Molecular and Integrative Toxicology

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1 Molecular and Integrative Toxicology Series editor Rodney R. Dietert, Department of Microbiology & Immunology, Cornell University College of Veterinary Medicine, Ithaca, New York, USA

2 More information about this series at

3 Srikanth S. Nadadur John W. Hollingsworth Editors Air Pollution and Health Effects

4 Editors Srikanth S. Nadadur Division of Extramural Research and Training National Institute of Environmental Health Sciences Research Triangle Park, NC USA John W. Hollingsworth Department of Internal Medicine Division of Pulmonary, Allergy, Critical Care and Sleep Medicine Ohio State University Columbus, OH USA ISSN ISSN (electronic) Molecular and Integrative Toxicology ISBN ISBN (ebook) DOI / Library of Congress Control Number: Springer London Heidelberg New York Dordrecht Springer-Verlag London 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Humana Press is a brand of Springer Springer-Verlag London Ltd. is part of Springer Science+Business Media (

5 Preface The health effects of air pollution were recognized after the Industrial Revolution with a transition to manufacturing processes that utilize fuel burning and the emergence of large and densely populated cities. One of the first reports highlighting the health effects of air pollution described the experience in London in 1952 where increased coal burning for heat resulted in dense smog that engulfed the city (Logan 1953, 1956). During a brief period of time, approximately 12,000 excess deaths were associated with increased levels of smog. This incident represents one of the first reports linking level of ambient air pollution and excess mortality. This epidemiological observation contributed to the passing of the Clean Air Act in 1956 by the Parliament of the United Kingdom, which began the process of eliminating the burning of coal in homes and in factories in England. Numerous scientific reports have followed supporting the notion that adverse health effects are associated with exposure to ambient air pollution. In an effort to protect public health and welfare, the US Clean Air Act was passed in 1970, which mandated setting national ambient air quality standards for specific common and widespread pollutants based on the latest science. Similarly the World Health Organization currently provides recommendations with regard to ambient air quality standards in an effort to protect global health and well-being. The body of literature supporting the broad health effects of ambient air pollution is expansive. The overall goal of this book is to highlight the weight of scientific evidence supporting our current understanding of the impact of air pollution on human health. Air pollution is emerging as a major contributing risk factor for the global burden of disease. With improved control of communicable diseases and population shifts, recent estimates from the Global Burden of Disease Study in 2010 place air pollution among the leading contributing risk factors for global disease burden. Ambient particulate matter air pollution, household air pollution from burning solid fuels, and tobacco smoke are among the top ten leading risk factors for disease. It was estimated that ambient particulate matter pollution accounted for 3.1 million deaths and household air pollution from solid fuels accounted for 3.5 million deaths in 2010 (Lim et al. 2012). A recent report from the World Health v

6 vi Preface Organization estimated an air pollution-related global mortality of about seven million people in This represents one in eight of total global deaths is related to air pollution, and these estimates identify air pollution as the single largest environmental health risk factor globally ( WHO press release March 25, 2014, ). This very high attributed mortality is, in part, based on the recognition that air pollution impacts cardiovascular disease. Recognition that exposure to particulate matter (PM) air pollution contributes to cardiovascular morbidity and mortality is supported by a scientific statement from the American Heart Association (Brook et al. 2004, 2010). While the health effects of air pollution were initially associated with pulmonary related morbidity and mortality, our current understanding of health impacts has considerably expanded to also include: cardiovascular, neuronal/ cognitive, cancer, infectious disease, reproductive, and developmental effects. Together, growing evidence support that excess mortality related to air pollution is primarily associated with increased risks of ischemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lung cancer, and respiratory infections. This book begins with an introduction to the chemistry and physics of ambient air pollutants. Topics focus on specific recognized health effects of air pollution including: reproductive function, pregnancy/preterm birth, asthma, COPD, potential mechanisms of action for known carcinogens in the ambient air, diabetes/metabolic syndrome, cardiovascular disease, central nervous system health, and immunological function. Authors highlight host genetic factors that are recognized to contribute to physiological responses to air pollution. Air pollution clearly presents a global health problem and there are dedicated chapters to discuss both global health and indoor air pollution in developing countries. The book concludes with a discussion of regulatory science. There is clearly an increased awareness of health effects of air pollution. Authors have made a sincere attempt to include as much discussion as possible on the contributions of air pollution morbidity in the context of regulatory guidelines and incremental increase in air quality. Detailed insight into the levels of evidence supporting the adverse consequence of exposure to air pollution in this book will provide insight for readers interested in furthering their knowledge and potential future research directions in translating basic to epidemiological and the clinical research continuum and will also serve as a resource book on the impact of the environment on human health. An expanding body of literature supports a clear recognition of air pollution as a major risk factor for human disease. Environmental health science is challenged by the fact that many common exposures can impact multiple organ systems and either directly or indirectly contribute to numerous disease conditions. It is our goal that the reader will gain appreciation for the broad health consequences of air pollution covered by recognized experts in each chapter of this book. Improved understanding of the health consequences related to air pollution will both provide insight into disease pathogenesis and could provide new opportunities to beneficially impact human health. Columbus, OH, USA Research Triangle Park, NC, USA John W. Hollingsworth Srikanth S. Nadadur

