Ambient air pollution and population health: overview

In November 2003 approximately 200 researchers, stakeholders, and policymakers from more than 40 countries gathered to discuss the science and policy implications of air pollution and human health as part of the AIRNET/NERAM Strategies for Clean Air and Health initiative. The purpose of this paper is to review the more than 35 research posters presented at the conference, including exposure, toxicological, and epidemiological studies of air pollution. Collectively, these papers support previous evidence that both short- and long-term exposures to particulate air pollution have adverse population health impacts, including effects on children. Cellular studies also suggest that air pollution can cause mutagenic and oxidative effects, raising concerns about carcinogenicity and cellular regeneration. Studies of biomarkers, such as Clara-cell proteins and lymphocyte damage assessment, provide further evidence of air pollution effects at the cellular level. Other studies have focused on improvements to measurement and sources of air pollution. These studies suggest that particle mass rather than particle composition may be a more useful indicator of potential human health risk. It is well known that emissions from transportation sources are a major contributor to ambient air pollution in large urban centres. Epidemiologic researchers are able to reduce bias due to misclassification and improve exposure assessment models by allocating air pollution exposure according to distance from traffic sources or land-use patterns. The close association between traffic patterns and air pollution concentrations provides a potential basis for the development of transport policies and regulations with population health improvements as a primary objective. The results of the research presented here present opportunities and challenges for the development of policies for improvements to air quality and human health. However, there remains the challenge of how best to achieve these reductions.     

Biomarkers of exposure,effect, and susceptibility in occupational exposure to traffic-related air pollution: A review

There is a well-recognized association between environmental air pollution exposure and several human diseases. However, the relationship between diseases related to occupational air pollution exposure on roads and high levels of traffic-related air pollutants (TRAPs) is less substantiated. Biomarkers are essential tools in environmental and occupational toxicology, and studies on new biomarkers are increasingly relevant due to the need to determine early biomarkers to be assessed in exposure conditions. This review aimed to investigate the main advances in the biomonitoring of subjects occupationally exposed to air pollution, as well as to summarize the biomarkers of exposure, effect, and susceptibility. Furthermore, we discuss how biomarkers could be used to complement the current application of methods used to assess occupational exposures to xenobiotics present in air pollution. The databases used in the preparation of this review were PubMed, Scopus, and Science Direct. Considering the significant deleterious effects on health associated with chronic occupational exposure to xenobiotics, this topic deserves attention. As it is difficult to avoid occupational exposure to TRAPs, biomonitoring should be applied as a strategy to reduce the toxic effects of workplace exposure.     

Extracellular vesicles released in response to respiratory exposures: implications for chronic disease

Extracellular vesicles (EV) are secreted signaling entities that enhance various pathological processes when released in response to cellular stresses. Respiratory exposures such as cigarette smoke and air pollution exert cellular stresses and are associated with an increased risk of several chronic diseases. The aim of this review was to examine the evidence that modifications in EV contribute to respiratory exposure-associated diseases. Publications were searched using PubMed and Google Scholar with the search terms (cigarette smoke OR tobacco smoke OR air pollution OR particulate matter) AND (extracellular vesicles OR exosomes OR microvesicles OR microparticles OR ectosomes). All original research articles were included and reviewed. Fifty articles were identified, most of which investigated the effect of respiratory exposures on EV release in vitro (25) and/or on circulating EV in human plasma (24). The majority of studies based their main observations on the relatively insensitive scatter-based flow cytometry of EV (29). EV induced by respiratory exposures were found to modulate inflammation (19), thrombosis (13), endothelial dysfunction (11), tissue remodeling (6), and angiogenesis (3). By influencing these processes, EV may play a key role in the development of cardiovascular diseases and chronic obstructive pulmonary disease and possibly lung cancer and allergic asthma. The current findings warrant additional research with improved methodologies to evaluate the contribution of respiratory exposure-induced EV to disease etiology, as well as their potential as biomarkers of exposure or risk and as novel targets for preventive or therapeutic strategies.     

