In obstructive sleep apnea, fragmented sleep and recurrent hypoxemia resulting from periodic occlusion of the upper airway have been associated with significant daytime hypersomnolence, increased traffic fatalities, systemic and pulmonary hypertension, cardiac dysrhythmias and cerebrovascular disease. while the prevalence of obstructive sleep apnea is estimated between 2-4% in the general population, the prevalence of partial rather than complete upper airway obstruction during sleep in snorers and obstructive hypopnea patients who are potentially at risk for developing this syndrome is significantly higher. Although the pathogenesis of upper airway obstruction in this disorder is not well understood, it has been suggested that varying degrees of obstruction are related to structural abnormalities in the upper airway and/or alterations in neural control. Nevertheless, clear anatomic or functional differences among these groups have not been discerned. This proposal, applying principles of flow through collapsible conduits to the study of the human upper airway during sleep, tests the hypothesis in Specific Aim #1 that varying degrees of obstruction among groups along a continuum from health to disease are related to quantitative difference in critical pressure (Pcrit).
In Specific Aim #2, we will demonstrate that quantitative differences in Pcrit among these groups account for observed reductions in inspiratory airflow during sleep. In intervention studies, this proposal will examine whether changes in the severity of obstructed breathing in response to specific etiologic, structural and neural interventions are due to alterations in Pcrit (Specific Aims #3, 4). This approach draws on the expertise of senior faculty in Pulmonary Physiology at Johns Hopkins Univ. in the areas of pressure-flow mechanics, sleep respiratory physiology and ventilatory control, thereby facilitating an integrated approach studying the pathogenesis of periodic obstructive sleep apnea. Furthermore, this work will provide the foundation for more basic investigations which will examine the role of upper airway mechanoreceptor and pulmonary stretch receptor activity in the maintenance of airway patency. The training program outlined in this proposal will provide expert guidance, and specific and general research skills to a well- qualified PI recently appointed to the faculty who has already demonstrated his abilities as a researcher in this field.
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