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Aerosol probes of emphysema progression in dogs treated with all trans retinoic acid--an exploratory study. 全反式维甲酸治疗犬气肿进展的气溶胶探针——一项探索性研究。
Frank S Rosenthal

This study used aerosol probes and lung function tests to investigate whether all trans retinoic acid (RA) can reverse experimental emphysema in dogs. Three dogs were evaluated with lung mechanics tests, including inspiratory capacity (IC), total lung capacity (TLC), and the ratio of forced expired volume in 0.5 sec to forced vital capacity (FEV0.5/FVC), an aerosol-derived measure of pulmonary airspace size (effective airspace diameter, EAD), and an aerosol-derived measure of nonuniform ventilation (aerosol dispersion, AD). Emphysema was induced by exposure to aerosolized papain. At 11 or 12 weeks post-papain exposure, dogs received oral RA (2 mg/kg/day) for 8 weeks, and were followed for an additional 4 weeks after stopping RA treatment. In all dogs, lung injury increased in the first 11-12 weeks following papain exposure, as evidenced by increasing trends of inspiratory capacity IC, TLC, EAD, and AD, and a decreasing trend of FEV0.5/FVC. These parameters of lung injury partially and transiently reversed their trends between 2 and 6 weeks following the initiation of RA treatment. A sham RA-treated group was not studied. However, similar reversals of lung injury were not seen in a previous study of dogs treated with papain but not RA, suggesting that RA altered emphysema progression in the current study. The limited reversal of lung injury in this study contrasts with more pronounced treatment effects seen in previous studies with rats. This paper discusses possible reasons for differences in these studies, as well as suggestions for improved experimental investigations of emphysema therapies.

本研究采用气溶胶探针和肺功能试验来研究所有反式维甲酸(RA)是否能逆转实验性狗肺气肿。对3只狗进行肺力学测试,包括吸气量(IC)、总肺活量(TLC)、0.5秒内强制呼气容积与强制肺活量的比值(FEV0.5/FVC)、气溶胶衍生的肺空域大小(有效空域直径,EAD)和气溶胶衍生的非均匀通气(气溶胶分散度,AD)。暴露于雾化木瓜蛋白酶诱导肺气肿。在木瓜蛋白酶暴露后11或12周,狗接受口服RA (2 mg/kg/天)8周,并在停止RA治疗后再随访4周。在暴露于木瓜蛋白酶后的前11-12周,所有狗的肺损伤都有所增加,这可以从吸气量IC、TLC、EAD和AD的增加趋势和FEV0.5/FVC的下降趋势中得到证明。这些肺损伤参数在RA治疗开始后的2 - 6周内部分和短暂地逆转了它们的趋势。假ra治疗组未进行研究。然而,在先前的研究中,用木瓜蛋白酶治疗的狗没有发现类似的肺损伤逆转,但没有发现类风湿关节炎,这表明类风湿关节炎改变了当前研究中肺气肿的进展。在这项研究中,肺损伤的有限逆转与先前在大鼠研究中看到的更明显的治疗效果形成对比。本文讨论了这些研究差异的可能原因,并提出了改进肺气肿治疗实验研究的建议。
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引用次数: 6
Peak inspiratory flow rates generated through the Novolizer and the Turbuhaler dry powder inhaler devices by children with stable asthma. 稳定哮喘儿童通过Novolizer和Turbuhaler干粉吸入器装置产生的峰值吸气流量。
Andrea von Berg, Hans-Joachim Kremer, Barbara Ellers-Lenz, Frank Conrad, Katharina Erb, Joachim Maus, Robert Hermann

We compared the peak inspiratory flows (PIF) generated through a novel dry powder inhaler device, the Novolizer (PIF-N), and the Turbuhaler (PIF-T). Forty-six pediatric patients with stable bronchial asthma were randomized in an open-label, multicenter, crossover trial. No drug was administered during the inhalation maneuvers that were spaced by 10 min. There was neither a carryover nor a sequence effect. The patients were characterized by mean age of 8.5 years, mean FEV(1) of 1.79 L, and mean PIF without any device (baseline, PIF-B) of 185 L/min. Through the devices mean PIF-N of 94 L/min and mean PIF-T of 69 L/min were achieved, calculated from the maxima of three inhalations. This resulted in p < 0.0001 for the difference. The median PIFN/PIF-T ratio was estimated as 1.39. Each child achieved a higher PIF-N than PIF-T and was able to release the feedback mechanisms of the Novolizer indicating sufficient inhalation performance. We conclude that the PIF through the Novolizer is higher than the PIF through the Turbuhaler in stable asthmatic children. The flow rates achieved through the Novolizer allow for sufficient lung deposition even in children as young as 6 years.

