Trial Information

Effects of Bronchodilation on CT Parameters Reflecting Airways Remodelling, and Pulmonary Emphysema Extent: Comparisons Between CT Scans Obtained Before and After Bronchodilation and Relationships With Pulmonary Function Tests.

Patients : COPD patients aged 40 years or more, with a smoking history of > 10 pack-years
(PY) and a post-bronchodilator forced expiratory volume in one second to vital capacity
ratio (FEV1/VC) < 0.7 will be included. Exclusion criteria are: COPD exacerbation or
respiratory infection in the 4 weeks before the begin of the study, concomitant pulmonary
disease (tuberculosis, significant bronchiectasis, lung cancer), pulmonary resection, active
malignancy or malignancy of any organ system within the past 5 years.

Procedures:

At Visit 1, after obtaining the written informed consent of the patient, medical history,
smoking status and patient's treatment will be collected. They will be asked to discontinue
bronchodilator therapies as follows, such that pulmonary function tests (PFT) and CT scan
will be initially evaluated in a medication wash-out period at Visit 2:

- Short acting a2 agonists and anticholinergics: 8 wash-out

- Long acting a2 agonists: 12h wash-out

- Long acting anticholinergics: 48h wash-out

- Theophylline preparations: 48h wash-out

- Antileucotrienes: 48h wash-out

At visit 2, PFT will be performed, including vital capacity (VC), forced vital capacity
(FVC), functional residual capacity (FRC), total lung capacity (TLC), residual volume (RV),
forced expiratory volume in one second (FEV1), diffusion lung capacity for carbon monoxide
(DLCO), and alveolar volume (VA) measurements (either in absolute values and percentage of
predicted values). A first CT scan will be performed using the following technique:

- Supine CT scan after full inspiration.

- Acquisition parameters: (Topogram 35 mA 120 kV 512 mm length) 90 quality ref mAs with
care-dose ON 120 kV Pitch 1.4 Rotation time 0.33 s Acquired images 64 x 0.6 mm

- Reconstructions parameters:

B60f 1mm-thick every 0.7 mm B20f 1mm-thick every 10.0 mm B35f 1mm-thick every 0.7 mm B60f
5mm-thick every 5.0 mm B35f 5mm-thick every 5.0 mm

After the initial PFT and CT scan, the patient will receive 80 µg of ipratropium bromide(=
4X20µg Atrovent, via Metered-Dose Inhaler + spacer, 30 seconds between each dose) and 60
minutes later, 400 µg salbutamol (=4X100 µg Ventolin).

A second PFT will be performed 30 min after salbutamol inhalation, followed by a second CT
Scan.

Data analysis:

- Emphysema index: from B20f reconstructions, calculation of RA960 using Pulmo CT
software.

- Airway index: from B60f reconstructions (1mm-thick every 0.7 mm), calculations of
luminal area and wall area for several bronchi.

Statistical analyses : Comparisons of CT parameters values or derived values (for example :
wall area to airway area ratio) reflecting emphysema and airways remodelling, before and
after bronchodilation. Correlations with PFT values and derived values.