10

Research Recommendations

As part of their charge, the committees responsible for producing the Agent Orange reports make recommendations concerning the need, if any, for additional scientific studies to resolve uncertainties concerning the health effects of the compounds sprayed in Vietnam —2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), picloram, and cacodylic acid. This chapter summarizes the present committee's research recommendations.

Although great strides have been made over the last several years in understanding the health effects of exposure to the chemicals sprayed in Vietnam and in elucidating the mechanisms underlying those effects, there are still important gaps in our knowledge. The scope of potential research on these chemical compounds is wide, but information from some kinds of research would be more informative for the committee 's charge than information from others. Because of the importance of epidemiologic and other human studies to the committee's conclusions, the focus of these recommendations is on such studies. The lack of discussion of a particular kind of research should not be interpreted as a lack of value in it.

VIETNAM-VETERAN STUDIES

As did the previous committees in their reports (IOM, 1994, 1996, 1999, 2000, 2001, 2002), on the basis of its review of the epidemiologic evidence and consideration of the quality of available exposure information, especially from studies of Vietnam veterans, this committee concludes that continuation of epide-



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Veterans and Agent Orange: Update 2002 10 Research Recommendations As part of their charge, the committees responsible for producing the Agent Orange reports make recommendations concerning the need, if any, for additional scientific studies to resolve uncertainties concerning the health effects of the compounds sprayed in Vietnam —2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), picloram, and cacodylic acid. This chapter summarizes the present committee's research recommendations. Although great strides have been made over the last several years in understanding the health effects of exposure to the chemicals sprayed in Vietnam and in elucidating the mechanisms underlying those effects, there are still important gaps in our knowledge. The scope of potential research on these chemical compounds is wide, but information from some kinds of research would be more informative for the committee 's charge than information from others. Because of the importance of epidemiologic and other human studies to the committee's conclusions, the focus of these recommendations is on such studies. The lack of discussion of a particular kind of research should not be interpreted as a lack of value in it. VIETNAM-VETERAN STUDIES As did the previous committees in their reports (IOM, 1994, 1996, 1999, 2000, 2001, 2002), on the basis of its review of the epidemiologic evidence and consideration of the quality of available exposure information, especially from studies of Vietnam veterans, this committee concludes that continuation of epide-

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Veterans and Agent Orange: Update 2002 miologic studies of veterans could yield valuable information. That is true especially because diseases of aging could emerge as the population grows older, and as a new exposure-reconstruction model is developed and validated. Air Force Health Study The Air Force Health Study (AFHS) is an epidemiologic study whose purpose is to determine whether exposure to the herbicides used in Vietnam might underlie any adverse health conditions observed in a cohort of Air Force personnel (termed the Ranch Hands) who conducted aerial spray missions (Operation Ranch Hand). A baseline morbidity study of them and a matched comparison cohort was conducted in 1982, and there were follow-up assessments in 1985, 1987, 1992, and 1997. In accordance with the study protocol, one additional assessment is under way and will be completed in April 2003. A final report will be issued in early 2005 (personal communication, Joel Michalek, Brooks Air Force Base, September 17, 2002). The AFHS is one of the few primary sources of information on the health of Vietnam veterans known to be exposed to Agent Orange and other herbicides. The study is coming to its scheduled end as the cohorts are reaching the age at which several health outcomes of interest may be expected to manifest, such as cancers and diseases related to aging. The committee recommends continuing the study past its planned completion date to enable further study of those diseases. Given the increased incidence of such diseases as amyotrophic lateral sclerosis, Parkinson's disease, prostatic cancer, and brain cancer in aging populations and the increasing age of the Vietnam-veteran cohort, research should specifically examine those diseases in the Vietnam veterans. Such studies should be conducted with an appropriate control population. Similarly, continued study of other exposed cohorts (for example, the cohort studied by the National Institute for Occupational Safety and Health) could also provide information on diseases of aging. The committee also recommends retaining and maintaining medical records and samples on the AFHS cohort so that—with proper respect for the privacy of the study participants—they can be available for future research. The federal government should examine how the various forms of data and specimens collected in the course of the AFHS might be maintained and what form of oversight should be established for their future use. Any extension of the research or future use of the records would, of course, have to have the full knowledge and consent of the AFHS population and respect for the privacy of the participants. The committee's judgment is that continued research on the health of the Ranch Hands and comparison veterans is likely to yield important information on the determinants of health and disease in those who served in Vietnam and perhaps in their offspring.

