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研究生:張光男
研究生(外文):Kuang-Nan Chang
論文名稱:局部微粒肺部沉積之研究
論文名稱(外文):Study on the regional lung deposition
指導教授:陳志傑陳志傑引用關係
口試委員:林文印蔡春進吳惠東許德仁陳友剛
口試日期:2012-07-17
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:91
中文關鍵詞:帶電微粒肺部沉積鏡像力
外文關鍵詞:lung depositioncharge particleimage fore
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呼吸是微粒進入人體呼吸道的主要途徑,微粒進入人體呼吸道後,會因為其沉積在不同的區域有不一樣的健康效應,因此評估微粒進入人體後會沉積在哪個區塊是很重要的,例如,較大的微粒會停留在上呼吸道造成刺激而引起打噴嚏,但較小的微粒則有可能進入到呼吸道深層,如肺泡區,進而引起相關的疾病,微粒的沉積受到其粒徑大小、帶電量或是密度而影響,雖然有相關的研究探討微粒或是帶電微粒在人體內的沉積,但是這些研究大多數是外國人的資料而且在研究上有其限制,例如研究需要較高的微粒濃度或是實驗過程相當的耗時。藉由吸入器來投遞要物的方式已經廣泛的在醫界被使用,主要的原因為吸入器的使用方便,而且藥物可以較快速的被人體呼吸系統吸收,但在這方面的研究往往都只探討到藥物的劑量,卻忽略了如何讓藥物輸送到標的組織才是最終的目標,並且這些藥物經由吸入器的高速射出因為撞擊的關係,往往會帶有許多的靜電荷,因此有必要對微粒的帶電與沉積率做一些探討。

本研究的主要目的為建立一個快速量測局部微粒肺部沉積的系統,探討國人的局部肺部沉積資料與國外的相關資料是否有差異,再來研究將探討微粒帶電在人體肺部沉積的影響,最後本研究將利用不同管徑大小的金屬管,來探討帶電微粒通過金屬管受到鏡像力的影響,並利用現有的經驗式來驗證。

局部肺部沉積研究的量測系統包含了嘴部套管、呼吸流量計以及微粒計數器,嘴部套管會與呼吸流量計串聯以便即時的量測呼吸流量,為了找出有最快反應時間的儀器,研究中一共比較了三台不同型號的凝結核微粒計數計,凝結核微粒計數搭配PC-LabCard擷取卡其採樣頻率可高達100 Hz,研究中一共招募了12位健康的受測者依照著標準的呼吸條件來進行測試。帶電微粒方面的實驗則是利用改良式的振動噴口氣膠產生器產生1 um的帶電微粒,以1 um的微粒來看最高帶電量可以高達24000,實驗中也用了不同管徑及管長的金屬管以及控制不同的表面風速來探討鏡像力對微粒沉積的影響,微粒的粒徑分布主要用氣動粒徑分徑儀來量測,而微粒的總帶電量則是利用電流計來量測,利用量測到的微粒濃度以及微粒的總帶電量,便可計算出微粒的平均帶電量,實驗結果也會利用現有的經驗式來驗證。

研究中建立了一套可以快速量測局部微粒肺部沉積的系統,其採樣的構造主要由最大管徑的pneumotachograph呼吸流量計組成,因為其具有最低的阻抗,微粒的計數計則是選用反應時間最快的CPC 3025。初步的台灣人局部肺部沉積資料顯示,國人的肺部沉積資料與西方人用Bolus所量測出來的資料整體趨勢上來說非常的接近,目前的方法與過去所使用的Bolus比較起來,目前的方法具有相當大的便利性及省時。在帶電微粒方面,1.4 um微粒在人體的總沉積率隨著微粒的帶電量由不帶電提高到7000個基本電荷,總沉率由15%提高到57%。在金屬管方面的研究,帶電微粒的沉積量會隨著微粒的帶電量與管長增加而增加,主要的原因為高帶電量會提升鏡像力的影響,而在相同風速下管長增加會影響到微粒在管道內的時間也有助於微粒的沉積,另外在相同條件下,平均風速越低微粒的沉積量越高,主要的因素也是來自於微粒在管道內的時間增長增加沉積積率,其他條件不變下,管道直徑越小越有利於帶電微粒的沉積。


Inhalation is the most important route of entry for aerosol particles. Further, it is necessary to determine the specific region of particle deposition in the respiratory tract for properly evaluating human health risk. For example, a larger particle such as pollen may deposit in the upper airway and merely cause a sneeze, while smaller particles could deposit in the alveoli and result in serious diseases. The particle deposition on the respiratory system depends on the particle size, particle charge condition, and particle density. However, the currently available lung deposition data are mostly on Caucasians. Lung deposition data on Taiwanese are very limited. Inhaled drugs are becoming popular because they are quick and non-invasive. The drug particles are inhaled directly into the lung and systemically absorbed. However, most inhaler studies only care about the drug dosage, they do not investigate the relations between the particle properties and lung deposition rates especially the particle charge conditions.

