Makker H K, Holgate S T
Immunopharmacology Group, University of Southampton, Southampton General Hospital, England.
J Allergy Clin Immunol. 1993 Jul;92(1 Pt 1):82-8. doi: 10.1016/0091-6749(93)90041-d.
Hypertonic saline induces bronchoconstriction in most patients with asthma; however, the mechanisms involved are not clearly understood. We have investigated the role of neurogenic mechanisms in hypertonic saline-induced bronchoconstriction.
The effect of pretreatment with the anticholinergic drugs atropine and ipratropium bromide and the local anesthetic drug lidocaine on hypertonic saline responsiveness was studied in 11 subjects with asthma. Ultrasonically nebulized hypertonic saline challenge was given in a dose-response manner to determine the provocative dose of hypertonic saline-laden air required to produce a fall in forced expiratory volume in 1 second (FEV1) of 20% or greater (PD20HS). A control PD20HS with no pretreatment was measured before randomization, and on the next three visits PD20HS was determined after pretreatment with each of the following: intramuscularly administered atropine, inhaled ipratropium bromide, and inhaled lidocaine.
The baseline mean FEV1 values increased by 3.5% and 4% 30 minutes after administration of atropine and ipratropium bromide, respectively, and decreased by 5.8% at 10 minutes after inhalation of lidocaine. These changes in the baseline FEV1 were not significant and did not have any effect on the PD20HS response. Premedication with atropine, ipratropium bromide, and lidocaine resulted in increases of 2.5, 2.0, and 2.6 times in mean PD20HS, respectively.
The protection afforded by the drugs was variable in the individual subjects and not related to age, sex, baseline FEV1, provocative concentration of histamine causing a 20% fall in FEV1 or use of the inhaled corticosteroids. The protection afforded by anticholinergic and local anesthetic drugs suggests the contribution of neurogenic reflexes in the pathogenesis of hypertonic saline-induced bronchoconstriction in asthma.
高渗盐水可导致大多数哮喘患者出现支气管收缩；然而，其中涉及的机制尚不清楚。我们研究了神经源性机制在高渗盐水诱导的支气管收缩中的作用。
在11例哮喘患者中，研究了抗胆碱能药物阿托品和异丙托溴铵以及局部麻醉药利多卡因预处理对高渗盐水反应性的影响。以剂量反应方式给予超声雾化高渗盐水激发试验，以确定导致第1秒用力呼气量（FEV1）下降20%或更多所需的高渗盐水负载空气的激发剂量（PD20HS）。在随机分组前测量未预处理的对照PD20HS，在接下来的三次就诊中，分别在以下每种预处理后测定PD20HS：肌肉注射阿托品、吸入异丙托溴铵和吸入利多卡因。
分别在给予阿托品和异丙托溴铵后30分钟，基线平均FEV1值增加了3.5%和4%，而在吸入利多卡因后10分钟下降了5.8%。基线FEV1的这些变化不显著，对PD20HS反应也没有任何影响。用阿托品、异丙托溴铵和利多卡因预处理后，平均PD20HS分别增加了2.5倍、2.0倍和2.6倍。
药物提供的保护在个体受试者中各不相同，且与年龄、性别、基线FEV1、导致FEV1下降20%的组胺激发浓度或吸入糖皮质激素的使用无关。抗胆碱能药物和局部麻醉药提供的保护表明神经源性反射在哮喘患者高渗盐水诱导的支气管收缩发病机制中起作用。
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