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Systemic Inflammation in Chronic Obstructive Pulmonary Disease (COPD)

Conditions
Chronic Obstructive Pulmonary Disease
Registration Number
NCT00850863
Lead Sponsor
Top Institute Pharma
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
240
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Systemic inflammation assessed by measurement of expression of established and newly developed markers on innate immune cells; genomic and proteomic analysis of innate immune cells and measurement of pro- and anti-inflammatory cytokines in plasma/serum4 years
Secondary Outcome Measures
NameTimeMethod
Extensive clinical characterisation of: a) young healthy individuals with low number of pack years who have a high and low familial risk to develop COPD; b) older individuals with higher number of pack years with either a normal lung function or COPD.4 years
Important clinical endpoints include symptoms, lung function, Bode-index, CT-scanning of the lung.4 years
Distribution of candidate genes (SNPs) for COPD between the different groups and relations with systemic inflammation.4 years

Trial Locations

Locations (1)

University Medical Center Utrecht

🇳🇱

Utrecht, Netherlands

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