitivity and by excessive maximal airway narrowing. Long-term inhalation therapy with nedocromil sodium has been shown to reduce increased airway sensitivity in asthma. However, it is unknown whether it also attenuates excessive airway narrowing. We studied the long-term effects of nedocromil on the maximal degree of airway narrowing to methacholine. Twenty-seven atopic asthmatic adults (21–39 years), with a measurable maximal-response plateau on the dose-response curve (20–55% fall in FEV1), were randomly allocated into two parallel treatment groups. They received either inhaled nedocromil 4 mg q.i.d. or placebo, for 8 weeks following a 2 week baseline period. Every 2 weeks, complete dose-response curves to inhaled methacholine were obtained. The response was measured by FEV1 and by volume history standardized partial expiratory flow-volume curves (V̇40p). A maximal-response plateau was considered if three or more of the highest data points fell within a 5% response range, the maximal response being the average value on the plateau (MFEV1, MV̇40p). Airway sensitivity was defined as the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20FEV1) or 40% fall in V̇40p (PC4040p). Twenty-four subjects completed the study. Baseline FEV1 or V̇40p did not change during either treatment (P>0.07). There were no significant changes in MFEV1, or MV̇40p during treatment with nedocromil (P>0.07). Neither were these changes significantly different between the two groups (P>0.25). During treatment with nedocromil there was an increase in PC20FEV1 and PC4040p, which was maximal at 6 weeks (mean change±s.d.: 1.0±0.9 doubling dose (DD), and 0.8±0.7 DD, respectively, P= 0.002). The changes in PC20 and PC40 were significantly different between the nedocromil and the placebo group (P<0.05). We conclude that long-term treatment with nedocromil, in spite of reducing airway sensitivity, does not reduce the maximal degree of airway narrowing to methacholine in mild to moderate asthmatics. This suggests that nedocromil may not be sufficient in the prevention of excessive airway narrowing in asthma.