Degree of throat deposition can explain the variability in lung deposition of inhaled drugs
Degree of throat deposition can explain the variability in lung deposition of inhaled drugs
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DOI：
10.1089/jam.2006.19.473
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发表时间：
2006-12-01
期刊：
影响因子：
--
通讯作者：
Thorsson, Lars
中科院分区：
文献类型：
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作者：
Borgstrom, Lars;Olsson, Bo;Thorsson, Lars
吸入是治疗哮喘的主要方法，肺沉积可被视为随后临床效果的替代标志物。不仅绝对肺沉积，而且其变异性也是令人感兴趣的，因为它表明了个体患者在处方药物时预期的肺沉积范围以及使用药物时预期的每日变异性。记录研究的进一步特征，例如受试者是健康还是哮喘患者，成人还是儿童，以及使用了什么器械。共纳入187个数据点。对于整个数据集及其子集，将肺沉积的变异性描述为平均肺沉积的函数。与器械类型或受试者类别无关，高肺沉积与低相对变异性相关，反之亦然。使用已发表的喉部沉积模型，观察到的肺沉积变异性与平均肺沉积的相关性可以解释为主要由喉部沉积的程度和变异性决定。我们假设咽喉沉积是吸入气溶胶肺沉积的主要决定因素，其绝对变异性将在很大程度上由咽喉沉积的绝对变异性决定。因此，肺沉积的相对可变性对于低肺沉积将趋于高，而对于高肺沉积将趋于低。因此，只有在实现高肺沉积的情况下，才能实现肺沉积的低相对可变性。
Inhalation is a mainstay for treatment of asthma, and lung deposition can be seen as a surrogate marker for the ensuing clinical effects. Not only absolute lung deposition, but also its variability is of interest, as it indicates the range of expected lung deposition in an individual patient when prescribing the drug and the expected day-to-day variability when using it. A literature survey found 71 studies with relevant information on lung deposition and its variability. Further characteristics of the studies, such as if the subjects were healthy or asthmatics, adults or children, and what device that was used, were noted. In all, 187 data points were included. Variability in lung deposition was depicted as a function of mean lung deposition; for the entire data set and for subsets thereof. Independent of device type or subject category high lung deposition was associated with low relative variability and vice versa. Using a published throat deposition model, the observed correlation of lung deposition variability to mean lung deposition could be explained as being determined largely by the extent of and variability in throat deposition. We hypothesize that throat deposition is the major determinant for lung deposition of an inhaled aerosol, and its absolute variability will largely be determined by the absolute variability in throat deposition. The relative variability in lung deposition will therefore tend to be high for low lung deposition and low for high lung deposition. Consequently, low relative variability in lung deposition can only be attained if high lung deposition is achieved.