High-Efficiency Nose-to-Lung Aerosol Delivery in an Infant: Development of a Validated Computational Fluid Dynamics Method

Abstract

Background: Computational fluid dynamics (CFD) provides a powerful tool for developing new high-efficiency aerosol delivery strategies, such as nose-to-lung (N2L) aerosol administration to infants and children using correctly sized aerosols. The objective of this study was to establish numerically efficient CFD solution methods and guidelines for simulating N2L aerosol administration to an infant based on comparisons with concurrent in vitro experiments. Materials and Methods: N2L administration of a micrometer-sized aerosol (mass median aerodynamic diameter [MMAD] ¼ 1.4 lm) was evaluated using concurrent CFD simulations and in vitro experiments. Aerosol transport and deposition was assessed in a new nasal airway geometry of a 6-month-old infant with a streamlined nasal cannula interface, which was constructed as a CFD mesh and three-dimensionally printed to form an identical physical prototype. CFD meshes explored were a conventional tetrahedral approach with nearwall (NW) prism elements and a new polyhedral mesh style with an equally refined NW layer. The presence of turbulence in the model was evaluated using a highly efficient low-Reynolds number (LRN) k-x turbulence model, with previously established NW corrections that accounted for anisotropic wall-normal turbulence as well as improved NW velocity interpolations and hydrodynamic particle damping. Results: Use of the new polyhedral mesh was found to improve numerical efficiency by providing more rapid convergence and requiring fewer control volumes. Turbulent flow was found in the nasal geometry, generated by the inlet jets from the nasal cannula interface. However, due to the small particle size, turbulent dispersion was shown to have little effect on deposition. Good agreement was established between the CFD predictions using the numerically efficient LRN k-x model with appropriate NW corrections and in vitro deposition data. Aerosol transmission efficiencies through the delivery tube, nasal cannula, and infant nasal model, based on experimental and CFD predictions, were 93.0% and 91.5%, respectively. Conclusions: A numerically efficient CFD approach was established to develop transnasal aerosol administration to infants and children. Small particle aerosols with aerodynamic diameters of *1.5 lm were confirmed to have low inertial depositional loss, and have low deposition from turbulent dispersion, making them ideal for high-efficiency lung delivery through an infant nasal cannula interface.

Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned

“…the liquid volume that remains in the nebulizer after the end of a treatment) and the absence of added air-flow to the ventilation circuit. Further, aerosol particles exit the nebulizer at high velocity after jet nebulization: high velocity flows increase the extra-thoracic aerosol deposition due to inertial impaction within the NIV circuit, patient interface, and upper airways [78]. Conversely, vibratingmembrane nebulizers release slow, highly-concentrated aerosols that can be more readily delivered to the patient by the bias flow through the NIV circuit ( Fig.…”

“…This increase in diameter improves the lung retention of the particles. This method reduces extrathoracic aerosol deposition in an adult replica of the upper airways in in vitro and in silico studies and is a potentially interesting approach for aerosol delivery to premature neonates [78,118]. In this regard, a recent study by Kamga Gninzeko et al used this approach to treat surfactant-deficient rats with a novel formulation of spray-dried pulmonary surfactant composed of Beractant (Survanta ® ), mannitol, and leucine [119].…”

“…liquid breakup or powder degradation), to evaluate and improve the aerosol generator device performance [191], to aid the design of circuits and devices (e.g. patient interfaces) aimed at reducing extra-thoracic deposition of aerosols [78,118], and to investigate the regional airway deposition of new aerosol delivery strategies [192].…”

Measurements of deposited aerosol dose in infants and small children

“…High rates of oropharyngeal deposition could potentially be controlled using smaller or less-dense aerosols. Some groups are exploring the use of hygroscopic aerosols that are very small when delivered through the nose but grow within the humid environment of the lungs, allowing for effective sedimentation and deposition in target lung zones (31,32). Efficiency might also be further increased through the use of controlled breathing patterns that limit inhalation velocity, increase tidal volume, deliver aerosol only during specific portions of the breath (bolus delivery), or incorporate slight breath holds (33)(34)(35).…”

Flow and Particle Modelling of Dry Powder Inhalers: Methodologies, Recent Development and Emerging Applications

“…Bass et al [ 76 ] developed a computational methodology and guidelines to model nose-to-lung aerosol administration to an infant and validated the model with in vitro experiments. The Reynolds number in the tube connecting to the nasal cavity was about 900.…”