This is an R01 funded project that focuses on the utility of metabolomics as a biomarker for OSA. Aims 1 and 3 leverages banked samples previously collected from subjects with and without OSA at the University of Pennsylvania and University of Iceland. Aim 2 is a prospective study that will collect serum samples from OSA subjects at the University of Pennsylvania and the University of Iceland.

The primary objective of Aim 2 is to conduct a prospective observational study to evaluate the metabolomic changes in response to six months of positive airway pressure (PAP) treatment among OSA patients. Newly diagnosed OSA patients (AHI>5) will undergo additional measurements including: accelerometer x one week (to inform the metabolomics), Type 2 home sleep test (to assist with OSA subtyping), next morning blood draw, 24-hour diet recall (to inform the metabolomics), questionnaires and PVT.

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 30-75 years old
4. In good general health as evidenced by medical history and diagnosed with Obstructive Sleep Apnea (defined as AHI>5)
5. Ability to use accelerometer, perform Type 2 sleep test at home and agree to use PAP treatment.
6. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.

Exclusion Criteria:

1. Current use of PAP treatment or mandibular advancement device or INSPIRE device
2. Presence of active cancer treatment or heart failure (ejection fraction <40%)
3. Pregnancy or lactation
4. Known allergic reactions to components of the plastic (used in PAP mask)
5. Febrile illness within 2 weeks of signing consent
6. Current drug or alcohol abuse
7. Known diagnosis and treatment of diabetes because this will independently alter metabolomic results.
8. Previously drawn laboratory Hemoglobin A1C above normal range (indicative of diabetes).

Prospective recruitment of female and male OSA subjects n=500/site: Site #1 is University of Pennsylvania; Site #2 is University of Iceland for a total of n=1000 cases.

Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be transmitted to and stored in REDcap. This will not include the participant's contact or identifying information. Rather, individual participants and their research data will be identified by a unique study identification number. The study data entry and study management systems used by clinical sites and by the University of Pennsylvania research staff will be secured and password protected. At the end of the study, all study databases will be de-identified and archived at figshare <https://figshare.com\> [blocked].

IPD will be available to research teams within 1 year following study completion.

Data collected for this study will be analyzed and stored in figshare <https://figshare.com\> [blocked]. After the study is completed, the de-identified, archived data will be transmitted to and stored in figshare <https://figshare.com\> [blocked], for use by other researchers including those outside of the study.