Study Background

It is now well understood that complex diseases are the result of host-by-environment interactions. These interactions occur at any stage of life (proof preconception to old age) and can influence the development and exacerbation of disease, or conversely the maintenance of homeostasis and health. However, the mechanisms and nature of these complex interactions remain poorly elucidated. This natural history protocol will allow for targeted pilot studies, using low-risk approaches and environmental exposure modeling, both in vivo (through detailed history, or targeted recruitment of individuals with a specific exposure history, e.g., smoking or a specific occupation) and in vitro (noxious or injurious environmental stimuli), to determine the pathomechanism of host-environment interactions in human health and disease.

The mission of the National Institute of Environmental Health Sciences is to discover how the environment affects people in order to promote healthier lives. Environmental health sciences encompass the study of all levels of biological organization – molecular, biochemical pathway, cellular, tissue, organ, system, model organism, individual, and population – at all stages across the lifespan, from preconception through old age. Recent scientific findings indicate that while genetic variation plays a role in many common diseases, these diseases may only manifest themselves when certain environmental factors are present. Heart disease, breast cancer, and osteoporosis are such examples. In addition, diseases and conditions traditionally classified as “environmental,” such as lead exposure in children, HIV and other infectious diseases, adverse drug effects, and nutritional status, may each be influenced by a genetic component. Furthermore, comorbidities or occupational exposures may influence the response to environmental agents and therefore the susceptibility to injury, as recently evidenced by the increased morbidity and mortality of COVID-19 in individuals with pre-existing conditions. Thus, it is paramount to understand the mechanisms of these interactions, in order to develop targeted therapeutic and preventative measures. Recent advances in medical science have enabled us to model some of these interactions using low-risk methods (e.g., obtaining easily and safely accessible tissues and body fluids like blood, urine, skin, airway epithelia) and modeling exposures either in vitro (e.g., cigarette smoke exposure) or by having a detailed understanding of medical history and exposures (e.g., by recruiting individuals based on occupation, exposure, comorbidities, or genetics). This allows for mechanistic insights in humans without exposing the human subjects to increased risk due to environmental exposures. This study will utilize such approaches in order to examine the mechanisms of environmentally induced injury and inflammation that ultimately lead to human disease.