Health Research and Surveillance Needs
Despite the large body of evidence of adverse effects of particulate matter (PM) in susceptible subgroups in the general population, the effects of PM on military personnel deployed in the Middle East are not well characterized. Extrapolation from general population-based epidemiologic studies may not provide appropriate estimates of the effects on health, because the chemical composition of PM, the magnitudes of exposure, and the characteristics of deployed military personnel are different from those in the general population. The deployed personnel may be considered relatively healthy compared to the general population with regard to past medical history and physical fitness; however, deployed personnel are exposed to dangerous, stressful conditions and adverse environmental exposures that may affect their overall health adversely. Thus, epidemiologic research to address the question of whether exposure to PM in the Middle East is associated with increased risk of illness in military personnel is needed.
This chapter will discuss the rationale for conducting research on the health effects of exposure to PM in U.S. military personnel in the Middle East theater and the study design features, exposure-assessment needs, and health-outcome data requirements for such research to be successful. It will also review the epidemiologic and toxicologic work presented by staff of the U.S. Army Center for Health Promotion and Preventive Medicine (USACHPPM) and the Naval Health Research Center at the July 2009 committee meeting (see Appendix C).
It is important to note the differences between health surveillance and research. Health surveillance is the continuous, routine collection of data related to health or exposures of populations over the long term and the associated analysis, interpretation, and dissemination of the results. In an occupational setting, surveillance involves the systematic assessment of the health of employees, in this case military personnel, who are exposed to occupational hazards. The fundamental purpose of surveillance is to detect and eliminate the exposures to hazards to prevent adverse health effects. Research is the search for knowledge
through systematic investigation. Health-effects research typically uses the scientific method, which involves the formulation and testing of hypotheses and the collection of data through observation and experimentation. Results of research can lead to the initiation of surveillance and vice versa, but the two activities are not synonymous.
THE NEED FOR HEALTH SURVEILLANCE OF MILITARY PERSONNEL DEPLOYED IN THE MIDDLE EAST
After the first Persian Gulf War in 1991, many veterans who had been deployed to that military theater complained of persistent respiratory symptoms. Multiple reports in the published literature have shown associations between deployment to the gulf region during the war and increases in various respiratory outcomes (Richards et al. 1993; Iowa Persian Gulf Study Group 1997; Proctor et al. 1998; Gray et al. 1999; Petruccelli et al. 1999; Gray et al. 2000; Lange et al. 2002; Kelsall et al. 2004). Because the ambient environment during and immediately after the 1991 Gulf War was characterized by high concentrations of particulate matter and other pollutants due to windblown dust and smoke from oil fires, exposure to PM has been suggested to be responsible for the reported increase in respiratory symptoms among veterans (Richards et al. 1993; Petruccelli et al. 1999; Cowan et al. 2002; Kelsall et al. 2004). The health risks of PM generated in the Gulf War may not be confined to veterans of the conflict. A risk assessment of civilian mortality in Saudi Arabia estimated that over 1,000 excess deaths during 1991-1992 could be attributed to increases in PM due to the war (White et al. 2008).
With the renewed U.S. military activity in the Middle East (Afghanistan and Iraq) over the last 9 years, deployed military personnel are again experiencing exposure to high concentrations of wind-blown dust. They are also exposed to other types of PM, including diesel-exhaust particles and smoke from open-pit burning that has been used at military bases to dispose of various waste materials. A cross-sectional survey of personnel deployed in the Middle East during 2003 and 2004 found that respiratory illness was the second-most common condition to result in short-term disability and hospitalization of deployed troops (Sanders et al. 2005).
MORBIDITY AND MORTALITY IN POPULATIONS EXPOSED TO COARSE PARTICLES
Air pollution in the Middle East is characterized by episodes of resuspended windblown dust from desert regions, which increase particle concentrations to levels above the Military Exposure Guidelines (MEGs) many times each year. As noted above, high concentrations of both coarse particles (PM10-2.5) and fine particles (PM2.5) have been measured by the military during both the Afghanistan and Iraq conflicts. A recent study of PM in Kuwait also documented
relatively high concentrations of PM10, probably because of the resuspension of dust from the desert crust (Brown et al. 2008). There is abundant evidence that exposure to fine PM in urban centers—arising mainly from combustion of oil, gasoline, and natural gas—increases the risks of acute cardiac events (such as myocardial infarction, arrhythmia, and exacerbation of congestive heart failure), acute respiratory events (such as pneumonia and exacerbation of asthma), and cardiopulmonary mortality (Pope and Dockery 2006). In addition, controlled human-exposure studies have shown that exposure to particles can affect sub-clinical cardiovascular responses (Brook 2008). It is not clear, however, whether high concentrations of PM from crustal sources pose the same risks to cardiovascular and respiratory health as PM from anthropogenic combustion. In fact, there is a body of evidence that demonstrates that the chemical composition of PM and its size fraction affect the relationship between PM exposure and human health (Laden et al. 2000; Lippmann et al. 2006; Bell et al. 2009; Peng et al. 2009).
Several studies have shown links between coarse particles and human health (Ostro et al. 1999; Ostro et al. 2000; Middleton et al. 2008; Peng et al. 2008; Perez et al. 2008; Malig and Ostro 2009). Specifically, studies have shown associations between windblown dust from the Mongolian desert and increased cardiac and respiratory morbidity in Taiwan and Korea (Kwon et al. 2002; Chen and Yang 2005; Yang et al. 2005; Bell et al. 2008; Cheng et al. 2008; Chiu et al. 2008; Yang et al. 2009). In Taiwan, analyses indicate that Asian dust storms may result in increases in daily hospital admissions for chronic obstructive pulmonary disease (Chiu et al. 2008), cardiovascular disease (Chen and Yang 2005), congestive heart failure (Yang et al. 2009), asthma (Yang et al. 2005), allergic rhinitis (Chang et al. 2006), conjunctivitis (Yang 2006), and pneumonia (Cheng et al. 2008), although none of the associations were statistically significant. In contrast, some studies in North America have not found an association between coarse PM and adverse health effects. In a time-series study conducted over a 6-year period in Spokane, Washington, there were multiple episodes when coarse PM concentrations were high in the absence of increased fine-particle concentrations, and results of the study showed that high-dust days did not have an effect on mortality (Schwartz et al. 1999). Another study of hospital admissions in the greater Vancouver area (Bennett et al. 2006) showed no effect of clouds of dust that were transported from the Gobi Desert to Canada. In a study of the effect of PM on mortality in Salt Lake City, Utah, the PM-mortality association was strengthened when days with high concentrations of windblown dust were excluded (Pope et al. 1999). In another study in the Coachella Valley of California, there was less effect of PM on mortality on windy days (Ostro et al. 2000).
Given the paucity of studies and the relative uncertainty about the toxicity of coarse PM in the epidemiologic literature, a well-designed investigation of the effects of windblown dust on the health of military personnel in the Middle East could contribute considerably to scientific understanding of the potential risks associated with exposure to coarse PM. In addition, military personnel constitute a unique population (for example, they are typically healthier and
more physically fit than the general public; they have different age and sex distributions, different activity patterns, and different rates of smoking; and they are potentially under greater stress), and this is another reason that studies of military personnel are important for understanding the effects of coarse PM. An important issue is that in most of the epidemiologic studies, adverse effects have been observed in elderly persons who had pre-existing cardiopulmonary disease, a group that is quite different from the healthy military population.
