The Impact of Salmeterol-Fluticasone on Sleep in Patients With COPD

Chronic obstructive pulmonary disease (COPD) is a common and clinically important disease
characterized by chronic, irreversible airflow obstruction. Poor sleep quality and insomnia
are well described phenomena in patients with COPD. Several studies suggest sleep
disturbance adversely affects quality of life and may worsen daytime pulmonary function in
COPD patients. Improving sleep quality in patients with COPD, therefore, may not only
improve health quality, but also attenuate the decline in daytime pulmonary function.

Previous studies investigating the effects of inhaled bronchodilators on sleep quality in
COPD have shown conflicting results. These conflicting data prompted us to perform a
retrospective study on patients with COPD and co-existing sleep apnea (OSA) investigating
the effects of mechanical lung function impairment and lung hyperinflation on sleep. Our
study found a significant correlation between increased lung hyperinflation and reduced
sleep efficiency (a measure of sleep quality), and this relationship was preserved in a
multivariable regression model.

We hypothesize that Advair Diskus improves sleep quality by reducing lung hyperinflation in
COPD. To test this hypothesis, we propose a double-blinded, placebo controlled cross-over
study of Advair Diskus in patients with COPD and lung hyperinflation.

It was mutually decided by the sponsor and principal investigator to terminate the study
early due to study subject enrollment difficulties.

Inclusion Criteria:

- Age ≥ 40 years of age

- BMI<30

- Former smokers with ≥ 10 pack-year history

- Diagnosis of COPD, as defined by the American Thoracic Society (FEV1/FVC < 70 with
history of exposure to noxious particles or gases)

- Moderate to severe COPD as defined as an FEV1 ≤ 80% predicted

- Functional residual capacity > 120% or inspiratory capacity < 80% predicted on
pulmonary function testing

- Poor subjective sleep quality: All subjects included must answer "yes" to at least
one of the following questions:

1. Do you have trouble falling asleep?

2. Do you have trouble staying asleep?

3. Do you not get enough sleep?

4. Do you wake up too early and not be able to get back to sleep?

5. Do you fall asleep during the day?

Exclusion Criteria:

- Conditions that in the judgment of the investigator would interfere with subject
participation in the study

- BMI > 30

- History of or physician diagnosed pulmonary disorder other than COPD

- History of significant obstructive sleep disordered breathing (apnea-hypopnea index >
15) or presence of central sleep apnea

- History of narcolepsy, primary hypersomnia, periodic limb movement disorder, or
parasomnia

- History of psychiatric illness

- Presence of decompensated heart failure

- Use of prednisone, antibiotic therapy, or new medication for COPD in the previous 3
months

- Use of any sleep aids

- History of ≥ 1 COPD exacerbation (defined as requiring oral corticosteroids and/or
antibiotics as either an outpatient or inpatient)

- Known allergy or significant adverse reactions to inhaled beta2-agonists and inhaled
corticosteroids (not including thrush and dysphonia)

- Pregnancy or lactating

- Inability or unwillingness to provide informed consent

- Inability to effectively use study medication or perform baseline measurements

- Inability to be contacted by phone