我们比较了新型干粉吸入器Novolizer (PIF- n)和Turbuhaler (PIF- t)产生的峰值吸气流量(PIF)。46例稳定型支气管哮喘患儿在一项开放标签、多中心、交叉试验中随机分组。在间隔10分钟的吸入操作期间不给药。既没有遗留效应,也没有顺序效应。患者的平均年龄为8.5岁,平均FEV(1)为1.79 L,无任何装置时的平均PIF(基线,PIF- b)为185 L/min。通过该装置,平均PIF-N为94 L/min,平均PIF-T为69 L/min,根据三次吸入的最大值计算。这导致p < 0.0001的差异。PIFN/PIF-T比值中位数估计为1.39。每个儿童的PIF-N均高于PIF-T,并且能够释放Novolizer的反馈机制,表明吸入效果足够。我们的结论是,在稳定的哮喘儿童中,通过Novolizer的PIF高于通过Turbuhaler的PIF。通过Novolizer实现的流量允许足够的肺沉积,即使是6岁的儿童。
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引用次数: 10
Facemasks and aerosol delivery by metered dose inhaler-valved holding chamber in young children: a tight seal makes the difference. 在幼儿中,面罩和气溶胶通过计量吸入器阀控制室输送:紧密密封使其不同。
H M Janssens, H A W Tiddens

A facemask on a valved holding chamber (VHC) facilitates the inhalation of aerosols from metered dose inhalers (MDI) for young children. Only recently the facemask has been recognized as a vital part for efficient aerosol delivery. Several in vitro and in vivo studies show that a tight seal of the facemask is crucial for optimal aerosol deposition to the lungs. Even a small leak can reduce the dose delivered to the lungs considerably. However, a tight seal is difficult to obtain when a child is not cooperative. Depending on the design of the facemask, it is easier to obtain a good seal. Factors such as dead space, shape, and material should be considered when designing a facemask. However, when a child is upset and not cooperative during the administration, aerosol deposition will be minimal, even with the best-designed facemask.

带阀保持室(VHC)上的面罩有助于幼儿从计量吸入器(MDI)吸入气溶胶。直到最近,口罩才被认为是有效输送气溶胶的重要组成部分。几项体外和体内研究表明,口罩的紧密密封对于最佳的气溶胶沉积到肺部至关重要。即使是很小的泄漏也会大大减少输送到肺部的剂量。然而,当孩子不合作时,很难获得紧密的密封。根据口罩的设计,更容易获得良好的密封。设计口罩时应考虑死区、形状和材料等因素。然而,当孩子在管理期间心烦意乱且不合作时,即使使用设计最好的口罩,气溶胶沉积也将是最小的。
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引用次数: 35
Design of facemasks for delivery of aerosol-based medication via pressurized metered dose inhaler with valved holding chamber: key issues that affect performance. 通过带阀室的加压计量吸入器输送气雾剂药物的面罩设计:影响性能的关键问题。
R W Morton, J P Mitchell

Valved holding chambers (VHCs) are widely prescribed for use with pressurized metered dose inhalers (pMDIs) for the treatment of respiratory disease by aerosol therapy. The facemask is the preferred patient interface for use by infants and small children, as well as by geriatric patients, due primarily to poor coordination skills. However, care is required in the design of the facemask-VHC system to optimize the delivery of medication. In particular, it is essential to achieve an effective mask-to-face seal and to minimize the volume of dead space. It is also important to ensure that the fit of the facemask is comfortable to the patient when applied with sufficient force to create a seal. We review each of these design principles and their application in the evolution of a range of VHCs from the same family of devices during the past fifteen years. We also examine the various methods available for evaluating VHC-facemasks as a system, recommending where future work might be directed.