7 Preface vii References Brook RD, Franklin B, Cascio W, Hong Y, Howard G et al (2004) Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 109: Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A et al (2010) Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 121: Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K et al (2012) A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, : a systematic analysis for the Global Burden of Disease Study Lancet 380: Logan WP (1953) Mortality in the London fog incident, Lancet 1: Logan WP (1956) Mortality from fog in London, January, Br Med J 1:

9 Contents 1 Reactive Ambient Particles... 1 Philip K. Hopke 2 Impacts of Air Pollution on Reproductive Health Mariana Matera Veras, Natália de Souza Xavier Costa, Laís Fajersztajn, and Paulo Hilário Nascimento Saldiva 3 Air Pollution and Pregnancy Outcomes Sharon Edwards, Pamela Maxson, Nicole Sandberg, and Marie Lynn Miranda 4 Air Pollution and Asthma David B. Peden 5 Air Pollution and Chronic Obstructive Airway Disease Imre Redai and Angela Haczku 6 Airborne Carcinogens: Mechanisms of Cancer Anuradha Mudipalli 7 Molecular Epidemiology Focused on Airborne Carcinogens Pavel Rossner Jr., Blanka Binkova, Andrea Rossnerova, and Radim J. Sram 8 Diabetes and Metabolic Syndrome Xiaoquan Rao, Cuiqing Liu, and Sanjay Rajagopalan 9 Air Pollution, Lipids and Atherosclerosis Jesus A. Araujo and Michael E. Rosenfeld 10 Particulate Air Pollution and CNS Health Alison Elder, Joel Schwartz, and Günter Oberdörster 11 Air Pollution and Immune Function Robert M. Tighe, Jennifer Wheeler, and John W. Hollingsworth ix

10 x Contents 12 Genetics Talat Islam and Frank Gilliland 13 Urban Air Pollution and Health in Developing Countries Junfeng (Jim) Zhang and Drew Day 14 Indoor Biomass Burning and Health Consequences John R. Balmes 15 Using Science to Shape Policy Jason D. Sacks, Neal Fann, Elizabeth Oesterling Owens, and Daniel L. Costa Index

11 Contributors Jesus A. Araujo, M.D., Ph.D. Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA John R. Balmes, M.D. Department of Medicine, Division of Occupational and Environmental Medicine, University of California, San Francisco, CA, USA Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA, USA Blanka Binkova, Ph.D. Department of Genetic Ecotoxicology, Institute of Experimental Medicine, AS CR, Prague 4, Czech Republic Daniel L. Costa, Sc.D., DABT E205-09, Office of Research and Development, U.S. EPA, Research Triangle Park, NC, USA Natália de Souza Xavier Costa, M.S. Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, São Paulo State, Brazil Drew Day, B.A., B.S. Nicholas School of the Environment & Duke Global Health Institute, Duke University, Durham, NC, USA Sharon Edwards, MStat School of Natural Resources and Environment, University of Michigan, Ann Arbor, MI, USA Alison Elder, Ph.D. Department of Environmental Medicine, University of Rochester, Rochester, NY, USA Laís Fajersztajn, M.S. Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, São Paulo State, Brazil Neal Fann, M.P.P. Offi ce of Air Quality Planning and Standards, Office of Air and Radiation, C539-07, U.S. EPA, Research Triangle Park, NC, USA xi

