NEW RESEARCH: USC investigators contribute to a landmark study about the genetics of allergies

Study significantly expands the known genetic markers to household and seasonal allergies

USC investigators at the Southern California Environmental Health Sciences Center,  Zhanghua Chen, Frank Gilliland, and W. James Gauderman, were contributing authors to a study published this month in Nature Genetics. The meta-analysis, involved over 80 contributing authors, analyzed known genetic links to allergic rhinitis as well as identified new genes associated with the allergy diagnosis. The population studied included almost 60,000 cases of allergic rhinitis in people of European ancestry and compared these cases to a control group (people who had not been diagnosed with allergic rhinitis) of over 150,000 people. “In order for this size of study analysis to be accomplished, many cases must be analyzed to provide sufficient power to detect genetic markers related to disease.  We became involved in this study because we have genetic information of nearly five thousand children who participated in the Children’s Health Study. Once all study criteria were met for this analysis, our team contributed genetic data from 587 cases and 965 controls to the entire GWAS study sample,” said Keck School of Medicine post-doctoral research associate Zhanghua Chen.

The study identified 42 genetic markers that are known to be associated with risk for developing allergic rhinitis, 21 of which had not been previously reported in other research studies.

“This study helps to enhance our scientific knowledge about the genetic network that plays a critical role in the causes of allergic rhinitis. The findings highlight the involvement of immune activity in the development of allergic rhinitis. These genetic findings may help clinicians to prevent and treat people who have higher genetics risk to develop allergic rhinitis,” said Chen.

In the United States, 6.1 million children and 20 million adults are affected with allergic rhinitis per year.  A medical diagnosis of allergic rhinitis indicates that a person’s nasal passages become irritated and inflamed. Their health and quality of life is affected as they have allergies to pollens (seasonal) and/or indoor allergens (year-round) to things such as dust mites, feathers, animal dander and mold.

Allergic rhinitis is a complex disease caused by both genes and environment, and numerous genes contribute to the cause of the disease. This type of genetic study requires a very large sample size to have sufficient power to detect significant disease-related markers. Therefore, the large consortium of researchers assembled for this study has the advantage to pool samples from their research, to increase the sample size and discover new genetic variants for this common genetic condition.

To participate in this study, the USC researchers received funding from:

The CHS and related research was supported by the Southern California Environmental Health Sciences Center (grant P30ES007048); National Institute of Environmental Health Sciences (grants 5P01ES011627, ES021801, ES023262); P01ES009581, P01ES011627, P01ES022845, R01 ES016535, R03ES014046), National Cancer Institute (PO1 CA196569, P50CA180905), National Heart, Lung, and Blood Institute (R01HL061768, R01HL076647, R01HL087680, and RC2HL101651), the Environmental Protection Agency (grant #s RD83544101, R826708, RD831861, and R831845), and the Hastings Foundation.

The study can be found at: https://doi.org/10.1038/s41588-018-0157-1

The USC Children’s Health Study is the study that keeps on giving

The USC Children’s Health Study, the well known longitudinal study on children’s respiratory health that began in 1993 and continued until 2013 with over 12,000 participants, has set an example for researchers across the globe. Most recently, USC Keck School of Medicine Professor W. James Gauderman has collaborated with a group of researchers at Queen Mary University of London as they design a similar study to assess how air pollution reduction strategies being implemented in London may contribute to changes in children’s respiratory health.  Check out the video about the study below. More information about the study can be found on the website.

Featured in NIEHS PEPH Newsletter: Shrinking Salton Sea Threatens Children’s Respiratory Health

Our team of researchers was featured in the National Institute of Environmental Health Sciences (NIEHS) Partnerships for Environmental Public Health  (PEPH) Newsletter for May 2018: 

Children living in Imperial Valley, California, have higher rates of respiratory problems compared to children elsewhere in the U.S., according to a survey conducted by NIEHS-funded researchers from the Environmental Health Sciences Core Center at the University of Southern California (USC). The survey is part of a larger community-based research project to understand how dust from the drying Salton Sea may be affecting children’s respiratory health.