有阀保持室(vhc)被广泛规定与加压计量吸入器(pmdi)一起使用,用于通过气溶胶疗法治疗呼吸系统疾病。由于协调能力差,口罩是婴儿和幼儿以及老年患者使用的首选患者界面。然而,在面罩- vhc系统的设计中需要注意优化药物的输送。特别是,必须实现有效的面罩到面部密封,并尽量减少死区的体积。同样重要的是要确保口罩的贴合对患者来说是舒适的,当使用足够的力量来形成密封时。我们回顾了这些设计原则及其在过去十五年中来自同一系列器件的一系列vhc的发展中的应用。我们还研究了用于评估vhc面罩作为一个系统的各种方法,并建议了未来工作的方向。
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引用次数: 30
Design optimization of a novel pMDI actuator for systemic drug delivery. 新型pMDI致动器系统给药的设计优化。
Prashant P Kakade, Henk K Versteeg, Graham K Hargrave, Perry Genova, Robert C Williams Iii, Daniel Deaton

Pressurized metered dose inhalers (pMDIs) are the most widely prescribed and economical respiratory drug delivery systems. Conventional pMDI actuators-those based on "two-orifice-and-sump" designs-produce an aerosol with a reasonable respirable fraction, but with high aerosol velocity. The latter is responsible for high oropharyngeal deposition, and consequently low drug delivery efficiency. Kos' pMDI technology is based on a proprietary vortex nozzle actuator (VNA), an innovative actuator configuration that seeks to reduce aerosol plume velocity, thereby promoting deep lung deposition. Using VNA development as a case study, this paper presents a systematic design optimization process to improve the actuator performance through use of advanced optical characterization tools. The optimization effort mainly relied on laser-based optical diagnostics to provide an improved understanding of the fundamentals of aerosol formation and interplay of various geometrical factors. The performance of the optimized VNA design thus evolved was characterized using phase Doppler anemometry and cascade impaction. The aerosol velocities for both standard and optimized VNA designs were found to be comparable, with both notably less than conventional actuators. The optimized VNA design also significantly reduces drug deposition in the actuator as well as USP throat adapter, which in turn, leads to a significantly higher fine particle fraction than the standard design (78 +/- 3% vs. 63 +/- 2% on an ex valve basis). This improved drug delivery efficiency makes VNA technology a practical proposition as a systemic drug delivery platform. Thus, this paper demonstrates how advanced optical diagnostic and characterization tools can be used in the development of high efficiency aerosol drug delivery devices.

加压计量吸入器(pmdi)是处方最广泛和最经济的呼吸药物输送系统。传统的pMDI致动器——基于“双孔-贮槽”设计——产生的气溶胶具有合理的可吸入部分,但气溶胶速度很高。后者是高口咽沉积的原因,因此药物递送效率低。Kos的pMDI技术基于专有的涡流喷嘴致动器(VNA),这是一种创新的致动器配置,旨在降低气溶胶羽流速度,从而促进肺部深部沉积。本文以VNA的开发为例,介绍了一种系统的设计优化过程,通过使用先进的光学表征工具来提高驱动器的性能。优化工作主要依赖于基于激光的光学诊断,以更好地了解气溶胶形成的基本原理和各种几何因素的相互作用。采用相位多普勒风速法和级联冲击法对优化后的VNA设计进行了性能表征。发现标准和优化VNA设计的气溶胶速度具有可比性,两者都明显小于传统执行器。优化的VNA设计还显著减少了致动器和USP喉部适配器中的药物沉积,这反过来又导致比标准设计明显更高的细颗粒分数(78 +/- 3% vs. 63 +/- 2%)。这种给药效率的提高使得VNA技术作为系统给药平台成为一个实用的命题。因此,本文展示了先进的光学诊断和表征工具如何用于开发高效的气溶胶给药装置。
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引用次数: 15
Comparison of three carbon monoxide monitors for determination of smoking status in smokers and nonsmokers with and without COPD. 三种一氧化碳监测仪测定吸烟者和非吸烟者(伴和不伴COPD)吸烟状况的比较。
Lieke Christenhusz, Frans de Jongh, Paul van der Valk, Marcel Pieterse, Erwin Seydel, Job van der Palen

