• 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 characterize the switch to…
ID
Source
Brief title
Condition
- Congenital respiratory tract disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Local inflammation before and after cigarette smoking assessed by exhaled
breath condensate, microprobe sampling and bronchial biopsies.
• Systemic inflammation before and after cigarette smoking assessed by the
expression of established and newly developed markers on innate immune cells
associated with pre-activation.
• Extensive clinical characterisation including life style factors, lung
function, CT scanning of the lung.
• Corticosteroid responsiveness of epithelial cells in vitro.
• Distribution of candidate genes (SNPs) for COPD between the 5 different
groups and associations with the inflammatory responses on acute smoking.
Secondary outcome
n.a.
Background 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. 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.
Study 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 characterize the switch to chronicity of COPD and demonstrate phase
differences between local pulmonary and systemic components
• 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.
Study design
This is an observational study without a therapeutical intervention.
Study burden and risks
• Totally 22 hours will be spend in the hospital during 5 visits
• Metacholine provocation may cause temporary bronchoconstriction in subjects
with increased hyperresponsiveness.
• CT-scanning of the lung is associated with a radiation burden of 0,8-1,6 mSv
depending on the weight of the participant.
• Two bronchoscopies with taking central biopsies after local anaesthesia with
lidocaine 2%.
• Smoking 3-4 cigarettes during one hour.
• Sputuminduction with possible airway obstruction and dyspnoe.
Hanzeplein 1
9713 GZ Groningen
NL
Hanzeplein 1
9713 GZ Groningen
NL
Listed location countries
Age
Inclusion criteria
• Age 18-75 years
• Age, pack years, FEV1/FVC and FEV1% predicted must fit in one of the 5 groups of table 4.1
• Able to stop smoking for 10 days and start smoking 3-4 cigarettes within 1 hour
• 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, IPF, silicosis, hypersensitivity pneumonitis
• 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,Sintrom tablets
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL23440.042.08 |
| Other | Wordt nog gedaan |