Ozone exposure and systemic biomarkers: Evaluation of evidence for adverse cardiovascular health impacts

Abstract

The US Environmental Protection Agency (EPA) recently concluded that there is likely to be a causal relationship between short-term (< 30 days) ozone exposure and cardiovascular (CV) effects; however, biological mechanisms to link transient effects with chronic cardiovascular disease (CVD) have not been established. Some studies assessed changes in circulating levels of biomarkers associated with inflammation, oxidative stress, coagulation, vasoreactivity, lipidology, and glucose metabolism after ozone exposure to elucidate a biological mechanism. We conducted a weight-of-evidence (WoE) analysis to determine if there is evidence supporting an association between changes in these biomarkers and short-term ozone exposure that would indicate a biological mechanism for CVD below the ozone National Ambient Air Quality Standard (NAAQS) of 75 parts per billion (ppb). Epidemiology findings were mixed for all biomarker categories, with only a few studies reporting statistically significant changes and with no consistency in the direction of the reported effects. Controlled human exposure studies of 2 to 5 hours conducted at ozone concentrations above 75 ppb reported small elevations in biomarkers for inflammation and oxidative stress that were of uncertain clinical relevance. Experimental animal studies reported more consistent results among certain biomarkers, although these were also conducted at ozone exposures well above 75 ppb and provided limited information on ozone exposure-response relationships. Overall, the current WoE does not provide a convincing case for a causal relationship between short-term ozone exposure below the NAAQS and adverse changes in levels of biomarkers within and across categories, but, because of study limitations, they cannot not provide definitive evidence of a lack of causation.     

Biomarkers for oxidative stress status of DNA, lipids, and proteins in vitro and in vivo cancer research

Oxidation and the production of free radicals are an integral part of human metabolism, and oxidative stress is related to many diseases, including cancer and heart disease. The use of biomarkers for oxidative stress may provide further evidence of a causal relationship between oxidative damage to macromolecules (DNA, lipids, and proteins) and cancer. A wide variety of functional assays, both in vivo and ex vivo, include various measures of DNA oxidation (oxidized DNA bases such as 8-OHdG, autoantibodies to oxidized DNA, modified comet assay), lipid oxidation (thiobarbituric acid-reactive substances, exhaled pentane/ethane, low-density lipoprotein resistance to oxidation, isoprostanes), and protein oxidation (protein carbonyls). The objective of this review is to discuss characteristics and methodologic issues for studies involving biomarkers of exposure to antioxidant nutrients and of oxidative stress status. This paper provides an overview on the current knowledge of oxidative DNA, lipid, and protein damage and cancer incidence.     

Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress

The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary objectives, it was to evaluate if the change of filtered to nonfiltered environment could protect the cortex of rats against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into four groups (n?=?12/group): pre and post-natal exposure until adulthood to filtered air (FA); pre-natal period to nonfiltered air (NFA-FA); until (21st post-natal day) and post-natal to filtered air until adulthood (PND21); pre-natal to filtered air until PND21 and post-natal to nonfiltered air until adulthood (FA-NFA); pre and post-natal to nonfiltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a significant increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730?±?0.217; NFA-FA: 1.101?±?0.217; FA-NFA: 1.014?±?0.300; NFA: 5.978?±?1.920?nmol MDA/mg total proteins; p?=?0.007). NFA group presented a significant decrease in short-term discriminative (FA: 0.603?±?0.106; NFA-FA: 0.669?±?0.0666; FA-NFA: 0.374?±?0.178; NFA: ?0.00631?±?0.106?sec; p?=?0.006) and an improvement in habituation memories when compared to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative memory and cortical oxidative stress may mediate this process.     

Effect of diesel exhaust inhalation on blood markers of inflammation and neurotoxicity: a controlled,blinded crossover study

Context: Epidemiological studies and animal research have suggested that air pollution may negatively impact the central nervous system (CNS). Controlled human exposure studies of the effect of air pollution on the brain have potential to enhance our understanding of this relationship and to inform potential biological mechanisms.

Objectives: Biomarkers of systemic and CNS inflammation may address whether air pollution exposure induces inflammation, with potential for CNS negative effects.

Materials and methods: Twenty-seven healthy adults were exposed to two conditions: filtered air (FA) and diesel exhaust (DE) (300?μg PM_2.5/m³) for 120?min, in a double-blinded crossover study with exposures separated by four weeks. Prior to and at 0, 3, and 24?h following each exposure, serum and plasma were collected and analyzed for inflammatory cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α), the astrocytic protein S100b, the neuronal cytoplasmic enzyme neuron-specific enolase (NSE), and serum brain-derived neurotrophic factor (BDNF). We hypothesized that IL-6, TNF-α, S100b and NSE would increase, and BDNF would decrease, following DE exposure.