In this (CAMOXI) study, three carbon monoxide (CO) monitors and salivary cotinine are assessed regarding their ability to distinguish smokers from nonsmokers, both in chronic obstructive pulmonary disease (COPD) and healthy people. Twenty-six healthy smokers, 25 healthy nonsmokers, 25 smoking, and 25 former smoking stable COPD patients (age 40-72 years) were included based on self-report (N = 101). All volunteers were measured following a 12-h abstinence period. Sensitivity, specificity, and predictive values of a positive and negative test result were assessed for a range of cutoff points for both CO and salivary cotinine. The prescribed 9-ppm cutoff point of the Breath CO generates a sensitivity of 68% and 42% for COPD patients and healthy people, respectively. Using the prescribed cutoff point (10 ppm) the Smokelyzer produces 56% sensitivity for COPD patients and 23% for healthy people. Both monitors generate 100% specificity in both groups. The cutoff point for the Micro CO meter (5 ppm) generates 88% sensitivity and 92% specificity for COPD patients, and for healthy people 92% and 88%, respectively. The optimal cutoff points depend upon the goal of the test. Salivary cotinine has a 100% sensitivity, specificity, positive predictive value, and negative predictive value over the range of 15 ng/mL through 40 ng/mL for healthy participants and at 10 ng/mL for COPD patients. The prescribed cutoff points for all three CO monitors generate misleading results concerning the determination of the smoking status in both populations. Salivary cotinine measurement outperforms CO measurements and a combination of the two tools is recommended.

在这项(CAMOXI)研究中,评估了三种一氧化碳(CO)监测仪和唾液可替宁区分慢性阻塞性肺疾病(COPD)和健康人吸烟者和非吸烟者的能力。根据自述纳入26例健康吸烟者、25例健康非吸烟者、25例吸烟和25例曾经吸烟稳定的COPD患者(40-72岁)(N = 101)。所有志愿者在12小时的戒断期后都进行了测量。敏感性、特异性和阳性和阴性检测结果的预测值被评估为CO和唾液可替宁的截止点范围。对于COPD患者和健康人来说,规定的9 ppm的呼吸CO临界值分别产生68%和42%的敏感性。使用规定的截止点(10ppm), Smokelyzer对COPD患者的敏感性为56%,对健康人的敏感性为23%。两种监测仪在两组中均产生100%的特异性。Micro CO计(5 ppm)的截止点对COPD患者的灵敏度为88%,特异性为92%,对健康人的灵敏度为92%,特异性为88%。最佳的截止点取决于测试的目标。唾液可替宁在15 ng/mL至40 ng/mL范围内对健康参与者具有100%的敏感性、特异性、阳性预测值和阴性预测值,在10 ng/mL范围内对COPD患者具有阴性预测值。所有三种一氧化碳监测仪的规定截止点在确定两种人群的吸烟状况方面产生了误导性的结果。唾液可替宁测量优于一氧化碳测量,建议两种工具的组合。
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引用次数: 27
A novel quantitative method for analyzing the distributions of nanoparticles between different tissue and intracellular compartments. 一种新的定量分析纳米颗粒在不同组织和细胞内分布的方法。
Christian Mühlfeld, Terry M Mayhew, Peter Gehr, Barbara Rothen-Rutishauser

The penetration, translocation, and distribution of ultrafine and nanoparticles in tissues and cells are challenging issues in aerosol research. This article describes a set of novel quantitative microscopic methods for evaluating particle distributions within sectional images of tissues and cells by addressing the following questions: (1) is the observed distribution of particles between spatial compartments random? (2) Which compartments are preferentially targeted by particles? and (3) Does the observed particle distribution shift between different experimental groups? Each of these questions can be addressed by testing an appropriate null hypothesis. The methods all require observed particle distributions to be estimated by counting the number of particles associated with each defined compartment. For studying preferential labeling of compartments, the size of each of the compartments must also be estimated by counting the number of points of a randomly superimposed test grid that hit the different compartments. The latter provides information about the particle distribution that would be expected if the particles were randomly distributed, that is, the expected number of particles. From these data, we can calculate a relative deposition index (RDI) by dividing the observed number of particles by the expected number of particles. The RDI indicates whether the observed number of particles corresponds to that predicted solely by compartment size (for which RDI = 1). Within one group, the observed and expected particle distributions are compared by chi-squared analysis. The total chi-squared value indicates whether an observed distribution is random. If not, the partial chi-squared values help to identify those compartments that are preferential targets of the particles (RDI > 1). Particle distributions between different groups can be compared in a similar way by contingency table analysis. We first describe the preconditions and the way to implement these methods, then provide three worked examples, and finally discuss the advantages, pitfalls, and limitations of this method.