Exposure assessment is the process of estimating or measuring the magnitude, frequency, and duration of exposure to an agent in a specific exposed population. Ideally, it describes the sources and routes of exposure, the dose delivered to target tissues, and relevant uncertainties. Proper assessment of exposure is essential for the validity of any environmental epidemiologic study.
In addressing the relationship between exposure of military personnel deployed in the Middle East theater to airborne PM and the risk of adverse health effects, exposure assessment is a critical component. There are many levels on which exposure can be assessed, including a broad geographic level and a personal level. Ideally, the dose to target organs is the gold standard, but it is not practical to measure the concentration of inhaled particles in the airways and lungs of exposed military personnel. Personal measurements of exposures in breathing zones are possible, but these could be conducted in a war zone only with great difficulty.1 When measurements for each individual are impractical, a surrogate can be constructed by using the route of exposure (for example, inhalation), the magnitude or intensity of exposure (for example, particle concentration in micrograms per cubic meter of air), the duration of exposure (for example, minutes, hours, or days), and the frequency of exposure (for example, daily, weekly, or monthly). Those characteristics of exposure and the physical, chemical, and biologic properties of the complex mixture of particles can be used to determine indirectly the amount of particles to which a person is exposed, the amount deposited in the airways, and ultimately the dose that specific organs may receive. There are no data that specifically address whether PM fixed-site monitoring stations in the Middle East theater correlate with personal PM exposures among military personal. However, there is evidence that measurements of daily fluctuations in urban populations, specifically PM2.5, correlate well with most daily measurements of personal exposures (Oglesby et al. 2000; Liu et al. 2003; Brunekreef et al. 2005; Sarnat et al. 2009). It is important to note that daily fluctuations in PM2.5 concentrations are different from long-term average PM2.5 exposures, and the contribution of long-term ambient PM2.5 concentrations
to personal PM2.5 concentrations and how this relationship varies with averaging time is not well understood.
If the available exposure data are not sufficient to characterize adequately the likely exposures of people for whom health-outcome data are collected, then an epidemiologic study of associations between the exposure of interest and the outcomes of interest will not provide valid results. The committee concluded that the exposure data contained in the Department of Defense (DOD) Enhanced Particulate Matter Surveillance Program (EPMSP) report, although informative, were insufficient to characterize the exposure of most deployed personnel during the period of monitoring for the purpose of linking exposure to health. Therefore, any linkage of the exposure data with health-outcome data should be viewed with caution.
HEALTH FOLLOWUP BY THE U.S. ARMY CENTER FOR HEALTH PROMOTION AND PREVENTIVE MEDICINE
Several presentations were made by members of the Environmental Medicine Program of the USACHPPM to the committee (see Appendix C for the meeting agendas). Preliminary results of two epidemiologic studies that used EPMSP data collected from deployed personnel were presented (Abraham 2009).
The first study evaluated the association between acute (short-term) exposures to PM and the risk of an adverse health response in an effort to answer the question, “If exposure to particles on a specific day increases, does the risk of adverse health outcomes increase on that day or subsequent days?” The study used a case-crossover design to evaluate the association of daily average concentrations of PM2.5, PM10, and total suspended particulates with reported in-theater visits to health-care facilities for cardiovascular and respiratory outcomes. There was no mention of lags or moving averages in the presentation given to the committee. For the sampling period (late 2005 to early 2007) at the 15 EPMSP sites, health-outcome data were obtained from electronic medical records (gathered with JMeWS, a web-based medical surveillance tool), an evacuation database (TRANSCOM Regulating and Command & Control Evacuation System), and in-garrison inpatient and outpatient medical records (gathered with the Defense Medical Surveillance System Standard Inpatient Data Record and Standard Ambulatory Data Record). The cardiovascular and respiratory outcomes identified in the health databases were myocardial infarction, other ischemic heart disease, other forms of heart disease, acute respiratory infections, pneumonia and influenza, and chronic obstructive pulmonary disease and related conditions. Demographic data from the Defense Manpower Data Center, personnel-location data (gathered with Defense Theater Accountability Software), and meteorologic data from the Air Force Combat Climatology Center were also used in the analyses. An initial base-camp-specific analysis was followed by a pooled analysis over base camps; only 10 of 15 base camps had
data sufficiently complete for inclusion in the analysis. No associations were found between any of the PM metrics and cardiovascular or respiratory health outcomes. Although this was the first study of its kind in a deployment setting and may inform the design of future studies, the results are difficult to interpret because the study suffered from limited statistical power owing to the short period of study, few health-outcome events, incomplete health-outcome data, and misclassified and relatively sparse exposure data as a result of the 1-day-in-6 EPMSP sampling protocol (see Chapters 2 and 3). Thus, the null findings do not necessarily indicate that there is no association.
In the second study, a retrospective cohort design was used to assess persistent health effects of exposure to PM. The study was used to examine long-term rather than short-term effects on health. Personnel deployment and location data were used to define the cohort, EPMSP data were used to assess exposures (quartiles of time-weighted-average PM2.5 or PM10; see Chapters 2 and 3), post-deployment cardiovascular or respiratory disease diagnoses were the outcomes evaluated2, and the Cox Proportional Hazards model was used to estimate exposure-disease associations. No rates of diagnoses were found to be associated with exposure to particles in analyses that accounted for potential confounding factors—sex, age, marital status, service branch, rank, deployment, and preexisting conditions. Limitations of the study include potential misclassification of exposure and outcomes, a relatively short followup after deployment, and a lack of smoking data. As was the case with the first study, care should be taken not to overinterpret the results or to conclude that there is no association.
In recognition of occupational exposure of deployed military personnel to potentially hazardous PM, some USACHPPM teams endeavored to conduct medical surveillance of exposed soldiers. A pilot surveillance project conducted at one military base (Joint Base Balad) used spirometry to assess respiratory effects of exposure to PM (Ross 2009). Over 670 soldiers deployed at the base underwent spirometry from September to October 2005. Followup spirometry of 103 of the soldiers after deployment was completed. Mean postdeployment forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1) were not different from values obtained during deployment. A small number of soldiers tested did have a greater than 15% decline in FVC, FEV1, or both; this indicated the possibility of a more susceptible subgroup. Two other medical-surveillance projects conducted during 2007-2009 deployments (n = 29 and n = 39) also showed predeployment-to-postdeployment FVC and FEV1 changes
consistent with that possibility. None of these medical-surveillance activities were designed as research studies, and they all suffer from inadequate statistical power, lack of specific exposure data, probable selection bias, and possible inadequate data-quality assurance. Those initial Army surveillance efforts are commendable, but implementation of a medical-surveillance program that includes the continued systematic collection of health data over a long term is required to provide information that can lead to effective interventions to reduce exposures to hazardous agents.
TOXICOLOGIC STUDIES OF PARTICULATE MATTER COLLECTED BY THE ENHANCED PARTICULATE MATTER SURVEILLANCE PROGRAM
Toxicologic studies of samples collected through the EPMSP can test hypotheses about the potential of components of PM to cause adverse health effects. Such studies may provide insight into potential mechanisms, dose-response relationships, relative toxicity among different sources, and interactions with coexposures, such as smoking, that may enhance responses. The committee heard an overview presentation by a member of the Naval Health Research Center Environmental Health Effects Laboratory (see Appendix C) on inhalation-toxicology studies that used EPMSP samples (Stockelman 2009). Soil samples were selected from Middle East military-theater sites and were studied in vitro and in vivo for PM toxicity. Three rodent studies were conducted: 1) particle exposure by single intratracheal instillation of PM (identified as desert-sand PM10) with up to a 6-month postinstillation evaluation, 2) oral gavage of Iraqi PM from Camp Victory for 28 days, and 3) sand and smoke exposure that used cigarette smoke and aerosolized sand over a total period of 6 weeks.
