Bel E H, Timmers M C, Zwinderman A H, Dijkman J H, Sterk P J
Department of Pulmonology, University Hospital, Leiden, The Netherlands.
Am Rev Respir Dis. 1991 Jan;143(1):109-13. doi: 10.1164/ajrccm/143.1.109.
Airway hyperresponsiveness in asthma is characterized by an increase in sensitivity and in maximal response to airway-narrowing stimuli. Long-term therapy with inhaled corticosteroids is known to reduce airway hypersensitivity in asthmatic patients. To investigate whether these drugs also reduce the maximal degree of airway narrowing we studied the effects of inhaled budesonide on the maximal response plateau of the dose-response curve to inhaled methacholine in mildly asthmatic patients in whom a raised plateau could be measured. Sixteen atopic patients with mild asthma were placed randomly into two parallel treatment groups to receive double-blindly either budesonide (400 micrograms twice daily) or placebo, inhaled via a Turbuhaler, for 4 wk. Before treatment, after 2 and 4 wk of treatment, and after 2 and 4 wk of wash-out, complete dose-response curves to methacholine were obtained using a standardized 2-min tidal breathing method. The response was measured by FEV1, expressed in % fall from baseline. A plateau on the log dose-response curve was considered if three or more data points fell within a 5% response range. The maximal response was obtained by averaging the values on the plateau (MFEV1), and the sensitivity was calculated from the provocative concentration of methacholine, causing a 20% fall in FEV1 (PC20). After 4 wk of budesonide treatment, mean MFEV1 decreased from 41.6 to 33.7% fall (p = 0.0004). The changes in MFEV1 were significantly different between placebo and budesonide (p = 0.03). The geometric mean PC20 increased from 3.4 to 6.3 mg/ml (p = 0.02), but the changes in PC20 were not different between the two groups (p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)
哮喘中的气道高反应性表现为对气道狭窄刺激的敏感性增加和最大反应增强。吸入性糖皮质激素的长期治疗已知可降低哮喘患者的气道高敏感性。为了研究这些药物是否也能降低气道狭窄的最大程度,我们在轻度哮喘患者中研究了吸入布地奈德对吸入乙酰甲胆碱剂量反应曲线最大反应平台的影响,这些患者的反应平台升高是可以测量的。16名患有轻度哮喘的特应性患者被随机分为两个平行治疗组,双盲接受布地奈德(每日两次,每次400微克)或安慰剂,通过都保吸入,持续4周。在治疗前、治疗2周和4周后以及洗脱2周和4周后,使用标准化的2分钟潮气呼吸法获得对乙酰甲胆碱的完整剂量反应曲线。反应通过第一秒用力呼气容积(FEV1)测量,以相对于基线的下降百分比表示。如果三个或更多数据点落在5%的反应范围内,则认为对数剂量反应曲线上存在一个平台。最大反应通过平均平台上的值(MFEV1)获得,敏感性通过引起FEV1下降20%的乙酰甲胆碱激发浓度(PC20)计算。布地奈德治疗4周后,平均MFEV1从下降41.6%降至33.7%(p = 0.0004)。安慰剂组和布地奈德组之间MFEV1的变化有显著差异(p = 0.03)。几何平均PC20从3.4毫克/毫升增加到6.3毫克/毫升(p = 0.02),但两组之间PC20的变化没有差异(p = 0.23)。(摘要截短于250字)