超细颗粒和纳米颗粒在组织和细胞中的渗透、转运和分布是气溶胶研究中的一个具有挑战性的问题。本文描述了一套新的定量显微方法,通过解决以下问题来评估组织和细胞截面图像中的颗粒分布:(1)观察到的空间间隔之间的颗粒分布是随机的吗?(2)哪些隔室优先被颗粒靶向?(3)观察到的粒子分布在不同实验组之间是否发生了移位?这些问题都可以通过检验一个适当的零假设来解决。这些方法都需要通过计算与每个定义的隔室相关的粒子数来估计观察到的粒子分布。为了研究隔室的优先标记,还必须通过计算随机叠加的测试网格命中不同隔室的点数来估计每个隔室的大小。后者提供了关于粒子随机分布时所期望的粒子分布的信息,即粒子的期望数目。从这些数据中,我们可以计算出相对沉积指数(RDI),即用观察到的颗粒数除以期望的颗粒数。RDI表示观察到的颗粒数量是否与单独由隔室大小(RDI = 1)预测的颗粒数量相对应。在一组中,观察到的和预期的颗粒分布通过卡方分析进行比较。总卡方值表示观察到的分布是否随机。如果不是,部分卡方值有助于识别那些是颗粒优先目标的隔室(RDI > 1)。不同组之间的颗粒分布可以通过列联表分析以类似的方式进行比较。我们首先描述了这些方法的前提条件和实现方法,然后提供了三个工作示例,最后讨论了该方法的优点、缺陷和局限性。
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引用次数: 50
A 6-month inhalation study to characterize the toxicity, pharmacokinetics, and pharmacodynamics of human insulin inhalation powder (HIIP) in beagle dogs. 一项为期6个月的吸入研究,以表征人胰岛素吸入粉(HIIP)在比格犬体内的毒性、药代动力学和药效学。
Andrew Vick, Ronald Wolff, Alan Koester, Rachel Reams, Daniel R Deaver, Shawn Heidel

The purpose of this study was to characterize the toxicity, pharmacokinetics, and pharmacodynamics of human insulin inhalation powder (HIIP) in beagle dogs when administered daily as an aerosolized dry powder formulation for 26 weeks via head-only inhalation. Conscious beagle dogs were exposed for 15 mins/day to an air control, placebo, maximal placebo (approximately three-fold the placebo dose), or one of three doses of HIIP (mean inhaled doses of 80, 240, or 701 microg/kg/day for the HIIP-low, HIIP-mid, and HIIP-high dose, respectively), The mass median aerodynamic diameters (MMAD) were between 2 and 3 microm and geometric standard deviation (GSD) values were approximately 2 across the groups, which is the ideal size range for favorable lung deposition. All groups were comprised of four dogs/sex, with the air control, HIIP-high, and maximal placebo groups having an additional two dogs/sex as recovery subgroups. Concentrations of serum insulin and glucose were determined from blood samples obtained following the first and last exposure for evaluation of the pharmacokinetics and pharmacodynamics of HIIP. Dose-related exposure (C(max), AUC) to inhaled insulin was observed with rapid absorption and no apparent gender differences or accumulation after repeated inhalation exposures for 26 weeks. The expected pharmacological effect of insulin was observed with dose-related decreases in serum glucose levels following HIIP administration. There were no toxic effects observed including no HIIP or placebo treatment-related effects on mean body weights, absolute body weight changes, clinical observations, food consumption, respiratory function parameters, ophthalmic examinations, electrocardiograms, heart rates, clinical pathology, or urinalysis. Similarly, there were no HIIP or placebo treatment-related effects on pulmonary assessments that included respiratory function parameters, bronchial alveolar lavage assessments, organ weights, or macroscopic and microscopic evaluations, including lung cell proliferation indices. HIIP was considered to have either low or no immunogenic potential in dogs. The no-observed-adverse-effect level (NOAEL) and maximum tolerated dose were the average inhaled dose of 701 microg insulin/kg/day.

