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気管前庭気道モデルにおける乾燥粉末吸入器のエアロゾル沈着。in vitroデータを用いたCFD予測の検証
Dry powder inhaler aerosol deposition in a model of tracheobronchial airways: Validating CFD predictions with in vitro data.
PMID: 32663586 DOI: 10.1016/j.ijpharm.2020.119599.
抄録
肺への効果的な薬物送達は，世界中で数百万人が罹患している肺疾患の管理に重要な役割を果たしています．本研究の主な目的は，ヒトの気管気管支気道の現実的なモデルを用いて，気流構造，および吸入流量の違いによるミクロンサイズの粒子の輸送と沈着を研究することである．気道モデルは、健康な48歳女性のCT画像に基づいて開発され、第4世代までの胸腔外気道、気管、気管支気道を含む。吸入粒子の輸送と沈着を予測するために計算流体力学（CFD）シミュレーションを行い、その結果を我々の以前のin vitro実験と比較した。気流構造は、乱流の発生、逆流とその後の渦の形成、喉頭ジェットが気流と沈着パターンの形成に重要な現象であることが判明した胸腔外領域の速度等高線と流線を通して研究された。沈着データは、インパクションパラメータとストークス数に対する沈着効率(DE)と沈着率(DF)によって示された。いずれの吸入流量においても、沈着率が最も高い値を示したのは、それぞれ口中(MT)、気管前木(TB)、気管(Tra)であった(60L/min時：MT=6.7%, TB=5.3%, Tra=1.9%)。数値沈着データは、ほとんどの気道領域で実験沈着データと良好な一致を示した（例えば、気管気門領域での沈着率の差は10％以下であった）。気道領域のすべてにおいて吸入流量を増加させると、粒子の慣性および乱流レベルの増加に起因する沈着率の上昇傾向が見られた。さらに，胸腔外，気管，気管前木を含むすべての部位で吸入流量の増加に伴う粒子沈着量の増加が見られ，慣性力の増加により慣性圧迫が支配的な沈着メカニズムであることが示唆された．結論として，検証されたCFDモデルは，市販の吸入器のエアロゾル沈着に関するこれまでの実験的調査の限界をカバーする機会を提供し，さらなる研究のための効率的な方法となった．
Effective drug delivery into the lungs plays an important role in management of pulmonary diseases that affect millions all around the world. The main objective of this investigation is to study airflow structure, as well as transport and deposition of micron-size particles at different inhalation flow rates in a realistic model of human tracheobronchial airways. The airway model was developed based on computed tomography (CT) images of a healthy 48-years-old female, which includes extrathoracic, trachea, and bronchial airways up to fourth generations. Computational fluid dynamics (CFD) simulations were performed to predict transport and deposition of inhaled particles and the results were compared to our previous in vitro experiments. Airflow structure was studied through velocity contours and streamlines in the extrathoracic region, where the onset of turbulence, reverse flow and subsequently vortex formation, and laryngeal jet are found to be critical phenomenons in the formation of airflow and deposition patterns. The deposition data was presented by deposition efficiency (DE) and deposition fraction (DF) against impaction parameter and Stokes number. At all of the inhalation flow rates, highest values of deposition fractions were devoted to the mouth-throat (MT), tracheobronchial tree (TB), and trachea (Tra), respectively (At 60 L/min: MT = 6.7%, TB = 5.3%, Tra = 1.9%). The numerical deposition data showed a good agreement with the experimental deposition data in most of the airway regions (e.g. less than 10% difference between the deposition fractions in the tracheobronchial region). Enhancing inhalation flow rate in all of the airway regions led to an uptrend in deposition rate due to the increase of particles inertia and turbulence level. In addition, the increase of particle deposition with enhancing inhalation flow rate in all of the sections including extrathoracic, trachea, and tracheobronchial tree suggesting that inertial impaction is the dominant deposition mechanism due to the increase of inertial force. In conclusion, the validated CFD model provided an opportunity to cover the limitations of our previous experimental investigation on aerosol deposition of commercial inhalers and became an efficient method for further studies.
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