Mcivor R A, Pizzichini E, Turner M O, Hussack P, Hargreave F E, Sears M R
Firestone Regional Chest and Allergy Unit, St. Joseph's Hospital-McMaster University, Hamilton, Ontario, Canada.
Am J Respir Crit Care Med. 1998 Sep;158(3):924-30. doi: 10.1164/ajrccm.158.3.9802069.
We hypothesized that regular use of long-acting beta-agonists could delay recognition of ("mask") increasing airway inflammation. We studied steroid-sparing and "masking" effects of salmeterol versus placebo in 13 asthmatic individuals requiring >= 1,500 microgram inhaled corticosteroid daily. Corticosteroid doses were reduced weekly until criteria were met for an exacerbation or the corticosteroid was fully withdrawn. Subjects were restabilized on their original dose of inhaled corticosteroid for 4 wk before crossover to the alternative treatment. Subjects maintained symptom and peak expiratory flow (PEF) diaries, and underwent weekly spirometric, methacholine challenge, sputum eosinophil, and serum eosinophil cationic protein (ECP) measurements. Mean corticosteroid dose was reduced by 87% during salmeterol treatment, versus 69% with placebo (p = 0.04). Sputum eosinophils increased before exacerbation despite stable symptoms, FEV1, and PEF. In the week before clinical exacerbation, sputum eosinophil counts were higher in the salmeterol-treatment arm (19.9 +/- 29.8% [mean +/- SD], versus placebo 9.3 +/- 17.6%; p = 0.006). Five subjects showed > 10% sputum eosinophilia before exacerbation during salmeterol treatment, as compared with two receiving placebo. In this model, salmeterol controlled symptoms and lung function until inflammation became significantly more advanced. We conclude that the bronchodilating and symptom-relieving effects of salmeterol can mask increasing inflammation and delay awareness of worsening asthma.
我们假设长期使用长效β受体激动剂可能会延迟对气道炎症加重的察觉（“掩盖”效应）。我们研究了沙美特罗与安慰剂对13名每日需要吸入≥1500微克皮质类固醇的哮喘患者的类固醇节省和“掩盖”效应。每周减少皮质类固醇剂量，直至达到病情加重标准或完全停用皮质类固醇。在交叉接受替代治疗前，让受试者以其原来的吸入皮质类固醇剂量重新稳定4周。受试者记录症状和呼气峰值流速（PEF）日记，并每周进行肺活量测定、乙酰甲胆碱激发试验、痰液嗜酸性粒细胞及血清嗜酸性粒细胞阳离子蛋白（ECP）测量。在沙美特罗治疗期间，平均皮质类固醇剂量减少了87%，而安慰剂组为69%（p = 0.04）。尽管症状、第一秒用力呼气容积（FEV1）和PEF保持稳定，但在病情加重前痰液嗜酸性粒细胞增多。在临床加重前一周，沙美特罗治疗组的痰液嗜酸性粒细胞计数更高（19.9±29.8%[平均值±标准差]，安慰剂组为9.3±17.6%；p = 0.006）。与接受安慰剂的两名受试者相比，五名受试者在沙美特罗治疗期间病情加重前痰液嗜酸性粒细胞增多>10%。在这个模型中，沙美特罗可控制症状和肺功能，直至炎症明显加重。我们得出结论，沙美特罗的支气管扩张和症状缓解作用可掩盖炎症加重并延迟对哮喘恶化的察觉。
