Inhaled Salmeterol and Salbutamol in Asthmatic Patients: An Evaluation of Asthma Symptoms and the Possible Development of Tachyphylaxis

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Abstract
Salmeterol (SM) is a new .beta.2-adrenoceptor agoanist for inhaled use that has been shown to produce long-lasting bronchodilation in asthmatic patients. In the present study, evaluating efficacy and possible development of tachyphylaxis after SM, 12 patients with stable asthma were included after the demonstration of reversibility in FEV1 of at least 15% to 200 .mu.g salbutamol (SB) or 20% to 500 .mu.g SB. At inclusion all patients were receiving treatment with inhaled .beta.2-agonists, and 11 of the 12 patients were also receiving inhaled corticosteroids. The patients were treated for two 2-wk periods with either inhaled SM 50 .mu.g twice a day or SB 200 .mu.g four times a day, following a double-blind, double-dummy, randomized design. The treatment periods were separated by a washout period of 1 wk. Dose-response curves to inhaled SB were obtained the day before and the day after each treatment period. On each of these days, basal FEV1, tremor, heart rate, and blood pressure were recorded and were then followed after the inhalation of 100 + 300 + 900 .mu.g SB to obtain a cumulative dose-response curve. During the treatment periods, as well as during the washout week after each treatment, the patients recorded their morning and evening peak expiratory flow (PEF) each day before the inhalation of the study drug. Subjective asthma symptoms were monitored by a visual analog scale after each treatment period. The dose-response curves to SB revealed no signs of a reduced response to SB after any of the treatments, but significant increases in basal FEV1 and FVC were seen after the SM period (p < 0.05). The PEF values were also significantly higher, both in the morning (p < 0.001), and the evening (p < 0.01), during the SM period compared with that during the SB period. The morning PEF during the week after the SM period was significantly higher (p < 0.05) compared with the week after the SB treatment. The patients'' VAS-score showed a significantly better nights sleep and a lower degree of dyspnea during the SM period (p < 0.05). Of the 12 patients, 10 preferred SM and two had no preference. The use of rescue SB inhalations was about 50% lower during the SM period (p < 0.05). We conclude that inhaled SM 50 .mu.g twice a day produces a better control of asthma symptoms than does SB 200 .mu.g four times a day. There was no evidence of an increased risk for tachyphylaxis in the pulmonary response to .beta.2-stimulation with the more long-acting SM. However, it should be considered that 11 of 12 patientes were receiving treatment also with inhaled steroids, which may have prevented the development of tachyphylaxis.