Developmental exposure to organophosphorus pesticide to evaluate airway hyperreactivity Epidemiological studies have linked organophosphorus pesticide (OP) exposure to increased risk of asthma in children and adults, yet preclinical evidence supporting this causal link is limited. Dr. Grodzki’s previous work has shown that the OP chlorpyrifos causes airway hyperreactivity (AHR) at low doses that do not inhibit acetylcholinesterase. However, current understanding of the mechanisms involved in OP-induced AHR is incomplete and the question of whether developmental OP exposure could lead to asthmatic symptoms has not been addressed in preclinical models. Dr. Grodzki is investigating the effects of developmental chlorpyrifos exposures on AHR using physiological measurements of lung function and markers of neurogenic inflammation in animal models.
Health effects of airborne particulate matter near the Salton Sea: A Community-based exploratory project in the Imperial Valley, CA. The Salton Sea is a man-made, saline lake, located in southeastern California, in the Imperial and Coachella valleys. As a result of climate change, drought, agricultural practices, rural-urban water transfers, the Salton Sea is a polluted and shrinking lake. Communities are concerned about high rates of asthma and the potential role of the Salton Sea as a source of air pollution, both from hydrogen sulfide from the lake bed, and airborne dust and toxic particulate matter, and other health hazards stemming from the lake’s deteriorating water quality and increasingly exposed banks. For this project, Dr. Pinkerton and his team are investigating how particulate matter (ambient PM2.5 and PM10) might sensitize the immune system to house dust mite (HDM) allergen. In particular, the researchers are interested in understanding the role of inflammation, oxidative stress and other pathways of PM-mediated immunotoxicity in the Imperial Valley. The team is working in collaboration with The Environmental Justice Coalition for Water (EJCW) and Comité Cívico del Valle (CCV), and the communities of of Brawley and Calipatria.
Immune mechanisms of ozone-induced lung inflammation in non-human primates Persistent exposure to air pollution leads to changes in immune function in the respiratory system. These changes can trigger allergic asthma and increase susceptibility to respiratory infections. Exposure to high levels of ozone, a major toxic air pollutant, worsens asthma and COPD symptoms. While the exact mechanisms of ozone induced airway disease are not understood, Dr. Haczku and her team are investigating the role of innate lymphoid cells (ILC), specifically the activation of pulmonary and circulating ILC following ozone exposure and the relationship between ILC counts and the extent of airway hyperresponsiveness (a major feature of asthma).
Postnatal Neuroimmune Integration of Environmental Stresses Over the last 40 years, epidemiological studies have shown a disturbing trend of increasing incidence of allergic asthma in children. A wide range of stressors in the womb or during early life can increase the risk of developing allergic childhood asthma. Given the broad spectrum of stressors, it is likely that numerous systems in the body (i.e., the nervous and immune systems) contribute to the observed increase in allergic childhood asthma. Specialized tissues in the body serve to coordinate immune responses and are required for the development of allergic asthma. These tissues are still developing in the lung during early life and receive signals from various systems that control body functions. We hypothesize that the developing tracheal- and bronchial-associated mediastinal lymph nodes are critical sites where environmental exposures change normal development and set the stage for allergic asthma. The stages of development in humans and other primates is not clear; this study will first examine normal development and the consequences of environmental exposures on immune cells.