ITHS Small Pilot Project Grants

Associations Between Sleep & Disease Activity in Juvenile Idiopathic Arthritis 

Sarah Ringold

Sarah Ringold, MD, MS

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic illness, the most common cause of acquired disability in children, and the sixth most common chronic childhood disease. Despite earlier disease recognition and expanded treatment options, children with JIA continue to report lower health-related quality life, increased fatigue, and increased sleep disturbances as compared to their healthy peers. The etiology of sleep disturbance and increased fatigue in JIA is not well-understood and their relationship to disease activity (e.g. inflammation) in unknown. In order to explore the associations among sleep, fatigue, and disease activity in JIA and to test the hypothesis that sleep disturbance and fatigue are manifestations of disease activity in JIA, we propose to collect data regarding sleep (actigraphy), disease activity (physician assessment, biomarkers), and patient and parent/proxy reports of fatigue and sleep, from a cohort of 20 children with polyarticular or extended-oligoarticular JIA. We anticipate that the results of this pilot study will enable us to better understand the relationship between sleep disturbance, fatigue, and disease activity in JIA and, in doing so, will allow us to identify potential interventions that will result in improvement in both of these outcomes and also in health-related quality of life for children with JIA.

Transcriptional Effects of Sleep Disordered Breathing on Adipose Tissue

Sina Gharib

Sina Gharib, MD

Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent collapse of the upper airway during sleep leading to period of intermittent hypoxia and sleep-wake disturbances. OSA is associated with significant cardiovascular and neurocognitive morbidities, and has been recently linked to metabolic perturbations including insulin resistance, impaired glucose tolerance, and dyslipidemia. Obesity–a chronic illness of pandemic proportions, is one of the strongest risk factors for sleep apnea, yet the impact of OSA on adipose tissue biology is poorly understood. In this application, we intend to systematically explore the effects of sleep-wake disturbances (as manifested by OSA) on adipose tissue obtained from obese individuals. Our primary hypothesis is that OSA activates distinct transcriptional programs in adipocytes that mediate the metabolic and systemic disturbances observed in this disorder. To test our hypothesis, we will harvest subcutaneous and visceral fat from obese patients undergoing ventral hernia repair surgery. Participants will wear a home OSA monitor prior to surgery to determine sleep apnea severity. Whole genome expression profiling of adipose tissue will be performed followed by state-of-the-art computational analysis to determine biological pathways and genetic networks activated in adipocytes of obese subjects suffering from OSA.

Sleep-wake Disturbances in Adolescents Following Mild to Moderate Traumatic Brain Injury

See Wan Tham

See Wan Tham, MBBS

Traumatic brain injury (TBI) is a leading cause of disability in the United States, occurring frequently in the pediatric population with over 700,000 hospitalizations per year, and a peak incidence in adolescents. Sleep-wake disturbances have recently been recognized as common with 28% to 43% of samples reporting sleep problems up to six years post-injury. However, there are not yet data on the specific nature and diagnostic characteristics of these sleep-wake disturbances in the pediatric population. The aims of this application are to 1) characterize the type of sleep-wake disturbances experienced by adolescents with TBI, 2) identify clinical and behavioral risk factors for sleep disturbances, and 3) examine the relationship between sleep disturbances and daytime fatigue. A cohort of 60 adolescents, ages 12 to 18 years, with mild to moderate TBI within the prior 3 – 12 months will be recruited. Subjective and actigraphic assessment of sleep (10 days of recordings) will be conducted. Data from a same-age healthy cohort are available for comparison. This study will provide preliminary data for future investigations that may allow for the development of new interventions designed to decrease sleep disturbances in adolescents with TBI.