Addressing Children's Environmental Health Concerns in the Yakima Valley

Dr. Catherine Karr
Dr. Catherine Karr, a member of the Center for Ecogenetics and Environmental Health (CEEH) and Director of the Northwest Pediatric Environmental Health Specialty Unit (PEHSU) spoke November 10th at the Environmental Protection Agency's Children's Health Month brownbag webinar in Seattle. Her topic was Addressing Children’s Environmental Health Concerns in the Yakima Valley.

Dr. Karr and her team work with community groups to understand environmental exposures and health effects on children in the Yakima Valley. Their research studies, part of El Proyecto Bienestar (The Well-Being Project), include indoor and outdoor air pollution and childhood asthma, pesticide exposure, and nitrate-contaminated drinking water from wells. Their goal is to make conditions better for the community.

The Yakima Valley is an agricultural area. 50% of the population is Hispanic and an additional 6% belong to the Yakama Nation. Health disparities are widespread. Compared to all US children, children in the Yakima Valley experience higher than average rates of poverty, obesity, premature birth, asthma hospitalizations, and adverse childhood events. Children in the Yakima Valley are found to have organophosphate pesticide metabolites in their urine, substances that are associated with neurological issues such as Attention Deficit Hyperactivity Disorder (ADHD). The Yakima Valley is also home to a birth defect cluster of anencephaly and spina bifida that is 4-times the expected occurrence. The cause has not been determined.

Dr. Karr's research begins with the community who, through El Proyecto Bienesta, identified their priorities for environmental health research. The first topic the community wanted to investigate was why so many kids have asthma. This is important new research as most air pollution studies have looked at pollution from city traffic. 

58 children with asthma enrolled in the Aggravating Factors of Asthma in a Rural Environment (AFARE) study. The kids were followed for 2 years. Their lung capacity (FEV1) was measured daily, the community health worker called each family every 2 weeks to assess control of asthma symptoms, and participants' lung function was tested once a year by health providers. To assess air pollution, daily measures of small particulate matter (PM 2.5), fine dust that gets deep into the lungs, were taken in the community, and ammonia monitors were placed at some kids' homes.

Haze from air pollution
The number of days with PM 2.5 levels above federal standards was found to be more days than in Seattle. In the winter, 5% of days had PM 2.5 above federal standards. High PM 2.5 is caused by winter inversions, woodsmoke, agricultural burning, and ammonia, from animal feeding operations (AFOS).

Karr reports that initial findings show evidence of more asthma symptoms and worse lung function the day after high air pollution days. Only 26% of the children had consistently “well-controlled” asthma, based on symptoms and medication use. But over the course of the study, all of the children improved. Karr attributes this to frequent monitoring and follow-up by the community health worker.

The study suggests that community air pollution contributes to asthma morbidity, and that efforts to reduce air pollution from AFOS and PM 2.5 may reduce asthma morbidity and benefit children. 

Even as Karr prepares to publish the AFARE study findings, she and her team are embarking on a follow-up study. Thanks to a new $2.5 million grant from the National Institute of Environmental Health Sciences, they will conduct an interventional study to evaluate the effectiveness of high-efficiency particulate air and ammonia (HEPA/NH3) purifiers in the homes of a new group of children with uncontrolled asthma. The 5-year study is called HAPI: Home Air in Agriculture Pediatric Intervention Study. Enrollment is now underway. 

Responding to a question from listeners, Dr. Karr said her personal recommendation for an air filter is a HEPA filter with a pre-filter for odor (ammonia). She suggested not using an ionizing filter as it would contribute to harmful ozone in the home.

CEEH provided pilot funding for a component of the AFARE study. Others involved in Dr. Karr's research in the Yakima Valley include CEEH researchers Chris Simpson, Edmund Seto, and Mike Yost, researchers in the Pacific Northwest Agricultural Safety and Health Center (PNASH), Heritage University, Yakima Valley Farm Workers Clinic, and the Northwest Community Action Center, which includes Radio KDNA.

Read more about Dr. Karr's research in this February 2015 article in HS Newbeat.

