Title: Exploring the role of pulmonary sensory receptors in sympathetic regulation of cardiorespiratory function to ozone pollution
Thesis Supervisor: Dr. Bill Sheel
Committee Members: Dr. Michael Koehle and Dr. Chris Carlsten
Chair: Dr. David Wright
Abstract: Traffic related air pollution contains a heterogeneous mixture of gaseous and solid particulates that compromise human cardiorespiratory health. The individual pollutant components within traffic pollution exert differing effects through several different physiological pathways that may include autonomic dysfunction via increased sympathetic outflow. Ground level ozone (O3) has traditionally been examined as a respiratory “irritant” that promotes airway obstruction, resulting in reduced pulmonary function, respiratory discomfort, and airway hyper-responsiveness. Several underlying mechanisms are attributed to the respiratory responses observed during O3 exposure: i.) heightened airway oxidative stress, ii.) local inflammation, and iii.) activation of specific pulmonary sensory “irritant receptors” (i.e., bronchial C fibers and rapid adapting receptors) that detect and respond to air pollution related airway irritation. A small handful of O3 exposure studies have also implicated cardiovascular dysfunction may be present through possible activation of similar pulmonary irritant receptors that result in heightened sympathetic outflow to the heart and vasculature, though this pathway has yet to be established. O3 exposure also promotes both rapid and shallow breathing, which may alter within breath modulation patterns of sympathetic outflow through interactions between pulmonary irritant receptors and pulmonary mechanoreceptors (i.e., slow adapting stretch receptors). ProposedDissertation Theme: To explore the physiological interaction across the respiratory, autonomic, and cardiovascular systems in response to ground level O3 exposure, which has yet to be established in humans. This theme will be explored through three inter-related questions and two proposed studies that overall address one potential pathway that may link both the activation and interaction of pulmonary sensory receptor subgroups with heightened sympathetic outflow and subsequent cardiovascular responses to one component of traffic pollution. Question 1: Does O3 exposure promote sympathetic activation and subsequent cardiovascular dysfunction at baseline and in response to further physiological stress? Question 2: What is the mechanistic role of the pulmonary irritant receptors on the sympathetic and cardiovascular responses to O3 exposure? Question 3:Does O3-induced activation of the pulmonary irritant receptors influence pulmonary mechanoreceptor activity and the subsequent within-breath modulation patterns of sympathetic outflow?