In the first study, sand (defined as PM10 desert sand), titanium dioxide, or silica was administered to rats via a single intratracheal instillation of 1, 5, or 15 mg suspended in 400 μl of sterile saline. Sacrifice times were 1, 3, 7, and 35 days and 6 months after instillation. The end points measured were inflammation and injury to the lungs, lung endotoxin, histopathologic findings in major organs, and the presence of heavy metals in major organs. Clear effects were seen 1, 3, and 7 days after a dose of 5 or 15 mg of Iraqi PM10 sand. The effects included dose-related alveolitis, perivascular eosinophilic infiltrates, and limited nephropathy and hepatic inflammation. Resolution of those effects was almost complete by 35 days after instillation, and no further effects were noted 6 months after instillation.
The second study exposed rats to suspended Iraqi PM from Camp Victory via oral gavage for 28 days. The doses administered were 0-20 mg/kg per day diluted in 200 μl of sterile saline. The study end points were gross and microscopic pathologic and immunotoxicologic conditions. The interim conclusions from the study were that concentrations of B cells were increased and that the
immune response to staphylococcal enterotoxin B (which activates T and B cells) was depressed in the PM groups.
The third study was performed to examine the toxic effects of desert sand (Iraqi PM) alone and in combination with inhaled cigarette smoke. Pure silica sand from a site in the United States was used as a control. The experiments evaluated the tissue burdens of PM constituents after inhalation and the biologic activity of soluble PM constituents. The study began with a nose-only preexposure period of 4 weeks, during which time rats were exposed to air or cigarette smoke. The main-exposure period lasted for 2 weeks and used nose-only exposure to cigarette smoke or air and whole-body exposure to Iraqi PM, purified silica sand, or air. Respirable particles were generated from both the Iraqi soil samples collected from the field and purified silica. The mass median aerodynamic diameter, exposure times, and inhaled mass were well controlled.
Following the 2-week main-exposure period, pulmonary and systemic effects were measured in blood and plasma and in bronchoalveolar lavage fluid (BALF) with cytokine assays, enzymes, and cytology. Lung histopathology, protein analysis, and proteomics were also used. After exposure to dusts and/or cigarette smoke, BALF failed to demonstrate changes in numbers of cells recovered or a shift in cell types. Protein and lactate dehydrogenase measurements were also unchanged by dust and/or cigarette-smoke exposure. Lung histopathology demonstrated a mild to moderate hyperplasia of the tracheal epithelium after the 2-week exposures. However, exposure to cigarette smoke created far greater lung changes that were not exacerbated by inhalation exposure to sand. Protein analysis of BALF suggested that exposure to cigarette smoke caused a greater effect on chitinase, kininogen, and the pi form of glutathione-S-transferase than exposure to sand. An interesting finding was that cigarette smoke appeared to suppress the responses associated with Iraqi PM and purified silica.
Chemical analysis of PM soil specimens from different Middle East military sites demonstrated similarities in composition for a wide variety of elements. In vitro studies of soluble extracts of soil from military sites used cell lines and demonstrated cell death and selective cytotoxity that varied with time and the region from which the soil sample was collected.
In summary, the Navy evaluated the potential for desert sand to induce pulmonary and systemic injury; exposures were benchmarked against silica as a positive control and titanium dioxide as a negative control. It also evaluated the potential for cigarette smoke to potentiate injury that was due to desert sand. The studies showed that high-dose exposures to desert sand caused modest injury that could be characterized as transient. When monitored over long periods, much of the pulmonary injury resolved. The data suggested that the inhaled silica was of an amorphous form that does not have the toxicity of crystalline silica. That was confirmed by scanning electron microscopy analysis of the particles. The observation that injury and inflammation from cigarette smoke were substantially higher than those caused by desert sand was interesting. The toxicologic studies conducted by Navy investigators provide initial insight into the
potential pulmonary hazard posed by desert sand. Although healthy animals may not represent susceptible populations, such as the elderly and people who have pre-existing conditions, the preliminary data suggest that healthy subjects may not be at markedly increased risk for acute responses to desert sand. However, the studies are limited in that the exposures did not include the full array of constituents that military personnel are exposed to, they did not investigate chronic effects, and humans may respond differently from rodents. Future studies may also consider other biologic responses of interest, such as cardiovascular responses, and may look at the effects of direct or interactive exposures to other sources of interest, such as burn pits. It should be noted that the Navy considered burn pits as an important item for future study.
THE VALUE OF THE DEPARTMENT OF DEFENSE ENHANCED PARTICULATE MATTER SURVEILLANCE PROGRAM
The EPMSP was impressive in many ways, especially given that it was one of the first efforts to characterize environmental exposures of deployed military personnel that could potentially affect human health. The project faced many challenges in assessing exposures to PM in a military operation, doing it with limited resources, and doing it in conditions in which the primary job functions of many of the personnel conducting the monitoring were unrelated to the investigations. Challenges included the need for easy-to-use equipment so that monitors could be operated by personnel without previous experience and the presence of extreme temperature and magnitudes of pollution that were often outside the design specifications of the instrumentation. The usefulness of the monitoring campaign’s results to studies of the health of deployed troops has been limited largely by the combination of uncertainties regarding the actual exposures, the small number of study subjects, and the limited amount of exposure data. The 1-day-in-6 sampling schedule provided relatively sparse exposure data, and this hinders the study of both acute and chronic exposures.
Regardless, the results of the EPSMP clearly show that military personnel deployed to the Middle East during the current Afghanistan and Iraq conflicts are often exposed to high concentrations of PM and that the composition of PM varies considerably over both time and space. Those characteristics of exposure could be exploited to address some of the current gaps in data on the toxicity of windblown PM and could potentially be used to understand the toxicity of open-pit burning of waste materials. That is, the results of the EPMSP can be viewed as a pilot exposure-assessment study that could form the basis of the design of specific objectives for a followup research project that would carefully link exposure measurements to health data. The results of the EPMSP can also be viewed as providing sufficient evidence of occupational exposure to a potential hazard, ambient PM, that would justify the implementation of a comprehensive medical-surveillance program to assess PM-related health effects in military
personnel deployed to the Middle East theater. Moreover, the committee can envision a health-surveillance program that could be linked to research studies.
SURVEILLANCE: CONTINUING ASSESSMENT OF THE HEALTH OF ARMED FORCES PERSONNEL
The health status of personnel can be determined with medical surveillance, which can include periodic administration of symptom questionnaires and tests for specific respiratory and cardiovascular adverse effects (for example, pulmonary-function testing) and the collection, storage, and analysis of regularly collected data (for example, data in medical records or in clinical information systems). The weight of evidence of an association between data on exposure to a specific hazard, such as ambient PM, and various types of health-status data is generally based on evidence in the epidemiology and toxicology literature. If “sufficient evidence” of a hazard is available in the literature, it is advisable to link the exposure and medical-surveillance data in an effort to reduce exposures and prevent adverse effects (see Box 4-1, which describes such surveillance). If the evidence of hazard is deemed insufficient, the design and conduct of a new epidemiologic study to address the data gap may be appropriate.