Dust from the exposed Salton Sea lakebed, shown above, is blown into nearby communities and contributes to poor air quality. (Photo courtesy of Liam O'Fallon)
Dust from the exposed Salton Sea lakebed, shown above, is blown into nearby communities and contributes to poor air quality.
(Photo courtesy of Liam O’Fallon)

“The communities near the Salton Sea are some of the poorest in California and already face disproportionate environmental health disparities. As the Salton Sea shrinks and air quality is expected to worsen, we want to understand what that means for local communities and how to best protect public health,” said Jill Johnston, Ph.D., who is co-leading the project with Shohreh Farzan, Ph.D.

Dry lake bed of the Salton Sea (Photo courtesy of Jill Johnston)

Johnston and Farzan surveyed parents of first and second graders at four elementary schools near the Salton Sea. They found high rates of respiratory problems: up to 43% of parents said their children experienced wheezing, and up to 30% said their child had asthma. According to Farzan, these rates are much higher than state and national averages.

Agricultural runoff from nearby farms is the main source of water for the Salton Sea. As runoff from farms decreases, the lakebed is exposed and turns to dust. Wind blows the playa, or dry lakebed, dust into nearby communities, contributing to poor air quality.

Working with Comité Cívico Del Valle, a local environmental justice organization, the researchers collected dust and soil samples to better understand the health risks of playa dust. They sent the samples to NIEHS-funded researchers at the University of Iowa’s Environmental Health Sciences Research Center, who analyzed them for toxic chemicals and other contaminants. Because water from surrounding farms feeds into the Salton Sea, researchers are concerned the playa dust may contain pesticides and heavy metals. Previous research has found these contaminants in Salton Sea sediments, aquatic life, and water.

Infographic by USC team

“The collaboration with researchers at the University of Iowa allowed us to quickly learn about the toxicity of playa dust and how it may contribute to airway inflammation based on their animal models,” said Johnston. “Preliminary results suggest that playa dust may lead to adverse changes in the movement of immune cells into the lung immediately following exposure.” The researchers are still determining whether these immune changes are associated with pesticides and metals in the dust.

The USC researchers also are using air monitors at three schools bordering the lake to assess air quality. “The goal is to see whether the dust looks different in different areas and ultimately to identify a ‘signature’ of the dust coming from the Salton Sea,” Farzan said in a Desert Sun article. “We want to know what’s mobilized into the air and what people are breathing at the community level.”

In November 2017, the California State Water Resources Control Board approved a 10-year plan to build thousands of acres of wetlands and ponds in Imperial Valley. The plan will help restore the Salton Sea and control playa dust. Ahead of the vote to approve the plan, Johnston presented preliminary study results to ensure decision-makers understood the potential health effects playa dust poses to Imperial Valley communities.

“It’s really important to think about how we clean up the air in the region, both existing sources of pollution and then also making sure that the Salton Sea is not going to be an additional burden on the communities,” Johnston said in the Desert Sun article. “Kids have a right to play outside, to breathe clean air, so we need to be thinking about strategies and policies to make that happen.”

To learn more, see the Salton Sea Pollution infographic created by the USC team. The infographic is also available in Spanish.

NEW RESEARCH: Pregnant women deficient in vitamin D may give birth to obese children

Vitamin D supplements during pregnancy might help curb childhood obesity

by Zen Vuong

Vitamin D deficiency in pregnant women could pre-program babies to grow into obese children and adults, according to a Keck School of Medicine of USC-led study.

Researchers found that 6-year-olds born to mothers with very low vitamin D levels during their first trimester had bigger waists — about half an inch plumper on average — than peers whose mothers had enough vitamin D in early pregnancy. These kids also had 2 percent more body fat.

