Taylor D R, Sears M R, Herbison G P, Flannery E M, Print C G, Lake D C, Yates D M, Lucas M K, Li Q
Department of Medicine, University of Otago Medical School, Dunedin, New Zealand.
Thorax. 1993 Feb;48(2):134-8. doi: 10.1136/thx.48.2.134.
A comparison of the effects of regular upsilon as needed inhaled beta agonist treatment on the control of asthma in the last 16 weeks of each of two 24 week treatment periods has been reported. This paper presents additional information on exacerbations of asthma and trends in lung function, airways hyperresponsiveness to methacholine, and bronchodilator responsiveness during the entire 24 week periods of regular or as needed beta agonist treatment.
Subjects undertook a year long randomised, double blind crossover study of regular upsilon as needed inhaled beta agonist treatment. Fenoterol (400 micrograms) or matching placebo was inhaled as a dry powder four times daily for 24 weeks, then subjects crossed over to the alternative regimen. Treatment with inhaled corticosteroids was used by 50 of the 64 subjects in constant doses throughout the study. Symptoms, peak expiratory flow rates, and drug use were recorded daily, spirometry was performed every four weeks, and methacholine and bronchodilator responsiveness were measured every eight weeks.
Exacerbations of asthma symptoms occurred earlier and more often during regular treatment with fenoterol and four of five severe exacerbations requiring admission to hospital occurred during the period of regular treatment. Prebronchodilator forced expiratory volume in one second (FEV1) was on average 0.15 litres lower (95% confidence interval (95% CI) 0.11-0.19) and vital capacity (VC) 0.12 litres lower (95% CI 0.08-0.16) than during the placebo period. Morning peak flow rates were significantly lower and evening peak flow rates significantly higher, with an increase in diurnal variation from 9.8% (95% CI 6.9-12.8) to 17.5% (95% CI 13.8-21.3) during regular treatment. Geometric mean concentration of methacholine causing a 20% fall in FEV1 from the value after saline (PC20) decreased significantly from 1.63 to 1.15 mg/ml, indicating increased bronchial hyperresponsiveness during regular treatment. Response to bronchodilator, as measured by the % increase in postbronchodilator FEV1 related to prebronchodilator FEV1, was maintained with no evidence for tachyphylaxis.
Chronic use of inhaled fenoterol resulted in more exacerbations, a significant decline in baseline lung function, and an increase in airway responsiveness to methacholine in asthmatic subjects, but did not alter bronchodilator responsiveness. These findings support the previous report that regular inhaled beta agonist treatment is deleterious in the long term control of asthma.
已有报道比较了按需吸入β受体激动剂常规治疗在两个24周治疗期的最后16周对哮喘控制的效果。本文提供了关于哮喘加重情况以及在24周常规或按需β受体激动剂治疗期间肺功能、气道对乙酰甲胆碱的高反应性和支气管扩张剂反应性趋势的更多信息。
受试者进行了一项为期一年的随机、双盲交叉研究，比较按需吸入β受体激动剂常规治疗的效果。非诺特罗（400微克）或匹配的安慰剂以干粉形式每日吸入4次，共24周，然后受试者交叉接受另一种治疗方案。64名受试者中有50名在整个研究期间持续使用固定剂量的吸入性糖皮质激素。每天记录症状、呼气峰值流速和药物使用情况，每四周进行一次肺量测定，每八周测量一次乙酰甲胆碱和支气管扩张剂反应性。
在非诺特罗常规治疗期间，哮喘症状加重出现得更早且更频繁，5次需要住院治疗的严重加重中有4次发生在常规治疗期间。支气管扩张剂使用前一秒用力呼气量（FEV1）平均比安慰剂治疗期间低0.15升（95%置信区间（95%CI）0.11 - 0.19），肺活量（VC）低0.12升（95%CI 0.08 - 0.16）。早晨呼气峰值流速显著降低，晚上呼气峰值流速显著升高，常规治疗期间日变化率从9.8%（95%CI 6.9 - 12.8）增加到17.5%（95%CI 13.8 - 21.3）。使FEV1从盐水激发后的值下降20%的乙酰甲胆碱几何平均浓度（PC20）从1.63显著降至1.15毫克/毫升，表明常规治疗期间支气管高反应性增加。以支气管扩张剂使用后FEV1相对于使用前FEV1的增加百分比衡量的支气管扩张剂反应性得以维持，没有快速耐受的证据。
哮喘患者长期使用吸入性非诺特罗导致更多的病情加重、基线肺功能显著下降以及气道对乙酰甲胆碱的反应性增加，但未改变支气管扩张剂反应性。这些发现支持了之前的报告，即常规吸入β受体激动剂治疗对哮喘的长期控制有害。
