Study On The Regularity Of Inhalable Particles Deposition In The Pulmonary Acinus And The Effect Of Drug Aerosol Inhalation

In recent years,the atmospheric environment is worsening,public health emergencies occur frequently,and the threat of bioterrorism has appeared,such as the inhalation of virus aerosol particles into the body through the respiratory system,the mucous membrane of the respiratory tract and lung diffusion,deposition,replication,attack,which have aroused widespread concern and urgent solution in the whole society,because they pose the serious harm to human health and life safety and bring great influence to the economic,social and public safety.Epidemiological studies have shown that inhalable particles are closely related to increase respiratory symptoms,decrease lung function,mortality of lung cancer and increase incidence of cardiovascular and cerebrovascular diseases.Studies have shown that fine particles with particle size below 2.5 μm could cause asthma,bronchitis and cardiovascular diseases after being breathed into the bronchioles and alveolar areas,which has produced great harm to human health.Due to complex and relative samller size of alveolar structure,it is extremly difficult to set up realistic computer or entity model.Current research on the pulmonary acinus are more concentrated in the computer model or single alveolar experimental model analysis.However,the large scale simplification of the model leads to the lack of reliability on the simulation results.In addition,previous studies have rarely considered the biomechanical and morphological changes under the condition of pulmonary alveolar pathology,which can neither fully reflect the respiratory physiological characteristics of real pulmonary alveoli,nor further reveal the effects of the formation and development of diseases concerning inhalable particles deposition.So it is essential to establish the experimental model and systematically study the mechanism of inhalable particles deposition affected by various respiratory,environmental condition and the of shape pulmonary acinus in the pulmonary acinus.Therefore,based on the previous study,this thesis aims to construct the pulmonary acinus to simulate with human physiological and pathological characteristics,and systematically study the deposition regularity of inhalable particles at different particle size,breathing patterns,relative humidity and pathological conditions for the purpose of optimizing the atomization inhalation conditions of commonly drugs used in the clinical.The main work and research results are as follows:(1)Total deposition rates of different size of inhalable particles in the lung lesions were calculated and analyzed under the condition of different tidal volume,lung volume,respiratory rate,chronic obstructive pulmonary disease(COPD)through the construction of the deposition probability theory calculation method based on three mechanism--Weibel A analysis model of inhalable particles in gravity deposition,inertial impaction deposition and diffusion.Based on the calculation method established in this paper,the results show that the total lung deposition rate of particulates corresponding with the experimental data can be calculated.(2)According to widely recognized data concerning pulmonary anatomic structure,size and biomechanical,the experimental device is built for various particle sizes of inhalable particles deposition in the bronchioles and alveoli under the different conditions of breathing patterns,humidity and alveolar morphology.The device innovatively uses flow cytometry to count the particles deposited on the model.The similarity between the model and the real human pulmonary acinus is ensured through theoretical analysis and calculation of aerodynamic similarity and sedimentary similarity of the experimental model.(3)The rules of deposition rate of different diameter particles in bronchioles and pulmonary acinus area have been studied by changing the respiratory functional residual capacity in multi-cluster experimental pulmonary acinus model.The deposition rates of particulate matter in alveolar alveoli are consistent with previous computer simulation results.Inertial collision deposition deposition and diffusion deposition play a leading role.When these two deposition methods achieve equilibrium,particles reach the maximum deposition rate,that is,the particle deposition rate of 1μm diameter has the highest deposition rate.10% functional residual capacity breathing mode leads to the highest particles deposition retaining in the deposition zone of pulmonary among three kinds of functional residual capacity modes.Functional residual capacity of 50% is the lowest.The deposition rate under two conditions doubles more.But in different functional residual capacity mode,law of particle size on the deposition rate has not changed,which demonstrates that even if the residual rate has reached 10%,the air flow within the alveoli is still a steady laminar flow instead of the turbulent flow.(4)The particle deposition laws in the alveoli of healthy alveolar,atrophic and dilated lesions were investigated experimentally in the paper.The morphology of the alveoli has a significant influence on the deposition of particles.The deposition rate of particles increased after alveolar atrophy,and the deposition rate of adjacent alveolar cells slightly increased,which explained the clinical cause of chronic atrophy of pulmonary atrophy.The deposition rate of particles decreased significantly under the condition of alveolar dilatation,and the deposition was concentrated in the upper level of pulmonary acinus and bronchus,which has been consistented with the theoretical analysis of this paper.(5)Through establishing size changing experimental models of hygroscopic NaCl monodisperse aerosol in different relative humidity and that of total deposition of NaCl inhalable particles in human lung alveolar region,the growth regularity of the NaCl monodisperse aerosol hygroscopic and total deposition rate has been analyzed in different relative humidity.The results have showed that the particle size of NaCl aerosol would change significantly under different relative humidity.As the relative humidity has being increased,the moisture absorption of the particles has grown markedly.When the relative humidity has reached 100%,the moisture absorption has increased to the maximum.The hygroscopic growth of NaCl aerosol also significantly affects the deposition rate in the human pulmonary acinar area,but its essence is the change of particle size.(6)In the specially designed air tightness test cabin,using 6 channel laser particle counter,three commonly used methods were tested for the aerosol size distributions,such as quantitative atomization inhalation,dry powder inhalation and solution inhalation,and relative drug atomization inhalation experiment.Meanwhile the influence of relative humidity was taken into consideration.The experimental results show that there is a significant difference in the particle size distribution of the drugs under different drugs and atomization methods.The particle size of the drug produced by quantitative atomization inhalation drugs is concentrated in the range of 2 μm to 5 μm,and the proportion of 5 μm is the largest.There was a significant difference in the particle size distribution of the aerosol inhalation of dry powder,and the randomness of the difference was larger.The particle size of the same dry powder in different environmental relative humidity is also significantly different.The larger the relative humidity is,the larger the proportion of large particle aerosol.Drug aerosol size distribution generated by ultrasonic atomization and compressed air atomization inhalation methods concentrated in the 1μm to 2μm range.The proportion of the total aerosol accounts for more than 80%,and that affected by drug concentration is not significant.In summary,the deposition regularity of inhalable particles in human alveolar area is studied by terms of theoretical analysis and experimental modeling in this paper.The theoretical analysis and computer simulation results of particle deposition in pulmonary acinus in the past are further verified.Its scientific significance lies in providing a directly vitro experimental research method on particles deposition in pulmonary acinus at disease and different respiratory pattern.It also provides a necessary means to optimize treatment way for drug inhalation atomization of emphysema and other diseases.The results concerning moisture absorption properties,deposition rule of hygroscopic particles and medicine and atomization inhalation method that is commonly used in clinical have great practical value to verify the inhalation effect,to develop new formulations and to optimize clinical treatment of the drug.