The prevalence of pregnant women with vitamin D deficiencies has increased in the last 20 years, researchers say. (Photo/iStock)

“These increases may not seem like much, but we’re not talking about older adults who have about 30 percent body fat,” said Vaia Lida Chatzi, senior author of the study and an associate professor of preventive medicine at the Keck School of Medicine. “Even a half-inch increase in waist circumference is a big deal, especially if you project this fat surplus across their life span.”

The study, published in the journal Pediatric Obesity in January, examined the data of 532 mother-child pairs in Greece. Maternal vitamin D concentrations were measured during the first prenatal visit. The child’s health and weight were measured at 4 and 6 years.

The ‘sunshine vitamin’
Some 75 percent of U.S. teenagers and adults have too little vitamin D in their system, according to a 2009 study. Deficiency in this “sunshine vitamin” has been linked to increased risk of heart disease, cancer, multiple sclerosis and Type 1 diabetes.

A newborn’s vitamin D status mostly depends on mom. So infants are at risk of vitamin D deficiency if their mothers are vitamin D deficient or are close to it.

About 95 percent of the vitamin D produced in your body comes from sunshine, Chatzi said. The remaining 5 percent is derived from eggs, fatty fish, fish liver oil and fortified foods such as milk, cheese, yogurt and cereal.

“We’re not sure why there is vitamin D deficiency even in places with abundant sunshine, but maybe people are spending too much time indoors with their screens or typing away in their office cubicles,” Chatzi said. “Or maybe they’re using excessive amounts of sunscreen, which inhibits vitamin D production.”

Pregnant women lack sufficient vitamin D
The prevalence of vitamin D deficiency among pregnant women has increased in the last two decades, Chatzi said. About 66 percent of the pregnant women in the study had insufficient vitamin D in the first trimester, a critical period for organ development.

Previous studies by others provide hints to why low vitamin D levels is a problem. Animal studies have shown that vitamin D suppresses pre-fat cells (adipocytes) from maturing into fat cells. Test tube studies of human fat cells also showed that vitamin D may hinder pre-fat cells from turning into fat cells.

“It’s possible that children of mothers with low vitamin D have higher body mass index and body fat because vitamin D appears to disrupt the formation of fat cells,” Chatzi said. “Optimal vitamin D levels in pregnancy could protect against childhood obesity, but more research is needed to confirm our findings. Vitamin D supplements in early pregnancy is an easy fix to protect future generations.”

Advice to moms: Take prenatal vitamins
None of the Greek women in the study took prenatal vitamin D supplements. Most American doctors recommend that women start taking prenatal vitamins before trying to conceive to make sure folic acid, iron, calcium and other nutritional levels are adequate to prevent birth defects. Most prenatal vitamins contain 400 international units (IU) (10 micrograms) of vitamin D per tablet.

The federal government has not set a recommended daily intake of vitamin D, though many agree the dietary intake of the vitamin should increase with age.

The Institute of Medicine of The National Academies recommends that females 1 to 70 years old consume 600 IU (15 micrograms) of vitamin D daily, regardless of their pregnancy status. The group sets tolerable maximum levels at 4,000 IU (100 micrograms) for pregnant and non-pregnant women who are 19 and older. Lower levels are advised based on age.

Too much vitamin D can cause damage to the heart, blood vessels and kidneys, according to the National Institutes of Health.

“It’s too early for researchers to recommend increasing the standard amount of vitamin D contained in prenatal vitamins,” Chatzi said. “First we need to conduct randomized clinical trials.”

Vasiliki Daraki from the University of Crete was the first author of the study. Theano Roumeliotaki, Georgia Chalkiadaki, Marianna Katrinaki, Marianna Karachaliou, Vasiliki Leventakou, Marina Vafeiadi, Katerina Sarri and Stathis Papavasiliou from the University of Crete; Maria Vassilaki from Mayo Clinic; and Manolis Kogevinas from the Barcelona Institute of Global Health also contributed to the study. Data was obtained from the Rhea project, which was supported by European funds and the Greek Ministry of Health.