-- Marilyn Hair

Joel Kaufman finds a connection between air pollution and heart disease

Joel Kaufman, Professor of Medicine, Environmental and Occupational Health Sciences, and Epidemiology and Deputy Director of the University of Washington Center for Ecogenetics and Environmental Health, was recently featured on a National Institutes of Enviromental Health Sciences (NIEHS) podcast, Air Pollution and Your Heart. NIEHS podcasts are part of the Partnerships in Public Health (PEPH) program of the NIEHS Division of Extramural Research and Training.

Most people think of air pollution as a cause of respiratory problems like coughing and asthma. It turns out that air pollution is also a significant risk factor for developing heart disease, the #1 cause of death in the United States (see statistics from CDC). It appears that high air pollution can trigger heart attacks and strokes in those who are at risk. As evidence, there is often a spike in the number of heart attacks on and after days with bad air pollution.

And now there is growing evidence that living in areas with higher air pollution puts people at risk for heart disease in the long term. Lab studies show that exposure to air pollution can lead to atherosclerosis (hardening of the arteries), high blood pressure, changes in the size and structure of the heart, and increased likelihood of the blood clots that trigger heart attacks and strokes.

There are ways to reduce your risk. One example is to avoid exercising near roads with heavy traffic or at high traffic times. The benefits of being outdoors, exercising and being active outweigh the risks from air pollution, so if you have to choose, choose to be outdoors and exercise. You can reduce inside air pollution by keeping windows closed or by installing a HEPA air filter. Those who have a heart condition can check daily air quality and stay indoors on bad air days.

Yet finally, air pollution is a societal issue which has to be addressed not by individuals but by society. Joel observes that over the past 40 years, the United States has been extremely successful at reducing air pollution. The story is a public health triumph. There is, however, research still to be done. We know that further reducing air pollution levels would reduce negative health effects. We don't know if there a level where air pollution is no longer a health concern. Also, we measure air pollution by measuring fine particulate matter while traffic exhaust is a mix of pollutants. One or a few agents in the mix may cause the worst health effects; if these can be identified, we could target our public health dollars more specifically and perhaps more effectively.

For more on Joel Kaufman's and NIEHS air pollution research, see this video of the Virtual Forum, Near Roadway Pollution and Health, with NIEHS Director Linda Birnbaum and other NIEHS researchers.

--Marilyn Hair

Kidney toxicity screening tool developed by National Toxicology Program Collaborative Team