本研究的目的是描述人胰岛素吸入粉(HIIP)在beagle犬体内的毒性、药代动力学和药效学,每天以雾化干粉形式通过头部吸入,持续26周。有意识的比格犬每天暴露于空气控制、安慰剂、最大安慰剂(约为安慰剂剂量的三倍)或三种剂量HIIP中的一种(HIIP低剂量、HIIP中剂量和HIIP高剂量分别为80、240或701微克/千克/天),质量中位数空气动力学直径(MMAD)在2至3微米之间,几何标准偏差(GSD)值在2左右。这是有利于肺沉积的理想尺寸范围。所有组由4只狗/性别组成,空气控制组、hiip高组和最大安慰剂组有另外2只狗/性别作为恢复亚组。从首次和最后一次暴露后获得的血液样本中测定血清胰岛素和葡萄糖浓度,以评估HIIP的药代动力学和药效学。吸入胰岛素的剂量相关暴露(C(max), AUC)在26周的重复吸入暴露后迅速吸收,无明显的性别差异或积累。预期的胰岛素药理作用是观察到HIIP给药后血清葡萄糖水平的剂量相关降低。没有观察到毒性作用,包括HIIP或安慰剂治疗对平均体重、绝对体重变化、临床观察、食物消耗、呼吸功能参数、眼科检查、心电图、心率、临床病理或尿液分析的相关影响。同样,HIIP或安慰剂治疗对肺部评估没有影响,包括呼吸功能参数、支气管肺泡灌洗评估、器官重量或宏观和微观评估,包括肺细胞增殖指数。HIIP被认为在犬中具有低或无免疫原性潜能。无观察到的不良反应水平(NOAEL)和最大耐受剂量为平均吸入剂量701微克胰岛素/kg/天。
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引用次数: 13
Computational analyses of a pressurized metered dose inhaler and a new drug-aerosol targeting methodology. 一种加压计量吸入器的计算分析和一种新的药物气雾剂靶向方法。
Clement Kleinstreuer, Huawei Shi, Zhe Zhang

The popular pressurized metered dose inhaler (pMDI), especially for asthma treatment, has undergone various changes in terms of propellant use and valve design. Most significant are the choice of hydrofluoroalkane-134a (HFA-134a) as a new propellant (rather than chlorofluorocarbon, CFC), a smaller exit nozzle diameter and attachment of a spacer in order to reduce ultimately droplet size and spray inhalation speed, both contributing to higher deposition efficiencies and hence better asthma therapy. Although asthma medicine is rather inexpensive, the specter of systemic side effects triggered by inefficient pMDI performance and the increasing use of such devices as well as new targeted drug-aerosol delivery for various lung and other diseases make detailed performance analyses imperative. For the first time, experimentally validated computational fluid-particle dynamics technique has been applied to simulate airflow, droplet spray transport and aerosol deposition in a pMDI attached to a human upper airway model, considering different device propellants, nozzle diameters, and spacer use. The results indicate that the use of HFA (replacing CFC), smaller valve orifices (0.25 mm instead of 0.5 mm) and spacers (ID = 4.2 cm) leads to best performance mainly because of smaller droplets generated, which penetrate more readily into the bronchial airways. Experimentally validated computer simulations predict that 46.6% of the inhaled droplets may reach the lung for an HFA-pMDI and 23.2% for a CFC-pMDI, both with a nozzle-exit diameter of 0.25 mm. Commonly used inhalers are nondirectional, and at best only regional drug-aerosol deposition can be achieved. However, when inhaling expensive and aggressive medicine, or critical lung areas have to be reached, locally targeted drug-aerosol delivery is imperative. For that reason the underlying principle of a future line of "smart inhalers" is introduced. Specifically, by generating a controlled air-particle stream, most of the inhaled drug aerosols reach predetermined lung sites, which are associated with specific diseases and/or treatments. Using the same human upper airway model, experimentally confirmed computer predictions of controlled particle transport from mouth to generation 3 are provided.