Results: At no time-point following exposure to DE was a significant increase in concentration from baseline seen for IL-6, TNF-α, S100b, or NSE relative to FA exposure. Similarly, no significant decrease in BDNF concentration from baseline was seen following DE exposure, relative to FA. Furthermore, the repeated measures ANOVA considered for all time-points and biomarkers revealed no significant time-exposure interaction.

Discussion and conclusion: These results suggest that short-term exposure to DE amongst healthy adults does not acutely affect the systemic or CNS biomarkers that we measured.     

Systemic inflammatory response induced by particulate matter air pollution: the importance of bone-marrow stimulation

The relationship between the level of particulate air pollution (PM(10)) and the mortality and morbidity rates from respiratory and cardiovascular diseases is well established, but the biological mechanisms responsible for these associations are still unclear. The injurious effects of particulate air pollution may be either local (in the lung) or systemic. Bone-marrow release of leukocytes and platelets is an important component of the systemic inflammatory response. We have developed methods to quantify bone-marrow stimulation and showed in animals that acute exposure to ambient particles accelerates the transit of polymorphonuclear leukocytes (PMN) through the marrow whereas chronic exposure expands the size of the bone marrow pool of PMN. Human studies showed that an episode of severe air pollution stimulates the bone marrow in a manner similar to that observed in animals. In vitro and in vivo studies suggest that alveolar macrophage produce the mediators implicated in the bone marrow response to ambient particles. Cytokines produced in the lung due to deposition of ambient particles also appear in the circulation. In vitro and in vivo studies have shown that PMN recently released from the bone marrow preferentially sequester in pulmonary capillaries, are less chemotactic, and contain more damaging granular enzymes, all factors that potentate their ability to damage alveolar tissue. In animals that naturally develop atherosclerosis, deposition of ambient particles in the lung causes progression of atherosclerotic plaques with phenotypic changes in atherosclerotic plaques characteristic of lesions vulnerable to rupture. We conclude that exposure to ambient particulate matter air pollution induces a systemic inflammatory response that includes the release of inflammatory mediators into the circulation that stimulate the bone marrow to release leukocytes and platelets. We postulate that this systemic response to particulate air pollution augments lung inflammation and changes the phenotype of atherosclerotic plaques to make them more vulnerable to rupture.     

Biomarkers for oxidative stress: clinical application in pediatric medicine

Loads of reactive oxygen species (ROS), including superoxide anion and nitric oxide, that overburden antioxidant systems induce oxidative stress in the body. Major cellular targets of ROS are membrane lipids, proteins, nucleic acids, and carbohydrates. Circumstantial evidence suggests that ROS play a crucial role in the initiation and progression of various diseases in children and adolescents. The involvement of ROS and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in young subjects and appropriate methods for its measurement remain to be defined. Recently, specific biomarkers for oxidative damage and antioxidant defense have been introduced into the field of pediatric medicine. This review is intended to provide an overview of clinical applications of oxidative stress biomarkers in the field of pediatric medicine. First, this review presents the biochemistry and pathophysiology of ROS and antioxidant defense systems. Second, it presents a list of clinically applicable biomarkers, along with pediatric diseases in which enhanced oxidative stress might be involved. The discussion emphasizes that several reliable biomarkers are easily measurable using enzyme-linked immunosorbent assay. Third, this review presents age-related reference normal ranges of oxidative stress biomarkers, including urinary acrolein-lysine, 8-hydroxy-2'-deoxyguanosine, nitrite/nitrate, and pentosidine, and the changes of the parameters in several clinical conditions, including atopic dermatitis and diabetes mellitus. New and interesting data on oxidative stress and antioxidant defenses in neonatal biology are also presented. Fourth, this review discusses the ever-accumulating body of data linking oxidative stress to disturbances of the nitric oxide system and vascular endothelial activation/dysfunction. Finally, this review describes the reported clinical trials that have evaluated the efficacy of antioxidants for oxidative-stress related diseases. Suggestions are advanced for the direction of future trials using antioxidant therapies. Repeated measurement of appropriate parameters will enable us to discern the pathophysiological patterns of pediatric diseases and guide our therapies appropriately.     

