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

Patients with both sleep apnea and COPD have overlap syndrome, but their optimal management is not known. We plan to conduct a randomized trial of of bi-level PAP vs. night time oxygen to asses the impact of intervention on cardiac MRI and biomarkers.

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.

Eligibility Criteria:
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.