Characterization of the airway response to inhaled leukotriene D4 in normal subjects.
Characterization of the airway response to inhaled leukotriene D4 in normal subjects.
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正常受试者对吸入白三烯 D4 的气道反应特征。
DOI：
10.1164/arrd.1986.133.6.1127
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Bernstein,PR
中科院分区：
文献类型：
--
作者：
Kern,R;Smith,LJ;Patterson,R;Krell,RD;Bernstein,PR
为了更好地了解白三烯D4（LTD4）在气道高反应性发病机制中的作用，我们对6名正常受试者多次雾化吸入LTD4，并通过身体体积描记术和部分用力呼气动作（V30 P）在30%肺活量时的流速测量比气道传导率（SGaw）。从标准支气管激发试验产生的剂量反应曲线显示，LTD 4作为支气管收缩剂的效力是乙酰甲胆碱的280至590倍。对于SGaw（r = 0.86，p < 0.05）和V30 P（r = 0.95，p <0.005），在不同日期给予单次支气管收缩剂量的LTD 4的气道反应是可重复的。在同一天进行的3次连续单剂量LTD 4激发的反应，允许SGaw和V30 P在激发之间恢复到> 90%的对照值，证明了快速耐受性：对于SGaw（p < 0.001）和V30 P（p < 0.01），对第三剂量的反应显著低于对第一剂量的反应。在标准乙酰甲胆碱剂量反应激发前给予单次支气管收缩剂量的LTD 4，降低了降低V30P 30%（p < 0.05）和SGaw 35%（p = 0.09）所需的乙酰甲胆碱浓度。在标准乙酰甲胆碱激发前单次支气管收缩剂量的乙酰甲胆碱没有这种作用。LTD4和乙酰甲胆碱表现出累积的剂量效应时，逐步吸入更高的浓度。总之，对LTD 4的气道反应是可重现的，表现出快速耐受性，并出现累积剂量效应。同时，LTD4增加了正常气道对乙酰甲胆碱的反应性。
To better understand the role of leukotriene D4(LTD4) in the pathogenesis of airway hyperreactivity, we administered aerosolized LTD4on multiple occasions to 6 normal subjects and measured specific airway conductance (SGaw) by body plethysmography and the flow rate at 30% of vital capacity from partial forced expiratory maneuvers (V30P). Dose-response curves generated from standard bronchoprovocation tests revealed that LTD4was 280 to 590 times more potent as a bronchoconstrictor than was methacholine. The airway response to single bronchoconstricting doses of LTD4administered on separate days was reproducible for SGaw (r = 0.86, p < 0.05) and V30P (r = 0.95, p < 0.005). The response to 3 consecutive single-dose LTD4challenges performed on the same day, allowing SGaw and V30P to return to > 90% of the control value between challenges, demonstrated tachyphylaxis: the response to the third dose was significantly less than the response to the first dose for SGaw (p < 0.001) and for V30P (p < 0.01). A single bronchoconstricting dose of LTD4, given before a standard methacholine dose-response challenge, lowered the concentration of methacholine needed to decrease V30P 30% (p < 0.05) and SGaw 35% (p = 0.09). A single bronchoconstricting dose of methacholine preceding a standard methacholine challenge did not have this effect. LTD4and methacholine demonstrated a cumulative dose-effect when progressively higher concentrations were inhaled. In summary, the airway response to LTD4is reproducible, exhibits tachyphylaxis, and a cumulative dose-effect occurs. As well, LTD4increases the responsiveness of normal airways to methacholine.