Human interindividual variability in susceptibility to airborne particles
Human interindividual variability in susceptibility to airborne particles
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DOI：
10.1111/0272-4332.214137
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发表时间：
2001-08-01
期刊：
影响因子：
3.8
通讯作者：
Chu, M
中科院分区：
文献类型：
--
作者：
Hattis, D;Russ, A;Chu, M
关于死亡率和发病率与空气中颗粒相对适度的环境暴露之间存在关联的持续流行病学发现的部分解释可能是，有些人比其他人更容易受到颗粒引起的反应。本研究收集了一个定量观察数据库，其中包括可能影响颗粒反应的药代动力学和药效学参数的个体差异。研究的药效学反应包括来自甲胆碱、面粉粉和其他引起肺功能急性变化的药物剂量的流行病学研究数据。一般来说，这些药效学反应参数的个体间变异性大于药代动力学参数（呼吸速率、沉积和清除）的变异性。定量结果表明，人类呼吸频率和主要药代动力学参数（总沉积和气管支气管清除率）的个体间变异性在Log(GSD) = 0.1至0.2范围内(对应的几何标准差为10（1)-10(2)或1.26-1.58）。肺深部（肺泡区）的沉积变化更大：Log（GSD）约为0.3 （GSD约为2）。在药效学参数中，臭氧和代谢亚硫酸盐（一种据说主要作用于肺部神经受体的物质）对FEV1的影响在Log(GSD) 0.2至0.4的范围内。然而，对甲胆碱（一种作用于平滑肌的药物）的类似反应似乎有更多的可变性（0.4到略高于1.0，取决于研究人群的类型）。颗粒过敏原的数值也同样高。这种变异性的中心估计，以及数据与对数正态分布的密切对应，表明99.9百分位个体可能在比中位数个体所需剂量少150至450倍的剂量下产生反应。具有如此多变性的急性反应似乎可能构成与细颗粒环境暴露有关的死亡率增加的流行病学观察的部分机制基础。
Part of the explanation for the persistent epidemiological findings of associations between mortality and morbidity with relatively modest ambient exposures to airborne particles may be that some people are much more susceptible to particle-induced responses than others. This study assembled a database of quantitative observations of interindividual variability in pharmacokinetic and pharmacodynamic parameters likely to affect particle response. The pharmacodynamic responses studied included data drawn from epidemiologic studies of doses of methacholine, flour dust, and other agents that induce acute changes in lung function. In general, the amount of interindividual variability in several of these pharmacodynamic response parameters was greater than the variability in pharmacokinetic (breathing rate, deposition, and clearance) parameters. Quantitatively the results indicated that human interindividual variability of breathing rates and major pharmacokinetic parameters-total deposition and tracheobronchial clearance-were in the region of Log(GSD) = 0.1 to 0.2 (corresponding to geometric standard deviations of 10(1)-10(2) or 1.26-1.58). Deposition to the deep lung (alveolar region) appeared to be somewhat more variable: Log(GSD) of about 0.3 (GSD of about 2). Among pharmacodynamic parameters, changes in FEV1 in response to ozone and metabisulfite (an agent that is said to act primarily on neural receptors in the lung) were in the region of Log(GSD) of 0.2 to 0.4. However, similar responses to methacholine, an agent that acts on smooth muscle, seemed to have still more variability (0.4 to somewhat over 1.0, depending on the type of population studied). Similarly high values were suggested for particulate allergens. Central estimates of this kind of variability, and the close correspondence of the data to lognormal distributions, indicate that 99.9th percentile individuals are likely to respond at doses that are 150 to 450-fold less than would be needed in median individuals. It seems plausible that acute responses with this amount of variability could form part of the mechanistic basis for epidemiological observations of enhanced mortality in relation to ambient exposures to fine particles.