Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide and causes debilitating and often fatal breathing problems, with few effective treatments available. COPD posits a significant burden on society by causing major expenses to the health care systems and greatly reducing quality of life for many people. Therefore, developing more effective treatment options would benefit individuals and society as a whole. One hurdle for developing more effective treatment options is the common use of animals in COPD research, such as rodents. Rodents do not naturally develop COPD but have to be induced artificially and even then they do not develop key aspects of human COPD, such as airway disease, including inflammation and narrowing. This limits the types of disease mechanisms and treatments that can currently be investigated for drug discovery. In particular, we hypothesize that in order to develop innovative and effective treatment options, we need to understand how COPD affects the airways, as this is where the disease often starts in humans. Therefore, my team develops innovative in vitro models of human airways, such as so called airways-on-chip, small miniature models of human trachea and bronchioles that can be exposed to cigarette smoke and other triggers of COPD. Additionally, airways-on-chip allow us to test the effect of breathing motions and air flow on the airways to investigate if these rhythmic forces are important for health and, conversely, if their lack due to impaired breathing accelerates diseases progression. Our objectives are to identify risk factors of developing COPD, such as certain air pollutants and diet, and to identify protective mechanisms, such as mechanical stimulation and exercise. We aim to understand how these factors act on the airways in order to identify potential diagnostic markers and drug targets for treatment and regeneration.