Effects of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease (COPD)
Effects of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease (COPD)
Human and animal studies have shown that inhaled corticosteroids (ICS) decrease airway blood
 flow . This effect is immediate (within 30 minutes), transient (lasting 90 minutes), and in
 animal studies independent of gene expression. In COPD patients, decrease in bronchial blood
 flow may also decrease mucosal edema, airway resistance and improve small airway function. If
 such an effect exists, then we should be able to measure improvements in airway conductance
 and reduce lung hyperinflation, which would have salutary effects on dyspnea and exercise
 endurance.

 To our knowledge, no study has examined the immediate effect of ICS on small airway function
 in COPD. The purpose of this study is to examine the effects of nebulized Pulmicort on small
 airway function (spirometry, plethysmographic lung volumes, airways resistance, closing
 volume, partial flow-volume loop analysis) and exercise endurance in patients with moderate
 to severe COPD.

 HYPOTHESIS

 1. Nebulized ICS will immediately improve airway function compared with placebo (nebulized
 saline).

 2. Enhanced lung emptying and reduced operating lung volumes during rest and exercise
 following ICS therapy will translate acutely into clinically important reductions in
 exertional dyspnea and improvements in exercise endurance.
This will be a single site, pilot, randomized, double-blinded, placebo-controlled, cross-over
 study that will be conducted at this centre. Subjects will be required to complete four (4)
 visits to the laboratory over a one-month period.

 At Visit 1, subjects who meet all study inclusion and exclusion criteria, will have a full
 set of pulmonary function tests (PFT) done and complete a symptom-limited incremental cycle
 exercise test. At Visit 2, subjects will have a partial set of pulmonary function tests (PFT)
 done and complete a symptom-limited constant load cycle exercise test. On the third and
 fourth visit subjects will be randomized to treatment with either nebulized saline or
 nebulized Pulmicort® in a double blinded, cross-over design, subsequent to which they will
 have their PFT's and symptom limited constant load exercise testing done.
Inclusion Criteria:

 -  FEV1 less than/equal to 70 % predicted, FEV1/FVC ratio less than/equal to 70%, and FRC
 greater than/equal to 120 % predicted

 -  Moderate to severe chronic activity-related dyspnea (modified Baseline Dyspnea Index
 focal score less than/equal to 6)

 -  Clinically stable as defined by no changes in medication dosage or frequency of
 administration with no exacerbations or hospital admissions in the preceding four
 weeks

 -  Males or females greater than 40 years of age;

 -  A cigarette smoking history of at least 20 pack-years

 -  Able to perform all study procedures and sign informed consent

 Exclusion Criteria:

 -  History of asthma, atopy or nasal polyps

 -  Recent history of cardiovascular disease (< 1 year) or other significant disease that
 could contribute to dyspnea or exercise limitation

 -  Oxygen saturation less than 80% during exercise on room air