Deposition of micrometer-sized aerosol particles in neonatal nasal airway replicas

Abstract

The nasal aerosol filtration properties of infants 0-3 months old have been quantified through in vitro measurements. Computed tomography (CT) scan data was obtained of seven individuals with ages of 5-79 days. Nasal airway replicas based on these images were manufactured using rapid prototyping. Deposition in the replicas was measured using an electrical low pressure impactor (ELPI) to measure the concentration of aerosol particles in the inertial regime. Comparing the difference in concentration when sampling through the model versus sampling through a blank line gave the deposition fraction. Deposition was measured for particles with aerodynamic diameters between 0.53 and 5.54 mm. Nonlinear least squares curve fitting was performed to collapse intersubject variability and represent the data with a single curve. To achieve satisfactory intersubject variability collapse, a non-dimensional pressure drop, the Euler number (Eu), was required in addition to the Reynolds number (Re) and the particle Stokes number (Stk) where the dimensionless parameters are evaluated with a length scale, D, defined as the airway volume divided by the airway surface area. The equation describing the deposition fraction, h, is h D 1-(14590 / (14590 C Stk 1.2201 Re 1.7742 Eu 1.5772)) 0.3687. An analysis of the expected intersubject variability in in vivo deposition was also performed, yielding a method for predicting variance in neonatal nasal airway deposition.

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

“…The aerosol size considered in the current study is similar to that recommended by Longest et al, (12) who demonstrated 45%-60% lung deposition in an infant model of invasive mechanical ventilation. A recent correlation from Tavernini et al, (9) which built upon work from Storey-Bishoff et al, (8) estimates that for the monodisperse case presented in the current study, *1.23% of particles that enter the nostril will deposit in the nasal cavity and nasopharynx. Furthermore, Clark et al (43) demonstrated the need for using smaller aerosol sizes to maximize lung aerosol delivery to preterm infants.…”

“…The patient height and weight both fell within the 25th and 75th percentiles for a 6-month-old infant. (22) Therefore, it was expected that the model was representative of the 6 month target age, (9) despite being *1 month younger. Of the available scans, the selected scan was chosen because the infant's mouth was closed, it was complete from the nostrils through the larynx, and the slice resolution was sufficiently small at 1 mm.…”

“…(6,7) It is expected that using small diameter particles (mass median aerodynamic diameter [MMAD] <2 lm) for N2L aerosol administration leads to high-efficiency lung delivery, as the likelihood of impaction deposition is reduced. (8,9) Computational fluid dynamics (CFD) provides a valuable research tool for developing respiratory drug delivery strategies, such as N2L aerosol administration, and associated devices. (10) CFD simulation divides the region of interest, such as an airway model, into small control volumes and numerically solves the equations governing mass, momentum, and energy transport within these control volumes.…”

Optimizing Aerosolization Using Computational Fluid Dynamics in a Pediatric Air-Jet Dry Powder Inhaler

“…That said, it is valuable insight for developing devices that may target older patients that inhale at higher flow rates. One final consideration regarding actuating DPIs with higher flow rates is the resultant impaction parameter (typically given as d a 2 Q, where d a is aerodynamic particle diameter) may be higher, which would suggest the possibility of increased extrathoracic losses (40)(41)(42)(43).…”

Use of computational fluid dynamics deposition modeling in respiratory drug delivery

“…Based on decades of experimental research, intersubject variability in airway deposition is known to be very large for healthy subjects and in cases of airway disease [198, 199, 200]. In vitro models have helped to quantify expected intersubject variability for orally inhaled pharmaceutical products [11, 12, 184, 201], and for nasally inhaled aerosols in pediatric and infant populations [33, 202, 203, 204]. While CFD is well suited to study intersubject variability and diseased airway effects, studies have been relatively infrequent.…”