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Project

Impact of Chronic Obstructive Pulmonary Disease (COPD) severity and disease phenotypes on bronchial epithelial cell immune responses to (non-)infective triggers.

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality. Acute exacerbations of COPD are heterogeneous and predominantly clustered in viral, bacterial, or eosinophilic exacerbations. Bronchial epithelial cells synthesise and release several proinflammatory mediators both constitutively and in response to these (non-)infective stimuli, thereby influencing inflammatory responses. The extend of these epithelial immunomodulatory responses may however differ with COPD disease severity and disease phenotypes. However, this has not been investigated before. In the present study we will develop in vitro human bronchial epithelial cell cultures from explant lungs from pre-COPD, mild to very severe COPD patients undergoing lobectomy or lung transplantation. Using micro-CT, in-depth characterization of ex-vivo morphology and loss of the small airways, extend of mucus plugging, and degree of emphysema will further phenotype COPD patients. Bronchial epithelial cell immunomodulatory responses to infective and non-infective triggers, including anti-viral responses and pro-inflammatory responses will be assessed in relation to disease severity (GOLD I-IV) and disease phenotypes (emphysema, mucus plugging, small airway loss). In addition, the relation between in vitro epithelial mucin expression and small airway mucus plugging will be explored. Improved understanding of these epithelial immunomodulatory responses to infective and non-infective triggers of exacerbations in relation to COPD disease severity and phenotypes may improve our understanding of COPD pathogenesis and may be important to develop targeted treatment options.
Date:1 Oct 2022 →  Today
Keywords:CELL CULTURE, BRONCHIAL EPITHELIAL CELLS, CHRONIC OBSTRUCTIVE PULMONAY DISEASE
Disciplines:Respiratory medicine