Biomarkers for Obstructive Sleep Apnea
Condition: Obstructive Sleep Apnea (OSA)
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Observational

Summary: 
      The purpose of the study is to:

        -  recruit subjects with untreated sleep apnea; assess overnight changes in their blood and
           urine chemicals

        -  review the overnight changes in blood and urine chemicals after they have been treated
           for sleep apnea

        -  assess the overnight changes in blood and urine chemicals in healthy individuals with no
           sleep problems

        -  compare the amount of fat in the belly using a Magnetic Resonance Imaging (MRI) scanner
           on all subjects
    

Detailed description: 
      The overall goal of this project is to address the postulate that the optimal molecular
      signature for the common disorder obstructive sleep apnea (OSA) is change in relevant
      biomarkers during the sleep period. In sleep apnea, events lead to sleep fragmentation and
      cyclical deoxygenation/reoxygenation. It is proposed that these changes will lead to
      molecular consequences can be detected by assessing biomarkers in blood. To determine which
      changes are due to OSA and which to circadian/sleep mechanisms, studies will be done in
      patients with OSA before and after effective treatment with Continuous Positive Airway
      Pressure (CPAP) and also in controls of similar visceral adiposity without OSA. Multiple
      assessments of biomarkers will be made before, during and after sleep. Since it is proposed
      that the magnitude of these dynamic changes across the sleep period will be affected by
      degree of visceral obesity and be greater in OSA subjects with cardiovascular comorbidities,
      studies will be done in 4 groups of subjects: lean and obese with and without such
      morbidities. In assessing biomarkers the primary outcome variables will be: urinary
      isoprostanes (oxidative stress); plasma tumor necrosis factor alpha (TNFα) (inflammation);
      plasma norepinephrine (sympathetic activation); and free fatty acids. Secondary biomarkers
      will be: Interleukin 6 (IL-6), urinary norepinephrine; urinary normetanephrine; glucose,
      Intercellular Adhesion Molecule (ICAM), leptin. To complement assessment of circulating
      biomarkers, an approach utilizing a cellular window will be used. Monocytes will be separated
      from each blood sample (before, during and after sleep) and RNA extracted. Expression of key
      genes will be assessed by RT-PCR and microarray studies will be performed in a subset of
      subjects to assess changes in expression of all genes as a result of OSA. A particular focus
      will be investigating differences between individuals with OSA with and without
      cardiovascular comorbidities. Three aspects will be evaluated: a)whether individuals with
      comorbidities have more oxidative stress and inflammatory change for equivalent degrees of
      OSA than individuals without such comorbidities; b) whether individuals with comorbidities
      have lower levels of protective mechanisms-melatonin (an anti-oxidant secreted during sleep),
      IL-10 (antiinflammatory); c) different gene variants based on a genetic association study
      using a recently developed CV SNP array. Finally, data will be used to determine whether
      there is a diagnostic urine and/or blood test for OSA.
    

Intervention name(s): CPAP
Intervention type(s): Device
Intervention description(s): Use CPAP for 4-6 weeks as clinically prescribed.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        OSA patients with moderate to severe disease as confirmed by apnea-hypopnea index (AHI >
        15) in a polysomnography. Healthy controls, both snorers and nonsnorers, with an
        apnea-hypopnea index (AHI < 5) in a polysomnography.
      
Biospecimen description: 
      Primary outcome variables: tumor necrosis factor alpha (TNFα); plasma norepinephrine, and
      free fatty acids. Secondary biomarkers: Interleukin 6 (IL-6), urinary norepinephrine; urinary
      normetanephrine; glucose, Intercellular Adhesion Molecule (ICAM), leptin. Monocytes will be
      separated from each blood sample (before, during and after sleep) and RNA extracted.
      Expression of key genes will be assessed by RT-PCR and microarray studies will be performed
      in a subset of subjects to assess changes in expression of all genes as a result of OSA. We
      will evaluate: a)whether individuals with comorbidities have more oxidative stress and
      inflammatory change for equivalent degrees of OSA than individuals without such
      comorbidities; b) whether individuals with comorbidities have lower levels of protective
      mechanisms-melatonin, IL-10; c) different gene variants based on a genetic association study
      using a recently developed CV SNP array.