The structural and functional impact of CFTR dysfunction on the lung

In Europe, CF is the most common life shortening inherited disorder. Median survival is 37 years. Most patients die from lung disease (CFLD). Much can be gained from prevention or better treatment of early CFLD. Since CF newborn screening is available in many European countries, this task becomes even more important. CFLD is thought to affect the small airways early in life. So far no one has managed to directly show this as the small airways (<2mm) are difficult to image. It remains unknown if the CF lung is entirely normal at birth nor how infections during infancy change its architecture. Obtaining insight in early CFLD is crucial for forming new hypotheses and treatment strategies in CF. We aim at construing the structure of a normally developing lung and show how CF changes the normal course. We can do so by a new comprehensive imaging technique: microCT. MicroCT requires a high radiation dose which prevents studying living people. We thus image the lungs of transplanted patients to elucidate severe CFLD. People with early CFLD do not get transplanted. Hence we will study the CF pig: a transgenic pig that naturally develops CFLD and is considered an excellent animal model. By comparing normal to CF we analyze the CF lung at birth and identify early changes. Additionally we compare normal piglet lungs with human tissue from intrauterine and postnatal deaths and CF pig lungs with well-preserved areas from CF explant lungs.This will help set targets for future treatment.

Jaar van publicatie:2018

Toegankelijkheid:Closed