Headshot of Vishal Vaidya
Vaidya received the 2015 Achievement Award from the Society of Toxicology, for his significant early career contributions to the field of toxicology. In 2011, he received an NIEHS Outstanding New Environmental Scientist award. (Photo courtesy of Vishal Vaidya)
Headshot of Auerbach
Auerbach is with the NTP Molecular Toxicology and Informatics Group, where he focuses on the analysis and interpretation of multivariate datasets and oversees the DrugMatrix database. (Photo courtesy of Steve McCaw)
A team of researchers including CEEH members Ed Kelly and Jonathan Himmelfarb, along with other NIEHS grantees and National Toxicology Program (NTP) scientists, developed the first method to test for kidney toxicity using high throughput screening (HTS). Because drugs and environmental chemicals can cause injury to kidneys, the new test could help reduce a significant health burden for patients and decrease the financial risk for pharmaceutical and chemical companies.
The team, led by Vishal Vaidya, Ph.D., of Harvard Medical School, and including molecular toxicologist Scott Auerbach, Ph.D., from NTP, published their approach Aug. 10 in the Journal of the American Society of Nephrology. “This high-throughput assay allows, for the first time, rapid and robust screening of kidney toxic compounds, to support chemical risk assessment and facilitate elimination of drug candidates early in the process before they reach humans,” Vaidya said.
High throughput screens were lacking
HTS, which has been advanced by the Tox21 collaboration, is rapidly becoming the standard tool for predictive toxicology, which aims for early detection of adverse health effects from chemical compounds, including medicines.
“The lack of adequate models to accurately predict human toxicity contributes to an underestimation of the kidney toxic potential of new therapeutic candidates,” the scientists wrote, “which also explains why nephrotoxic effects in patients are often only detected during late phase clinical trials, or in some cases, after regulatory approval.”
Using the right cells
The authors reported three important advances. First, they confirmed that the cells they used were suitable for the job. A particular type of kidney cell, called human proximal tubular epithelial cells (HPTECs), is the predominant target of most substances that are toxic to the kidney.
The researchers characterized the structure and function of HPTECs. The cells were shown to possess characteristics of differentiated epithelial cells, which made them desirable for use in in vitro systems.
Finding a biomarker
Next, the team identified a biomarker more sensitive than the currently used assays — cell viability and cell death — to indicate toxicity before changes occurred that might damage the cells.
“A few years ago at the Society of Toxicology annual meeting, Vishal stopped by the NIEHS booth, where we were demonstrating DrugMatrix,” Auerbach said. DrugMatrix is a molecular toxicology database that contains toxicogenomic profiles for hundreds of compounds. “DrugMatrix enabled us to provide a list of prototype kidney toxicants for him to test,” he said.
After exposing the HPTEC cells to nine kidney toxins and analyzing the expression of 1,000 genes, the researchers found that expression of one gene, HO-1, was significantly increased in the presence of the toxins.
The team validated the HO-1 biomarker in two ways. University of Washington researchers Edward Kelly, Ph.D., and Jonathan Himmelfarb, M.D., found that, following a kidney toxicant challenge, HO-1 was induced in a kidney-on-a-chip system that uses living tissue to accurately model organ function. Auerbach, collaborating with Dan Svoboda, Ph.D., of Sciome, LLC, examined two rat toxicogenomic databases and identified a significant association between HO-1 expression and kidney injury.
Additional analyses helped the team refine the assay. “Sensitivity and specificity can be improved even further by combining the readout for HO-1 concentration and the total cell number, measured in the same well,” reported the authors.
Developing and validating the test
Finally, the team developed a new assay to measure HO-1 in a rapid and cost-efficient manner. They used a test called a homogeneous time resolved fluorescence (HTRF) assay (see image below). “The HO-1 levels obtained in response to most of the [39 tested] compounds … correlated well with immunofluorescence,” the authors wrote.
The authors noted some limitations to the method. For example, a chemical might undergo modification in the liver and produce a metabolite toxic to the kidney. This could be missed by the new tool.
However, the authors remarked that it is an important step forward, providing a test that is robust — it detects kidney toxicants from multiple classes of chemicals; it is sensitive, because it picks up toxicants at a high rate; and it is specific, which means it correctly identifies compounds that are not kidney toxicants.

CitationAdler M, Ramm S, Hafner M, Muhlich JL, Gottwald EM, Weber E, Jaklic A, Ajay AK, Svoboda D, Auerbach S, Kelly EJ, Himmelfarb J, Vaidya VS. 2015. A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol; doi:10.1681/ASN.2015010060 [Online 10 Aug 2015].
Scheme of the HTRF assay performed in a 384-well plate
Scheme of the HTRF assay performed in a 384-well plate. When the acceptor labeled antibody and the donor labeled antibody      bind to HO-1, the two dyes are brought into close proximity with each other. Excitation of the donor with a light source triggers a fluorescence resonance energy transfer toward the acceptor. The emission fluorescence can be detected after incubation for four hours. This signal is proportional to the amount of human HO-1 present in the cell lysate. (Photo courtesy of Vishal Vaidya)

--Marilyn Hair
Based on an article in Environmental Factor by Kelly Lennox

Protect Yourself from Wildfire Smoke

The 2015 wildfire season in the Pacific Northwest is the worst yet. Hundreds of fires are burning in Washington, Idaho, Montana, northern California, Oregon and British Columbia. In Washington, it's the largest wildfire complex in state history.

Smoke is much worse this year because of the huge size of the wildfires and an inversion layer that is preventing the smoke from dissipating. Choking smoke has blanketed much of Central and Eastern Washington and some days has even traveled west across the Cascade Mountains. The smoke stings the eyes and throat and causes coughing, runny nose, and headache. These symptoms may happen sooner for children and older adults, those with heart or lung disease, and outdoor workers. People are concerned.