Antioxidant responses in Carassius auratus and Lolium perenne exposed to the laboratory pollution

Experiments conducted in the laboratories can produce numerous wastes, which could potentially affect the health of the researchers. In this study, the antioxidant responses in liver of Carassiua auratus and leaf of Lolium perenne were investigated after chronic exposure to the air pollution in four different laboratories. The obtained data showed that oxidative stress was induced in some laboratories, as indicated by some significantly altered biochemical parameters. Additionally, the toxicity order was tentatively proposed based on these responses. The results indicated that these biochemical indices can be used as the oxidative stress biomarkers to assess the effect of environmental pollution on the living organisms, and this study can facilitate the understanding of the risk assessment of laboratory pollution.     

Reconstructing human exposures using biomarkers and other "clues"

Biomonitoring is the process by which biomarkers are measured in human tissues and specimens to evaluate exposures. Given the growing number of population-based biomonitoring surveys, there is now an escalated interest in using biomarker data to reconstruct exposures for supporting risk assessment and risk management. While detection of biomarkers is de facto evidence of exposure and absorption, biomarker data cannot be used to reconstruct exposure unless other information is available to establish the external exposure-biomarker concentration relationship. In this review, the process of using biomarker data and other information to reconstruct human exposures is examined. Information that is essential to the exposure reconstruction process includes (1) the type of biomarker based on its origin (e.g., endogenous vs. exogenous), (2) the purpose/design of the biomonitoring study (e.g., occupational monitoring), (3) exposure information (including product/chemical use scenarios and reasons for expected contact, the physicochemical properties of the chemical and nature of the residues, and likely exposure scenarios), and (4) an understanding of the biological system and mechanisms of clearance. This review also presents the use of exposure modeling, pharmacokinetic modeling, and molecular modeling to assist in integrating these various types of information.     

Reconstructing Human Exposures Using Biomarkers and other “Clues”

Biomonitoring is the process by which biomarkers are measured in human tissues and specimens to evaluate exposures. Given the growing number of population-based biomonitoring surveys, there is now an escalated interest in using biomarker data to reconstruct exposures for supporting risk assessment and risk management. While detection of biomarkers is de facto evidence of exposure and absorption, biomarker data cannot be used to reconstruct exposure unless other information is available to establish the external exposure–biomarker concentration relationship. In this review, the process of using biomarker data and other information to reconstruct human exposures is examined. Information that is essential to the exposure reconstruction process includes (1) the type of biomarker based on its origin (e.g., endogenous vs. exogenous), (2) the purpose/design of the biomonitoring study (e.g., occupational monitoring), (3) exposure information (including product/chemical use scenarios and reasons for expected contact, the physicochemical properties of the chemical and nature of the residues, and likely exposure scenarios), and (4) an understanding of the biological system and mechanisms of clearance. This review also presents the use of exposure modeling, pharmacokinetic modeling, and molecular modeling to assist in integrating these various types of information.     

Structural and functional alterations in Malpighian tubules as biomarkers of environmental pollution: synopsis and prospective

Although a number of biomarkers of pollutant exposure have been identified in invertebrate species, little is known about the effect on Malpighian tubules playing an essential role in excretion and osmoregulation. Analyses of structural and functional alterations on this organ can be useful to predict the effects at the organism and population level in monitoring studies of environmental pollution. The aim of the present review is to provide a synthesis of existing knowledge on cellular damages induced by xenobiotics in Malpighian tubules both under laboratory and field conditions. We compared studies of exposure to pesticides and heavy metals as mainly environmental contaminants from anthropogenic activities. This report provided evidence that the exposure to xenobiotics has an effect on this organ and reinforces the need for further research integrating molecular biomarkers with analysis on Malpighian tubules. Copyright © 2017 John Wiley & Sons, Ltd.     

