The Cardiovascular Consequences of Sleep Apnea Plus COPD (Overlap Syndrome)

For Aim 1, we will perform a cross-sectional clinical study that will allow us to test the hypothesis that individuals with OVS have increased markers of vascular risk compared with matched individuals with OSA alone or COPD alone. This aim will also allow us to compare the magnitude of the effect of OSA vs. COPD vs OVS for design of subsequent basic and clinical studies.

For Aim 2, we will perform a randomized 1:1 clinical trial stratified by sex that will allow us to test the hypothesis that bi-level PAP therapy is superior to oxygen in the treatment of individuals with OVS from the standpoint of right ventricular mass (primary outcome) and other cardiovascular risk parameters/outcomes. We will use these interventions as tools to explore their impacts on important biomarkers of interest e.g., miR210 may predict risk of atherosclerosis and changes in levels may give insight into mechanisms of our interventions. There is no sub-study analysis. The aim of the interventional section of this study (aim 2) is to analyze the effect on cardiovascular outcomes of both nocturnal oxygen therapy and bi-level therapy on patients with COPD-OSA overlap syndrome.

Participants will undergo the following activities:

• Eligibility screening (online or via phone; ~10 minutes)
• Subjects who screen positive: In-person eligibility assessment (~1.5 hours) including a history, exam, questionnaires, spirometry, and an overnight home sleep test.
• Participants who are eligible: Will come to the research lab for an overnight visit (~12 hours) which includes the following activities: general exam, questionnaires, blood test, measures of cardiovascular health (e.g., blood pressure), neurocognitive function (e.g., a memory test), a pulmonary function test, and an overnight sleep study to assess the severity of sleep apnea.
• After overnight visit 1, participants will come to day time visit 2 for the cardiac MRI. After this visit, participants who are only COPD or only OSA will have completed the study. Participants with OVS will be offered to continue the study. Participants will come to the research lab for a mask adaptation day visit; if they can tolerate a bilevel mask, they will be randomized to the oxygen versus the bi-level arm. We will ask participants to be on the therapy for 6 months, during which time the research team will make weekly calls to check adherence to the therapies.
• After 6 months on the treatment, OVS participants will come back to an overnight visit which includes the following tests: general exam, questionnaires, blood test, measures of cardiovascular health (e.g., blood pressure), neurocognitive function (e.g., a memory test), and an overnight sleep study. Additionally, they will have a day time visit for the Cardiac MRI.

Researchers will compare the effects of bi-level PAP on cardiovascular health with the effects of oxygen to see if bi-level may be an effective treatment for select patients with OVS.

Inclusion criteria

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Persons aged 40-79.
• For women, only postmenopausal women will be included
• Diagnosed with untreated moderate to severe obstructive sleep apnea (apnea-hypopnea index ≥15 events/hr and ≤80 events/hr) and/or diagnosed with COPD with FEV1/FVC ratio <0.7 and will be on stable medications as assessed by a board-certified pulmonologist.

Exclusion criteria

• Premenopausal women (i.e. women are pregnant or may become pregnant) or lactation
• Presence of specific devices: cardiac implantable electronic device (CIED) such as pacemakers, implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) devices, metallic foreign bodies, implantable neurostimulation systems, cochlear implants/ear implant, drug infusion pumps (insulin delivery, analgesic drugs, or chemotherapy pumps), metallic fragments such as bullets, shotgun pellets, and metal shrapnel , cerebral artery aneurysm clips, magnetic dental implants, and artificial limb.
• Known allergic reactions to components of the study intervention: (if getting contrast, MRI contrast (gadolinium)).
• Concurrent severe sleep disorders (such as periodic limb movements, restless legs syndrome, narcolepsy, idiopathic hypersomnia, etc).
• Exhibit Cheyne-Stokes respiration or central sleep apnea (> 25 % of events central)
• Take potentially confounding medications or hormones that affect breathing.
• Subjects will be excluded if they are deemed medically unstable with active neurological, cardiac, liver, endocrine, and infectious diseases.
• We will also exclude participants with pulmonary disease apart from COPD.
• We will exclude participants with active cancer treatment.
• We will exclude azotemia (estimated glomerular fraction rate < 30ml/min) as there is some concern about giving gadolinium to these patients (if getting contrast MRI).
• people with exposures deemed to be problematic for the research e.g. any smoking in bedroom by participant or household member, major second-hand smoke, e-cigarettes, tetrahydrocannabinol, major drug or alcohol consumption (>3 oz/day) and other environmental pollution effects (indoor and outdoor).
• Individuals who are already on continuous O2 for COPD or PAP treatment for OSA.
• Patients with sustained desaturations below 89% during wake time will be excluded for ethical reasons since withholding oxygen in hypoxemic patients would be at odds with standard of care.
• Individuals with OSA (AHI range 15-80/hr) will be screened for pathological sleepiness and will be excluded if ESS >18/24, history of motor vehicle accident or near miss accident, or high-risk occupation.
• COPD individuals with arterial PCO2 higher than 52 mmHg will be excluded.
• Individuals who are currently incarcerated.