Louis R E, Radermecker M F
Dept. of Pneumology, CHU Sart-tilman, Liege, Belgium.
Eur Respir J. 1996 Jul;9(7):1414-20. doi: 10.1183/09031936.96.09071414.
Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma but controversies exist about bronchial responsiveness toward this mediator in asthma. We have compared the variations in the specific conductance (sGaw) and forced expiratory volume in one second (FEV1) in 12 asthmatics and 12 normal subjects after inhalation of doubling doses of PAF (15-120 micrograms) and methacholine (18 to at least 144 micrograms). In order to take into account a possible tachyphylaxis, we compared PAF dose-response curves performed on one day with the curves obtained by giving the same doses separately on different days. Repeated inhalations of doubling doses of PAF caused sGaw and FEV1 to plateau after the second dose in each group, whereas methacholine provoked a dose-related decrease in sGaw and FEV1. A dose-dependent decrease in the functional indices was restored when the different doses of PAF were administered on separate days. In both groups, the fall in sGaw after inhalation of 60 micrograms as a single dose was higher than that achieved when this dose was given during a full bronchial challenge. The falls in sGaw and FEV1 after PAF inhalation were significantly higher in the asthmatics than in the normal subjects. The provocative dose of PAF causing a 35% fall in sGaw (PD35,sGaw) PAF was only twofold lower in the asthmatics than in the normal subjects (p < 0.05), while it was 11 fold lower for methacholine (p < 0.001). When the PD35,sGaw values were compared, PAF was found on a molar basis to be 33 fold more potent than methacholine in the normal subjects, but only fivefold more potent in the asthmatics (p < 0.05). The percentage falls in FEV1 (calculated by interpolation) for a 35% fall in sGaw, were greater in asthmatics than in normals both for methacholine (p < 0.05) and PAF (p = 0.09). Our results demonstrate a tachyphylaxis after inhalation of platelet-activating factor in normal subjects and asthmatics, and show that asthmatics develop a greater bronchial obstruction than normal subjects even if methacholine is more sensitive than platelet-activating factor at discriminating between the two groups.
血小板活化因子（PAF）可能在哮喘的病理生理学中起作用，但关于哮喘患者对这种介质的支气管反应性存在争议。我们比较了12名哮喘患者和12名正常受试者在吸入双倍剂量的PAF（15 - 120微克）和乙酰甲胆碱（18至至少144微克）后，比气道传导率（sGaw）和一秒用力呼气容积（FEV1）的变化。为了考虑可能的快速减敏反应，我们比较了同一天进行的PAF剂量反应曲线与在不同日期分别给予相同剂量所获得的曲线。在每组中，重复吸入双倍剂量的PAF导致sGaw和FEV1在第二次给药后达到平台期，而乙酰甲胆碱引起sGaw和FEV1与剂量相关的下降。当在不同日期给予不同剂量的PAF时，功能指标的剂量依赖性下降得以恢复。在两组中，单次吸入60微克时sGaw的下降高于在完整支气管激发试验中给予该剂量时的下降。哮喘患者吸入PAF后sGaw和FEV1的下降明显高于正常受试者。导致sGaw下降35%的PAF激发剂量（PD35，sGaw）在哮喘患者中仅比正常受试者低两倍（p < 0.05），而乙酰甲胆碱则低11倍（p < 0.001）。当比较PD35，sGaw值时，发现以摩尔为基础，PAF在正常受试者中比乙酰甲胆碱强33倍，但在哮喘患者中仅强五倍（p < 0.05）。对于sGaw下降35%，哮喘患者中乙酰甲胆碱和PAF导致的FEV1下降百分比（通过插值计算）均高于正常受试者（乙酰甲胆碱，p < 0.05；PAF，p = 0.09）。我们的结果表明，正常受试者和哮喘患者吸入血小板活化因子后存在快速减敏反应，并且表明即使乙酰甲胆碱在区分两组时比血小板活化因子更敏感，哮喘患者仍比正常受试者出现更严重的支气管阻塞。
