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Project

Translationeel onderzoek naar Bronchiolitis Obliterans Syndrome na longtntatie.

Chronic rejection remains the most important cause of late mortality after lung transplantation. Recently our group described two different phenotypes of chronic rejection: the first, called NRAD (neutrophilic reversible airways dysfunction) is characterized by neutrophilic inflammation in the airways and its response to neo-macrolides which may reverse the pathology. The second phenotype, called fBOS (fibrotic bronchiolitis obliterans syndrome) is very difficult to treat and neo-macrolides have no clear effect. In the present research project we will further characterize both phenotypes by investigating the chemo- and cytokine levels in lavage fluid of lung transplant patients. We will futhermore try to investigate potential new drugs to treat the fBOS phenotype such as anti-inflammatory (non-antibiotic) neo-mactolides, doxycycline and montelukast. This will be investigated in an in vitro model of chronic rejection using cultured human airways smooth muscle cells. We will also further develop our mouse lung transplant model and modulate it to a model of fBOS type chronic rejection to further investigate the aforementioned possible new treatment modalities and to unravel its pathophysiology.
Datum:1 jan 2010 →  31 dec 2015
Trefwoorden:Chronic rejection, Neomacrolides, Montelukast, NRAD, BOS, Lung transplantation