This thesis is aimed at understanding the effective operation of the Bubble CPAP System when treating neonates with respiratory distress syndrome (RDS). It is also aimed at determining the effect that pressure oscillations have on respiratory performance in terms of the work of breath (WOB) and surfactant dynamics. The principle objectives were to: • Create an original multi-compartmental model of the neonatal lung that includes compartment-specific inertance and viscoelasticity for 128 day (premature) and 142 day (near-term) gestation lambs. • Validate the model with experimental data obtained from clinical trials. • Use the model to determine the effect of pressure oscillations as produced by the Bubble CPAP System on respiratory performance. • Determine the frequencies of oscillation that provide the optimal respiratory support. • Build a surface tension model that simulates surface tension dynamics in an alveolus exposed to pressure oscillation frequencies in the range typically produced by the Bubble CPAP System. • Validate the surface tension model with experiments conducted on a custom-built pulsating bubble surfactometer (PBS). To fulfill the first four objectives, a mathematical model of the neonatal ovine lung was developed in Simulink within the Matlab environment. Mechanical and physical parameters that were required for the model were either empirically determined from measurements on preterm lamb lungs or derived from the literature. Simulations were then performed to determine the effectiveness of Bubble CPAP and the use of ‘optimal frequencies’ in neonatal respiration. To study the surface tension dynamics, a PBS was constructed to study the effect of frequencies on a surfactant bubble which simulated an alveolus. Modulated frequencies (10-70 Hz) were superimposed on the breath cycle at 3 different amplitudes expressed as a percentage of the tidal volume (TV) excursion (15%TV, 22.5%TV and 30%TV). A numerical model was also built in Matlab to characterize the surfactant behaviour and help determine the mechanisms responsible for any observed changes in surface tension.

The experimental results and computer simulations resulted in the following conclusions: • The model is able to accurately predict the respiratory parameters at the airway opening during CPAP and Bubble CPAP operation. • The model shows the ability to predict the uneven ventilation profiles in the neonatal lung. • Both model predictions and experimental measurements show the trend that the mechanical WOB is greater (improved) during ventilation under Bubble CPAP when compared to CPAP. • Pressure oscillation frequencies which show improved WOB measures in the 128 day gestation lamb lung were identified as 19, 23, 28, 33, 44, 49, 54, 81, 88, 99, 111 and 113 Hz. • Model predictions showed that the improvement in WOB (due to mechanical effects) relative to CPAP-only treatment was 1-2% when introducing single frequencies at the generator, but increased to 4-6% when introducing ‘mixed frequencies’ at the generator and 4-10% when introducing ‘mixed frequencies’ at the patient interface. • It was shown that the Bubble CPAP System delivers frequencies similar to the identified optimal frequencies of the 128 day gestation lung (17 and 23 Hz) which contribute to the noticed improvement in WOB. • The average trends of all the experiments on a PBS and results from the numerical model revealed that the minimum and maximum surface tension in an alveolus decreases with increasing frequency and increasing amplitude. • The mechanism of improvement of surface tension in the alveolus with frequency and amplitude is due to the increased diffusion and adsorption of surfactant molecules to the air-liquid interface, increasing the interfacial surface concentration and decreasing the surface tension.