Symbicort in Airway Predominant Chronic Obstructive Pulmonary Disease (COPD)

Subjects from the COPDGene study who have airway-predominant COPD on chest CT scan will be
enrolled; a total of 40 subjects is planned.

Subjects will all have background ipratropium-albuterol administered four times daily.
Subjects will be randomized to receive budesonide (180 ug twice daily) or
formoterol-budesonide (160/4.5 ug twice daily) for 12 weeks.

The main objective is to explore novel outcomes: blood biomarkers and chest CT scan.
Outcomes include lung function, walk distance, respiratory disease-specific health status,
and expiratory chest CT scan gas trapping as an exploratory outcome.

The primary outcome measure will be FEV1 pre-bronchodilator 12 hours after the last dose of
study medication at the end of 12 weeks of treatment. FEV1 will be measured in the morning 6
hours after the last dose of ipratropium/albuterol and 12 hours after the last dose of
budesonide and budesonide/formoterol

Inclusion Criteria:

1. COPD GOLD Stage 2 and 3 (post-bronchodilator FEV1 35-80% predicted and FEV1/FVC <0.7
at the time of enrollment in COPDGene) by spirometry.

2. Less than 15% of the lung <-950 Hounsfield Units on COPDGene high-resolution
inspiratoryChest CT scan (i.e. no evidence of significant emphysema)

3. Greater than 10% gas trapping on COPDGene expiratory CT scan (i.e. evidence of small
airway disease).

4. No history of recent use (within the pat 8 weeks) of an inhaled or systemic
corticosteroid.

5. Body weight <100 kg (low dose CT scans in subject with increased boyd weight can not
be reliably analyzed).

Exclusion Criteria:

1. Exacerbation of COPD or other respiratory illness requiring antibiotics within the
past 8 weeks.

2. Previous adverse reaction to inhaled steroids, long-acting beta agonists, or
long-acting anticholinergic medications.

3. Symptomatic, untreated benign prostate hypertrophy.

4. Allergy to peanuts.

5. Glaucoma