C108-07 Oropharyngeal Enlargement Alters Airflow Dynamics and Inhaled Drug Delivery to the Lower Airways in Patients With Obstructive Lung Disease

Rationale Despite the growing interest, the impact of upper airway remodeling on inhaled drug delivery in obstructive lung disease (OLD) has not been comprehensively understood. Recent quantitative computed tomography (qCT) study found oropharyngeal enlargement in patients with OLD (PMID 40959168). This study aimed to unveil how oropharyngeal enlargement affects oropharyngeal airflow dynamics and drug delivery to the lung in patients with OLD. Methods Of 185 participants with upper airway qCT analysis (86 asthma, 73 COPD, and 26 healthy), 21 representative cases were selected for computational fluid dynamics (CFD) airflow and particle transport simulations: 7 from each of asthma (60.4±6.7 yr), COPD (68.9±8.3 yr), and healthy (58.4±6.7 yr) groups. In-house software was used for upper airway CT-based three-dimensional (3D) computational fluid dynamics (CFD) simulations of airflow and 4-µm particle transport by dry powder inhaler (DPI) and metered dose inhaler (MDI). Inspiratory capacities and DPI and MDI-specific parameters (PMID 22290350) determined subject-specific flow waveforms. Statistical analyses included Welch’s t-test and Spearman correlation, with significance by p < 0.05. Results Enlarged oral space in patients with OLD formed recirculating flow (fractional recirculating zone of OLD vs healthy: 52.1% vs 37.5%, p < 0.001), reducing oropharyngeal aerodynamic power (5.6±4.3 W vs 0.7±0.6 W, p = 0.023) and delay particle transport to the lower airways (DPI: 0.205 s vs 0.143 s; MDI: 0.235 s vs 0.173 s; Figure 1A). The upper airway delay caused the particles to enter the trachea at higher flow rates (DPI: 0.51 vs 0.36; MDI: 0.49 vs 0.32). Despite the delay, more particles eventually entered the lower airways in OLD than healthy controls (DPI: 75% vs 67%, p = 0.046; MDI: 84% vs 79%, p = 0.040, Figure 1B), due to less oropharyngeal deposition (DPI: r = −0.96, p < 0.001; MDI: r = −0.90, p < 0.001), which is interestingly associated with longer pharyngeal length (DPI: r = −0.52, p = 0.016; MDI: r = −0.45, p = 0.040). Between the two inhalers, MDI delivered more particles to the lower airway than DPI (83% vs 73%; p < 0.001) across all subjects, attributable to the lower flowrate in MDI (48±16 L/min) than in DPI (95±32 L/min; p < 0.001), which leads to less oropharyngeal deposition. Conclusion Oropharyngeal enlargement in OLD causes inhaled drug particles to enter the lower airways at higher flow rates, altering airflow dynamics. This may alter lower respiratory particle deposition patterns. Findings underscore the need for unified upper-lower respiratory modeling for effective patient-specific assessment of drug inhalation in the patients with OLD.