CONSIDERATIONS FOR INVESTIGATING THE HEALTH EFFECTS OF EXPOSURE OF MILITARY PERSONNEL TO POLLUTANTS
It is plausible that exposure to ambient pollution in the Middle East theater is associated with a number of adverse health outcomes. Some may present themselves as acute effects that are manifested during service in the theater and some as chronic effects that occur many years later. Further investigation is warranted to understand the health burden that results from exposure to potentially toxic mixtures of pollutants that vary in time and concentration. Important sources of exposure include open-pit burning upwind of personnel operations, diesel fumes, and resuspended dust from deserts and sandstorms.
It is suggested that future investigations consider characteristics of the military target population—activity patterns, baseline health status, occupations, and other characteristics—that differ from those of the general population. For example, in most occupational settings, exposures to hazards occur only during work hours, but military personnel deployed at some bases in the Middle East may be exposed to ambient PM 24 hours a day, 7 days a week. (The military has established 1-year MEGs3 for PM2.5 of 15 μg/m3. See Box 4-2 for a discussion of
General Approach to Medical Surveillance
An important complement to environmental monitoring is medical surveillance, which is recommended by the National Institute for Occupational Safety and Health when workers are exposed to hazardous materials. The recommendation is clearly applicable to exposure of military personnel deployed in the Middle East to ambient PM. Surveillance describes any use of health or exposure data to identify cases or monitor trends; direct medical evaluations of people at risk for the development of particular disorders (screening for cases) is one source of health data (Murthy and Halperin 1995).
In this brief review, medical surveillance refers to the continuing application of medical tests and procedures to workers who may be at risk for morbidity because of exposure to hazardous material. The elements of a medical-surveillance program generally include the following:
The importance of a well-functioning surveillance system is discussed in great detail in IOM (2008). The report describes this type of system as follows, “A fully functioning surveillance system would track military exposures and health outcomes, during military service and after discharge, and maintain a repository of data and biological specimens so that emerging and unanticipated questions could be retrospectively addressed” (IOM 2008, p. 21).
Interpretation of Military Exposure Guidelines for Particulate Matter
The EPMSP study found PM concentrations to exceed the USACHPPM 1-Year Military Exposure Guideline (MEG) of 15 μg/m3 for PM2.5 (Engelbrecht et al. 2008). The chemical composition of the particles was related to the area’s geology, and indicated elevated concentrations of crustal materials, such as calcium and silicon. Such metals as lead and zinc were also identified. PM0.5 was found to have a different chemical structure, with more combustion-related products. The authors of the study concluded that PM “dusts” were similar in composition to those in other regions and that the three primary origins of air pollution were geologic dust, burn pits, and sources of metals, such as lead smelting and manufacturing sites. Those conclusions are plausible, but the true sources of the pollution and relative contributions are not well characterized.
Challenges arise in extrapolating results of studies of associations of PM with adverse human health outcomes to other regions, populations, or periods. As noted, military personnel deployed in the Middle East differ greatly from the U.S. general population. In addition, the chemical composition of PM is hypothesized to affect its toxicity. Studies have shown that for a given size distribution of particles, relative rates of health outcomes differ by region, season, and source (for example, Laden et al. 2000, Peng et al. 2005, Dominici et al. 2006, Andersen et al. 2007, Bell et al. 2009, Peng et al. 2009, Qu et al. in press). Similarly, the chemical composition of PM follows regional and seasonal patterns (Bell et al. 2007).
Therefore, the health effects of exposure to the PM measured in the EPMSP are likely to differ from those of exposure to other types of PM. Typical PM in an urban environment in the United States would have lower concentrations of crustal components than PM in the EPMSP. Comparing measured concentrations of PM with regulations or guidelines poses similar limitations. The MEGs were designed to help characterize health risks associated with environmental exposures during deployment, with recognition that assessing data in the context of the MEGs should incorporate professional judgment (USACHPPM 2003). It is important to emphasize that there is no guarantee that health effects will not occur below the MEGs. Comparison of observed PM concentrations with the MEGs or U.S. Environmental Protection Agency regulatory guidelines (the National Ambient Air Quality Standards) should be interpreted in relation to the uncertainties in the current scientific literature regarding how the chemical composition of particles influence their effects on human health.
the challenges of interpreting the MEGs for PM.) Despite the potential for continuously high exposures during deployment, the types of associations with ambient PM that are found in the general population—such as increases in daily emergency-department visits, in hospitalizations, and in mortality—may not be observed in this relatively young, healthy, and physically fit population. However, there may be exceptions in personnel who have particular chronic diseases, such as asthma, that may be exacerbated by exposure to short-term increases in ambient PM. The incidence of most chronic diseases increases with age; given that some personnel are middle-aged and older, there may be relatively large groups that are more susceptible. Other acute or chronic detrimental health outcomes may also result, given the high exposures and the unique sources encountered. Acute exposures to toxicants from burn pits and other sources could lead to immediate and possibly severe reactions.
Detection of short-term effects of exposure to ambient PM in deployed military personnel may be difficult because the effects can be relatively small and sample sizes can be small, so complex panel studies with measurements of both selected physiologic parameters and personal exposures may be required. Moreover, some of the acute effects observed may lead to chronic health conditions. For example, evidence is emerging from controlled human exposure studies of young healthy persons that exposure to particles and secondhand tobacco smoke can induce acute changes in vascular function and increases in blood pressure (Heiss et al. 2008; Brook et al. 2009). In addition, epidemiologic studies have demonstrated associations between exposure to PM and increased systemic inflammation (Liu et al. 2009) and literature reviews have discussed pulmonary and cardiovascular effects related to PM exposure (Alfaro-Moreno et al. 2007; Brook 2008). The current medical data collected routinely by the Army in its health-informatics systems may offer an opportunity to assess potential long-term health outcomes that may be associated with air pollution (such as hypertension and diabetes).
The composition of air pollutants in the Middle East theater is clearly distinct from that in urban centers in industrialized countries, and it probably varies from site to site within the theater. The effects of weather may also be important. The design of an exposure monitoring strategy of deployed personnel must be tailored to the specific health effect questions to be assessed either with continuing surveillance or with directed research. In particular, the exposure assessment required for the study of potential persistent effects, such as the development of asthma or chronic obstructive pulmonary disease, may be different from that for the study of acute effects, such as respiratory symptoms that vary day to day or heart-rate variability.
There is a notable dearth of exposure data from previous wars, particularly the Vietnam War and the first Gulf War. That has led to barriers to the understanding of chronic health effects and to the provision of appropriate compensation for war-related diseases. The recent large-scale efforts to conduct exposure assessment indicate that the military takes the issue of PM exposure seriously, and the committee commends the work reported by Engelbrecht et al. (2008),
Abraham (2009), Ross (2009), and Stockelman (2009) that was presented to it (see Appendix C).
