ARSENIC AND NON-MALIGNANT RESPIRATORY HEALTH OUTCOMES: EPIDEMIOLOGICAL EVIDENCE AND THE NEED FOR INTERVENTIONS IN AMERICAN INDIAN COMMUNITIES

Inorganic arsenic, an established toxicant, has been associated with numerous health outcomes, including cancer of the lung. Evidence on the impact of arsenic exposure on nonmalignant respiratory outcomes, however, is less conclusive as studies examining low-moderate levels (<50 µg/L) of water arsenic exposure are limited. In the US, elevated arsenic disproportionately affects populations relying on private well water, including many American Indian communities. Additionally, these American Indian communities have historically been at an increased risk of tuberculosis. This dissertation aimed to better understand the relationships between arsenic exposure and nonmalignant respiratory health outcomes in a population exposed to low-moderate arsenic from drinking water. We used data from the Strong Heart Study (SHS), a prospective cohort of American Indian adults, and the Strong Heart Water Study (SHWS), a randomized controlled trial aiming to reduce arsenic exposure in American Indian communities. First, we conducted an analysis in 2,132 SHS participants to evaluate associations of arsenic exposure with lung health using urinary arsenic measurements at baseline (1989-1991) and spirometric measurements at Visit 2 (1993-1995). Arsenic exposure was positively associated with restrictive pattern, airflow obstruction, lower lung function, self-reported emphysema and having to stop for breath, independent of smoking and other lung disease risk factors. Second, we evaluated the relationship between a history of active tuberculosis and subsequent lung function in 2,463 SHS participants. We observed that a history of active tuberculosis was associated with airflow obstruction, restrictive pattern, and respiratory symptoms. We found a reduced odds of tuberculosis with increasing arsenic exposure, contrary to our hypothesis, but suggestive evidence of a possible synergistic interaction between arsenic and tuberculosis on worse lung function. Third, we conducted a pilot study, in preparation for the SHWS, of 371 households to identify households with arsenic ≥10 µg/L. Arsenic ≥10 µg/L was found in 26.1% of households and median water arsenic concentration was 6.3 µg/L, ranging from