Díaz O, Barberà J A, Marrades R, Chung K F, Roca J, Rodriguez-Roisin R
Departament de Medicina, Hospital Clínic, Universitat de Barcelona, Spain.
Am J Respir Crit Care Med. 1997 Jul;156(1):17-22. doi: 10.1164/ajrccm.156.1.9610100.
Salbutamol inhibits neutropenia, increased airway resistance, and gas exchange abnormalities provoked by platelet-activating factor (PAF) challenge in normal persons. To further explore the intriguing dissociation between spirometric abnormalities and gas exchange defects shown in patients with asthma, we investigated whether the salbutamol-induced improvement in gas exchange disturbances after PAF is the result of bronchodilation by comparing this effect with that of ipratropium bromide. We hypothesized that ipratropium bromide, an anticholinergic agent without vascular effects, should block PAF-induced bronchoconstriction but not interfere with its systemic, neutropenic, and gas exchange effects. We studied eight nonsmokers with mild asthma (26 +/- 2.0 SE yr of age) who, prior to PAF challenge (18 micrograms), inhaled either ipratropium bromide (80 micrograms) or salbutamol (300 micrograms) in a randomized, double-blind, crossover fashion 1 wk apart. Peripheral blood neutrophils, respiratory system resistance (Rrs), arterial blood gases and ventilation-perfusion (VA/Q) inequalities were measured 5, 15, and 45 min after PAF. Compared with pretreatment with salbutamol, ipratropium bromide also blocked the increase of respiratory system resistance (Rrs) but did not prevent facial flushing and neutropenia (p < 0.03) at 5 min nor the decrease of PaO2 (p = 0.08 and 0.05), the increase of AaPO2 (p < 0.02 each), and the deterioration of VA/Q relationships (p < 0.05 each) at 5 and 15 min, respectively. This functional pattern was similar to that observed previously in normal subjects and in nonpremedicated asthmatic patients after PAF, with return to baseline values at 45 min. By contrast, salbutamol blocked PAF-induced increased Rrs, in addition to all the other PAF-induced abnormalities. These findings indicate that, in patients with mild asthma, salbutamol inhibits PAF-induced neutropenia and gas exchange abnormalities by mechanisms involving other than airway smooth muscle narrowing, possibly by acting on both the bronchial and pulmonary circulations.
沙丁胺醇可抑制正常人因血小板活化因子（PAF）激发引起的中性粒细胞减少、气道阻力增加及气体交换异常。为进一步探究哮喘患者肺量计异常与气体交换缺陷之间有趣的分离现象，我们通过将这种效应与异丙托溴铵的效应进行比较，研究了PAF后沙丁胺醇诱导的气体交换障碍改善是否是支气管扩张的结果。我们推测，异丙托溴铵作为一种无血管效应的抗胆碱能药物，应能阻断PAF诱导的支气管收缩，但不会干扰其全身、中性粒细胞减少及气体交换效应。我们研究了8名轻度哮喘的非吸烟者（年龄26±2.0岁，标准误），在PAF激发（18微克）前，以随机、双盲、交叉方式，间隔1周吸入异丙托溴铵（80微克）或沙丁胺醇（300微克）。在PAF后5、15和45分钟测量外周血中性粒细胞、呼吸系统阻力（Rrs）、动脉血气及通气/灌注（VA/Q）不均一性。与沙丁胺醇预处理相比，异丙托溴铵也能阻断呼吸系统阻力（Rrs）的增加，但在5分钟时不能预防面部潮红和中性粒细胞减少（p<0.03），在5分钟和15分钟时也不能预防PaO2降低（p = 0.08和0.05）、AaPO2升高（各p<0.02）以及VA/Q关系恶化（各p<0.05）。这种功能模式与之前在正常受试者和未用药的哮喘患者PAF激发后观察到的相似，45分钟时恢复到基线值。相比之下，沙丁胺醇除了能阻断PAF诱导的Rrs增加外，还能阻断所有其他PAF诱导的异常。这些发现表明，在轻度哮喘患者中，沙丁胺醇通过涉及气道平滑肌狭窄以外的机制抑制PAF诱导的中性粒细胞减少和气体交换异常，可能是通过作用于支气管和肺循环来实现的。
