Essentials for aerosol delivery to term and pre-term infants

Area of Science:

• Pediatric Pulmonology
• Pharmaceutical Sciences
• Biomedical Engineering

Background:

• Infant lung aerosol delivery faces challenges due to physiological differences (obligatory nose breathing, small airways, low tidal volumes).
• In vivo studies in neonates are ethically restricted, necessitating the use of modeling for research.
• Understanding regional aerosol deposition is crucial for optimizing drug delivery in this population.

Purpose of the Study:

• To utilize computational modeling to understand aerosol deposition in neonatal lungs.
• To establish a theoretical framework for selecting optimal aerosol sizes for maximal lung delivery and minimal variability.
• To investigate the impact of age, aerosol characteristics, and ventilation on deposition patterns.

Main Methods:

• Coupling recent nasal aerosol deposition data with a scalable lung deposition model.
• Simulating aerosol deposition in term and preterm infants (30-week GA) across various aerosol sizes and ventilation parameters.
• Analyzing the effects of Geometric Standard Deviations (GSDs) on deposition and variability.

Main Results:

• Term infants showed 25-35% lung deposition, with larger GSDs minimizing intrasubject variability but reducing mean deposition.
• An optimal GSD of approximately 1.75 was identified to balance deposition and variability.
• Preterm infants (30-week GA) exhibited slightly higher deposition than term infants, likely due to lower inhaled flow rates.
• Direct tracheal delivery showed increased lung deposition with larger aerosol sizes, peaking at 2-3 µm, but practical limitations cap delivery.

Conclusions:

• Aerosol delivery optimization in neonates requires careful consideration of aerosol size and GSD.
• A GSD of 1.75 offers a promising compromise for maximizing lung deposition while minimizing variability in term and preterm infants.
• Further research into practical delivery methods, like endotracheal tube administration, is needed to overcome transport limitations and improve deposition.