An observational study to obtain normal values of inflammatory variables in induced sputum, exhaled breath, and bronchial biopsies from healthy smoking and non-smoking individuals

Smoking induces an inflammatory reaction in the airways which can ultimately
result in persistent damage and the development of a Chronic Obstructive
Pulmonary Disease (COPD). However, not all subjects who smoke end up with COPD.
After long-term smoking, approximately 20% of subjects develop COPD. At this
time, it is unclear why some subjects develop COPD, whereas others maintain a
normal lung function.

In addition, smoking has important consequences in asthma. Patients with asthma
who smoke have a more severe asthma and more often experience an asthma
exacerbation. In addition, it has been shown that inhaled corticosteroids are
less effective in smoking asthmatics.

With this research project, we will investigate the effects of smoking on the
airways. To this end, we will compare markers of airway inflammation, lung
function and symptoms between healthy smokers and non-smokers of varying age.
In addition, we will compare those healthy subjects with patients with asthma
and COPD which are characterized in earlier studies.

ONDERZOEKSVRAAGSTELLINGEN
1. Are differences with respect to markers of airway inflammation, lung
function and symptoms between smokers
and non-smokers of varying age?
2. Which aspects of airway inflammation are associated with symptoms and lung
function?
3. What is the effect of smoking on corticosteroid responsiveness (as can be
investigated with laboratory techniques in
sputum and blood.
4. Are there differences with respect to the effects of smoking between healthy
subjects and patients with asthma or COPD.
5. Is there a genetic difference between healthy smokers and smokers who have
developed COPD.

This is an observational study. A total of 120 healthy subjects will be
included, subdivided into 4 groups of 30 subjects each:
1. 30 individuals * 40 years, who currently smoke * 10 cigarettes/day and >
10
packyears.
2. 30 individuals * 40 years, who have not smoked during the last year, have
never smoked for as long as a year (i.e. at least one cigarette per day
or
one cigar per week, AND have < 0.5 packyear.
3. 30 individuals above 40 years, who currently smoke * 10 cigarettes per
day,
and > 20 packyears.
4. 30 individuals above 40 years, who have not smoked during the last year,
have
never smoked for as long as a year, and have < 0.5 packyear.

These subjects will be extensively characterized with respect to symptoms, lung
function parameters and inflammatory parameters in sputum, blood, and bronchial
biopsies.

- Questionnaires (Asthma Control Questionnaire, Clinical COPD Questionnaire
(CCQ), Asthma Control Questionnaire (ACQ), Co-Morbidity Questionnaire (ACE-27),
Short QUestionnaire to Assess Health-enhancing Physical Activity (SQUASH).
- ECG.
- AGE reader.
- Spirometrie, CO diffusion.
- Induced sputum
- CO diffusion.
- Blood and urine.
- Bronchoscopy.
- Skin prick test.
- Measurement of exhaled NO.

This study is not associated with large risks. Possible adverse reactions may
be:
- Blood collection may be painful and cause skin bruising.
- The provocation test with methacholine or AMP may cause temporary dyspnea.
- The HRCT scan of the lung is associated with radiation which may be harmful.
- The bronchoscopy may cause irritation of the airways and the bronchial biopsy
may cause local bleeding.