Use of airway epithelial cell culture to unravel the pathogenesis and study treatment in obstructive airway diseases.

Asthma and chronic obstructive pulmonary disease (COPD) are considered as two distinct obstructive diseases. Both chronic diseases share a component of airway epithelial dysfunction. The airway epithelium is localized to deal with inhaled substances, and functions as a barrier preventing penetration of such substances into the body. In addition, the epithelium is involved in the regulation of both innate and adaptive immune responses following inhalation of particles, allergens and pathogens. Through triggering and inducing immune responses, airway epithelial cells contribute to the pathogenesis of both asthma and COPD. Various in vitro research models have been described to study airway epithelial cell dysfunction in asthma and COPD. However, various considerations and cautions have to be taken into account when designing such in vitro experiments. Epithelial features of asthma and COPD can be modelled by using a variety of disease-related invoking substances either alone or in combination, and by the use of primary cells isolated from patients. Differentiation is a hallmark of airway epithelial cells, and therefore models should include the ability of cells to differentiate, as can be achieved in air-liquid interface models. More recently developed in vitro models, including precision cut lung slices, lung-on-a-chip, organoids and human induced pluripotent stem cells derived cultures, provide novel state-of-the-art alternatives to the conventional in vitro models. Furthermore, advanced models in which cells are exposed to respiratory pathogens, aerosolized medications and inhaled toxic substances such as cigarette smoke and air pollution are increasingly used to model e.g. acute exacerbations. These exposure models are relevant to study how epithelial features of asthma and COPD are affected and provide a useful tool to study the effect of drugs used in treatment of asthma and COPD. These new developments are expected to contribute to a better understanding of the complex gene-environment interactions that contribute to development and progression of asthma and COPD.