A76-06 E-Cigarette Puff Frequency Amplifies Inflammatory Effects on Airway Function: A Multiscale Modelling Study

Rationale E-cigarette (EC) use has risen rapidly, particularly among adolescents and young adults, yet its long-term respiratory effects remain poorly understood. Experimental studies indicate that EC exposure can trigger airway inflammation, defective tissue repair, and tissue remodelling, which may lead to small airway dysfunction. However, the link between cellular injury and organ-level ventilation impairment remains unresolved. Addressing this, the current study presents a multi-scale computational framework integrating EC-induced inflammatory remodelling with functional consequences on airway mechanics and ventilation. Methods An agent-based model (ABM) of airway inflammation and remodelling, originally developed for asthma (Saunders et al., 2019), was adapted to reflect EC-specific pathophysiology. Model rules incorporated experimental data describing EC effects on mucus production, fibroblast proliferation, neutrophil activity, and epithelial integrity. The ABM predicted time-dependent changes in the proportion of airway smooth muscle cells and fibroblasts under varying puff frequencies. These outputs informed airway wall thickness, stiffness, and lumen narrowing in a whole-lung ventilation model (Swan et al., 2012) which was extended to incorporate these parameters, enabling investigation of EC effects on airway resistance and work of breathing. Simulations were performed for control (no EC exposure), low (Puff Frequency 1; PF1), and high (Puff Frequency 2; PF2) EC exposure conditions, differentiated by the extent of epithelial compromise and alterations in neutrophil behaviour. Results Both EC exposure cases exhibited progressive airway wall thickening and increased stiffness relative to the Control. PF2 induced a greater increase in airway resistance and ventilation heterogeneity than PF1, with airway resistance rising 2.17-fold in PF2 and 1.27-fold in PF1 relative to Control. Pressure–volume loops generated with model outputs demonstrated increasing hysteresis with EC exposure, corresponding to rising work of breathing. Simulations demonstrated peripheral ventilation defects and hyperinflated regions consistent with air trapping in line with imaging case studies from the literature. Statistical analyses confirmed significant differences between both exposure cases and the Control (p < 0.01), and between exposure cases (p < 0.05). Conclusions This integrated multi-scale model links EC-induced cellular inflammation to airway remodelling and organ-level ventilatory impairment. The findings suggest that EC exposure may drive a distinct phenotype of small airway disease, characterised by early ventilation heterogeneity and air trapping. This framework provides a predictive platform for assessing long-term EC-related respiratory risk and supports the development of early diagnostic biomarkers.