However, to gain a better understanding of the exposures experienced by deployed military personnel and their potential health effects, an essential first step should be to conduct an inventory of potentially toxic compounds (Froines at al. 1989). That would entail generating a list of possible sources, emissions, and exposure pathways, and it would include the processes and substances used on site and those anticipated to result from items being placed in the burn pits. Such a list could be reviewed with regard to known and suspected human-health outcomes of exposure to these compounds, and this information could help to guide the design of exposure studies and health-surveillance and research studies. One potential advantage of epidemiologic studies of military populations is that they can be followed relatively easily over time, in this case, before, during, and after deployment to the Middle East theater. However, a problem with many previous studies of deployed military personnel is the lack of data on relevant exposures. If the decision is made to conduct a long-term follow-up study of deployed personnel in Iraq or Afghanistan, the collection of adequate exposure data to appropriately classify study participants will be of paramount importance.
Utilizing the Millennium Cohort Study
One possibility for conducting an epidemiologic study of the effects of PM on deployed military personnel in the Middle East is for the USACHPPM to work collaboratively with the Millennium Cohort Study (Gray et al. 2002). That study was launched in October 2000 in response to a DOD recommendation for a coordinated effort to study the potential health effects of deployment-related exposures (Secretary of Defense 1998) and the Institute of Medicine recommendation for a systematic, longitudinal, population-based assessment of service members' health (IOM 1999). Enrollment for the 21-year longitudinal study began in July 2001 and was completed in June 2003. The millennium cohort consists of 77,047 consenting military service members who were enrolled through both Web and U.S. Postal-Service-based submission options (36% response rate of those invited to participate) (Ryan et al. 2007). The invited personnel were sampled through electronic personnel records representing about 11.3% of the 2.2 million men and women who were in service as of October 1, 2000. U.S. military personnel serving in the Army, Navy, Coast Guard, Air Force, and Marine Corps were recruited. The Millennium Cohort Study participants have already been used to investigate the incidence of self-reported respiratory symptoms (persistent or recurring cough or shortness of breath), asthma, and chronic bronchitis or emphysema among the 46,077 participants who completed baseline and followup (June 2004-February 2006) questionnaires (Smith et al. 2009). Similar rates of asthma, chronic bronchitis, and emphysema were observed in deployed and nondeployed personnel. Deployment was, however, associated
with increased respiratory symptoms in Army and Marine Corps personnel but not in Navy or Air Force personnel. That result was independent of smoking status; duration of deployment was linearly associated with increased reporting of symptoms by Army personnel. In deployed personnel, increased risk of symptoms was associated with land-based as opposed to sea-based deployments. The investigators commented that their results suggest that environmental exposures may be responsible for the increased respiratory symptoms reported by land-based combat troops. They specifically cited the EPMSP results reported in Inhalation Toxicology (Engelbrecht et al. 2009a,b) as support for the need to conduct further research to address this issue.
The USACHPPM team could collaborate with the Millennium Cohort Study investigators to devise an environmental monitoring strategy to assess PM exposures of deployed members of the millennium cohort before the next round of questionnaire completion. The millennium cohort is large enough to avoid the sample-size issues that beset the initial efforts by USACHPPM to conduct epidemiologic studies of cardiopulmonary outcomes. In addition, the cohort has many nondeployed participants who could serve as nonexposed controls.
GUIDING PRINCIPLES FOR ASSESSING THE HEALTH OF SOLDIERS IN THE MIDDLE EAST CONFLICTS
Predicting likely acute and chronic health effects is complex and difficult. For example, in the case of Agent Orange, although there was a priori concern over its potential carcinogenicity, the findings of excess risk of diabetes came as a surprise to many (Henriksen et al. 1997). That is not atypical; prediction of health effects is highly constrained by current knowledge. Nevertheless, some guiding principles could be stated to help to define the objectives of surveillance and research programs:
It is possible that the health responses for the military population will differ from those of the general population, given differences in factors such as baseline health, age, and smoking status. Some acute responses may be identified only through subtle physiologic changes, such as vascular responses and increased concentrations of markers of inflammation. The very high concentrations of particles may lead to an overload of the pulmonary clearance system (Ballew et al. 1995; Oberdörster 2002) and could conceivably be manifested in respiratory and cardiovascular outcomes. Coupled with that could be effects arising from other routes of exposure to pollutants (for example, dermal exposure and ingestion). A carefully designed surveillance program is essential and should include inventories of pollutants from the enhanced monitoring program and a detailed review of human and toxicologic studies. As in any epidemiologic investigation of acute or chronic effects, consideration of concomitant illnesses (for example, infectious diseases), stress, and other environmental factors is required. Studies of subacute effects could conceivably be carried out in personnel
not involved directly in the conflict, such as clerical and administrative personnel; this would lessen any burden on military operations, but the issue that exposures of these personnel differ from exposures of other military personnel would need to be addressed.
The investigation of chronic effects should have high priority in any health-surveillance programs that the Army implements. A cohort of exposed people should be developed and followed to assess associations with indicators of their health and exposures in the theater. That type of surveillance, although complex, is not unique in a military setting; for example, there are standard methods for the U.S. Air Force Ranch Hand Study that examined health effects of Agent Orange. The committee concluded that the Army is in an excellent position to develop cohorts for study, but detailed assessment of baseline exposure in the theater would be required. Questionnaires and specific medical assessments can be administered through time. The clinical-informatics systems of the Army and of the Department of Veterans Affairs, in addition to the usual methods of followup (such as the National Death Index and state cancer registries), can be used to identify the incidence and prevalence of health conditions.
Development of testable research questions and specific objectives to address the questions are required for the conduct of any epidemiologic research study. The objectives should be used to motivate essential study-design features. Examples of those features are subject to eligibility criteria, size and demographic characteristics of the cohort (particularly for statistical-power purposes), length of followup required, health outcomes and the frequency required to assess them, critical periods of exposure, and potential confounding and modifying factors that would need to be measured. Careful consideration should be given to the design of the exposure assessment for the cohort, including accounting for duration of exposure, activity patterns, and changes in deployment locations, so that potential associations with health outcomes can be appropriately evaluated.
An independent oversight committee composed of internal and external members who have expertise in air pollution, analytic chemistry, exposure assessment, epidemiology, toxicology, biostatistics, and occupational and environmental medicine should be established to provide guidance and to review specific objectives, study designs, protocols, and results of the various exposure and health-surveillance or research programs that are developed. Such a committee could provide an essential peer-review function, as well as an oversight function, lending scientific credibility to the investigations. An example is the advisory committee that was established to oversee the conduct of the Air Force Ranch Hand Study (FDA 2009).
The location of monitoring sites needs to account for where the largest numbers of military personnel are stationed and where they are working in the ambient environment to maximize study power and minimize exposure misclassification. Daily sampling frequency, for at least PM mass, would greatly increase the amount of exposure data available for an analysis of acute effects on health. Measurement of other relevant pollutants will greatly aid any efforts.
Conducting a well-designed epidemiologic study of the potential adverse health effects of exposure to PM in deployed military personnel in the current Middle East conflicts will require a major effort in many units and possibly multiple military branches. Such a study will be organizationally and logistically challenging, given the temporally and spatially comprehensive monitoring of PM and other pollutants and the large sample sizes needed.
CONCLUSIONS AND RECOMMENDATIONS
The data presented by Engelbrecht et al. (2008) constitute compelling evidence that a large-scale assessment of the air-pollution exposures of military personnel and associated health risks is feasible and needed. The data that were collected are not adequate for performing a useful health-effects research study, but they afford a preliminary understanding of the composition of particles in the setting in question, which can help to guide the design of future surveillance and research programs. To assess health responses, it will be necessary to collect more data to increase statistical power, to account for effects of other exposures, and to improve data quality.
