【作者】 赵秀国；

【导师】 徐新喜；

【作者基本信息】 中国人民解放军军事医学科学院 ， 军事预防医学， 2008， 博士

【摘要】 空气污染物气溶胶对人类健康产生严重的威胁,人体通过呼吸道吸入有毒气溶胶会引发哮喘、肺气肿和支气管炎等呼吸道疾病,SARS和禽流感等疾病的爆发同样是病毒以生物气溶胶的形式通过呼吸道传播而引发感染;针对各种呼吸道疾病,气溶胶吸入治疗在呼吸道疾病的防治中表现出了明显的优势。人体上呼吸道内气流流场、气溶胶性质、呼吸模式及其几何特性决定了有毒气溶胶或吸入药物气溶胶的沉积位置和局部浓度,进而决定有毒气溶胶的危害程度或药物气溶胶的治疗效果。因此,研究人体呼吸道内的气流运动特性,探讨有毒气溶胶或药物气溶胶在人体呼吸道内的沉积规律,对于认识有毒气溶胶对人体的危害、进行剂量健康效应的评价以及继续深入探索有毒气溶胶的致病机理具有重要的实际意义,对于提高药物气溶胶的治疗效果具有重要的指导意义。本文在总结国内外研究工作的基础上,借鉴ARLA(Aerosol Research Laboratory of Alberta)的理想口-喉模型和Weible模型的气管-支气管模型,建立了具有口腔-咽-喉-气管-前三级支气管的完整的人体上呼吸道模型。运用CFD数值仿真和试验研究相结合的方法对人体上呼吸道内的气流运动特性和气溶胶运动沉积规律进行了全面、系统的研究。研究结果表明:稳态呼吸模式下,气流在咽部外壁、气管外壁发生分离现象,气流在气管内壁形成局部高速区域,容易造成较多的气溶胶沉积;在气管内的三个截面内分别形成两个对称的二次涡流运动,二次涡流运动使得气管内壁所受到的流动剪应力增大,而外壁面剪应力减小;同时轴向速度在气管内壁引起高剪应力分布,而外壁的剪应力较小,二次涡流容易造成气溶胶在气管内壁沉积较多;进入到支气管内的气流在分叉处发生分离,并且在下游支气管的内壁区域形成新的边界层,靠近支气管内壁速度较高,并且在支气管边界层的外缘速度达到最大值,靠近支气管外壁速度较低。循环吸气模式下,吸气加速阶段咽部、喉部和声门下游气管内壁形成局部高速区,容易造成气溶胶因惯性碰撞而沉积;在咽部外壁、声门下游气管上部外壁气流逐渐发生分离,形成分离区,使得气溶胶在这些部位随气流环流循环运动,滞留时间增加,容易造成一部分气溶胶在咽部外壁和气管外壁的沉积;支气管平面内形成抛物线型的速度分布,气流主流逐渐偏离支气管外壁,流向内壁,容易造成气溶胶在支气管内壁沉积较多;支气管内各个截面上形成的二次涡流运动的强度逐渐增强,二次涡流运动会造成气溶胶在内壁的沉积几率增加。吸气减速阶段,咽部外壁的分离区逐渐向内壁方向扩大,同时在咽部的内壁也发生气流分离现象,气管外壁的分离区向气管内壁方向扩大,同时向气管下游延伸;在第一级支气管外壁区产生气流分离现象,形成较小的分离区,在第二级和第三级支气管内没有发生类似现象。循环呼气模式下,呼气加速阶段与吸气加速阶段不同,气管平面内气流流速分布比较均匀;气管内逐渐形成四个二次涡流运动,气流在支气管内经过多级分支的效果是使速度分布均匀化,特别是在同级两个支气管轴线共处的平面内的速度分布在经过几级汇合后,轴线处的峰值分布现象会消失而变得均匀;在支气管内呈现典型的抛物线速度分布形式,支气管内的二次气流运动经历了从两个涡流到四个涡流的运动变化过程。呼气减速阶段,呼气终了时刻,在第一级和第二级支气管的内壁均出现了气流分离现象,在内壁形成分离区。循环呼吸模式下,咽部、喉部、气管以及支气管内高轴向速度区和二次涡流运动均是在呼吸过程中逐渐出现的,只是间歇性地产生,所以由此而引起的气道壁面的气流剪应力集中,形成的高剪应力区也是间歇性的,只在整个周期的部分时间出现。壁面受到的剪应力周期性地改变方向,引起壁面劳损和组织损伤的可能性增大,同时在这些部位容易造成气溶胶的沉积,还可能会引起各种呼吸道疾病。呼气阶段支气管内的气流运动、气流剪应力的分布和气溶胶的运动形式比吸气阶段更为复杂。采用激光快速成型技术(Stereo-Lithography,SL)制作了人体上呼吸道的试验模型,应用粒子图像速度仪(Particle Image Velocimetry,PIV)对人体上呼吸道内的稳态气流运动特性进行了试验研究,分析了在低强度呼吸条件下人体上呼吸道内的气流运动特性。研究结果表明,数值仿真结果与试验测量结果基本一致,证明了数值仿真方法的准确性和合理性。利用拉格朗日方法对气溶胶在上呼吸道内的运动进行仿真计算,分析了不同呼吸模式下气溶胶的沉积特点。惯性碰撞对于微尺度气溶胶沉积而言是主要的沉积机制,惯性参数是衡量碰撞作用造成颗粒沉积的一个重要的参数,人体上呼吸道内不同部位气溶胶沉积率随惯性参数的增加而增加;而湍流扩散、二次气流运动和环流气流运动对气溶胶在人体上呼吸道内的沉积同样具有重要的影响,人体的呼吸流量和气溶胶性质对气溶胶在上呼吸道内的沉积模式影响较小;惯性碰撞和湍流扩散的影响致使在喉部气溶胶沉积最多,气管中气溶胶的沉积效率要高于支气管中的气溶胶沉积效率。人体循环吸气模式下,气溶胶在人体上呼吸道内的沉积率要高于稳态吸气情况下的气溶胶的沉积率;循环吸气模式下的气溶胶沉积率远大于循环呼气模式下的气溶胶沉积率。建立了气溶胶在人体上呼吸道内沉积的试验台,对气溶胶在上呼吸道内的沉积进行了试验研究。数值仿真结果与试验结果基本一致,平均误差为11%,沉积变化趋势吻合较好。人体上呼吸道内气溶胶沉积的数值仿真方法,能够较好地预测气溶胶在上呼吸道内的沉积模式以及不同部位的沉积率,是我们获得上呼吸道内有毒气溶胶或药物气溶胶在不同部位沉积信息的一种有效的方法。更多还原

【Abstract】 Human health is threatened by air pollution aerosols and inhaled toxic aerosols through upper respiratory tract can result in respiratory diseases such as asthma, emphysema and bronchitis. The diseases, for example SARS and bird influenza, broke out because virus transmitted in the form of biological aerosols by human upper respiratory tract caused infection. In allusion to all kinds of respiratory diseases, inhaled pharmaceutical aerosols exhibit obvious advantage of preventing and treating the respiratory diseases. The deposition location and local concentration of toxic aerosols or drug aerosols, as well as the harmful degree of the toxic aerosols and the therapeutic efficiencies of drug aerosols are greatly determined by airflow field, aerosol properties, breathing patterns and geometric airway characteristics. Therefore, airflow movement characteristics in the upper respiratory tract were investigated and the deposition rule of toxic aerosols or drug aerosols in the human upper respiratory tract were discussed, which not only have significance of understanding the harm resulting from toxic aerosols, evaluating dosimetry-and-health-effect and exploring the mechanism for the diseases generation being attributed to toxic aerosols, but also play a very important role in improving therapeutic efficiencies