Cardiac Hemodynamics in Overlap Syndrome (COPD With Obstructive Sleep Apnea)

Presence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA)
in the same patient has been termed overlap syndrome, affecting 1% of the U.S. population.
Despite the high prevalence of overlap syndrome, little research has been done in this
field. Overlap syndrome has been recently reported to have higher death rate than COPD
alone, which is due to effect on the heart. However, the mechanisms by which overlap
syndrome affects the heart are not known well. Also, the ideal treatment for overlap
syndrome is not known.

This study is being done to find the mechanisms by which overlap syndrome affects the right
and left sides of heart (using cardiac MRI to study the heart). We will also compare the
effect of treatment with bi-level positive airway pressure device (BPAP) vs. night-time
oxygen on heart in overlap syndrome. These aims will allow us to test the hypothesis that
overlap syndrome patients have worse heart function than COPD only or OSA only, and
treatment with BPAP device will improve the heart function better than oxygen only.

At the baseline visit, the subject will undergo an overnight sleep study in the hospital. In
the morning, blood draw to measure serum inflammatory biomarkers (C-Reactive Protein,
interleukin-6, P-selectin, ICAM-1, TNF-alpha), urine catecholamine level, six-minute walk
test, questionnaire for health-related quality of life score and modified Medical Research
Council (MMRC) dyspnea score, lung function tests, ultrasound of forearm blood vessels and
cardiac MRI will be done. No follow-up visit is needed if the subject does not have sleep
apnea. If the subject has sleep apnea based on the sleep study, he/she will be allotted to
treatment with a BPAP device or night-time oxygen for 6 months. If the subject does not want
to be treated with BPAP or oxygen, CPAP device will be used to treat sleep apnea. During the
duration of study treatment, phone calls and a brief study visit at 3 months will be done to
make sure there is no discomfort related to the treatment. After 6 months of study
treatment, cardiac MRI, ultrasound of forearm blood vessels, lung function tests, blood draw
for serum inflammatory biomarkers, urine catecholamine level, six-minute walk test, and
questionnaires for dyspnea score and quality of life score will be repeated.

This study will help us in better understanding of mechanisms of high death rate due to
effects on the heart in overlap syndrome. It will also help us in understanding better ways
to treat sleep apnea in COPD patients.

Inclusion Criteria:

- Both men and women with age more than 18 years.

- Known diagnosis of COPD (GOLD stage 2 or higher).

Exclusion Criteria:

- Already using CPAP or BPAP device.

- Estimated GFR <30 ml/min/1.73 m2 or on hemodialysis.

- Women known to be pregnant or planning to be pregnant in next 6 months.

- Cardiac pacemaker, metallic heart valves, metallic implants, claustrophobic.

- Chronic atrial fibrillation or frequent premature ventricular contractions.

- Using lipid-lowering medications, aspirin, oral steroids, steroid-sparing medications
or anti-oxidant vitamin supplements.

- If taking sildenafil or related drugs, unable to stop it within 48 hours of the study
visit.

- Contraindications to stress cardiac testing: acute myocardial infarction within 48
hours, unstable angina not yet stabilized with medical therapy, ongoing chest pain,
active broncho-constriction, uncontrolled cardiac arrhythmia, symptomatic severe
aortic stenosis, aortic dissection, acute pulmonary embolism or pericarditis.

- Uncontrolled COPD or acute COPD exacerbation.

- Known chronic inflammatory diseases like lupus or active infection.