Efforts to conduct surveillance and research programs to assess effects of exposure to PM in military personnel deployed to the Middle East theater should follow the guiding principles outlined in this chapter.
The DO D should take an inventory of potentially toxic compounds to which deployed personnel may be exposed. That would entail generating a list of possible sources, emissions, and exposure pathways. Such a list could be reviewed with regard to known and suspected human-health effects of exposure to the compounds, and this information could help to guide the design of exposure and health-surveillance and research studies.
Surveillance efforts for potentially harmful exposures, such as exposure to ambient PM, and epidemiologic investigations could benefit greatly from coordination with other large-scale efforts that are under way. An example is the Millennium Cohort Study, which has explored the effect of deployment on respiratory health.
Although the EPMSP was intended to characterize exposure to particles, a full understanding of the air-pollution exposures of deployed personnel should include other key pollutants that may be relevant to human health. Examples are other criteria pollutants (such as ozone), metals, hazardous air pollutants (air toxics), and diesel exhaust.
Medical information collected routinely by the DOD should be analyzed in such a way that health outcomes that may be associated with air pollution can be identified with a view to developing a more robust surveillance system and to understanding the health effects of exposures. Care should be given to consideration of the original design and purposes of the medical databases, which were not intended for research purposes. The DOD should consider expanding medical surveillance, especially for deployed personnel, to include additional data that could be used to assess health effects. In light of the known respiratory effects of inhaled pollutants, consideration should be given to performing spirometry before, during, and after deployment to the Middle East theater.
In selected cases, complementary toxicologic studies of PM to the theater might yield insights. Emphasis should be placed on source characterization of collected particles from the Middle East theater to define more fully the relative toxicity of these particles compared with other reference materials.
An independent oversight committee should be formed. Such a committee—composed of internal and external members who have expertise in air pollution, analytic chemistry, exposure assessment, epidemiology, toxicology, biostatistics, and occupational and environmental medicine—would provide guidance and review specific objectives, study designs, protocols, and results of the various exposure and health-surveillance or research programs that are developed.
When possible, exposures should be minimized. There are a number of ways to accomplish that. For example, if there is a prevailing wind direction, emission sources (such as local generator farms, burn pits, and incinerators) should be located downwind of the bases. For periodic emissions, such as waste burning, burns could be conducted when meteorologic conditions favor dispersion of the emissions.
Abraham, J. 2009. Deployment-Related Exposure to Particulate Matter and Medical Encounters for Respiratory and Circulatory Health Outcomes. Presentation at the First Meeting on Review of the DOD’s Enhanced Particulate Matter Surveillance Program Report, July 9, 2009, Washington, DC.
Alfaro-Moreno, E., T.S. Nawrot, A. Nemmar, and B. Nemery. 2007. Particulate matter in the environment: pulmonary and cardiovascular effects. Curr. Opin. Pulm. Med. 13(2):98-106.
Andersen, Z.J., P. Wahlin, O. Raaschou-Nielsen, T. Scheike, and S. Loft. 2007. Ambient particle source apportionment and daily hospital admissions among children and elderly in Copenhagen. J. Expo. Sci. Environ. Epidemiol. 17(7): 625-636.
Ballew, M.A., D. Kroebel, and T.J. Smith. 1995. Epidemiologic application of a dosimetric model of dust overload. Am. J. Epidemiol. 141(7):690-696.
Bell, M.L., F. Dominici, K. Ebisu, S.L. Zeger, and J.M. Samet. 2007. Spatial and temporal variation in PM2.5 chemical composition in the United States for health effects studies. Environ. Health Perspect. 115(7):989–995.
Bell, M.L., J.K. Levy, and Z. Lin. 2008. The effect of sandstorms and air pollution on cause-specific hospital admissions in Taipei, Taiwan. Occup. Environ. Med. 65(2):104-111.
Bell, M.L., K. Ebisu, R.D. Peng, J.M. Samet, and F. Dominici. 2009. Hospital admissions and chemical composition of fine particle air pollution. Am. J. Respir. Crit. Care Med. 179(12):1115-1120.
Bennett, C.M., I.G. McKendry, S. Kelly, K. Denike, and T. Koch. 2006. Impact of the 1998 Gobi dust event on hospital admissions in the Lower Fraser Valley, British Columbia. Sci. Total Environ. 366(2-3):918-925.
Brook, R.D. 2008. Cardiovascular effects of air pollution. Clin. Sci. 115(6):175-187.
Brook, R.D., B. Urch, J.T. Dvonch, R.L. Bard, M. Speck, G. Keeler, M. Morishita, F.J. Marsik, A.S. Kamal, N. Kaciroti, J. Harkema, P. Corey, F. Silverman, D.R. Gold, G. Wellenius, M.A. Mittleman, S. Rajagopalan, and J.R. Brook. 2009. Insights into the mechanisms and mediators of the effects of air pollution exposure on blood pressure and vascular function in healthy humans. Hypertension 54(3):659-667.
Brown, K.W., W. Bouhamra, D.P. Lamoureux, J.S. Evans, and P. Koutrakis. 2008. Characterization of particulate matter for three sites in Kuwait. J. Air Waste Manag. Assoc. 58(8):994-1003.
Brunekreef, B., N.A.H. Janssen, J.J. de Hartog, M. Oldenwening, K. Meliefste, G. Hoek, T. Lanki, K.L. Timonen, M. Vallius, J. Pekkanen, and R.V. Grieken. 2005. Personal, Indoor, and Outdoor Exposures to PM2.5 and Its Components for Groups of Cardiovascular Patients in Amsterdam and Helsinki. Health Effects Institute. Report #127. February 2005 [online]. Available: http://pubs.healtheffects.org/view.php?id=94 [accessed March 20, 2010].
Chang, C.C., I.M. Lee, S.S. Tsai, and C.Y. Yang. 2006. Correlation of Asian dust storm events with daily clinic visits for allergic rhinitis in Taipei, Taiwan. J. Toxicol. Environ. Health A. 69(3):229-235.
Chen, Y.S., and C.Y. Yang. 2005. Effects of Asian dust storm events on daily hospital admissions for cardiovascular disease in Taipei, Taiwan. J. Toxicol. Environ. Health A. 68(17-18):1457-1464.
Cheng, M.F., S.C. Ho, H.F. Chiu, T.N. Wu, P.S. Chen, and C.Y. Yang. 2008. Consequences of exposure to Asian dust storm events on daily pneumonia hospital admissions in Taipei, Taiwan. J. Toxicol. Environ. Health A. 71(19):1295-1299.
Chiu, H.F., M.M. Tiao, S.C. Ho, H.W. Kuo, T.N. Wu, and C.Y. Yang. 2008. Effects of Asian dust storm events on hospital admissions for chronic obstructive pulmonary disease in Taipei, Taiwan. Inhal. Toxicol. 20(9):777-781.
Cowan, D.N., J.L. Lange, J. Heller, J. Kirkpatrick, and S. DeBakey. 2002. A case-control study of asthma among U.S. Army Gulf War veterans and modeled exposure to oil well fire smoke. Mil. Med. 167(9):777-782.
DOD/NIOSH (U.S. Department of Defense-and National Institute for Occupational Safety and Health). 2005. DOD-NIOSH Particulate Matter Research Workshop Meeting Proceedings, September 6-7, 2005 [online]. Available: http://usachppm.amedd.army.mil/doem/particle/FINALPMWorkshopProceedings2005.pdf [accessed Feb. 1, 2010].
