The investigators submit this grant application for a research award to study the pathophysiology of nocturnal asthma in children and determine its impact upon childhood well-being and cognitive function. Sleep-related asthma occurs in 61-74% of asthmatics and is characterized by awakenings associated with dyspnea, wheezing, coughing, and air hunger. The consequences of nocturnal asthma are frequent arousals and hypoxemia which may contribute to poor sleep, daytime sleepiness and fatigue, and impaired cognitive functioning. Episodes tend to cluster in the later part of sleep in the early morning. This apparent circadian fluctuation and impact of nocturnal asthma have been studied in adults but not in children. In response to RFA HL-99-011 (Nocturnal Asthma, Chronobiology, and Sleep), a multidisciplinary team of pediatric immunologists, pulmonologists, sleep medicine physicians and a neuropsychologist will use the facilities of the General Clinical Research Center to test the hypotheses that in children: (1) altered circadian variations in inflammatory response contribute to the worsening of asthma at night, (2) nocturnal asthma leads to greater disruption of nighttime sleep, breathing patterns during sleep, and tendency for daytime sleepiness, and (3) nocturnal asthma adversely affects daytime cognitive functioning, in respect to attention, concentration, and memory. Circadian variations in plasma chemokines and cytokines, blood eosinophils, and exhaled nitric oxide will be determined in a group of children with nocturnal asthma and two control groups (asthmatic children with no night symptoms and non-asthmatic children). The children will undergo overnight polysomnography, multiple sleep latency tests, and neuropsychological tests to characterize sleep and determine the impact of nocturnal asthma on daytime sleepiness and cognitive functioning. The occurrence of nocturnal asthma in children may impact on the natural history of asthma, leading to a more resistant and longer course which requires more and longer duration therapy. These studies will characterize the impact and increase the understanding of the pathophysiology of nocturnal asthma in children, thereby promoting optimal treatment of these children.
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