KFO 118:  Pathomechanisms and Therapy of Lung Fibrosis

• Subject Area: Medicine
• Term: from 2004 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5397057

Interstitial Lung Diseases (ILD, also termed "Lung Fibrosis" or "Diffuse Parenchymal Lung Disease") develop in the course of more than 120 different etiologies, of whom some affect only the lung, some the whole body. Almost half of all patients develop a slowly progredient disease which cannot be stopped by the established treatment options (mostly immunosuppressive drugs and steroids). As a consequence, increasing dyspnea, initially upon exercise, later on rest, alongside with a progredient limitation of the physical exercise and the quality of life, develops. In the later stages of the disease, almost all patients do have to perform a chronic oxygen therapy. Lung transplantation offers as the ultimative option but is characterised by profound limitations itself. In the worst case, patients are dying two years after settling the diagnosis. In Germany, there are about 100.000 patients with ILD, thus 100 times less than patients with asthma. However, every year more patients dye from fibrotic lung diseases than due to asthma, thus reflecting the aggressive nature of this disease.The primary goal of the Clinical Research Unit is to elucidate the molecular mechanisms underlying the onset and the progression of Lung Fibrosis. Based on these new insights new therapeutic strategies are thought to be developed and to be tested in the frame of animal models of ILD. The Clinical Research Unit is focussing on subjects such as genetic predisposition to IPF, disturbances in the process of alveolo(neo)genesis, intracellular signal transduction pathways of important growth factors, differential gene regulation under influence of these growth factors, cell-cell as well as cell-matrix interactions, regulation of surfactant and alveolar surface tension, regulation of the alveolar hemostasis system and pulmonary pharmacotherapy including aerosol strategies. Finally, a highly active "Out Patient Clinic" for Lung Fibrosis is fully integrated into this Clinical Research Unit. Despite the diversity of different methodological approaches, the ultimative mission statement of our Clinical Research Unit is very clear: elucidating the mechanisms and developing new therapeutic strategies in lung fibrosis.

• DFG Programme: Clinical Research Units

Projects

• Dysregulation of pericullar proteolysis and growth factor functions in lung fibrosis: haemostasis-related pathomechanisms and new therapeutic modalities (Applicant Preissner, Klaus T. )
• HEALFIB: Eine randomisierte, doppel-blinde, Placebo-kontrollierte Multicenter-Studie zur Sicherheit und Effizienz von inhalativem Heparin bei Idiopathischer Pulmonaler Fibrose (Applicant Günther, Andreas )
• Koordination der Klinischen Forschungsgruppe 118 (Applicant Günther, Andreas )
• Mesenchymal-epitheliale Interaktionen bei fibrosierenden Lungenerkrankungen (Applicant Rose, Frank )
• Pathogenetische Rolle und therapeutischer Nutzen des pulmonalen Surfactant-Systems bei fibrosierenden Lungenerkrankungen (Applicant Günther, Andreas )
• Role of Phosphodiesterases in Lung Fibrosis - Pathogenetic Mechanisms and Therapeutic Options (Applicant Savai Pullamsetti, Soni )
• Rolle der HIF/VEGF-Achse bei der Bronchopulmonalen Dysplasie (BPD): Entwicklung pharmakologischer und molekularer Interventionsstrategien (Applicant Schermuly, Ralph )
• TGF-ß aktivierte Signaltransduktion in der Epithelial-Mesenchymalen Transiton (EMT) im Rahmen der Lungenfibrose: kausale Beziehungen zwischen Transkriptionsfaktoraktivierung, DNA-Bindung und Fibrosierung (Applicant Eickelberg, Oliver )
• Untersuchungen zur klinischen Bedeutung und zum möglichen therapeutischen Nutzen antimikrobieller Proteine bei fibrosierenden Lungenerkrankungen (Applicant Markart, Philipp )

• Spokesperson: Professor Dr. Werner Seeger
• Leader: Professor Dr. Andreas Günther