12 xii Contributors Frank Gilliland, M.D., M.P.H., Ph.D. Division of Environmental Health, Department of Preventive Medicine, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA Angela Haczku, M.D., Ph.D. Translational Lung Biology Center, Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, CA, USA John W. Hollingsworth, M.D. Department of Internal Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Ohio State University, Columbus, OH, USA Philip K. Hopke, MA, Ph.D. Institute for a Sustainable Environment, Department of Chemical and Biomolecular Engineering, Clarkson University, Potsdam, NY, USA Talat Islam, M.B.B.S., Ph.D. Division of Environmental Health, Department of Preventive Medicine, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA Cuiqing Liu, Ph.D. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA Department of Physiology, Medical College, Hangzhou Normal University, Hangzhou, Zhejiang, China Pamela Maxson, Ph.D. School of Natural Resources and Environment, University of Michigan, Ann Arbor, MI, USA Marie Lynn Miranda, Ph.D. School of Natural Resources and Environment, University of Michigan, Ann Arbor, MI, USA Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA Anuradha Mudipalli, Ph.D. National Center for Environmental Assessment, Office of Research and Development, US EPA, Research Triangle Park, NC, USA Srikanth S. Nadadur, Ph.D. Division of Extramural Research and Training, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA Günter Oberdörster, D.M.V., Ph.D. Department of Environmental Medicine, University of Rochester, Rochester, NY, USA Elizabeth Oesterling Owens, Ph.D. National Center for Environmental Assessment, Office of Research and Development, U.S. EPA, Cincinnati, OH, USA David B. Peden, M.D., M.S. Division of Allergy, Immunology & Rheumatology, Department of Pediatrics, Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Sanjay Rajagopalan, M.D. Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

13 Contributors xiii Xiaoquan Rao, M.D., Ph.D. Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA Imre Redai, M.D., F.R.C.A. (deceased) Michael E. Rosenfeld, Ph.D. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA Pavel Rossner Jr., Ph.D. Department of Genetic Ecotoxicology, Institute of Experimental Medicine, AS CR, Prague 4, Czech Republic Andrea Rossnerova, Ph.D. Department of Genetic Ecotoxicology, Institute of Experimental Medicine, AS CR, Prague 4, Czech Republic Jason D. Sacks, M.P.H. National Center for Environmental Assessment, Office of Research and Development, B243-01, U.S. EPA, Research Triangle Park, NC, USA Paulo Hilário Nascimento Saldiva, M.D., Ph.D. Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, São Paulo State, Brazil National Institute for Integrated Analysis of Environmental Risk, São Paulo, São Paulo State, Brazil Nicole Sandberg, MURP School of Natural Resources and Environment, University of Michigan, Ann Arbor, MI, USA Joel Schwartz, Ph.D. Departments of Environmental Health and Epidemiology, Harvard School of Public Health, Boston, MA, USA Radim J. Sram, M.D., D.Sc. Department of Genetic Ecotoxicology, Institute of Experimental Medicine, AS CR, Prague 4, Czech Republic Robert M. Tighe, M.D. Department of Internal Medicine, Duke University Medical Center, Durham, NC, USA Mariana Matera Veras, Ph.D. Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, São Paulo State, Brazil National Institute for Integrated Analysis of Environmental Risk, São Paulo, São Paulo State, Brazil Jennifer Wheeler, Ph.D. Department of Internal Medicine, Duke University Medical Center, Durham, NC, USA Junfeng (Jim) Zhang, Ph.D. Nicholas School of the Environment & Duke Global Health Institute, Duke University, Durham, NC, USA

15 About the Editors John W. Hollingsworth is a physician-scientist committed to the study of the impact of the environment on health. He completed his training at the University of Texas Medical Branch and the Duke University Medical Center. He remained on faculty at Duke University before relocating to Ohio State University. The overall goal of Dr. Hollingsworth s research program is to better understand the complex interaction between exposure to common environmental factors and host vulnerability. Laboratory work has included using animal models of human airway disease to better understand the complex relationship between the environment and health. Srikanth S. Nadadur is a molecular toxicologist with over 25 years of research experience in environmental health. He graduated from Sri Venkateswara University, India, and obtained postdoctoral training in chemical carcinogenesis at Roswell Park Cancer Institute, Buffalo, NY. Dr. Nadadur s research on criteria air pollutants at US EPA was focused on integrating toxicogenomics efforts towards developing biomarkers of exposure. He is currently Program Director at the National Institute of Environmental Health Sciences, overseeing an extramural research program in air pollution cardiopulmonary health and nanotechnology environmental health and safety. xv

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