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Veterans and Agent Orange: Update 2002 Army Chemical Corps Studies Members of the Army Chemical Corps constitute the largest cohort of Vietnam veterans exposed directly to herbicides and TCDD. They were involved in the handling and distribution of the compounds in Vietnam. Preliminary studies of this cohort by scientists in the Department of Veterans Affairs (VA) have demonstrated increased TCDD concentrations in Chemical Corps veterans who reported spraying herbicides as part of their duties. Research on the health effects in this population has been and is being conducted. Continued careful and expanded long-term study of the cohort could be a valuable addition to current research on Vietnam veterans. As with all Vietnam-veteran research, the federal government should consider the form of oversight that best facilitates the research effort and ensures the scientific validity of such studies. Exposure-Reconstruction Study The committee is aware that an assessment of herbicide exposure of Vietnam veterans, being overseen by the Institute of Medicine Committee on the Assessment of Wartime Exposure to Herbicides in Vietnam, is nearing completion (see Chapter 5). The assessment should provide more accurate and precise data on the potential exposure of people to herbicides sprayed in Vietnam. The data could be used in epidemiologic studies, such as studies of ground troops, to examine possible associations between health effects and exposure to the herbicide mixtures used in Vietnam. Combining research into the health effects of the herbicides in Vietnam veterans and potential information from this database might provide better information on the health effects of the chemicals of interest. Other Studies of Vietnam Veterans Several other concerns have been raised by veterans that the committee considers worthy of further investigation. A case series of glioblastomas and possibly astrocytomas was brought to the attention of the committee at its public hearing in Seattle. Despite the fact that these tumors are currently classified in the no association category, the committee believes that these concerns should be further investigated. These are extremely rare tumors, and the likelihood of detected changes in their rates in occupational cohorts, the AFHS, or the Seveso population is low. Other methods, such as making use of or improving VA databases, might be appropriate first steps toward investigating these concerns. Although more-thorough studies of Vietnam veterans are needed if the actual health experience of the veterans is to be adequately understood, recording or monitoring of trends in diseases of aging Vietnam veterans and rare diseases could be especially useful for indicating which diseases might warrant futher study.

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Veterans and Agent Orange: Update 2002 STUDIES OF THE VIETNAMESE Another population that has been understudied is the Vietnamese, including those who served in the military during the war and civilians. Anecdotal evidence and studies published in non-English-language journals suggest an array of long-term health effects that could potentially be related to the chemicals used by US troops in Vietnam. This population provides several opportunities that others do not. First, there is a high probability that the number of exposed persons is substantially larger than the number previously studied. Second, exposures not only were high at the time of application of herbicides, but, because of persistence in the environment, continued long beyond the conclusion of military activities; studies suggest that body burdens and environmental concentrations might still be high in some areas of Vietnam (Schecter et al., 2002; Verger et al., 1994). Third, the establishment of diplomatic relations between the United States and Vietnam and a recent initiative overseen by the National Institute of Environmental Health Sciences (NIEHS) have opened the door for significant scientific collaborations. In March 2002, a US–Vietnamese Workshop on Health and Environmental Effects of the war was held in Hanoi. After the workshop, during a one-day meeting organized by the NIEHS, US and Vietnamese scientists held intensive discussions regarding types of studies that were deemed useful. Although the development of collaborative research between scientists from the two countries presents challenges, the committee believes that the hurdles might be overcome. Careful planning and the strategic building of local capacity in Vietnam through investment in training and infrastructure can lay the foundation for high-quality research. It must be stressed, however, that efforts to conduct research will have to be accompanied by efforts to build trust. Because such research has the potential to close a number of gaps in our understanding of the long-term health consequences of exposure to TCDD and herbicides used in Vietnam, the committee supports any further steps that can be taken to develop collaborative programs of research. The possibility of using the newly established exposure database to assess exposure of the Vietnamese is also worth consideration, although it should be recognized that the explicit purpose of the database was to determine exposures of US service personnel who spent time in Vietnam. OTHER RESEARCH As stated previously, the committee has focused its recommendations on studies of human populations. The committee believes, however, that experimental research in the mechanisms that might underlie the human health outcomes can provide information valuable for determining the risk of disease in Vietnam veterans and the interactions between various exposures that lead to disease. For example, experimental studies in animals could examine the interaction of smok-

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Veterans and Agent Orange: Update 2002 ing and TCDD exposure with health outcomes of interest to provide better information on potential confounders in epidemiologic studies. The committee recognizes that although it might be difficult to make conclusive links to effects in humans on the basis of such research, those studies could provide information useful for interpreting the results of epidemiologic studies, especially studies in which there might be multiple exposures or other factors that complicate the drawing of conclusions. REFERENCES IOM (Institute of Medicine). 1994. Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam Washington, DC: National Academy Press. IOM. 1996. Veterans and Agent Orange: Update 1996. Washington, DC: National Academy Press. IOM. 1999. Veterans and Agent Orange: Update 1998. Washington, DC: National Academy Press. IOM. 2000. Veterans and Agent Orange: Herbicide/Dioxin Exposure and Type 2 Diabetes Washington, DC: National Academy Press. IOM. 2001. Veterans and Agent Orange: Update 2000. Washington, DC: National Academy Press. IOM. 2002. Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans. Washington, DC: National Academy Press. Schecter A, Pavuk M, Constable Dai LC, Papke O. 2002. A follow-up: High level of dioxin contamination in Vietnamese from Agent Orange, three decades after the end of spraying. Journal of Occupational and Environmental Medicine 44:218–220. Verger P, Cordier S, Thuy LT, Bard D, Dai LC, Phiet PH, Gonnord MF, Abenhaim L. 1994. Correlation between dioxin levels in adipose tissue and estimated exposure to Agent Orange in South Vietnamese residents. Environmental Research 65(2):226–242.

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