A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis.
A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis.
复制标题
预测自身免疫性肺泡蛋白沉积症全肺灌洗期间蛋白质洗出动力学的数学模型。
DOI：
10.1152/ajplung.00239.2014
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
(7名略) Nakata K.
中科院分区：
文献类型：
--
作者：
Akasaka K;（12名略）， Tazawa R;(7名略) Nakata K.
全肺灌洗仍然是肺泡蛋白沉着症的标准治疗方法，在这个过程中，累积的表面活性物质用0.5-2.0%的L生理盐水冲洗10-30个周期。该方法是通过经验建立的。相比之下，蛋白质转移到灌洗液中的动力学无论在理论上还是在实践中都没有得到充分的评估。对17例自身免疫性PAP患者的肺进行了WLL术。我们为WLL的每个阶段制定了准确的时间表，即灌输、保留、排水和准备。随后，我们测量了滴注的生理盐水和引流的灌洗液的体积，以及引流的灌洗液中蛋白质的浓度。我们还提出了一个蛋白质转移到灌洗液中的数学模型，其中时间是一个单一变量，因为蛋白质随着简单的扩散而运动。测定的免疫球蛋白、转铁蛋白、白蛋白和β2-微球蛋白的浓度与通过微分方程式计算的相应理论值非常接近。β-2微球蛋白从血液到灌洗液的转移系数比免疫球蛋白、转铁蛋白和白蛋白高两个数量级。数学模型的模拟表明，蛋白质的累积消除量不受每个周期的持续时间的影响，但主要取决于总的洗涤时间，部分取决于滴注的体积。尽管内科医生很少注意到从肺到灌洗液的物质转移，但WLL似乎是一个遵循扩散数学模型的过程。
Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar proteinosis (PAP), a process in which accumulated surfactants are washed out of the lung with 0.5–2.0 l of saline aliquots for 10–30 wash cycles. The method has been established empirically. In contrast, the kinetics of protein transfer into the lavage fluid has not been fully evaluated either theoretically or practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We made accurate timetables for each stage of WLL, namely, instilling, retaining, draining, and preparing. Subsequently, we measured the volumes of both instilled saline and drained lavage fluid, as well as the concentrations of proteins in the drained lavage fluid. We also proposed a mathematical model of protein transfer into the lavage fluid in which time is a single variable as the protein moves in response to the simple diffusion. The measured concentrations of IgG, transferrin, albumin, and β2-microglobulin closely matched the corresponding theoretical values calculated through differential equations. Coefficients for transfer of β2-microglobulin from the blood to the lavage fluid were two orders of magnitude higher than those of IgG, transferrin, and albumin. Simulations using the mathematical model showed that the cumulative amount of eliminated protein was not affected by the duration of each cycle but dependent mostly on the total time of lavage and partially on the volume instilled. Although physicians have paid little attention to the transfer of substances from the lung to lavage fluid, WLL seems to be a procedure that follows a diffusion-based mathematical model.