A Pediatric Upper Airway Library to Evaluate Interpatient Variability of In Silico Aerosol Deposition

• Published in: AAPS PharmSciTech Vol. 24; no. 6; p. 162
• Main Authors: Kolewe, Emily L., Padhye, Saurav, Woodward, Ian R., Feng, Yu, Briddell, Jenna W., Fromen, Catherine A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 31.07.2023
• Subjects: Advances in Drug Delivery by Inhalation - Official Collection from AAPS Inhalation & Nasal Community (INC); Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Pharmacology/Toxicology; Pharmacy; Research Article; CFPD; anatomical development; interpatient variability; aerosol; pediatric
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-023-02619-3

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 ( θ E ), glottis to cricoid ring ratio (GC-ratio), and pediatric to adult trachea ratio ( H -ratio)), inhaler metrics (particle diameter, d p , 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 d p , Q , GC-ratio, θ E , 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. Graphical Abstract