Aerosols exhaled from the lungs have distinctive patterns that can be linked to the abnormalities of the lungs. Yet, due to their intricate nature, it is highly challenging to analyze and distinguish these aerosol patterns. Small airway diseases pose an even greater challenge, as the disturbance signals tend to be weak. The objective of this study was to evaluate the performance of four convolutional neural network (CNN) models (AlexNet, ResNet-50, MobileNet, and EfficientNet) in detecting and staging airway abnormalities in small airways using exhaled aerosol images. Specifically, the model’s capacity to classify images inside and outside the original design space was assessed. In doing so, multi-level testing on images with decreasing similarities was conducted for each model. A total of 2745 images were generated using physiology-based simulations from normal and obstructed lungs of varying stages. Multiple-round training on datasets with increasing images (and new features) was also conducted to evaluate the benefits of continuous learning. Results show reasonably high classification accuracy on inbox images for models but significantly lower accuracy on outbox images (i.e., outside design space). ResNet-50 was the most robust among the four models for both diagnostic (2-class: normal vs. disease) and staging (3-class) purposes, as well as on both inbox and outbox test datasets. Variation in flow rate was observed to play a more important role in classification decisions than particle size and throat variation. Continuous learning/training with appropriate images could substantially enhance classification accuracy, even with a small number (~100) of new images. This study shows that CNN transfer-learning models could detect small airway remodeling (<1 mm) amidst a variety of variants and that ResNet-50 can be a promising model for the future development of obstructive lung diagnostic systems.