Therefore, the aim of the first part was to develop an experimental system for rapid measurement of regional lung deposition and to characterize the regional lung deposition in Taiwanese. The second part of this study was to investigate the charged particle effects on lung deposition. The third part of this study was to investigate the effect of particle charge on the particle deposition efficiency through metallic tubes.

Overall, the sampling train consisted of a mouthpiece, a flow meter, and a particle counter. The mouthpiece was attached to a Fleisch pneumotachograph. Several TSI condensation particle counters (CPCs) and PC-LabCard and a personal computer were employed to measure the concentrations of test particles at 100 Hz. Twelve subjects were recruited and asked to follow the designated breathing patterns. In order to extend to higher aerosol charge, a TSI vibrating orifice monodisperse aerosol generator was modified to generate 1-um DEHS aerosols with charge up to 24,000 elementary units. Metallic tubes were employed to exclude the effect of Coulombic force. Tube diameter, tube length, and average velocity in tubes were among the major operating parameters. Aerosol charge was monitored using a TSI electrometer, while a TSI aerodynamic particle sizer was utilized to measure both aerosol concentrations and size distributions upstream and downstream of the tubes. In addition to the experimental work, a closed-form theoretical model, showing the deposition efficiency as a function of particle charge, was validated by the experimental data produced.

A rapid method for assessing regional lung deposition was employed in the study. The sampling train was equipped with the largest pneumotachograph to provide the lowest air resistance. Among the aerosol instrumented tested, CPC 3025A appeared to have the fastest response time and was used in the present study. The regional lung deposition data obtained in this work showed a good agreement with previous studies based on the bolus technique, indicating the difference in lung deposition between Taiwanese and Caucasians might be negligible. The local deposition efficiency increased with penetration volume. This increased trend was particularly prominent in the deep lung, which was likely due to the dilution effect caused by the relatively clean air in the functional residual capacity. The results showed the total lung deposition fraction obviously increased with greater particle charge. The total lung deposition fraction of 1.4 um particles was enhanced from 15% to about 57 % when the particle charge increased from 0 to about 7000 elementary units of charge. Also, the aerosol deposition efficiency increased with increasing aerosol charge and tube length, due to stronger image force and longer retention time, respectively. The deposition efficiency decreased with increasing average velocity because of shorter retention time. Under the same average velocity, the deposition loss decreased with increasing tube diameter. This is because the fraction of aerosols near the inner wall was higher for small diameter tube than that for large diameter tube.


口試委員審定書 i
致謝 iii
摘要 iv
Abstract vi
目錄 ix
表目錄 xi
圖目錄 xii
一、研究緣起與目的 1
二、文獻回顧 3
2-1 肺部沉積的量測方式 3
2-2 肺部結構 5
2-3 呼吸系統沉積機制 5
2-4 微粒的帶電機制 6
2-5 吸入器(Breathing inhaler) 8
2-6 帶電微粒的沉積機制 9
2-7 帶電微粒的沉積模式 10
三、實驗材料與方法 11
3-1 快速量測系統的建立 11
3-2 真人測試 13
3-3 帶電微粒的產生 15
3-3-1 擴散充電 15
3-3-2 誘發導電 (Induction charging) 16
3-4 帶電微粒對肺部沉積的影響 16
3-5 帶電微粒通過金屬管的影響 17
3-6 實驗儀器 18
四、結果與討論 20
4-1 快速量測系統建立 20
4-2 真人測試數據 22
4-3 帶電微粒在人體的沉積 25
4-4 帶電微粒受鏡像力影響之沉積 26
五、結論 29
六、參考文獻 32
七、附錄 63
7-1 A Sampling Train for Rapid Measurement of Regional Lung Deposition 63
7-2 Experimental Measurements of regional lung deposition in Taiwanese 75
7-3 Penetration of Charged Particles through Metallic Tubes 84



