Smog’s harmful effect on health is widely understood. The noxious mixture of ozone, nitrogen dioxide and fine particulate matter wreaks havoc on the entire body. Lung, brain and heart health suffer but it also has been linked to behavioral problems, Alzheimer’s disease and obesity.

However, none of this was established in 1992 when a team of USC public health researchers, led by the late John Peters, launched a long-term investigation into the effects of air pollution on children. More than 30 years later, the ongoing Southern California Children’s Health Study has changed the nation’s understanding of air pollution’s harms — and shown how clean air standards can make a difference.

“Air pollution health effects research has matured. The initial thought was, ‘If you’re breathing it, it must be a lung effect,’” said Ed Avol, a professor of clinical population and public health sciences at the Keck School of Medicine of USC and co-investigator on the study. “But then we came to appreciate that once it gets into the circulatory system [via the lungs], contaminants can travel to most any organ system.

“Now, we are seeing effects in the brain, in the heart and lungs, and in the metabolic system, affecting a whole number of health outcomes and diseases that we didn’t think initially were related to air pollution.”

The study’s significance is enormous. Seminal papers published in the New England Journal of Medicine and The Lancet led to policies resulting in cleaner air in L.A. and healthier lungs in children. Papers by Avol, William “Jim” Gauderman, Frank Gilliland and Rob McConnell have been cited in more than 16,300 articles by other researchers, according to data from the citation database Web of Science.

The work attracts top young researchers to USC’s Department of Population and Public Health Sciences and has inspired dozens of spinoff studies, including the latest funding award, USC’s designation as a Children’s Environmental Health Translation Center by the National Institute of Environmental Health Sciences.

Over the past three decades, the Children’s Health Study and associated research have been supported by roughly $35 million in federal funding. These studies have required the input from many experts in specialty fields. Contributors have included direct health data collectors, statewide air monitoring personnel, attendance office personnel at more than 50 different schools across the study communities, and a host of data analysts, biostatisticians, students and staff to manage, analyze and interpret the collected data.

“Easily hundreds, and more likely, a few thousand researchers have participated over the years,” Avol said.

USC Children’s Health Study ushers in ‘a cascade of changes’

Pollution was in decline when the study began in 1992, thanks to the passage of the Clean Air Act in the 1970s. Gone were the days when Angelenos incinerated trash in their backyards and orange growers burned tires to keep away the chill. But ozone as well as tiny PM2.5 particles from car exhaust penetrate deeply into the lungs, and they remained persistent problems. Little was known about how they affected children breathing them every day.

The USC research team decided to find out. With funding from the California Air Resources Board, they tracked levels of common pollutants such as ozone, nitrogen dioxide (NO2), acids and fine particulate matter in 12 Southern California communities while following the pulmonary health of children as they progressed from fourth grade to 12th grade. The communities included some of the most polluted areas in the greater Los Angeles Basin, as well as several lower-pollution sites outside the area for comparison.

Such studies take time, and the first big payoff was more than a decade in the making. In 2004, The New England Journal of Medicine — arguably one of the most important scientific journals in the world — published the team’s sobering discovery: By age 18, the lungs of many children who grew up in smoggy areas were underdeveloped and would likely never recover.

“In other words, a significant fraction of children breathing polluted air throughout their teen years were transitioning into adulthood with lung function at least 20% below normal,” Gauderman said.

“The findings led to a cascade of changes because it provided an objective assessment, a documentation of long-term impacts on children’s health,” Avol said. “And that really provided a rationale for the directives to meet the Clean Air Act to protect the public’s health.”

Avol, Gauderman and McConnell have all participated in Environmental Protection Agency committees related to the setting of national air quality standards. The Children’s Health Study was explicitly cited and quoted in terms of considerations and changes to the ozone, particulate matter and nitrogen dioxide standards.

Coming full circle: USC Children’s Health Study

In 2007 another significant finding from the study was published in The Lancet. The findings were especially damning for L.A.: Children living closest to freeways and busy highways had significant impairments in the development of their lungs that can lead to lifelong respiratory problems. That publication ignited fierce debate over the widening of highways and the siting of child care centers, parks, schools and residential construction.

“In L.A., there was a resolution passed by the school board to limit siting of schools to at least 500 feet from busy freeways, citing our study as part of the justification,” Gauderman said. “Our work demonstrated negative health impacts within 500 meters of a freeway, but when the resolution came out, the meters had become feet — 500 feet. We still thought that was a win even though it was three times closer. Before, there were no air pollution-based siting regulations.”

The team kept gathering data, recruiting more children, taking repeated lung-function measurements and examining the information through one lens and then another. Between 1994 and 2010, levels of air pollutants improved dramatically, as federal and state emission standards forced emissions reductions in California’s cars, diesel trucks, ships, trains and refineries.

For example, the average amount of fine particulate matter dropped 43% in Mira Loma. In Long Beach, annual nitrogen dioxide levels improved from 34.4 parts per billion to 20.3 parts per billion, a 41% reduction.

The direct impact of those improvements on child health was reported in 2015 in The New England Journal of Medicine. The USC team’s work had come full circle — first, by documenting pollution’s harms to children, and then demonstrating how health improved with cleaner air.

Over a 17-year period, USC scientists documented declining levels of PM2.5 and nitrogen dioxide. At the same time, they measured lung function in 2,120 children annually from three separate groups corresponding to three separate calendar periods: 1994-1998, 1997-2001 and 2007-2011. Children born in later years had bigger lungs than those born earlier when pollution levels were worse. Positive effects were seen in boys and girls, regardless of race and ethnicity.

“For the first time,” The New York Times reported, “researchers have shown that reducing air pollution leads to improved respiratory function in children ages 11 to 15, a critical period of lung development.”

Avol concedes that the work will probably never be done. As new research reveals connections between, say, pollution and Alzheimer’s-like brain changes, or demonstrates how cleaner air led to a reduction in new child asthma cases, the argument for tighter regulations only gets stronger.

At the same time, given the many sources of pollution — increased traffic at the Port of Los Angeles, the rapid proliferation of Amazon warehouses and longer commute times — “it does seem like we will always be trying to reduce or remove something from the air we all breathe,” Avol said.