Obstructive Sleep Apnea: Daytime Assessment And Treatment Of A Nighttime Disorder

Abstract

Obstructive sleep apnea (OSA) is a disease characterized by nighttime airflow limitation, hypoxemia, arousal from sleep, and elevated sympathetic activity and blood pressure. With time, this nighttime dysfunction gives rise to daytime hypertension and a heightened risk for cardiovascular disease. Current treatment options for OSA are not always effective for all patients and the gold-standard intervention, continuous positive airway pressure, has discouraging compliance rates. The work set forth in this dissertation has as its focus a novel intervention for sleep apnea known as inspiratory muscle training (IMT). IMT improves respiratory function and cardiovascular health but has not been implemented previously as a treatment for OSA. As such, Study 1 implements IMT in individuals with mild and moderate OSA, with the objective of assessing the effects of training on the cardio- respiratory parameters of this disease. We randomly assigned 24 individuals with mild- moderate OSA into one of two groups: training vs. placebo, to assess the effects of 6 weeks of training on overnight polysomnography, subjective sleep quality, blood pressure, circulating inflammatory T cells, and plasma catecholamine content. Our results show IMT- related improvements in sleep quality, reduction in the number of arousals from sleep and in periodic limb movements following 6 weeks of training. Most important, IMT was associated with a significant reduction in systolic (~12 mmHg) and diastolic (~5 mmHg) blood pressure, relative to sleep apneics who undertook 6 weeks of placebo training. Additionally, individuals in the training group exhibited ~30% lower levels of sympathetic activity, as measured by plasma catecholamines, relative to placebo trained peers. The mechanism(s) that underlie the IMT-related reductions in blood pressure and sympathetic activity remain to be determined. However, in an effort to determine the precise respiratory stimulus that contributes to the results obtained in Study 1, we subsequently assessed the specific respiratory components of IMT to determine which component (large intrathoracic pressures and/or large lung volumes) likely contributes to the reduction in blood pressure in Study 1. The results of this study conducted in normotensive adults show that respiratory training that entails either large negative or positive intrathoracic pressures reduces systolic and diastolic blood pressure in healthy young adults. Importantly, neither the generation of large lung volumes alone nor performance of daily paced breathing is sufficient to lower blood pressure. Study 3 is a methodologic study that has as its focus upper airway electromyography (EMG) and the utility of assessing EMG activity across a range of conditions and breathing tasks in wakefulness. Because OSA traditionally has been viewed as the result of neuromuscular dysfunction of the upper airway that occurs during sleep, the aim of this work was to develop a "fingerprint" of healthy electromyographic activities during the day in healthy adults across a range of breathing tasks, body positions, and from two different muscle compartments of the upper airway. The findings from this study demonstrate regional differences in muscle activity that vary as a function of body position and task. These data from healthy subjects provide the basis of comparison for subsequent studies in individuals with obstructive sleep apnea.