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Published on: April 6, 2017
A Pediatric Upper Airway Library to Evaluate Interpatient Variability of In Silico Aerosol Deposition
Emily L Kolewe1, Saurav Padhye1, Ian R Woodward1
1Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy St., Newark, Delaware, 19716, USA.
Insights
Pediatric airway geometry significantly impacts aerosol drug delivery. Inhaler design and patient anatomy, not age, are key factors for optimizing inhaled therapeutics in children.
Area of Science:
- Biomedical Engineering
- Pediatric Respiratory Medicine
- Computational Fluid Dynamics
Background:
- Pediatric airway anatomy undergoes significant developmental changes, posing challenges for effective aerosol therapy delivery.
- Current aerosol therapeutics often lack pediatric-specific designs, leading to suboptimal drug deposition and efficacy.
- Understanding geometric variations and their impact on aerosol deposition is crucial for developing targeted pediatric treatments.
Purpose of the Study:
- To quantify geometric variations in pediatric upper airways during development.
- To analyze aerosol deposition patterns in relation to anatomical, inhaler, and clinical metrics across pediatric and adult models.
- To identify key parameters influencing aerosol deposition for optimizing pediatric inhalable therapeutics.
Main Methods:
- Utilized a library of 24 pediatric and 4 adult computational models representing ages 3.5 months to 6.9 years.
- Performed computational fluid-particle dynamics simulations with particle sizes (0.1-10 μm) and flow rates (10-120 Lpm).
- Analyzed anatomical (epiglottis angle, GC-ratio, H-ratio), inhaler (particle diameter, flow rate), and clinical (age, sex, height, weight) metrics against aerosol deposition using multivariate regression and principal component analysis.
Main Results:
- All analyzed metrics (anatomical, inhaler, clinical) significantly influenced aerosol deposition, with varying degrees of impact.
- Principal component analysis revealed that particle diameter, flow rate, GC-ratio, epiglottis angle, and sex accounted for 90% of deposition variability.
- Age was not a significant factor in pediatric deposition but was influential when comparing adults; inhaler design metrics were highly influential.
Conclusions:
- Inhaler design and specific anatomical features are critical determinants of aerosol deposition in pediatric airways.
- Pediatric-specific inhalable approaches are essential for optimizing drug delivery and therapeutic outcomes.
- This study provides a framework for personalized aerosol medicine in pediatric populations.
Abstract:
The airway of pediatric patients' changes through development, presenting a challenge in developing pediatric-specific aerosol therapeutics. Our work aims to quantify geometric variations and aerosol deposition patterns during upper airway development in subjects between 3.5 months-6.9 years old using a library of 24 pediatric models and 4 adult models. Computational fluid-particle dynamics was performed with varying particle size (0.1-10 μm) and flow rate (10-120 Lpm), which was rigorously analyzed to compare anatomical metrics (epiglottis angle (θE), glottis to cricoid ring ratio (GC-ratio), and pediatric to adult trachea ratio (H-ratio)), inhaler metrics (particle diameter, [Formula: see text], and flow rate, Q), and clinical metrics (age, sex, height, and weight) against aerosol deposition. Multivariate non-linear regression indicated that all metrics were all significantly influential on resultant deposition, with varying influence of individual parameters. Additionally, principal component analysis was employed, indicating that [Formula: see text], Q, GC-ratio, θE, and sex accounted for 90% of variability between subject-specific deposition. Notably, age was not statistically significant among pediatric subjects but was influential in comparing adult subjects. Inhaler design metrics were hugely influential, thus supporting the critical need for pediatric-specific inhalable approaches. This work not only improves accuracy in prescribing inhalable therapeutics and informing pediatric aerosol optimization, but also provides a framework for future aerosol studies to continue to strive toward optimized and personalized pediatric medicine.
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