Modeling of inhaled corticosteroids delivery for topical croup treatment in pediatric upper airways

Croup is the most frequent cause of pediatric upper airway obstruction characterized by spindle-shaped stenosis in the subglottis mucosa. Inhaled corticosteroids (ICSs) serve as the first-line therapy for croup. Traditional ICS particles (1–4 μm in diameter) are primarily designed for trachea and lung diseases and show extremely low larynx deposition. Moreover, the specific correlation between airway minimal cross-sectional area (CSA) and airway resistance has not been fully understood. In this study, three healthy pediatric upper airway models with commercial nebulizer masks attached to their faces were reconstructed from computed tomography (CT) scans. Virtual mild, moderate, and severe croup were incorporated into these healthy models. To enhance the performance of conventional nebulizing drug delivery, the aerodynamic properties of croup with different degrees of stenosis were quantitatively analyzed, and the respiratory transit and deposition of ICS particles sized between 1 and 20 μm in our target area (glottis + subglottis) were modeled utilizing the Computational Fluid Particle Dynamics (CFPD) method. Results showed that in all models, maximum deposition fractions (DF) can be reached when the ICS particle sizes are 7–8 μm, and for particles sized at 8 and 9 μm, all models can achieve effective target area delivery (≥75% of the maximum DF), whereas the majority of traditional nebulizers produce smaller particles than what we recommended. Pediatric upper airway resistance is negatively correlated with the minimum airspace CSA (R ∝ CSA−1), which is in good agreement with the Bernoulli Obstruction Theory. Furthermore, when the constriction of the subglottis reaches a specific level (≥70% obstruction), the upper airway pressure drop abruptly surged and the dyspneic respiration symptoms of patients develop instantly.