Chronic obstructive pulmonary disease (COPD) is a common and serious lung disease for which there is no cure. It is mainly caused by smoking, but long-term exposure to air pollution, dust, fumes, or chemicals at work can also lead to the disease. Over sixty-five million people around the world live with COPD, and the number is still rising. COPD is now the third leading cause of death globally. People with COPD often experience sudden flare-ups, where symptoms become much worse. These flare-ups can cause lasting damage to the lungs and are a major reason why the disease progresses. Preventing such flare-ups is therefore one of the most important goals in COPD care. Many of these flare-ups are caused by infections with influenza (flu) and other respiratory viruses. However, we still do not fully understand how these viral infections worsen COPD or why they lead to a long-term decline in lung function. This gap in knowledge makes it difficult to develop effective treatments.
What Happens in the Lungs:
Even in the early stages, COPD causes narrowing of the small airways in the lungs. This happens because of long-lasting inflammation, too much mucus, and scarring (fibrosis) in the small airways. Recent research suggests that this small airway fibrosis plays a key role in making COPD worse, but the reasons behind it are still unclear.
The influenza virus infects the cells that line the airways (the epithelium). Beneath these cells is a layer of connective tissue made up of extracellular matrix (ECM), which is mainly produced by cells called fibroblasts. When too much ECM is deposited, fibrosis develops. The connection between influenza infection and the development of small airway fibrosis has not yet been explored.
Aim of the Study:
This project aims to uncover how influenza virus infection might cause small airway fibrosis and contribute to COPD progression. To study this, an in vitro co-culture model was used. This model combines airway epithelial cells and lung fibroblasts to simulate the interactions that occur in human lungs. It was based on a previously established system where epithelial cells from both COPD patients and healthy individuals were grown under air-liquid conditions. This setup forms an airway structure that behaves similarly to real human airways and responds strongly to influenza infection.
Objective 1: To study the molecular and cellular communication between epithelial cells and fibroblasts after influenza virus infection.
Objective 2: To identify differences in this communication between COPD-like and healthy airway cells.