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Ali, M., Reddy, R. N. and Mazumder, M. K. (2008). Electrostatic Charge Effect on Respirable Aerosol Particle Deposition in a Cadaver Based Throat Cast Replica. J. Electrostatics 66:401-406.
Anderson, P. J., Hardy, K. G., Gann, L. P., Cole, R. and Hiller, F. C. (1994). Detection of Small Airway Dysfunction in Asymptomatic Smokers Using Aerosol Bolus Behavior. Am. J. Respir. Crit. Care Med. 150:995-1001.
Asgharian, B., Price, O. T. and Hofmann, W. (2006). Prediction of Particle Deposition in the Human Lung Using Realistic Models of Lung Ventilation. J. Aerosol Sci. 37:1209-1221.
Blanchard, J. D. and Willeke, K. (1983). An Inhalation System for Characterizing Total Lung Deposition of Ultrafine Particles. Am. Ind. Hyg. Assoc. J. 44:846 - 856.
Brand, P., Friemel, I., Meyer, T., Schulz, H., Heyder, J. and Haubetainger, K. (2000). Total Deposition of Therapeutic Particles During Spontaneous and Controlled Inhalations. J. Pharm. Sci. 89:724-731.
Brand, P., Haussinger, K., Meyer, T., Scheuch, G., Schulz, H., Selzer, T. and Heyder, J. (1999). Intrapulmonary Distribution of Deposited Particles. J. Aerosol Med. 12:275-284.
Brand, P., Rieger, C., Schulz, H., Beinert, T. and Heyder, J. (1997). Aerosol Bolus Dispersion in Healthy Subjects. Eur. Respir. J. 10:460-467.
Brand, P., Tuch, T., Manuwald, O., Bischof, W., Heinrich, J., Wichmann, H. E., Beinert, T. and Heyder, J. (1994). Detection of Early Lung Impairment with Aerosol Bolus Dispersion. Eur. Respir. J. 7:1830-1838.
Chan, T. L. and Lippmann, M. (1980). Experimental Measurements and Empirical Modelling of the Regional Deposition of Inhaled Particles in Humans. Am. Ind. Hyg. Assoc. J. 41:399-409.
Cheng, Y. S., Yeh, H. C., Guilmette, R. A., Simpson, S. Q., Cheng, K. H. and Swift, D. L. (1996). Nasal Deposition of Ultrafine Particles in Human Volunteers and Its Relationship to Airway Geometry. Aerosol Sci. Technol. 25:pp. 274-291 ; PL:.
Grgic, B., Martin, A. R. and Finlay, W. H. (2006). The Effect of Unsteady Flow Rate Increase on in Vitro Mouth-Throat Deposition of Inhaled Boluses. J. Aerosol Sci. 37:1222-1233.
Hashish, A. H., Fleming, J. S., Conway, J., Halson, P., Moore, E., Williams, T. J., Bailey, A. G., Nassim, M. and Holgate, S. T. (1998). Lung Deposition of Particles by Airway Generation in Healthy Subjects: Three-Dimensional Radionuclide Imaging and Numerical Model Prediction. J. Aerosol Sci. 29:205-215.
Heyder, J., Armbruster, L., Gebhart, J., Grein, E. and Stahlhofen, W. (1975). Total Deposition of Aerosol Particles in the Human Respiratory Tract for Nose and Mouth Breathing. J. Aerosol Sci. 6:311-328.
Heyder, J., Blanchard, J. D., Feldman, H. A. and Brain, J. D. (1988). Convective Mixing in Human Respiratory Tract: Estimates with Aerosol Boli. J. Appl. Physiol. 64:1273-1278.
Heyder, J., Gebhart, J., Heigwer, G., Roth, C. and Stahlhofen, W. (1973). Experimental Studies of the Total Deposition of Aerosol Particles in the Human Respiratory Tract. J. Aerosol Sci. 4:191-208.
Heyder, J., Gebhart, J., Rudolf, G. and Stahlhofen, W. (1980). Physical Factors Determining Particle Deposition in the Human Respiratory Tract. J. Aerosol Sci. 11:505-515.
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Ali, M., Mazumder, M. K. & Martonen, T. B. (2009). Measurements of Electrodynamic Effects on the Deposition of Mdi and Dpi Aerosols in a Replica Cast of Human Oral-Pharyngeal-Laryngeal Airways. Journal of Aerosol Medicine and Pulmonary Drug Delivery 22:35-44.
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