A Pilot Study of Biomarkers in Obstructive Sleep Apnea (OSA): Is There a Correlation Between Cerebrospinal Fluid and Serum Markers of Inflammation in OSA?
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Obstructive Sleep Apnea
- Sponsor
- Hospital for Special Surgery, New York
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Serum IL-6 (Interleukin 6) Levels
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
Obstructive sleep apnea (OSA) is common and is a risk factor for postoperative complications, including respiratory and cardiac events and delirium. Despite this risk, however, there are currently no accepted biomarkers that can predict poor outcomes, making it unclear to see which patients will have complications after surgery, and who might need prolonged monitoring or an extended hospital stay. An improved understanding of the pathophysiology of OSA is required to identify potential biomarkers for outcomes after surgery, as well as to develop new treatments. The aim of this pilot study is to identify serum and cerebrospinal (CSF) biomarkers associated with obstructive sleep apnea (OSA). The presence of cytokines and neurotrophins will be determined and quantified in both patients with OSA and in controls. The CSF samples will additionally be analyzed by proteomic methods to identify potential biomarkers with significantly different levels present in patients with and without OSA. The working hypothesis is that OSA patients who are non-CPAP-compliant will have higher levels of circulating cytokines and lower levels of circulating neurotrophins in serum and CSF, compared to patients who are CPAP-compliant and/or controls.
Detailed Description
It is being increasingly understood that OSA represents an inflammatory state, with multiple studies showing increased levels of circulating cytokines, possibly providing the link between OSA and cardiovascular/pulmonary morbidity. In support of this, use of CPAP therapy is associated with a reduction in the levels of circulating cytokines in patients with OSA. Despite these data, to our knowledge, there are no studies that specifically examine the association between the presence of cytokines and surgical complications. The present investigation may be helpful for future studies looking at this relationship.Inflammation has recently been emphasized as a component of the CNS manifestations of OSA as well, including generalized cognitive deficits and post-operative delirium. It is possible that intermittent hypoxia leads to CNS inflammation/activation of microglia (as has been shown in in vitro studies), which, together with blood-brain barrier (BBB) breakdown (recently shown to be involved in OSA), results in elevated circulating peripheral levels of cytokines. Alternatively (or additionally), there could be direct peripheral activation of systemic macrophages as a consequence of sleep deprivation and the cortisol/stress response to this condition. In any event, to date, there are no studies exploring the presence or levels of cytokines in the CSF of patients with OSA. In addition to the release of inflammatory cytokines, activation of microglia causes the release of neuroprotective neurotrophins. Alterations in levels of several neurotrophins have been implicated in multiple CNS diseases. For example, in Parkinson's disease, there is a known elevation in cytokines with reduced circulating levels of CSF neurotrophins (BDNF and NGF) and this balance has been posited to underlie some of the symptoms and progression of the disease. BDNF has recently been shown to protect against the development of Alzheimer's disease and dementia, as well as to increase with caloric restriction and physical activity. Considering OSA is associated with obesity, it is possible that low BDNF may (at least in part) mediate some of the cognitive deficits seen in OSA. Additionally, low BDNF is associated with postoperative delirium in clinical studies. Currently, the role of neurotrophins in OSA remains underinvestigated. Of all the known neurotrophins, only BDNF has been studied in OSA patients, and the results are conflicting, with some studies suggesting reduced levels of serum BDNF and others showing no differences compared to control patients. This may in part be due to the detection methods employed or small sample sizes, and to date, no one has investigated CSF levels of neurotrophins in this patient population. Here we hypothesize that the detrimental effects of circulating cytokines in OSA may be balanced in some patients by beneficial effects exerted by neurotrophins, and that this differential balance may represent: 1) a tool for identifying which patients are at risk for post-operative complications in future studies, i.e., a useful biomarker for stratifying operative risk; 2) a new understanding of the pathophysiology of OSA; and 3) a role for neuroprotective strategies in the management of OSA.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients between the ages of 50 and 84
- •Treated and Untreated OSA Patients: Known OSA, diagnosed by polysomnography
- •Treated OSA Patients: Known CPAP prescription, dose used nightly, and compliance status
- •Controls: No suspicion for OSA, based on STOP-BANG screening score (\<3)
- •Any patient presenting for knee replacement surgery with prior consent for spinal or combined spinal-epidural anesthesia
Exclusion Criteria
- •Presence of dementia
- •Presence of cognitive disease
- •Presence of depression, anxiety, or other mood disorder(s)
- •Recent oral steroid therapy (within prior 6 months)
- •Requirement of stress-dose steroids pre-operatively
- •Autoimmune disease
- •Neurologic disease
- •Controls: Suspected OSA, either disclosed by patient, or by clinical suspicion based on STOP-BANG questionnaire (score ≥ 3)
- •Chronic renal disease
- •Chronic liver disease
Outcomes
Primary Outcomes
Serum IL-6 (Interleukin 6) Levels
Time Frame: Intraoperatively - Pre-Incision
The primary outcome, the levels of cytokine IL-6 in serum of OSA-treated, OSA-untreated and control patients presenting for knee replacement surgery with planned spinal or combined spinal-epidural anesthesia.
Secondary Outcomes
- Length of Stay in the Recovery Unit(Throughout stay in the recovery unit, or an average of 1-2 days.)
- Serum and CSF (Cerebrospinal Fluid) Levels of the Cytokines TNF-alpha (Tumor Necrosis Factor) , IL-6, IL-8, IL-10 (Interleukin)(Intraoperatively - Pre-Incision)
- Number of Participants With Respiratory, Cardiac, and/or CNS (Central Nervous System) Complications(Throughout hospital stay, or an average of 1 week.)
- Serum and CSF Levels of the Neurotrophins BDNF, IFN-gamma (Interferon Gamma)(Intraoperatively - Pre-Incision)
- Incidence of Intraoperative Obstructive Respiratory Events(Throughout hospital stay, or an average of 1 week.)
- Levels of Blood Oxygen Saturation(Throughout stay in the recovery unit, or an average of 1-2 days.)