Overview
Project 4 will assess the effects of aerosolized toxins on human health with a special focus on populations that are vulnerable due to pre-existing conditions, such as asthma. Project 4 will test the overall hypothesis that exposure to aerosolized cyanotoxins induces significant inflammation in the airway epithelium and that individuals with asthma are particularly susceptible to cyanobacterial harmful algal bloom (cHAB) aerosols with a series if complementary and innovative high-throughput screens, in vivo absorption, distribution, metabolism, and elimination (ADME) aerosolized cHAB exposure and translational human pulmonary health studies. An interdisciplinary and translational program will involve the first-ever prospective assessment of the pulmonary health impacts of cHAB aerosols in susceptible populations in Lake Erie’s Western Basin. Taken together with results from toxin transport modeling (Project 3) and environmental measurements of toxin distributions (Project 1, Project 2, and Project 3), this work will enable assessment of human health risks of cHAB toxins under current conditions and future climate scenarios.
Research Team
Robert McCullumsmith, MD, PhD
Principal Investigator
University of Toledo
College of Medicine & Life Sciences
More Details
Cyanobacterial harmful algal blooms (cHABs) are on the rise globally and pose serious health concerns due to the release of cyanotoxins, which are harmful to both humans and the environment. Microcystin-leucine arginine (MC-LR) and Microcystin-leucine alanine (MC-LA), two of the most toxic congeners of microcystin produced by cyanobacteria of the genus Microcystis, have recently been shown to have the highest concentration in lake aerosol particles. Adverse health effects following exposure to aerosolized MC-LA remain largely unknown. In the literature and our preliminary data, it has been observed that aerosolized MC-LR exposure of the airways leads to mixed granulocytic inflammation, with abundant indications of a Type 1 neutrophilic response. Granulocytic inflammation drives 4 of the 5 endotypes of asthma, which is the most common airway condition in the world and is associated with an increased risk of cardiovascular disease and stroke. However, the impact that aerosolized MC-LA and MC-LR exposure may have on the over 330 million patients with pre-existing asthma remains unknown. Furthermore, Microcystis constitutes just one subset of a host of toxin-producing species and complex mixtures of toxins in freshwater systems whose health effects are largely unknown. Therefore, the overall hypothesis is that exposure to aerosolized cyanotoxins induces significant inflammation in the airway epithelium and that individuals with asthma are particularly susceptible to cHAB aerosols.
Goals
- Interrogate the effects of MCs, such as MC-LA, MC-LR, as well as novel freshwater extracts from P1-3 on cell growth, inflammation and metabolism in primary cells and cell lines derived from physiologically distinct regions on the human respiratory tract from asthmatic and non-asthmatic subjects
- Expose an established pre-existing asthma model to aerosolized MC-LR and MC-LA (alone and in combination) for evaluation of pulmonary inflammation and toxicity in downstream target organ systems
- Perform a prospective cohort study in individuals that live, work, and recreate in the Western Lake Erie basin for the assessment of pulmonary function immediately before, during, and after cHAB seasons
- Results from the cohort study will provide targeted mechanistic data and will define host absorption, distribution, metabolism, and elimination (ADME) routes of toxins
- Inform communities around the world of the risks associated with exposure to aerosolized cyanotoxins, and how these environmental toxins may worsen disease in at-risk populations, potentially influencing local, state, and national policies to protect people living on or around affected bodies of water, as well as provide critical information to healthcare professionals.