In the news and upcoming events: Spring 2018

The California Chapter of the American Lung Association is hosting:
Health Professionals for Clean Air Phone Call
Friday, March 9 | 12:00 to 1:30 PM
They will provide an update on the Low Carbon Fuel Standard, freight issues, SB 375 and the Clean Power Plan. Please RSVP to Jenny.Bard@lung.org to receive call-in information.

March for Science: Los Angeles, April 14, 2018
More info at the website and Facebook page

National Air Quality Awareness Week: April 30 – May 4, 2018
More info here. Look for our social media channels to be sharing resources during that week.

Covered through our social media channels recently, we want to share the following stories and articles with you.

Our faculty members Shohreh Farazan and Jill Johnston are partnering with community based organization Comite Civico de Valle, in  Brawley, CA near the Salton Sea to look at children’s respiratory health and how it might be affected by the particle pollution near the shrinking Salton Sea. Read about some of their findings in this article from the Desert Sun. See our infographic that shows the environmental impacts that the shrinking sea has on surrounding communities.

USC staff Lisa Valencia and  CCV staff Beto Martinez work to set up a regulatory air quality monitor in Brawley, CA.

The Los Angeles Times has been covering the health impacts of air pollution. Recent stories that include quotes from our faculty members include:

Regulators warned against housing near freeways due to health risks. Now they’re warming to it (12/27/2017)

Freeway pollution travels farther than we thought. Here’s how to protect yourself (12/30/2017)

 

California officials say housing next to freeways is a health risk — but they fund it anyway (12/17/2017)

NEW RESEARCH: Teen Exposure to air pollution affects IQ

Southern California Environmental Health Sciences Center researchers JC Chen, Diana Younan, Meredith Franklin, and colleagues recently published work documenting their findings about how air pollution can affect the IQ of teens.

The study can be found here.

Wang, P., Tuvblad, C., & Younan, D., Franklin, M., Lurmann, F., Wu, J., Baker, L., Chen, J.C. (2017). Socioeconomic disparities and sexual dimorphism in neurotoxic effects of ambient fine particles on youth IQ: A longitudinal analysis. PLOS ONE. 12. e0188731. 10.1371/journal.pone.0188731.

Teen Exposure to Air Pollution Could Reduce IQ Levels Long Term

NEW RESEARCH: Increased air pollution linked to aggressive behavior in teens

Tiny, toxic particles creep into developing brains, cause inflammation and may damage brain pathways responsible for emotion and decisions, USC researcher finds.

Related coverage in news media:  U.S. News & World ReportNew York Daily NewsDaily Mail (UK), The Times (UK), The Telegraph (UK)Science News, USC News, Popular Science, Consumer Health Day, International Business Times UK

by Zen Vuong, USC

A new study linking higher levels of air pollution to increased teenage delinquency is a reminder of the importance of clean air and the need for more foliage in urban spaces, a Keck School of Medicine of USC researcher said.

Photo: iStock

Tiny pollution particles called particulate matter 2.5 (PM2.5) — 30 times smaller than a strand of hair — are extremely harmful to your health, according to Diana Younan, lead author of the study.

“These tiny, toxic particles creep into your body, affecting your lungs and your heart,” said Younan, a preventive medicine research associate at the Keck School of Medicine. “Studies are beginning to show exposure to various air pollutants also causes inflammation in the brain. PM2.5 is particularly harmful to developing brains because it can damage brain structure and neural networks and, as our study suggests, influence adolescent behaviors.”

The study, published on Dec. 13 in the Journal of Abnormal Psychology, suggests that ambient air pollution may increase delinquent behavior among 9- to 18-year-olds in urban neighborhoods in Greater Los Angeles. The insidious effects are compounded by poor parent-child relationships and parental mental and social distress, researchers said.

“Previous studies by others have shown that early exposure to lead disrupts brain development and increases aggressive behavior and juvenile delinquency,” Younan said. “It’s possible that growing up in places with unhealthy levels of small particles outdoors may have similar negative behavioral outcomes, though more research is needed to confirm this. Both lead and PM2.5 are environmental factors that we can clean up through a concerted intervention effort and policy change.”

