Emphysema is the permanent enlargement of air spaces in the respiratory regions of the lung due to destruction of the inter-alveolar septa. The progressive coalescence of alveoli and alveolar ducts into larger airspaces leads to the disruption of normal airway wall motion and airflow rates within the pulmonary acinus. To contribute to the understanding of the individual effects of emphysema during its earliest stages, computational fluid dynamics (CFD) simulations of airflow in mathematically derived models of the pulmonary acinus were performed. The here generated computational domain consists of two generations of alveolar ducts within the pulmonary acinus, with alveolar geometries approximated as closely packed, 14-sided polygons. Physiologically realistic airflow rates and wall motions were used to study airflow patterns within subsequent generations of alveolar ducts during the inspiratory and expiratory phases of the breathing cycle. The effects of progressive emphysema on the airway wall motion and flow rates were simulated by sequentially removing all alveolar septa within each alveolar duct. Parametric studies were presented to independently assess the relative influence of progressive septal destruction of airway motion and flow rates. The results illustrate that septal destruction lowers the flow resistance through the alveolar ducts but has little influence on the mass transport of oxygen into the alveoli. Septal destruction has a net effect on the flow field by favoring the development of recirculatory flow patterns in individual alveoli.