Translational Research in Obstructive Pulmonary Diseases: Projects

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airflow obstruction, chronic inflammation and airway remodelling. The laboratory has a longstanding tradition and vast expertise in the study of the pathogenesis of obstructive airway diseases. Animal models (mouse) have been developed to study the effects of specific and non-specific stimuli on lung mechanics, bronchial hyperresponsiveness and airway inflammation/remodelling. The laboratory is well equipped for cell biology (cell culture, flow cytometer, RT-PCR …) and immunohistochemistry.

The induction and the maintenance of allergic airway inflammation are crucial to the pathogenesis of asthma. In a mouse model the role of dendritic cells (DC) in the initiation and maintenance of allergic airway inflammation has been characterized. A hot topic that is currently under investigation is the interaction between air pollutants (e.g. cigarette smoke, particulate matter) and the development or aggravation of allergic airway inflammation.

Exposure to noxious stimuli such as cigarette smoke is critical in the development and the progression of COPD. Basic mechanisms in COPD are studied in mice that are exposed to cigarette smoke for up to 6 months. This exposure induces inflammation (in lung, in bronchoalveolar lavage fluid) as well as structural changes (airway wall remodelling and emphysema). Like in humans the innate and adaptive immunity play a crucial role in the response to cigarette smoke, leading to neogenesis of bronchus-associated lymphoid follicles. The cellular and molecular pathways in these processes is currently being explored by using spontaneous mutant mice or gene-targeted knockout mice, as well as blocking reagents. Hot topics such as the role of microRNAs, regulated cell death, innate immune signaling are being examined both in the mouse model, as well as in human lung material obtained at thoracotomy, illustrating the powerful translational approach of the research group.

In cooperation with the Erasmus University of Rotterdam, epidemiologic research on COPD and asthma is performed in a population-based prospective cohort study; the aim of these observational studies is to elucidate the pathogenesis of both diseases, including genetic and environmental risk factors. In collaboration with the CHARGE consortium, large-scale epidemiologic studies including GenomeWide Association (GWA) studies are performed on specific phenotypes of lung function and pulmonary diseases including COPD. Moreover, pharmaco-epidemiologic studies investigate the real-life effectiveness and safety of inhaled and oral treatments in patients with COPD.