Explorative Study on the Molecular Pathology of Lung Fibrosis by Combination of Clinical Assessment and System Biology

RESOLVE's objective is to identify and characterize validated molecular targets capable of shifting primary organ repair towards fibroproliferative wound healing. Work package 2 (WP2) of RESOLVE includes the clinical study protocols within the RESOLVE system evaluating different forms of pulmonary repair in humans ranging from normal repair over mainly inflammatory to predominantly fibroproliferative repair. Hypothesis Fibrosis of the lung is an aberrant and intensified form of wound healing. It is the result of an unresolved disturbance of both initiation and control of repair which is partly age-related. As a result of the relentlessly activated wound healing reaction, mechanisms of inflammation largely representing the condition of chronic inflammation within the peripheral bronchial tree will aggravate this abnormal form of repair. A systematic comparison of the molecular pathology of fibrotic repair representing * Varying intensity of fibrosis related to the pathology of usual interstitial pneumonia (UIP), * Varying inflammatory mechanisms (UIP vs. Hypersensitivity pneumonitis \[HP\], acute and chronic), and * Varying stages of age (Normal pulmonary repair in young and old individuals vs. acute/chronic HP vs. UIP) will be able to * identify molecules capable of shifting regular repair towards fibroproliferative repair and * elucidate their interrelationship with other molecules forming coordinated yet misdirected metabolic responses characteristic for fibroproliferative repair.