Acute kidney damage by PM2.5 exposure in a rat model

PM_2.5 exposure is associated with a glomerular filtration rate (GFR) reduction, and renal tissue damage. The goal of this study was demonstrate the acute effect of PM_2.5 on the kidney. Male rats were acutely exposed to PM_2.5 or filtered air. Blood pressure was mesure and early kidney biomarkers were evaluated in serum and urine samples, and also IL-1β, IL-6 and TNFα were determined. Oxidative biomarkers, angiotensin/bradykinin-related proteins, KIM-1, IL-6 and histology were determined. Blood pressure, GFR, and early kidney damage biomarkers increase together with oxidative biomarkers and angiotensin/bradykinin endocrine-related proteins increased after exposure to PM_2.5. Urinary IL-6 increased after exposure to PM_2.5, whereas in kidney cortex decreased. Histological changes were observed and accompanied by the induction of KIM-1. Acute exposure to PM_2.5 not decline kidney function. However, it can induce early kidney damage biomarkers, oxidative stress, inflammation and angiotensin mediators, which perhabs culminates in a lose of renal function.     

The roles of microRNAs in the pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by a progressive and irreversible airflow obstruction, with an abnormal lung function. The etiology of COPD correlates with complex interactions between environmental and genetic determinants. However, the exact pathogenesis of COPD is obscure although it involves multiple aspects including oxidative stress, imbalance between proteolytic and anti-proteolytic activity, immunity and inflammation, apoptosis, and repair and destruction in both airways and lungs. Many genes have been demonstrated to be involved in those pathogenic processes of this disease in patients exposed to harmful environmental factors. Previous reports have investigated promising microRNAs (miRNAs) to disclose the molecular mechanisms for COPD development induced by different environmental exposure and genetic predisposition encounter, and find some potential miRNA biomarkers for early diagnosis and treatment targets of COPD. In this review, we summarized the expression profiles of the reported miRNAs from studies of COPD associated with environmental risk factors including cigarette smoking and air pollution exposures, and provided an overview of roles of those miRNAs in the pathogenesis of the disease. We also highlighted the potential utility and limitations of miRNAs serving as diagnostic biomarkers and therapeutic targets for COPD.     

Development of a biomarkers database for the National Children's Study

The National Children's Study (NCS) is a federally-sponsored, longitudinal study of environmental influences on the health and development of children across the United States (). Current plans are to study approximately 100,000 children and their families beginning before birth up to age 21 years. To explore potential biomarkers that could be important measurements in the NCS, we compiled the relevant scientific literature to identify both routine or standardized biological markers as well as new and emerging biological markers. Although the search criteria encouraged examination of factors that influence the breadth of child health and development, attention was primarily focused on exposure, susceptibility, and outcome biomarkers associated with four important child health outcomes: autism and neurobehavioral disorders, injury, cancer, and asthma. The Biomarkers Database was designed to allow users to: (1) search the biomarker records compiled by type of marker (susceptibility, exposure or effect), sampling media (e.g., blood, urine, etc.), and specific marker name; (2) search the citations file; and (3) read the abstract evaluations relative to our search criteria. A searchable, user-friendly database of over 2000 articles was created and is publicly available at: . PubMed was the primary source of references with some additional searches of Toxline, NTIS, and other reference databases. Our initial focus was on review articles, beginning as early as 1996, supplemented with searches of the recent primary research literature from 2001 to 2003. We anticipate this database will have applicability for the NCS as well as other studies of children's environmental health.     

Evaluation of oxidative stress and genotoxicity in organophosphorus insecticide formulators

The aim of this study was to evaluate genotoxicity and oxidative stress in workers who formulate organophosphorus (OP) pesticides. In this survey, blood leukocytes and erythrocytes of a group of 21 pesticide formulating workers and an equal number of control subjects were examined for genotoxicity and oxidative stress parameters. The mean comet tail length and mean comet length were used to measure DNA damage. Lipid peroxidation level, catalase, superoxide dismutase (SOD) and glutathione peroxidase activities in erythrocytes were analysed as biomarkers of oxidative stress. In addition, the acetylcholinesterase activity was measured as a biomarker of toxicity. The average duration of employment of workers in the factory was 97 months. Results indicated that chronic exposure (multiple-dose, greater than or equal to 6 months duration) to OP pesticides was associated with increased activities of catalase, SOD and glutathione peroxidase in erythrocytes. The level of lipid peroxidation and acetylcholinesterase activity did not show any significant differences between the two groups. The results also indicated that chronic exposure to OP pesticides was associated with increased DNA damage. It is concluded that human chronic exposure to OP pesticides may result in stimulated antioxidant enzymes and increased DNA damage in the absence of depressed acetylcholinesterase levels. Routine genotoxicity monitoring concomitant to acetylcholinesterase activity in workers occupationally exposed to OP insecticides is suggested.     

