Comparing Fluticasone-salmeterol in Chronic Obstructive Pulmonary Disease (COPD) and Sleep

RATIONALE:

Chronic obstructive pulmonary disease (COPD) is a term that describes a disease state in
which there is chronic irreversible airflow limitation. It has been well documented that
patients with COPD have disturbed sleep. Certain published reports suggest that more than 50%
of COPD patients have sleep complaints (George et al., Drugs, 2003). These patients are found
to have sleep onset latency and poor sleep maintenance. While their sleep disturbance may be
explained in part by side effects of medications, it could also be a result of nocturnal gas
exchange abnormalities (Knutty 2004). In COPD there is worsening hypoxemia and hypercapnia
during sleep, particularly rapid eye movement (REM) sleep, and sleep disturbance seems to be
worse with more severe COPD. It is commonly believed that optimizing medical management of
the disease is important in improving the sleep quality of these patients and thus leading to
improved quality of life.

Fluticasone, an inhaled corticosteroid and salmeterol, a long-acting beta agonist, are
approved for use in the management of COPD. Fluticasone/salmeterol has been shown to
significantly improve FEV1 and decrease COPD symptoms (Calverley et al. 2003, 2007). Inhaled
corticosteroids have been shown to decrease frequency of COPD exacerbations (Gartlehner et
al. 2006) and long acting bronchodilators demonstrated a reduction in dyspnea, increased
airflow and reduction in hyperinflation in patients with symptomatic COPD (Ramirez-Venegas et
al. 1997). Specifically, salmeterol has also been shown to have a positive effect on symptoms
and health status of patients with COPD when added to usual treatment (Stockley et al. 2006).

Previous research of subjects from our group with asthma has shown salmeterol to be
associated with sustained improvements in morning PEF, protection from nighttime lung
function deterioration and improvement in patient perception of sleep (Wiegand et al. 1999).
This study has not been performed in patients with COPD nor has the effect of salmeterol with
fluticasone on sleep quality been assessed.

AIM:

The aim of this study is to determine the effect of fluticasone/salmeterol on sleep quality
in patients with COPD and to compare efficacy of Advair 250 compared to placebo on sleep.

The hypothesis is that there would be a significant improvement in sleep quality when
patients are placed on fluticasone/salmeterol as compared to placebo.

Inclusion Criteria:

1. Patients with moderate to severe COPD as per GOLD criteria

2. Insomnia, poor sleep, non-restorative sleep or daytime sleepiness by history

3. Age 45 to 75 years, male or female

4. FEV1 below 80% of predicted using CRAPO

5. FEV1/FVC < 70% predicted

6. Past or present tobacco smoker

7. Female patients must be postmenopausal for 1 year or be willing to use birth control
or abstain from sex.

Exclusion Criteria:

1. Asthma

2. Use of oral or injectable corticosteroids within 2 months

3. Previous diagnosis of sleep disorder breathing (sleep apnea, narcolepsy, etc.)

4. Lung or heart disease except for COPD

5. Deviated nasal septum, nasal polyps or anatomic obstruction of the nose

6. Obesity defined as BMI >30kg/m2

7. Inability to tolerate or history of allergy to long acting beta agonist or inhaled
corticosteroid therapy.

8. Inability to complete a 2 week run-in with albuterol prn as only therapy

9. Use of narcotics, sleep aids, sedating antihistamines, sedatives, MAO Inhibitors, and
other medications known to affect daytime somnolence or sleep quality

10. Excessive use of alcohol or use of "recreational drugs"

11. Use of narcotics, sleep aids, sedatives or sedating antihistamines.

12. Night shift workers

13. Women who are breast feeding or pregnant.