Last year we created a downloadable fact sheet, How to Protect Yourself From Wildfire Smoke with information about exposure to smoke and what to do.

These two websites give current information about smoke and air quality in Washington:

Washington Smoke Information
State air quality map, Washington Department of Ecology

As I write in late August, rain is forecast. Let's hope rain will slow the wildfires, help clear the smoke, and give firefighters and community members a chance to catch their breath.
-- Marilyn Hair

Center participates in National Conference of State Legislators Summit

Center for Ecogenetics & Environmental Health (CEEH) members and staff participated in the Environmental Health Sciences (EHS) Pre-Conference Session of the National Conference of State Legislators (NCSL) Summit on August 3rd at the Washington State Convention Center in Seattle. NCSL is a bipartisan public-policy organization. About 5,000 state lawmakers and staffers attended, including more than 70 Washington legislators.

Those who attended included from CEEH included Center members Terry Kavanagh, Gretchen Onstad, Kelly Edwards, and Rose James, as well as UW faculty Steve Gilbert, and Clarita Lefthand-Begay, and CEEH staff members Liz Guzy and Marilyn Hair. State legislators from California, Montana, Connecticut, Wisconsin, Arkansas, New York, and Maryland, among others, and a legislator and staff from Western Australia attended the EHS Pre-Conference Session. The American Chemical Council (ACC) and Scott's MiracleGro were also represented.

Dr. Onstad participated on a panel that addressed Water and Health: Quality and Quantity. Other panelists were Professor David Osterberg of the University of Iowa Environmental Health Sciences Research Center, Rep. Gary Scherer of Ohio, Assemblyman Adam Gray from California, and Ann Aquillo, Vice-President of Scotts Miracle-Gro. Dr. Lefthand-Begay served on a panel focused on Environmental Justice, along with Robin Fuchs-Young from the NIEHS Environmental Health Sciences Center at Texas A&M University, Johnnye Lewis from the University of New Mexico, and Elena Craft of the Environmental Defense Fund. A third panel presentation addressed Hydraulic Fracturing and Environmental Health.

Much of the session was devoted to audience interaction. Legislators were concerned about environmental health issues in their districts, and the concerns of their constituents, among them air quality; health effects of living near major roadways; silica sand mining in Wisconsin, industry-sponsored research on the health effects of fracking in North Dakota, toxic algal blooms from fertilizer runoff in the midwest, and increasing water capacity in central California's agricultural region, in the face of a continuing drought. The legislators were well informed and almost universally sympathetic to protecting public health.

Roundtable discussions were held over box lunches on five topics: Environmental Public Health Labs, PCBs in Schools, US-Mexico Border Environmental Health Concerns, Mining and Health, and Toxics and Chemicals.

Drs. Terry Kavanagh and Steve Gilbert
I joined the Toxics and Chemical discussion, facilitated by Terry Kavanagh. Three staff from the American Chemical Council, an industry group, joined the table. A dialog ensued between ACC representatives and EHS researchers regarding disclosing the components of products such as flame retardants and hydrofracking fluid. The ACC spoke up for propriety rights of industry, while the toxicologists defended the public's right to know what they're being exposed to. The ACC's defense of propriety rights was based on economics; they said information needs to be protected to keep others from using trade secrets and suggested we should wait and see what happens to people who live and work near fracking sites. Steve Gilbert shot back, "Who's going to be in that study?" and "We need to protect children from these chemicals so they can grow up to their full potential." The discussion was civil and respectful and it was good to have different perspectives talking to each other. But from a public health perspective, let's try it, wait and see, and trade secrets aren't good enough for protecting people's health.

The goal of the EHS workshop was to open a dialog between leading environmental health sciences researchers and outreach directors, and staff legislators and staff, with the intent to increase the level of scientific input into policy development and decisions. The workshop was supported by a grant from NIEHS, Dr. Robin Fuchs-Young, Principal Investigator.
--Marilyn Hair