NOCTURNAL ASTHMA--INCREASED BRONCHIAL RESPONSIVENESS

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The overall objective of this grant is to further our understanding of the nocturnal worsening of asthma in regard to the circadian increase in bronchial responsiveness during the night. This will enable better therapeutic interventions, based upon specific knowledge, for the treatment of this high frequency and morbidity entity. The methods of achieving this goal will focus on cellular, neural and structural changes within the airways on a circadian basis. These aspects will be correlated to the physiologic functioning of the airways. The specific experimental designs will be: 1. To measure and mechanically alter lung volume during sleep to determine the volume/resistance relationship and the effect of changing lung volume on inflammation, vagal tone and bronchial responsiveness. 2. To determine the role of inflammation by decreasing the airways cellularity, on bronchial responsiveness and the interaction of inflammation to volume and vagal tone. 3. To measure and block vagal tone as another factor of nocturnal asthma and increased bronchial responsiveness. 4. To determine the morphologic changes in the airways (endobronchial biopsies) and its relationship to changes in lung volume, airways resistance, airways inflammation, vagal tone and bronchial responsiveness.