More than just a lung and heart concern

The study followed 682 children in Greater Los Angeles for nine years starting when they were 9. Parents completed a child-behavior checklist every few years and noted if their child had engaged in 13 rule-breaking behaviors, including lying and cheating, truancy, stealing, vandalism, arson, or substance abuse. Up to four assessments were recorded per participant.

Researchers used 25 air quality monitors to measure daily air pollution in Southern California from 2000 to 2014. They computed each participant’s residential address and used mathematical modeling to estimate the ambient PM2.5 levels outside each home. About 75 percent of the participants breathed ambient air pollution that exceeded the federal recommended levels of 12 micrograms per cubic meter. Some areas had nearly double the recommended amount of these particles.

“It is widely recognized that ambient air pollution is detrimental to the respiratory and cardiovascular health of young and old alike. But in recent years, scientists have come to acknowledge the negative impact of air pollution on human brains and behaviors,” said Jiu-Chiuan Chen, an associate professor of preventive medicine at the Keck School of Medicine and senior author of the study.

Environmental scientists and economists have speculated that elevated air pollution levels could increase criminal activities in communities. Interestingly, data show that both ambient PM2.5 concentration and crime rates in Southern California have been on the decline, the study stated. Future studies need to examine whether that is mere coincidence or if tightened air regulations might have contributed to the declining crime rates in many metropolitan areas, the researchers said.

“Poor people, unfortunately, are more likely to live in urban areas in less than ideal neighborhoods,” Younan said. “Many affordable housing developments are built near freeways. Living so close to freeways causes health problems such as asthma and, perhaps, alters teenagers’ brain structures so that they are more likely to engage in delinquent behavior.”

This one-two hit may increase teenage delinquency

The study identified higher air pollution estimates near freeways and in neighborhoods with limited greenspace or foliage.

Researchers noticed more delinquent behavior from boys, African-Americans, adolescents from lower socioeconomic backgrounds and people who lived in downtrodden neighborhoods with limited greenspace when compared to their counterparts.

The bad behaviors associated with increased outdoor air pollution levels were magnified when children did not have good relationships with their parents, lived with depressed mothers or grew up in homes with higher levels of parental stress.

“If you live in an area with high air pollution, like near a freeway or in a neighborhood with little greenery, try to avoid being outside so much and keep windows closed as much as possible when the ambient PM2.5 levels are high,” Younan said. “Try to compensate for air pollution by having a good indoor environment and healthy family dynamics.

“A bad parent-child relationship causes a stressful family environment, and if this goes on for too long, the teenager could be in a chronic state of stress. This could wreak havoc on the body, making teens more vulnerable to the effects of exposure to small particles. Many scientists suspect PM2.5 causes inflammation in the brain or somehow travels directly into the brain and messes with neural network connections, resulting in the observed bad behaviors.”

The data was adjusted for gender, ethnicity, socioeconomic status, neighborhood socioeconomic characteristics and neighborhood quality.

More foliage and cleaner air needed

Younan and her colleagues at the USC Environmental Health Sciences Center have collaborated with researchers and engineers from different disciplines at USC for more than two decades to investigate the insidious effects of air pollution. They found that air pollution increases obesity, that teenagers in urban communities with less foliage (such as parks) tend to be more aggressive and that older women living in areas with PM2.5 levels exceeding the U.S. Environmental Protection Agency’s standard had nearly double the risk for dementia when compared to their counterparts.

Catherine Tuvblad and Laura A. Baker from USC; Meredith Franklin, Lianfa Li and Kiros Berhane from the Keck School of Medicine; Fred Lurmann from Sonoma Technology; and Jun Wu from the University of California, Irvine, contributed to the study.

The research was funded by grant funds from the National Institute of Environmental Health Sciences (R21 ES022369, F31 ES025080). Administrative support was provided by the Southern California Environmental Health Sciences Center. The USC Twin Cohort Study was funded by the National Institute of Mental Health (R01 MH058354).