of drug aerosols.Based on the present research, an entire human upper respiratory tract model with mouth, pharynx, larynx, trachea and triple bifurcation, combining the idealized mouth-throat model of ARLA(Aerosol Research Laboratory of Alberta) and the trachea-triple bifurcation of Weible’s model, was presented. The methods of integrating numerical simulation of CFD with experimental research were used to study airflow movement characteristics and deposition rule of aerosols. The main conclusions of the present work are summarized as follows:The phenomenon of airflow separation appears near the outer wall of the pharynx and the trachea in the steady respiratory patterns. The high velocity zone is created near the inner wall of the trachea, which may result in the aerosol deposition. Two symmetry rotating secondary vortices are generated in the cross sections of the trachea, which lead to the increase of the shearing strength acting on the inner wall of the trachea and the decrease of the shearing strength acting on the outer wall of the trachea, while the axial velocity cause the distribution of the high shearing strength on the inner wall of the trachea, on the contrary, the shearing strength acting on the outer wall of the trachea is low. Secondary vortices lead to the aerosol deposition on the inside wall of the trachea. The airflow splits at the divider and a new boundary layer is generated at the inner wall of the downstream bifurcation with the high velocity near the inner wall of the trachea, the maximum velocity at the exterior of the boundary layer and low velocity near the outer wall of the trachea.The high velocity zone is created in pharynx, larynx and upper part of the trachea downstream of the glottis during the accelerating inhalation phase in the cyclic inhalation pattern, which may induce aerosol deposition due to inertial impaction. The airflow separates gradually near the outer wall of the pharynx and near the outer wall for the upper part of the trachea downstream of the glottis with the features of the separation zone appearing, which result in aerosol circulatory movement following the recirculation airflow in separation zones and the increase of detention time, ultimately lead to a few aerosol deposition on the outside wall of the pharynx and on the outside wall of the upper part of the trachea downstream of the glottis. During the accelerating inhalation phase, the parabolic shape velocity profiles appear in the middle plane of the bifurcation. The mainstream deflecting from the outer wall of the bifurcation flows into the inner wall of the bifurcation, which result in aerosol deposition easily on the inside wall of the bifurcation. The secondary vortices strength is enhanced gradually in the cross section of the bifurcation, which cause the increase of the probability of aerosol deposition on the inside wall of the bifurcation. The separation zone coming into being near the outer wall of the larynx extends to the inner wall of trachea and the phenomenon for airflow separation is presented near the inner wall of the pharynx at the same time during the accelerating inhalation phase. The separation zone near the outer wall of the trachea extends to the inner wall of the trachea and downstream of the trachea. The phenomenon for airflow separation comes into being near the inner wall of the first bifurcation and a small separation zone appears. No similar phenomenon is observed at the second and third bifurcation.Unlike the accelerating inhalation phase, the airflow velocity profiles in the middle plane of the trachea are uniform during the accelerating exhalation phase. Four secondary vortices