Joos G F, Pauwels R A, Van der Straeten M E
Department of Respiratory Diseases, University Hospital, Ghent, Belgium.
J Allergy Clin Immunol. 1989 Mar;83(3):663-8. doi: 10.1016/0091-6749(89)90080-8.
We have previously demonstrated that the neuropeptide, neurokinin A (NKA) (substance K), causes bronchoconstriction in subjects with asthma. In a double-blind, crossover study we investigated the effect of nedocromil sodium on NKA-induced bronchoconstriction in subjects with asthma. Twelve patients with mild asthma (mean FEV1 percent predicted +/- SE, 87.3 +/- 3.4) inhaled on 2 separate days either nedocromil sodium, 4 mg, or placebo, as two puffs from a metered-dose aerosol, 30 minutes before challenge with NKA. NKA was inhaled at three concentrations (10(-7), 3.10(-7), and 10(-6) mol/ml). The specific airway conductance (SGaw) and FEV1 were measured before and 5 and 15 minutes after each concentration step. On the placebo-treatment day, NKA caused a concentration-dependent decrease in SGaw and FEV1 (mean log for the provocative concentration of NKA causing a 35% fall in SGaw [10(-7) mol/ml], 0.49; mean log for the provocative concentration of NKA causing a 15% fall in SGaw [10(-7) mol/ml], 0.90). The inhalation of 4 mg of nedocromil sodium reduced the decrease in both SGaw and FEV1. The maximal percentage decrease in SGaw on the nedocromil sodium-treatment day was 27 +/- 5.2 (versus placebo, 53.3 +/- 5.4; p less than 0.05), and the maximal percentage decrease in FEV1 was 5.5 +/- 1.4 (versus placebo, 12.4 +/- 2.3; p less than 0.05). The dose-response curves for NKA after nedocromil sodium treatment were significantly shifted to the right compared to the curve after placebo-treatment. We conclude that nedocromil sodium protects against NKA-induced bronchoconstriction in subjects with asthma.
我们之前已经证明，神经肽神经激肽A（NKA）（物质K）可导致哮喘患者出现支气管收缩。在一项双盲交叉研究中，我们调查了奈多罗米钠对哮喘患者NKA诱导的支气管收缩的影响。12名轻度哮喘患者（预计FEV1平均值±标准误，87.3±3.4）在2个不同日期，于接受NKA激发前30分钟，通过定量气雾剂吸入4毫克奈多罗米钠或安慰剂，每次2喷。以三种浓度（10⁻⁷、3×10⁻⁷和10⁻⁶摩尔/毫升）吸入NKA。在每个浓度阶段前后以及之后5分钟和15分钟测量比气道传导率（SGaw）和FEV1。在安慰剂治疗日，NKA导致SGaw和FEV1呈浓度依赖性下降（导致SGaw下降35%的NKA激发浓度的平均对数[10⁻⁷摩尔/毫升]，0.49；导致SGaw下降15%的NKA激发浓度的平均对数[10⁻⁷摩尔/毫升]，0.90）。吸入4毫克奈多罗米钠可减少SGaw和FEV1的下降。奈多罗米钠治疗日SGaw的最大百分比下降为27±5.2（与安慰剂相比，53.3±5.4；p<0.05），FEV1的最大百分比下降为5.5±1.4（与安慰剂相比，12.4±2.3；p<0.05）。与安慰剂治疗后的曲线相比，奈多罗米钠治疗后NKA的剂量反应曲线明显右移。我们得出结论，奈多罗米钠可预防哮喘患者NKA诱导的支气管收缩。
