Grimm D R, DeLuca R V, Lesser M, Bauman W A, Almenoff P L
Spinal Cord Damage Research Center, Veterans Affairs Medical Center, Bronx, New York 10468, USA.
Lung. 1997;175(5):333-41. doi: 10.1007/pl00007579.
Bronchial provocation studies performed in our research center have consistently demonstrated airway hyperresponsiveness to both inhaled methacholine and histamine in subjects with chronic cervical spinal cord injury (SCI). More recently, we reported that the airways of such subjects maintained on chronic baclofen (gamma-aminobutyric acid) therapy were not hyperreactive to inhaled methacholine. In this study we determined whether baclofen also blocks the effects of the bronchoprovocative agent histamine in subjects with cervical SCI. Twenty-four male subjects with cervical SCI participated in this study; 14 were maintained on oral baclofen, and 10 served as age-matched controls. The subjects were challenged with increasing concentrations of aerosolized histamine until either a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline (defined as PC20) was observed, or a maximum of 25 mg/ml histamine was administered. We found that 11 of the 14 baclofen subjects (78.5%) and 8 of the 10 control subjects (80%) responded (PC20 < 8 mg/ml) to the histamine challenge. Mean PC20 values among responders in the baclofen (PC20 = 2.91 +/- 2.3) and control (PC20 = 2.18 +/- 1.9) groups did not differ significantly. Because histamine acts directly on histamine receptors and indirectly on cholinergic pathways, our findings that baclofen blocks bronchoconstriction due to inhaled methacholine, but not that due to histamine, suggests that hyperresponsiveness in subjects with cervical SCI may be secondary to nonspecific airway hyperreactivity.
在我们的研究中心进行的支气管激发试验一直表明，慢性颈脊髓损伤（SCI）患者对吸入的乙酰甲胆碱和组胺均存在气道高反应性。最近，我们报告称，接受慢性巴氯芬（γ-氨基丁酸）治疗的此类患者的气道对吸入的乙酰甲胆碱无高反应性。在本研究中，我们确定巴氯芬是否也能阻断组胺这种支气管激发剂对颈脊髓损伤患者的作用。24名患有颈脊髓损伤的男性受试者参与了本研究；14名受试者接受口服巴氯芬治疗，10名作为年龄匹配的对照组。受试者接受递增浓度的雾化组胺激发，直至观察到1秒用力呼气量（FEV1）较基线下降20%（定义为PC20），或给予最大剂量25mg/ml的组胺。我们发现，14名接受巴氯芬治疗的受试者中有11名（78.5%），10名对照组受试者中有8名（80%）对组胺激发有反应（PC20<8mg/ml）。巴氯芬组（PC20 = 2.91±2.3）和对照组（PC20 = 2.18±1.9）有反应者的平均PC20值无显著差异。由于组胺直接作用于组胺受体并间接作用于胆碱能途径，我们的研究结果表明，巴氯芬可阻断吸入乙酰甲胆碱引起的支气管收缩，但不能阻断组胺引起的支气管收缩，这表明颈脊髓损伤患者的高反应性可能继发于非特异性气道高反应性。
