Clinical trial NCT00850863: Systemic Inflammation in Chronic Obstructive Pulmonary Disease (COPD)
Official title: 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).
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Inflammation
Smoking
Susceptibility
Lead sponsor: Top Institute Pharma
Sponsor class: OTHER
Collaborators: name: Academisch Ziekenhuis Maastricht
name: University Medical Center Groningen
name: UMC Utrecht
name: GlaxoSmithKline
name: Nycomed
First posted: 2009-02-25
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy individuels and COPD patients. For detail description see Groups/Cohorts.

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


Eligibility criteria: 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

Primary outcomes:
measure: 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/serum
timeFrame: 4 years
Secondary outcomes:
measure: 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.
timeFrame: 4 years
measure: Important clinical endpoints include symptoms, lung function, Bode-index, CT-scanning of the lung.
timeFrame: 4 years
measure: Distribution of candidate genes (SNPs) for COPD between the different groups and relations with systemic inflammation.
timeFrame: 4 years
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: UMC Utrecht
name: Jan-Willem Lammers, Dr. Prof. MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoonhorst SJ, Lo Tam Loi AT, Pouwels SD, Faiz A, Telenga ED, van den Berge M, Koenderman L, Lammers JW, Boezen HM, van Oosterhout AJ, Lodewijk ME, Timens W, Postma DS, Ten Hacken NH. Advanced glycation endproducts and their receptor in different body compartments in COPD. Respir Res. 2016 Apr 26;17:46. doi: 10.1186/s12931-016-0363-2.
citation: Hoonhorst SJ, ten Hacken NH, Lo Tam Loi AT, Koenderman L, Lammers JW, Telenga ED, Boezen HM, van den Berge M, Postma DS. Lower corticosteroid skin blanching response is associated with severe COPD. PLoS One. 2014 Mar 12;9(3):e91788. doi: 10.1371/journal.pone.0091788. eCollection 2014.
citation: Lo Tam Loi AT, Hoonhorst SJ, Franciosi L, Bischoff R, Hoffmann RF, Heijink I, van Oosterhout AJ, Boezen HM, Timens W, Postma DS, Lammers JW, Koenderman L, Ten Hacken NH. Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible to development of COPD: from specific disease phenotyping towards novel therapy. Protocol of a cross-sectional study. BMJ Open. 2013 Feb 1;3(2):e002178. doi: 10.1136/bmjopen-2012-002178. Print 2013.