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Many asthma patients remain symptomatic despite maintenance therapy with inhaled corticosteroids (ICS) and salbutamol as rescue medication. In the present study the relative efficacy and preference for as-needed formoterol compared with salbutamol was examined. In total, 211 patients with a mean age of 45 yrs (mean forced expiratory volume in one second (FEV1) 77% predicted normal), using ICS, were randomised to 3 weeks' double-blind treatment with as-needed formoterol 4.5 microg Turbuhaler and with as-needed salbutamol 100 mug Turbuhaler in a cross-over fashion. Overall, lung function and symptom control were better with as-needed formoterol than with as-needed salbutamol. During as-needed formoterol treatment daytime and night-time symptom scores were lower, peak expiratory flow and FEV1 were higher and patients experienced fewer disturbed nights (34%) compared with as-needed salbutamol. Patients preferred the formoterol treatment to salbutamol. Of the 162 patients expressing a preference, formoterol was preferred by 68% (95% confidence interval: 60-75). Subjective assessment of effectiveness also favoured formoterol, which was perceived as slightly faster acting than salbutamol. In conclusion, as-needed formoterol improved symptoms and lung function compared with salbutamol and was perceived as more effective and at least as fast acting for symptom relief.

The expression of the endogenous neuropeptide-degrading enzyme, neutral endopeptidase (NEP; CALLA, CD10, E.C.3.4.24.11) on cultured human airway epithelial cells can be upregulated by corticosteroids. We examined whether NEP expression in the airway epithelium or lamina propria in bronchial biopsies is enhanced in atopic asthmatics on regular inhaled steroids as compared with those without steroid treatment. Forty nonsmoking adults (age 19 to 48 yr) with mild to moderate asthma (forced expiratory volume in 1 s > or = 50% pred., histamine PC20 range 0.02 to 7.6 mg/ml) with (n = 23) or without (n = 17) regular inhaled steroids treatment entered the study. Biopsies were taken at (sub)segmental level from the right lower lobe, the middle lobe, and the main carina. Immunohistochemical staining was performed on cryostat sections using the VIL-A1 monoclonal antibody against CD10 (NEP). Intra- and inter-observer repeatability of a semiquantitative scoring method was good as assessed by weighted kappa (kappa(w) ranging from 0.66 to 0.81). In the airway epithelium, NEP-positive sites were within the basal layer and, in contrast with studies applying other antibodies, also at apical sites and within the lamina propria. In both the epithelium and lamina propria, NEP expression was not significantly different between the three biopsy sites (Friedman's nonparametric two-way analysis of variance; P > 0.68), nor was expression in the lamina propria associated with inhaled steroid usage (Mann-Whitney U test; P = 0.98). However, NEP expression was significantly enhanced in the airway epithelium in patients using inhaled steroids as compared with nonsteroid users (mean rank: 23.4 and 15.5, respectively; P = 0.02). Among nonsteroid-using subjects, NEP expression was related to symptoms and the methacholine PC20 (Rs: -0.69 and 0.49, respectively; P < or = 0.04). We conclude that the expression of NEP is enhanced in airway epithelium in bronchial biopsy specimens from patients with atopic asthma who are regularly using inhaled steroids as compared with patients who do not. This fits the hypothesis that the anti-inflammatory effect of corticosteroids within the airways is partially mediated by the upregulation of the endogenous neuropeptide-degrading enzyme NEP.