Chronic obstructive pulmonary disease (COPD), the 3rd most common cause of morbidity and death worldwide, is primarily caused by air pollution, especially so called “fine dust” or fine particulate matter (<2.5 μm; PM2.5). Yet only a fraction of people exposed to air pollution eventually develop COPD, indicating the immense resilience and effectiveness of barrier mechanisms against inhaled pollutants presented by the human respiratory system. Understanding why some people are more susceptible to COPD than others may also help identify urgently needed treatment and prevention options. Here, we hypothesize that in susceptible people, altered mucociliary mechanics impact the local diffusion and hence concentrations and dwelling time of PM2.5, subsequently increasing damage to the epithelium and causing macrophage dysregulation. We will address our hypothesis in two complementary and synergistic PhD projects using a unique combination of experimental biology, biophysical measurements, and theoretical models of transport in complex fluids. Our major goals are: (1) Elucidate the diffusion dynamics of PM2.5 in human airway mucus, (2) reveal how active ciliary beat shapes PM2.5 distribution in airway mucus, and (3), unveil how these mechanisms in combination with person-specific mucociliary environments can increase susceptibility to airway epithelial and macrophage dysfunction in response to PM2.5 exposure. Besides elucidating potential mechanisms involved in COPD, this work will also provide the tools to study delivery of drugs through the airway barrier in our future work.