are generated gradually in the trachea. The airflow flowing through the bifurcations make the velocity distribute uniformly, which especially make the maximum velocity around the axis disappear and the velocity profiles become uniform in the middle plane of the bifurcation. The typical parabolic velocity profiles appear in the middle plane of the bifurcation. The secondary flows in the bifurcation experience the change from two vortices to four vortices. During the decelerating inhalation phase, the airflow separation phenomenon is exhibited near the inner wall of the first and second bifurcation, finally the separation zone forms near the inner wall.The high axial velocity zone and secondary flow appear gradually in the pharynx, larynx, trachea and triple bifurcation, i.e., they are generated intermittently in the cyclic respiratory pattern. Therefore, the high shearing strength zone caused by the convergence of the airflow shearing strength acting on the airways wall form intermittently, only appear at the part time in the period. The direction of the shearing strength acting on the wall vary periodically, which not only result in the increase of the probability of the wall strain and tissue injury, but also lead to aerosol deposition easily in these areas at the same time, eventually may induce all kinds of respiratory diseases. The airflow movement, airflow shearing strength distribution and aerosol movement in the bifurcation during the exhalation phase are more complex than the inhalation phase.A replica of the human upper respiratory tract for experiment was constructed using stereolithography(SL). The experiment research was performed with the Particle Image Velocimetry(PIV) technique and inspiration flows were examined under steady flow conditions. The airflow movement characteristics in the human upper respiratory tract in the conditions of the low intensive respiratory patterns were discussed. The results show that the numerical simulation data are in reasonable agreement with experimental measurements, which verifies that the numerical simulation methods are accurate and reasonable.The Lagrangian method computed the trajectory of each aerosol in the human upper respiratory tract and the deposition characteristics of aerosols were investigated. Inertial impaction is the main mechanism of deposition for micro aerosols and inertial impaction parameter is an important parameter of evaluating particle deposition due to the inertial impaction. The DE(deposition efficiency) of aerosols in different zones of the upper respiratory tract increase with the increasing of inertial parameter, while turbulent dispersion, secondary flows and recirculation flows also influence aerosol deposition in the upper respiratory tract. The aerosol deposition patterns are little affected by the respiratory flow and aerosol properties. The high DE occurs in the larynx area due to the inertial impaction and turbulent dispersion. The DE is higher in trachea than in bifurcation, higher in cyclic inhalation pattern than in steady inhalation pattern and higher in cyclic inhalation pattern than in cyclic exhalation pattern.The test-bed for measuring aerosol deposition in upper respiratory tract was set up and the experiment for aerosol deposition was performed. The computed results agreed well with the experimental results. The average error is 11%. The numerical simulation method for aerosol deposition in the human upper respiratory tract can predict aerosol deposition patterns and the DE in different locations, and it is also an effective way of obtaining the deposition information for toxic aerosols or inhaled pharmaceutical aerosols.更多还原