常用的加压计量吸入器(pMDI),特别是用于哮喘治疗,在推进剂的使用和阀门设计方面经历了各种变化。最重要的是选择氢氟烷烃-134a (HFA-134a)作为新的推进剂(而不是氟氯化碳),较小的出口喷嘴直径和附加间隔器,以便最终减小液滴大小和喷雾吸入速度,两者都有助于提高沉积效率,从而更好地治疗哮喘。虽然哮喘病药物相当便宜,但由于pMDI性能不佳引发的全身性副作用,以及这类设备越来越多的使用,以及针对各种肺部和其他疾病的新型靶向药物气溶胶输送,使得详细的性能分析势在必行。考虑到不同的推进剂、喷嘴直径和间隔片的使用,实验验证的计算流体-颗粒动力学技术首次被应用于模拟附着在人体上呼吸道模型上的pMDI中的气流、液滴喷雾传输和气溶胶沉积。结果表明,使用HFA(代替CFC),较小的阀口(0.25 mm代替0.5 mm)和间隔器(ID = 4.2 cm)可以获得最佳性能,主要是因为产生的液滴更小,更容易渗透到支气管气道中。经实验验证的计算机模拟预测,HFA-pMDI和CFC-pMDI的吸入液滴可能分别有46.6%和23.2%到达肺部,两者的喷嘴出口直径均为0.25 mm。常用的吸入器是无方向性的,最多只能实现局部药物气溶胶沉积。然而,当吸入昂贵且积极的药物时,或者必须到达关键的肺部区域时,局部靶向药物气溶胶递送是必不可少的。因此,引入了未来“智能吸入器”系列的基本原理。具体来说,通过产生受控的空气颗粒流,大多数吸入的药物气溶胶到达预定的肺部部位,这些部位与特定疾病和/或治疗有关。使用相同的人类上呼吸道模型,实验证实了从口腔到第3代的受控粒子传输的计算机预测。
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引用次数: 99
Formoterol turbuhaler is as effective as salbutamol diskus in relieving adenosine-induced bronchoconstriction in children. 福莫特罗在缓解儿童腺苷性支气管收缩方面与沙丁胺醇diskus同样有效。
Israel Amirav, Renata Yacobov, Anthony S Luder
Salbutamol diskus (SD) and formoterol turbuhaler (FT) are both fast-acting beta(2) agonists delivery systems used to relieve bronchoconstriction, such as that which accompanies acute exacerbations of asthma. Although SD (which is used only on an as-needed basis) is flow independent, the FT (currently recommended for regular therapy) requires a forceful deep inspiration. Thus, the efficacy of FT in children with bronchoconstriction may be inferior to that of SD. We have studied the bronchodilatation response induced by FT after a standard adenosine-5-monophosphate (AMP) bronchial challenge, and compared it to that induced by SD, and placebo. Seventeen children (mean age +/- SD 10.3 +/- 1.7 y) with asthma underwent three AMP challenges, each time followed by inhalation of either placebo, SD (200 mug) or FT (9 mug), in random order. Patterns of bronchodilatation (forced expiratory volume in 1 second recovery) to 90% of baseline levels were compared. Both SD and FT were significantly better than placebo. FT was slightly better than SD, but this difference was not statistically significant. FT and SD are both effective bronchodilators and may be of comparable efficiency during acute bronchoconstriction in young children with asthma.
沙丁胺醇diskus (SD)和福莫特罗turbuhaler (FT)都是用于缓解支气管收缩的速效β(2)激动剂递送系统,如哮喘急性发作时的支气管收缩。尽管SD(仅在需要时使用)与血流无关,但FT(目前推荐用于常规治疗)需要强有力的深层灵感。因此,FT在支气管收缩患儿中的疗效可能不如SD。我们研究了标准腺苷-5-单磷酸腺苷(AMP)支气管刺激后FT诱导的支气管扩张反应,并将其与SD和安慰剂诱导的支气管扩张反应进行了比较。17名患有哮喘的儿童(平均年龄+/- SD 10.3 +/- 1.7岁)接受了三次AMP挑战,每次都随机吸入安慰剂、SD(200杯)或FT(9杯)。将支气管扩张模式(1秒恢复时用力呼气量)与基线水平的90%进行比较。SD和FT均显著优于安慰剂。FT略好于SD,但差异无统计学意义。FT和SD都是有效的支气管扩张剂,在幼儿哮喘急性支气管收缩时可能具有相当的效果。
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引用次数: 11
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Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine
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