Dominici, F., R.D. Peng, M.L. Bell, L. Pham, A. McDermott, S.L. Zeger, and J.M. Samet. 2006. Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA 295(10):1127-1134.
Engelbrecht, J.P., E.V. McDonald, J.A. Gillies, and A.W. Gertler. 2008. Department of Defense Enhanced Particulate Matter Surveillance Program (EPMSP). Final report. Desert Research Institute, Reno, NV. February 2008 [online]. Avail-
able: http://chppm-www.apgea.army.mil/foia/DOCS/Final%20EPMSP%20Report%20without%20appx%20Feb08.pdf [accessed Feb. 1, 2010].
Engelbrecht, J.P., E.V. McDonald, J.A. Gillies, R.K.M. Jayanty, G. Casuccio, and A.W. Gertler. 2009a. Characterizing mineral dusts and other aerosols from the Middle East, Part 1. Ambient sampling. Inhal. Toxicol. 21(4):297-326.
Engelbrecht, J.P., E.V. McDonald, J.A. Gillies, R.K. Jayanty, G. Casuccio, and A.W. Gertler. 2009b. Characterizing mineral dusts and other aerosols from the Middle East, Part 2. Grab samples and re-suspensions. Inhal. Toxicol. 21(4):327-336.
FDA (U.S. Food and Drug Administration). 2009. Charter of the Ranch Hand Advisory Committee. U.S. Food and Drug Administration [online]. Available: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/ToxicologicalResearch/RanchHandAdvisoryCommittee-SummaryofFindings/ucm164922.htm [accessed Nov. 25, 2009].
Froines, J., D. Wegman, and E. Eisen. 1989. Hazard surveillance in occupational disease. Am. J. Public Health. 79(Suppl.):26-31.
Gray, G.C., K.S. Kaiser, A.W. Hawksworth, F.W. Hall, and E. Barrett-Connor. 1999. Increased postwar symptoms and psychological morbidity among U.S. Navy Gulf War veterans. Am. J. Trop. Med. Hyg. 60(5):758-766.
Gray, G.C., T.C. Smith, H.K. Kang, and J.D. Knoke. 2000. Are Gulf War veterans suffering war-related illnesses? Federal and civilian hospitalizations examined, June 1991 to December 1994. Am. J. Epidemiol. 151(1):63-71.
Gray, G.C., K.B. Chesbrough, M.A. Ryan, P. Amoroso, E.J. Boyko, G.D. Gackstetter, T.I. Hooper, and J.R. Riddle; Millennium Cohort Study Group. 2002. The Millennium Cohort Study: A 21-year prospective cohort study of 140,000 military personnel. Mil. Med. 167(6):483-488.
Heiss, C., N. Amabile, A.C. Lee, W.M. Real, S.F. Schick, D. Lao, M.L. Wong, S. Jahn, F.S. Angeli, P. Minasi, M.K. Springer, S.K. Hammond, S.A. Glantz, W. Grossman, J.R. Balmes, and Y. Yeghiazarians. 2008. Brief secondhand smoke exposure depresses EPC activity and endothelial function: sustained vascular injury and blunted NO production. J. Am. Coll. Cardiol. 51(18):1760-1771.
Henriksen, G.L., N.S. Ketchum, J.E. Michalek, and J.A. Swaby. 1997. Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand. Epidemiology 8(3):252-258.
IOM (Institute of Medicine). 1999. Gulf War Veterans: Measuring Health. Washington, DC: National Academy Press.
IOM (Institute of Medicine). 2008. Improving the Presumptive Disability Decision-Making Process for Veterans. Washington, DC: National Academies Press.
Iowa Persian Gulf Study Group. 1997. Self-reported illness and health status among Gulf War veterans: A population-based study. JAMA 277(3):238-245.
Kelsall, H.L., M.R. Sim, A.B. Forbes, D.P. McKenzie, D.C. Glass, J.F. Ikin, P. Ittak, and M.J. Abramson. 2004. Respiratory health status of Australian veterans of the 1991 Gulf War and the effects of exposure to oil fire smoke and dust storms. Thorax 59(10):897-903.
Kennedy, K. 2008. Burn Pits a Balad Raise Health Concerns. Air Force Times, October 28, 2008 [online]. Available: http://www.airforcetimes.com/news/2008/10/military_burnpit_102708w/ [accessed Jan. 7, 2010].
Kwon, H.J., S.H. Cho, Y. Chun, F. Lagarde, and G. Pershagen. 2002. Effects of the Asian dust events on daily mortality in Seoul, Korea. Environ. Res. 90(1):1-5.
Laden, F., L.M. Neas, D.W. Dockery, and J. Schwartz. 2000. Association of fine particulate matter from different sources with daily mortality in six U.S. cities. Environ. Health Perspect. 108(10):941-947.
Lange, J.L., D.A. Schwartz, B.N. Doebbeling, J.M. Heller, and P.S. Thorne. 2002. Exposures to the Kuwait oil fires and their association with asthma and bronchitis among Gulf war veterans. Environ. Health Perspect. 110(11):1141-1146.
Lippmann, M., K. Ito, J.S. Hwang, P. Maciejczyk, and L.C. Chen. 2006. Cardiovascular effects of nickel in ambient air. Environ. Health Perspect. 114(11):1662-1669.
Liu, L., T. Ruddy, M. Dalipaj, R. Poon, M. Sztszkowicz, H. You, R.E. Dales, and A.J. Wheeler. 2009. Effects of indoor, outdoor, and personal exposure to particulate air pollution on cardiovascular physiology and systemic mediators in seniors. J. Occup. Environ. Med. 51(9): 1088-1098.
Liu, L-J. S., M. Box, D. Kalman, J. Kaufman, J. Koenig, T. Larson, T. Lumley, L. Sheppard, and L. Wallace. 2003. Exposure assessment of particulate matter for susceptible populations in Seattle. Enviorn. Health Persp. 111(7): 909-918.
Malig, B.J., and B.D. Ostro. 2009. Coarse particles and mortality: Evidence from a multicity study in California. Occup. Environ. Med. 66(12):832-839.
Middleton, N., P. Yiallouros, S. Kleanthous, O. Kolokotroni, J. Schwartz, D.W. Dockery, P. Demokritou, and P. Koutrakis. 2008. A 10-year time-series analysis of respiratory and cardiovascular morbidity in Nicosia, Cyprus: The effect of short-term changes in air pollution and dust storms. Environ. Health 7:39.
Murthy, L.I., and W.E. Halperin. 1995. Medical screening and biological monitoring. A guide to the literature for physicians. J. Occup. Environ. Med. 37(2):170-184.
Oberdörster, G. 2002. Toxicokinetics and effects of fibrous and nonfibrous particles. Inhal. Toxicol. 14(1):29-56.
Oglesby, L., N. Künzli, M. Röösli, C. Braun-Fahrländer, P. Mathys, W. Stern, M. Jantunen, A. Kousa. 2000. Validity of ambient levels of fine particles as surrogate for personal exposure to outdoor air pollution—results of the European EXPOLISEAS study (Swiss Center Basel). J. Air & Waste Manage. 50: 1251-1261.
Ostro, B.D., S. Hurley, and M.J. Lipsett. 1999. Air pollution and daily mortality in the Coachella Valley, California: A study of PM10 dominated by coarse particles.
