Respiratory Disease & Prevention

University of Southern California  

Respiratory Disease and Prevention
Frank Gilliland, Ph.D.
gillilan@usc.edu
http://www.usc.edu/medicine/cehc

Project Description

During its first five years, the Children's Environmental Health Center (CEHC) supported investigations of the roles of the environment and susceptibility in children's respiratory health. Important contributions were made supporting the growing consensus that current levels of ambient air pollutants and tobacco smoke have substantial adverse effects on children's respiratory health, especially among susceptible groups. The current overall scientific and translational theme of the CEHC is air pollution, susceptibility, and childhood airway disease. The Center’s objectives are: 1) to investigate the role of ambient air pollutants and genetic susceptibility in airway inflammation and in asthma occurrence during childhood; 2) to investigate the mechanism for the modulating effects of ambient air pollutants on allergic inflammation in children; 3) to implement a community-based participatory research program to respond to community concerns about the effects of regional ambient air pollutants and locally-emitted fresh, vehicle exhaust on early life asthma; 4) to provide a scientific resource for the broader community involved in protecting children's environmental health. The CEHC offers an innovative program of community-based participatory research, mechanistic and epidemiologic research to fill some pressing research and public health needs. The investigators pursue vigorous outreach and translation effort to ensure that communities, legislators, regulatory agencies, and other groups interested in children's environmental health are well informed about the evolving science and health impacts on children and communities. The research program is integrated scientifically by a biological model that hypothesizes that chronic oxidative and nitrosative stress mediate the chronic effects of air pollution on asthma and allergic rhinitis. The investigators have identified six key research and translation questions about the adverse effects of ambient air pollution on children's airway diseases: 1) Do regional ambient air pollutants such as 03 or locally-emitted fresh, vehicle exhaust increase the risk of early life asthma? 2) Is chronic airway inflammation a risk factor for new onset asthma? 3) Do ambient air pollutants or locally-emitted fresh, vehicle exhaust produce chronic airway inflammation? 4) Do levels of expression or polymorphic variants of genes in antioxidant pathways such as GSTM1 confer special airway sensitivity to air pollution? 5) Which pollutants are responsible for the effects we see? 6) Can scientific approaches and translation to the broader community involved in protecting children's environmental health be enhanced by community-based participatory research approaches? Because the burden of airway disease and the numbers of children exposed to unhealthful air are large and growing, answers to these questions are urgently needed. The CEHC research program offers a timely opportunity to efficiently answer these key questions using an integrated approach and unique population and exposure assessment resources. The Center’s collaborative multidisciplinary investigative team and strong working relationships with the community research partners, enhance the CEHC's ability to continue to contribute to understanding the effects of environmental exposures on childhood airway disease and to strengthen public health efforts to protect children.

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Project Highlights

Air Pollution and Children’s Respiratory Health
As described in several high-impact publications, Center investigators have observed that children exposed to elevated levels of ambient air pollutants including ozone, PM, NO2 and fresh traffic-related emissions show clinically important adverse effects on asthma pathogenesis, lung function development, respiratory symptoms and infections.  The quality and timeliness of the large, long-term cohort studies that facilitated these findings were greatly enhanced by support through the Center mechanism.

The Center facilitated the multidisciplinary collaborations that led to the development of cutting-edge exposure assessment methodology integrating spatial statistics, home-based measurement of air pollutants, environmental multi-level statistical modeling, geographical information systems (GIS), meteorology, and epidemiology. For example, the Center’s original studies in communities across southern California were designed to exploit variation in regional patterns and levels of pollution. Several important papers that documented the adverse respiratory health effects of the regional pollution relied on data developed by the exposure assessment core from measurements at regional monitoring sites and relied on statistical models developed for these analyses. In order to assess the impact of local exposures due to fresh traffic emissions, new residential and school exposure indices were developed, based on traffic volume, wind speed and direction and mixing layer height, using a GIS system. Using these models, Center investigators have demonstrated associations of asthma prevalence and incidence with traffic-modeled pollution and proximity to major roadways. Center investigators have now collected pollution data at a dense network of locations in each of our study communities. Using these measurements and spatial statistical techniques in a Bayesian framework, Center investigators have developed new methods for examining effects of traffic-related air pollution. With the development of sophisticated statistical techniques plus the advancement of exposure assessment technology, neither of which would have occurred without Center support, Center investigators were able to identify independent adverse pulmonary effects from both regional and local pollution. This observation will clearly have an impact on the policy approaches to dealing with this dual problem.

1. Gauderman W, Vora H, McConnell R, Berhane K, Thomas D, Avol E, Gilliland F, Lurmann F, Peters J. The effect of residential exposure to traffic on lung development from 10 to 18 years of age. Lancet 2007 Feb 17;369(9561):571-7.
2. Gauderman WJ, Avol E, Gilliland F, Vora H, Thomas D, Berhane K, McConnell R, Kuenzli N, Lurmann F, Rappaport E, Margolis H, Bates D, Peters J. The effect of air pollution on lung development from 10 to 18 years of age. N Engl J Med 2004; 351:1057-1067.

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Tobacco Smoke and Children’s Health
Center investigators have demonstrated that tobacco smoke has substantial adverse effects on the respiratory health of children that begins with exposure before birth and continues through the period of growth and development (Gilliland, Li, Dubeau, et al., 2002).  Maternal smoking has both direct effects on the development of early life asthma, as well as increasing asthma susceptibility soon after active smoking begins during adolescence. Further, susceptibility to the effects of tobacco smoke appears to be substantially larger in children who inherit common variants in genes involved in oxidant defense and inflammation. These findings have significant implications for clinical practice and preventive medicine. The prevention and cessation of smoking is clearly a critical clinical issue that needs to be an omnipresent intervention and prevention target that is integrated in all aspects of the clinical care of children and their parents.

1. Gilliland FD, Li YF, Dubeau L, Berhane K, Avol E, McConnell R, Gauderman WJ, Peters JM. Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med 2002; 166:457-463.
2. Gilliland FD, Islam T, Berhane K, Gauderman WJ, McConnell R, Avol E, Peters JM. Regular smoking and asthma incidence in adolescents. Am J Resp Crit Care Med 2006.

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