Pizzichini M M, Kidney J C, Wong B J, Morris M M, Efthimiadis A, Dolovich J, Hargreave F E
Dept of Medicine, St Joseph's Hospital, Hamilton, Ontario, Canada.
Eur Respir J. 1996 Mar;9(3):449-55. doi: 10.1183/09031936.96.09030449.
Salmeterol is a selective long-acting beta 2-agonist bronchodilator considered to have added anti-inflammatory effects, but this is controversial. We investigated the effects of a single dose of salmeterol, 100 micrograms, on the physiological and inflammatory responses to inhaled allergen and compared these with the effects of a single dose of beclomethasone, 500 micrograms, and of placebo. Eight atopic adults with mild stable asthma, treated only with inhaled short-acting beta 2-agonist when needed, attended the laboratory sequentially for screening tests, two single-blind control inhalation tests preceded 30 min by placebo or salmeterol and three allergen inhalation tests preceded by placebo, salmeterol or beclomethasone double-blind in random order. Airway responsiveness to methacholine (assessed as the provocative concentration of methacholine producing 20% fall in forced expiratory volume in one second (PC20)), induced sputum eosinophils, blood eosinophils and serum eosinophil cationic protein (ECP) were examined before and 7-48 h after treatment. The statistical power to detect twofold changes in blood and sputum parameters was > or = 90%. Salmeterol inhaled before allergen challenge completely prevented the early asthmatic response, late asthmatic response and fall in methacholine PC20 at 24 h, and produced additional bronchodilatation. These effects were similar to those obtained by the inhalation of a single dose of salmeterol before the control inhalation test, and significantly better than those observed after a single dose of beclomethasone inhaled before the allergen test. Beclomethasone had no effect on the early asthmatic response or on the fall in methacholine PC20 at 24 h but partially inhibited the late asthmatic response. Neither salmeterol nor beclomethasone had any significant effect on sputum or blood inflammatory changes 7-48 h after allergen inhalation. In conclusion, whilst salmeterol had no demonstrable anti-inflammatory action in sputum after allergen challenge in asthma, neither did a single dose of the positive anti-inflammatory control, beclomethasone. The latter result excludes a more positive judgement on the possible anti-inflammatory action of salmeterol. However, the results do indicate that potent functional effects of a single dose of salmeterol can mask the airway inflammatory cell influx caused by inhaled allergen.
沙美特罗是一种选择性长效β2受体激动剂支气管扩张剂,被认为具有额外的抗炎作用,但这存在争议。我们研究了单剂量100微克沙美特罗对吸入变应原的生理和炎症反应的影响,并将其与单剂量500微克倍氯米松和安慰剂的效果进行比较。八名患有轻度稳定哮喘的特应性成人,仅在需要时使用吸入短效β2受体激动剂治疗,依次到实验室进行筛查试验,在两次单盲对照吸入试验前30分钟给予安慰剂或沙美特罗,在三次变应原吸入试验前随机给予安慰剂、沙美特罗或倍氯米松双盲治疗。在治疗前及治疗后第7至48小时检测对乙酰甲胆碱的气道反应性(以引起一秒用力呼气量下降20%的乙酰甲胆碱激发浓度(PC20)评估)、诱导痰嗜酸性粒细胞、血液嗜酸性粒细胞和血清嗜酸性粒细胞阳离子蛋白(ECP)。检测血液和痰液参数两倍变化的统计效能≥90%。在变应原激发前吸入沙美特罗可完全预防24小时时的早期哮喘反应、迟发哮喘反应和乙酰甲胆碱PC20下降,并产生额外的支气管扩张作用。这些效果与在对照吸入试验前吸入单剂量沙美特罗所获得的效果相似,且明显优于在变应原试验前吸入单剂量倍氯米松后观察到的效果。倍氯米松对24小时时的早期哮喘反应或乙酰甲胆碱PC20下降没有影响,但部分抑制了迟发哮喘反应。在变应原吸入后第7至48小时,沙美特罗和倍氯米松对痰液或血液炎症变化均无显著影响。总之,虽然在哮喘变应原激发后沙美特罗在痰液中没有可证明的抗炎作用,但单剂量的阳性抗炎对照药倍氯米松也没有。后一结果排除了对沙美特罗可能的抗炎作用作出更肯定判断的可能性。然而,结果确实表明单剂量沙美特罗的强大功能作用可掩盖由吸入变应原引起的气道炎症细胞流入。