Health Effects of Organic Aerosols

Carbonaceous aerosol, a major component of particulate matter (PM), gases, and vapors in the atmosphere, has been associated with natural and anthropogenic air pollution, reduced visibility, climate modulation, material and ecosystem damage, and adverse health effects. More recently, epidemiological studies have indicated associations between organic fractions of ambient PM and adverse respiratory and cardiovascular health outcomes. The effects of the non-PM components of the organic aerosol have received less attention because their measurement in the general environment is not mandated. This article summarizes current knowledge of the nature, prevalence, and health effects of organic aerosols encountered in the outdoor environment, identifies key information gaps, and presents a conceptual framework for research priorities for resolving those gaps. The broad, diverse class of air contaminants comprising organic aerosols may be more important to public health than the modest attention given to them. This review focuses on hazard identification and exposure assessment for evaluating risks to public health from ambient organic aerosols. Current knowledge is insufficient to support a quantitative characterization of the aggregate risk from organic air contaminants. Assessments should be done for individual species or mixtures. Efforts should be taken to assemble and evaluate a common set of standard reference materials for both organic speciation and health response assays. A greater standardization of approaches across studies and laboratories would be useful to achieve uniformity in assessing health effects. Multidisciplinary research efforts are needed to improve the current regulatory-driven air quality monitoring networks for epidemiological studies. The limited array of biomarkers linking organic aerosols to health effects needs to be expanded and specific organic compounds or classes that are associated with biological effects in human cells or animal studies need to be tested for better understanding of the exposure-response relationship.     

Health effects of organic aerosols

Carbonaceous aerosol, a major component of particulate matter (PM), gases, and vapors in the atmosphere, has been associated with natural and anthropogenic air pollution, reduced visibility, climate modulation, material and ecosystem damage, and adverse health effects. More recently, epidemiological studies have indicated associations between organic fractions of ambient PM and adverse respiratory and cardiovascular health outcomes. The effects of the non-PM components of the organic aerosol have received less attention because their measurement in the general environment is not mandated. This article summarizes current knowledge of the nature, prevalence, and health effects of organic aerosols encountered in the outdoor environment, identifies key information gaps, and presents a conceptual framework for research priorities for resolving those gaps. The broad, diverse class of air contaminants comprising organic aerosols may be more important to public health than the modest attention given to them. This review focuses on hazard identification and exposure assessment for evaluating risks to public health from ambient organic aerosols. Current knowledge is insufficient to support a quantitative characterization of the aggregate risk from organic air contaminants. Assessments should be done for individual species or mixtures. Efforts should be taken to assemble and evaluate a common set of standard reference materials for both organic speciation and health response assays. A greater standardization of approaches across studies and laboratories would be useful to achieve uniformity in assessing health effects. Multidisciplinary research efforts are needed to improve the current regulatory-driven air quality monitoring networks for epidemiological studies. The limited array of biomarkers linking organic aerosols to health effects needs to be expanded and specific organic compounds or classes that are associated with biological effects in human cells or animal studies need to be tested for better understanding of the exposure-response relationship.     

Acute air pollution effects: consequences of exposure distribution and measurements

Acute effect air pollution studies estimate the effect of short-term change in exposure on a health outcome. The two designs most commonly used in air pollution epidemiology are panel studies and time-series studies. Typically, both designs rely on ambient concentration measurements and not the personal exposures of individuals. This article discusses how panel studies and time-series studies are related and reviews the use of ambient concentrations versus personal exposure measurements in the analyses. This work suggests that for estimating acute effects, ambient concentration measurements are quite adequate in time-series studies. In addition, time-series studies have ample power relative to panel studies, in spite of the ecologic nature of their design. Panel studies have the benefit of being able to use all the information from personal exposures in the analysis, but they are much more costly and difficult to conduct. Furthermore, nontraditional panel studies, where multiple repeat panels are followed over time, require additional considerations in the analysis.