Metabolic Profiling in Patients With Obstructive Sleep Apnea: From Plasma to Hypoxic Cell Model of Peripheral Monocyte

This three-year project aims to

1. Profile the differentially expressed metabolites in healthy patients with severe Obstructive sleep apnea (OSA) before and after six-month continuous positive airway pressure (CPAP) treatment
2. Identify the candidate metabolites involved in biologic pathways attributing to OSA phenotyping and response to CPAP treatment
3. Validate candidate metabolites in the intermittent-hypoxia model of peripheral monocytes

Obstructive sleep apnea is characterized with chronic intermittent hypoxia and sleep fragmentations. The sequels of OSA included excessive daytime sleepiness, cardiovascular disease, and neurocognitive dysfunction which could be reversed with continuous positive airway pressure (CPAP). A couple of biologic pathways have been associated with the phenotyping of OSA which included craniofacial morphology, ventilator control, body fat distribution/metabolism, and sleepiness vulnerability. Metabolomics, a recently developed technique to detect metabolomic profiles, could help to understand the disease pathophysiology and explore biomarkers. So far, only one paper studied the metabolomic profile in patients with OSA where putative identifications of 14 statistically significant features were profiled. Our pilot study comparing the metabolic profiling in OSA patients randomly assigned to therapeutic and subtherapeutic CPAP showed CPAP treatment did alter the metabolomic profile. Seventeen metabolites in three biologic pathways and 13 metabolites in the six biologic pathways were identified in therapeutic and subtherapeutic CPAP, respectively. Sixteen metabolites in three biologic pathways were identified by comparing two groups. However, there were a couple of weakness in studies in the literature and ours. Furthermore, the direct causal relationship of the profiled metabolites and OSA needs to be clarified. Therefore, we plan to compare the metabolic profiling in control subjects and healthy OSA patients, before and after six-month CPAP treatment, to identify candidate metabolites involved in biologic pathways attributing to phenotyping and response to CPAP treatment. Furthermore, candidate metabolites involved in biologic pathways, especially pathways of ROS, inflammation, and metabolism, will be validated in the intermittent hypoxia model of peripheral monocytes.

Eligibility Criteria:
OSA patients

Inclusion Criteria:

* male patients aged 20 to 90 year who have daytime sleepiness (ESS\>=10)
* newly diagnosed OSA (AHI\>30/hr) by overnight PSG but never been treated

Exclusion Criteria:

* unwilling or unable to perform testing procedure
* past or current smoking history
* medical condition (including cardiovascular disease, chronic pulmonary disease, diabetes, endocrinologic disease, chronic renal failure, and psychiatric disease)
* systemic inflammatory conditions (system lupus erythematosus, rheumatoid arthritis, sarcoidosis, Crohn's disease, and ulcerative colitis)
* active neurologic event
* active infection two weeks prior to screening
* enrolled in other trials in the study period
* other sleep disorders
* sleepy driver
* using maintenance medications

Control subjects

Inclusion Criteria:

* Age-, sex-, body weight-, height-matched subjects with enrolled OSA patients
* non-sleepy
* no OSA confirmed by home sleep study (AHI\<5/hr)

Exclusion Criteria:

* unwilling or unable to perform testing procedure
* past or current smoking history
* medical condition (including cardiovascular disease, chronic pulmonary disease, diabetes, endocrinologic disease, chronic renal failure, and psychiatric disease)
* systemic inflammatory conditions (system lupus erythematosus, rheumatoid arthritis, sarcoidosis, Crohn's disease, and ulcerative colitis)
* active neurologic event
* active infection two weeks prior to screening
* enrolled in other trials in the study period
* other sleep disorders
* using maintenance medications