Systemic Inflammation in Chronic Obstructive Pulmonary Disease (COPD)

Acute and Chronic Inflammatory Responses Induced by Smoking in Individuals Being Susceptible and Non-Susceptible for Development of COPD: From Specific Disease Phenotyping Towards Novel Therapy (Study 2).

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. Recently it has become clear that cigarette smoke-induced inflammation is not only present in the lungs but also in the blood, and that this systemic inflammation has important consequences for the clinical expression of COPD. The investigators hypothesize that healthy individuals who are susceptible to cigarette smoking demonstrate a higher and aberrant systemic 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 study systemic inflammation in individuals who are or are not susceptible to develop COPD.
• To characterize the switch to chronicity of the systemic inflmmatory response in COPD
• To determine whether the type and severity of the systemic inflammation contributes to the clinical outcome of COPD
• To compare between subjects who are or are not susceptible to develop COPD in peripheral blood, the corticosteroid responsiveness in vitro, and to unravel underlying mechanisms.
• 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
• To develop new biological and clinical markers for the early diagnosis and monitoring of COPD
• To define possible mediators involved in the early induction of COPD in susceptible smokers, and to define new drug targets

Inclusion Criteria:

Age ≥18 and ≤75 years

• Age, pack years, FEV1/FVC and FEV1% predicted must fit in one of the 9 groups of the study population
• Physically and mentally able to undergo the total study protocol
• Written informed consent

Exclusion Criteria:

• Participation in another study
• Alpha-1-antitrypsin deficiency
• Selected grade 1-3 co-morbidity listed in the ACE-27
• Active pulmonary infection like tuberculosis, pneumonia, flue, tracheobronchitis
• Active extra-pulmonary infection like hepatitis A-C, cystitis, gastro-enteritis etc
• Pulmonary diseases like sarcoidosis, pulmonary fibrosis, silicosis, hypersensitivity pneumonitis, asthma
• Life threatening diseases like carcinoma, AIDS (including HIV+), acute leukaemia etc
• Medication that may affect the results of the study: NSAID's, immunosuppressive agents like prednisolon, metotrexate, azathioprine