Harvey J E, Tattersfield A E
Thorax. 1982 Apr;37(4):280-7. doi: 10.1136/thx.37.4.280.
This study was designed to determine whether resistance to the airway effects of the beta-agonist, salbutamol, would develop in three groups of subjects while taking large doses of inhaled salbutamol. Six normal non-atopic, six atopic non-asthmatic, and eight atopic asthmatic subjects were studied by an identical technique. The development of resistance was assessed from salbutamol dose-response studies in which the airway response was measured as specific airway conductance (sGaw). Further evidence was sought in the atopic and asthmatic subjects by measuring the airway response to a standard histamine inhalation challenge and the protective effect of 100 micrograms salbutamol on this challenge, and by six-hourly peak flow recordings. Subjects were assessed before and during four weeks in which they took inhaled salbutamol regularly in doses increasing to 500 microgram quid in week 4. Normal subjects showed a progressive reduction in the bronchodilator (sGaw) response to salbutamol during the four weeks, indicating the progressive development of resistance. The atopic subjects, both asthmatic and non-asthmatic, showed no reduction in the response to salbutamol during the four weeks, nor any change in the response to histamine challenge or in regular peak flow readings. These results demonstrate that asthmatic patients do not develop bronchial beta-adrenoceptor resistance easily and suggests that they and atopic non-asthmatic subjects are less susceptible to its development than normal subjects.
本研究旨在确定三组受试者在大剂量吸入沙丁胺醇时是否会产生对β受体激动剂沙丁胺醇气道效应的耐受性。采用相同技术对6名正常非特应性、6名特应性非哮喘和8名特应性哮喘受试者进行了研究。通过沙丁胺醇剂量反应研究评估耐受性的产生,其中气道反应以比气道传导率(sGaw)来衡量。通过测量对标准组胺吸入激发试验的气道反应以及100微克沙丁胺醇对该激发试验的保护作用,以及每6小时记录一次峰值流速,在特应性和哮喘受试者中寻找进一步的证据。在四周内对受试者进行评估,在此期间他们定期吸入沙丁胺醇,剂量在第4周增加至500微克/日。正常受试者在四周内对沙丁胺醇的支气管扩张剂(sGaw)反应逐渐降低,表明耐受性逐渐产生。特应性受试者,包括哮喘患者和非哮喘患者,在四周内对沙丁胺醇的反应没有降低,对组胺激发试验的反应或定期峰值流速读数也没有任何变化。这些结果表明,哮喘患者不容易产生支气管β肾上腺素能受体耐受性,提示他们和特应性非哮喘受试者比正常受试者更不易产生耐受性。