Nelson J A, Strauss L, Skowronski M, Ciufo R, Novak R, McFadden E R
Division of Pulmonary and Critical Care Medicine, University Hospitals of Cleveland, OH 44106-5067, USA.
N Engl J Med. 1998 Jul 16;339(3):141-6. doi: 10.1056/NEJM199807163390301.
With long-term administration of salmeterol, the extent of protection afforded by the drug against experimental precipitants of asthma such as methacholine and adenosine may decrease. Whether this effect extends to a clinically relevant stimulus such as exercise is unknown.
We performed a random-order, double-blind, crossover trial in 20 patients with exercise-induced asthma. Each patient received inhaled salmeterol or placebo twice daily for a month, with a one-week washout period between treatments. The patients performed cycle ergometry while breathing frigid air 30 minutes after the morning dose and 9 hours later on the 1st, 14th, and 29th study days. The primary end point was the extent of the decrease in forced expiratory volume in 1 second (FEV1) 10 minutes after exertion.
With placebo, significant airway narrowing developed at all times (mean [+/-SE] decrease from base line in FEV1, 19+/-2 percent in the morning and 18+/-2 percent in the evening). The morning dose of salmeterol attenuated the degree of bronchoconstriction at all times (decrease in FEV1 on day 1, 5+/-2 percent; on day 14, 10+/-3 percent; and on day 29, 9+/-3 percent; P=0.10). Its ability to act throughout the day, however, decreased with long-term administration (decrease in FEV1 from morning to evening on day 1, 6+/-2 percent; on day 14, 15+/-3 percent; and on day 29, 14+/-3 percent; P=0.003).
Protection against exercise-induced asthma is maintained with long-term administration of salmeterol, but the length of time that the drug remains active after a single dose decreases.
长期使用沙美特罗时，该药物对哮喘实验诱发剂（如乙酰甲胆碱和腺苷）的保护作用可能会降低。这种效应是否会扩展到如运动这样的临床相关刺激尚不清楚。
我们对20例运动诱发性哮喘患者进行了一项随机顺序、双盲、交叉试验。每位患者每日两次吸入沙美特罗或安慰剂，为期1个月，治疗之间有1周的洗脱期。在第1、14和29个研究日的早晨给药后30分钟以及9小时后，患者在呼吸冷空气的同时进行蹬车运动测试。主要终点是运动后10分钟内1秒用力呼气量（FEV1）下降的程度。
使用安慰剂时，任何时候都会出现明显的气道狭窄（FEV1相对于基线的平均[±标准误]下降，早晨为19±2%，晚上为18±2%）。早晨剂量的沙美特罗在任何时候都能减轻支气管收缩的程度（第1天FEV1下降5±2%；第14天，10±3%；第29天，9±3%；P = 0.10）。然而，长期给药后，其全天发挥作用的能力下降（第1天从早晨到晚上FEV1下降6±2%；第14天，15±3%；第29天，14±3%；P = 0.003）。
长期使用沙美特罗可维持对运动诱发性哮喘的保护作用，但单次给药后药物保持活性的时间会缩短。
