Transcriptomics of the human airway epithelium reflect the physiologic response to inhaled environmental pollutants

Current methods for the risk assessment of environmental exposures commonly involve questionnaires, stationary monitoring, and personal air sampling. However, as these approaches do not capture the body's internal response, they lend minimal understanding to the biologic consequence of exposure. In order to address the unmet need of connecting external exposure measurements with signatures of internal exposure, this thesis examines the overarching hypothesis that transcriptomic changes in the human airway epithelium can serve as indicators of physiologic responses to inhaled pollutants. This is an extension of previous work that has demonstrated an airway ''field of injury'' effect where cigarette smoke exposure alters gene-expression in epithelial cells lining the respiratory tract. Specifically, I examine transcriptomic changes and the biologic responses associated with exposure to the following pollutants: environmental tobacco smoke (Aim 1), household air pollution from smoky coal combustion (Aim 2), and electronic cigarette vapor (Aim 3). First, I performed whole-genome transcriptional profiling of the nasal epithelium in children and adults and detected gene-expression changes associated with exposure to environmental tobacco smoke. Next, I employed similar approaches to detect a signature of coal smoke exposure in the buccal epithelium of healthy, non-smoking females exposed to household air pollution Xuanwei, China. The findings from these studies suggest that upper airway gene-expression can reflect the host response to prolific sources of environmental exposures that are major risk factors for chronic lung disease. Lastly, I examine the cellular and physiologic consequences of electronic cigarette (ECIG) aerosol exposure by analyzing transcriptomic profiles of human bronchial epithelial cells that have either been (1) differentiated and exposed in vitro or (2) acquired via bronchoscopy from the airway epithelium of ECIG users. The studies detailed in this dissertation offer valuable insight that will accelerate the efforts to evaluate the health effects of both well-established and emerging types of inhaled exposures in large-scale population studies. Furthermore, the transcriptomic strategies woven throughout the following chapters push for a novel assessment paradigm that may enable the public health community to rapidly characterize the physiologic host response to inhalation exposures of different sources, and to evaluate the biologic consequences of exposure-reduction initiatives.2017-05-01T00:00:00