Responses Induced by Smoking in Individuals Being Susceptible and Non-Susceptible for Development of COPD

COPD is ranked number 3 by the WHO list of important diseases worldwide and is the only disease with increasing mortality. The pathogenesis of cigarette smoke-induced COPD is obscure, therefore more insight is needed to design effective anti-inflammatory agents. We hypothesize that healthy individuals who are susceptible to smoking demonstrate a higher and aberrant inflammatory response to cigarette smoke. This susceptibility is caused by heterogeneous factors and is associated with various polymorphic genes that interact with each other and with the environment. Objective: * To define mediators involved in the early induction of COPD in susceptible smokers (and so to define new drug targets) * To develop new biological and clinical markers for the early diagnosis and monitoring of COPD * To compare between susceptible and non-susceptible individuals the corticosteroid responsiveness of bronchial epithelial cells in vitro, and to study the mechanisms of smoking-induced corticosteroid unresponsiveness. * To study the role of candidate genes that may play a role in the development of fixed airway obstruction, and to identify clues for patient's responsiveness to specific drugs.