Bel E H, van der Veen H, Dijkman J H, Sterk P J
Department of Pulmonology, University Medical Centre, Leiden, The Netherlands.
Am Rev Respir Dis. 1989 Feb;139(2):427-31. doi: 10.1164/ajrccm/139.2.427.
In normal humans in vivo, maximal airway narrowing to LTD4 is more severe than to methacholine. Moreover, LTD4 heightens the maximal response to methacholine for several days. To investigate whether or not this is due to inflammatory changes in the airway wall, we studied the effects of the corticosteroid budesonide on the dose-response curves to inhaled LTD4 and to methacholine. In a two-period, double-blind, placebo-controlled design, budesonide (400 micrograms twice a day) or placebo was inhaled by eight normal subjects on six consecutive days, with a 3-wk washout. Complete dose-response curves to LTD4 (0.36 to 43 nmol) were performed on Day 5, and to methacholine (1.28 to 655 mumol) on Days 4 and 6 of each period using a validated method. The response was measured by FEV1 and standardized partial expiratory flow-volume curves (V40p), and was expressed as the percent fall from baseline. A maximal response plateau was considered if more than two doses fell within a 5% response range. All subjects reached plateaus to methacholine and to LTD4. Budesonide reduced the maximal response to LTD4 (mean difference with placebo, 7.9% fall for FEV1, and 8.4% fall for V40p; p less than 0.05). During placebo the maximal response to methacholine 24 h after LTD4 was higher than 24 h before (mean change, 2.7% fall in FEV1 and 5.5% fall in V40p; p less than 0.05), but not during budesonide (mean change, -2.5% fall in FEV1 and -0.1% fall in V40p; p greater than 0.2), the changes being significantly different between the two periods (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
在正常人体的体内，对 LTD4 的最大气道狭窄程度比对乙酰甲胆碱更为严重。此外，LTD4 会在数天内增强对乙酰甲胆碱的最大反应。为了研究这是否归因于气道壁的炎症变化，我们研究了皮质类固醇布地奈德对吸入 LTD4 和乙酰甲胆碱的剂量反应曲线的影响。在一项为期两个阶段的双盲、安慰剂对照设计中，8 名正常受试者连续 6 天吸入布地奈德（400 微克，每日两次）或安慰剂，洗脱期为 3 周。在每个阶段的第 5 天对 LTD4（0.36 至 43 纳摩尔）进行完整的剂量反应曲线测定，在第 4 天和第 6 天对乙酰甲胆碱（1.28 至 655 微摩尔）进行测定，采用经过验证的方法。通过第一秒用力呼气容积（FEV1）和标准化部分呼气流量-容积曲线（V40p）测量反应，并表示为相对于基线的下降百分比。如果超过两剂落在 5% 的反应范围内，则认为达到最大反应平台期。所有受试者对乙酰甲胆碱和 LTD4 均达到平台期。布地奈德降低了对 LTD4 的最大反应（与安慰剂相比，FEV1 的平均差异为下降 7.9%，V40p 的平均差异为下降 8.4%；p < 0.05）。在安慰剂阶段，LTD4 后 24 小时对乙酰甲胆碱的最大反应高于之前 24 小时（平均变化，FEV1 下降 2.7%，V40p 下降 5.5%；p < 0.05），但在布地奈德阶段并非如此（平均变化，FEV1 下降 -2.5%，V40p 下降 -0.1%；p > 0.2），两个阶段的变化存在显著差异（p < 0.05）。（摘要截断于 250 字）
