Role of MU5AC Mucins in Airway Disease

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EXCEED THE SPACE PROVIDED. A number of research studies indicate that adult and pediatric ICU patients have severely disrupted sleep while in the ICU. Chronic sleep deprivation impairs physical and mental health. Pediatric burn patients exhibit symptoms of sleep deprivation, including increased metabolic rate, susceptibility to opportunistic infection, increased mortality, growth hormone insufficiency, and thermoregulatory abnormalities. Severe bums induce a hypermetabolic catabolism associated with reduced growth hormone secretion that may cause peripheral muscle wasting and impair tissue repair. Medications used for the management of pain and for treating symptoms of various injury-induced stress and anxiety disorders may also alter sleep architecture. We propose in this application to test the hypothesis that improvement of sleep quality will result in a less severe reduction in growth hormone secretion due to the well-documented relationship between slow wave sleep onset and growth hormone secretion. Such improvement in spontaneous growth hormone secretion patterns may aid in recovery by supporting tissue repair and by minimizing the hypermetabolic response to thermal injury. We will test this hypothesis by evaluating sleep of burned children that are receiving GH replacement. We anticipate the sleep of these children will be more consolidated and will be characterized by a higher percent of slow wave sleep (SWS) time. We wiii also explore several mechanisms by which responses to bum may lead to sleep disruption. These mechanisms include actions of various neuropeptides, hormones, and immune-active substances (cytokines). We plan to investigate these issues by evaluating sleep architecture in these patients and determining whether circulating levels ofcytokines known to modulate sleep (IL-lc_, IL-I-[3, IL-6, TNF, IL-10, cortisol and melatonin) are associated with sleep disruptions in burned children, or if the determinant of cytokine values in these children is more greatly dependent upon the other treatments they are receiving, and the percent of their burn. PERFORMANCE SITE ========================================Section End===========================================