Lung and Allergy Clinic, Department of Medicine at Karolinska University Hospital Huddinge and The Centre for Allergy Research, Karolinska Institutet, 141 86, Stockholm, Sweden.
Eur J Clin Pharmacol. 2012 Oct;68(10):1375-83. doi: 10.1007/s00228-012-1256-z. Epub 2012 Mar 29.
Leukotriene D(4) (LTD(4)) is a central mediator in asthma inducing bronchoconstriction and profound disturbances in pulmonary gas exchange in asthmatic subjects. The aim of the study was to compare, for the first time, the influence of the bronchodilators salbutamol (400 μg) and ipratropium (80 μg) on lung function changes induced by inhaled LTD(4).
Treatments were evaluated in a randomized, three-period, double-blind, placebo-controlled, cross-over study where spirometric and pulmonary gas exchange indices were followed in 12 subjects with mild asthma before and after LTD(4) challenge.
Compared with placebo, salbutamol provided significant protection against the fall in FEV(1) (forced expiratory volume in 1 s) after LTD(4) challenge. Salbutamol also abolished the LTD(4)-induced gas exchange disturbances [decreased arterial oxygen tension (PaO(2)) and increased alveolar-arterial oxygen tension difference (AaPO(2))]. Ipratropium provided significant but less marked attenuation of the changes in FEV(1) and arterial oxygenation induced by LTD(4).
Despite the equal bronchodilatory effects of salbutamol and ipratropium before the challenge with LTD(4), salbutamol was superior to ipratropium in preventing spirometric and gas exchange abnormalities. This result indicates a broader action of salbutamol on several of the disturbances that contribute to airway obstruction including, for example, exudation of plasma in the airway mucosa. The clinical implication of this new finding is that in this model of acute asthmatic airway obstruction, salbutamol was more effective than ipratropium.
白三烯 D4（LTD4）是一种在哮喘患者中引起支气管收缩和肺部气体交换严重紊乱的中枢介质。本研究的目的是首次比较支气管扩张剂沙丁胺醇（400μg）和异丙托溴铵（80μg）对吸入 LTD4 引起的肺功能变化的影响。
在一项随机、三周期、双盲、安慰剂对照、交叉研究中，评估了治疗方法，该研究纳入 12 例轻度哮喘患者，在 LTD4 激发前后进行了肺功能和肺气体交换指数的测定。
与安慰剂相比，沙丁胺醇能显著预防 LTD4 激发后 1 秒用力呼气量（FEV1）下降。沙丁胺醇还消除了 LTD4 引起的气体交换障碍[动脉血氧分压（PaO2）降低和肺泡-动脉血氧分压差（AaPO2）增加]。异丙托溴铵对 LTD4 引起的 FEV1 和动脉氧合变化也有显著但程度较轻的抑制作用。
尽管沙丁胺醇和异丙托溴铵在 LTD4 激发前的支气管扩张作用相同，但沙丁胺醇在预防肺功能和气体交换异常方面优于异丙托溴铵。这一结果表明，沙丁胺醇对导致气道阻塞的多种紊乱的作用更为广泛，例如气道黏膜中的血浆渗出。这一新发现的临床意义是，在这种急性哮喘气道阻塞模型中，沙丁胺醇比异丙托溴铵更有效。