Ostro, B.D., R. Broadwin, and M.J. Lipsett. 2000. Coarse and fine particles and daily mortality in the Coahella Valley, California: A follow-up study. J. Expo. Anal. Environ. Epidemiol. 10(5):412-419.
Peng, R.D., F. Dominici, R. Pastor-Barriuso, S.L. Zeger, and J.M. Samet. 2005. Seasonal analyses of air pollution and mortality in 100 U.S. cities. Am. J. Epidemiol. 161(6):585-594.
Peng R.D., H.H. Chang, M.L. Bell, A. McDermott, S.L. Zeger, J.M. Samet, F. Dominici. 2008. Coarse particulate matter air pollution and hospital admissions for cardiovascular and respiratory disease among Medicare patients. JAMA 299:2172-2179.
Peng, R.D., M.L. Bell, A.S. Geyh, A. McDermott, S.L. Zeger, J.M. Samet, and F. Dominici. 2009. Emergency admissions for cardiovascular and respiratory diseases and the chemical composition of fine particle air pollution. Environ. Health Perspect. 117(6):957-963.
Perez, L., A. Tobias, X. Querol, N. Künzli, J. Pey, A. Alastuey, M. Viana, N. Valero, M. González-Cabré, and J. Sunyer. 2008. Coarse particles from Saharan dust and daily mortality. Epidemiology 19(6):800-807.
Petruccelli, B.P, M. Goldenbaum, B. Scott, R. Lachiver, D. Kanjarpane, E. Elliott, M. Francis, M.S. McDiarmid, and D. Deeter. 1999. Health effects of the 1991 Kuwait oil fires: A survey of U.S. army troops. J. Occup. Environ. Med. 41(6):433-439.
Pope, C.A., III, and D.W. Dockery. 2006. Health effects of fine particulate air pollution: Lines that connect. J. Air Waste Manag. Assoc. 56(6):709-742.
Pope, C.A., III, R.W. Hill, and G.M. Villegas. 1999. Particulate air pollution and daily mortality on Utah's Wasatch Front. Environ. Health Perspect. 107(7):567-573.
Proctor, S.P., T. Heeren, R.F. White, J. Wolfe, M.S. Borgos, J.D. Davis, L. Pepper, R. Clapp, P.B. Sutker, J.J. Vasterling, and D. Ozonoff. 1998. Health status of Persian Gulf War veterans: Self-reported symptoms, environmental exposures, and the effect of stress. Int. J. Epidemiol. 27(6):1000-1010.
Qu, W., D. Wang, Y. Wang, L. Sheng, and G. Fu. In press. Seasonal variation, source, and regional representativeness of the background aerosol from two remote sites in western China. Environ. Monit. Assess.
Richards, A.L., K.C. Hyams, D.M. Watts, P.J. Rozmajzl, J.N. Woody, and B.R. Merrell. 1993. Respiratory disease among military personnel in Saudi Arabia during Operation Desert Shield. Am. J. Public Health 83(9):1326-1329.
Ross, R. 2009. Overview of Respiratory Function Assessment to Date in Deployed Units. Presentation at the First Meeting on Review of the DOD’s Enhanced Particulate Matter Surveillance Program Report, July 9, 2009, Washington, DC.
Ryan, M.A., T.C. Smith, B. Smith, P. Amoroso, E.J. Boyko, G.C. Gray, G.D. Gackstetter, J.R. Riddle, T.S. Wells, G. Gumbs, T.E. Corbeil, and T.I. Hooper. 2007. Millennium Cohort: Enrollment begins a 21-year contribution to understanding the impact of military service. J. Clin. Epidemiol. 60(2):181-191.
Sanders, J.W., S.D. Putnam, C. Frankart, R.W. Frenck, M.R. Monteville, M.S. Riddle, D.M. Rockabrand, T.W. Sharp, and D.R. Tribble. 2005. Impact of illness and noncombat injury during operations Iraqi Freedom and Enduring Freedom (Afghanistan). Am. J. Trop. Med. Hyg. 73(4):713-719.
Sarnat, J.A., K.W. Brown, S.M. Bartell, S.E. Sarnat, A.J. Wheeler, H.H. Suh, and P. Koutrakis. 2009. The relationship between averaged sulfate exposures and concentrations: results from exposure assessment panel studies in four U.S. cities. Environ. Sci. Technol. 43(13):5028-5034.
Schwartz, J., G. Norris, T. Larson, L. Sheppard, C. Claiborne, and J. Koenig. 1999. Episodes of high coarse particle concentrations are not associated with increased mortality. Environ. Health Perspect. 107(5):339-342.
Secretary of Defense. 1998. Report to the Committee on National Security, House of Representatives, and the Armed Services Committee, U.S. Senate, on Effectiveness of Medical Research Initiatives Regarding Gulf War illnesses. Washington, D.C.: Department of Defense.
Sheehy, J. 2009. Enhanced particulate matter surveillance in the U.S. Central Command theater of operations. Presentation at the First Meeting on Review of the DOD’s Enhanced Particulate Matter Surveillance Program Report, July 9, 2009, Washington, DC.
Smith, B., C.A. Wong, T.C. Smith, E.J. Boyko, G.D. Gackstetter; and M.A.K. Ryan for the Millennium Cohort Study Team. 2009. Newly reported respiratory symptoms and conditions among military personnel deployed to Iraq and Afghanistan: A prospective population-based study. Am. J. Epidemiol. 170(11):1433-1442.
Stockelman, M. 2009. Overview of Inhalational Toxicology Studies Using EPMS Particulate Matter. Presentation at the First Meeting on Review of the DOD’s Enhanced Particulate Matter Surveillance Program Report, July 9. 2009, Washington, DC.
UNEP (United Nations Environment Programme). 2007. Air quality and Atmospheric Pollution in the Arab Region. Draft. League of Arab States and United Nations
Economic and Social Commission for Western Asia [online]. Available: http://www.un.org/esa/sustdev/csd/csd14/escwaRIM_bp1.pdf [accessed Feb. 2, 2010].
USACHPPM (U.S. Army Center for Health Promotion and Preventive Medicine). 2003. Chemical Exposure Guidelines for Deployed Military Personnel. USACHPPM Technical Guide 230. Version 1.3- Updated May 2003. U.S. Army Center for Health Promotion and Preventive Medicine [online]. Available: http://chppm-www.apgea.army.mil/documents/TG/TECHGUID/TG230.pdf [accessed Feb. 19, 2010].
White, R.H., C.H. Stineman, J.M. Symons, P.N. Breysse, S.R. Kim, M.L. Bell, and J.M. Samet. 2008. Premature mortality in the Kingdom of Saudi Arabia associated with particulate matter air pollution from the 1991 Gulf War. Hum. Ecol. Risk Assess. 14:645-664.
Yang, C.Y. 2006. Effects of Asian dust storm events on daily clinical visits for conjunctivitis in Taipei, Taiwan. J. Toxicol. Environ. Health A 69(18):1673-1680.
Yang, C.Y., S.S. Tsai, C.C. Chang, and S.C. Ho. 2005. Effects of Asian dust storm events on daily admissions for asthma in Taipei, Taiwan. Inhal. Toxicol. 17(14):817-821.
Yang, C.Y., M.H. Cheng, and C.C. Chen. 2009. Effects of Asian dust storm events on hospital admissions for congestive heart failure in Taipei, Taiwan. J. Toxicol. Environ. Health A 72(5):324-328.