Veterans and Agent Orange Update 2014 (2016) / Chapter Skim
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14 Conclusions and Recommendations
14 Conclusions and Recommendations
Pages 903-926
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From page 903... ...
Although the studies published since Update 2012 are the subject of detailed evaluation here, the committee drew its conclusions in the context of the entire body of literature. The contribution of recent publications to the evidence database is emphasized in this report, but the totality of the weight 1 espite loose usage of "Agent Orange" by many people, in numerous publications, and even in the D title of this series, this committee uses "herbicides" to refer to the full range of herbicide exposures experienced in Vietnam, while "Agent Orange" is reserved for a specific one of the mixtures sprayed in Vietnam.
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From page 904... ...
In the absence of standardized designations that rely on reliable methods, herbicide exposure designations derived from medical records are no more reliable than entries based on the Agent Orange Registry or simply service during the Vietnam conflict. The committee also notes that considerable experimental data related to the biologic plausibility of the health conditions statistically associated with exposure to the components of the herbicides sprayed in Vietnam have emerged since the beginning of this series of VAO reports.
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From page 905... ...
Although the biologic plausibility of maternal exposure to toxic agents, specifically including the chemicals of interest, is well established, there are no existing epidemiologic data supporting increased incidence of spina bifida specifically following maternal exposure to the components of the herbicides sprayed in Vietnam as is required for identifying an association under the Agent Orange Act. Consequently, spina bifida in the offspring of both male and female veterans has been moved to the category of inadequate or insufficient evidence of an association with
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From page 906... ...
] to be presumptively related to service in Vietnam, on the basis of the total weight of available evidence the current committee reaffirmed the conclusions of previous VAO committees that these two health outcomes should be placed in the category of limited or suggestive evidence of association.
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From page 907... ...
Inadequate or Insufficient Evidence to Determine an Association The available epidemiologic studies are of insufficient quality, consistency, or statistical power to permit a conclusion regarding the presence or absence of an association. For example, studies fail to control for confounding, have inadequate exposure assessment, or fail to address latency.
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From page 908... ...
Neonatal or infant death and stillbirth in offspring of exposed people Low birth weight in offspring of exposed people Birth defects in offspring of exposed people (category change from Limited or Suggestive in Update 2012 for spina bifida) Childhood cancer (including acute myeloid leukemia)
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From page 909... ...
As evidenced in Table 14-2, the recommendations of previous VAO committees fall into four primary areas: • Management of information under the auspices of DOD and VA • Additional epidemiologic work • Improvement of exposure estimation • Priority areas for toxicologic research In instances in which the VAO committees have been aware of actions taken after a recommendation was made, the events are briefly delineated in the rightmost column of Table 14-2. After encouragement of the effort that matured into the model to estimate individual opportunity of herbicide exposure based
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From page 910... ...
Update 2006 efforts undertaken by VA to assess a possible Melanoma Update 2006 role for herbicides in the occurrence of the other Amyotrophic lateral sclerosis Update 2002 conditions listed here. Parkinson disease Update 2002 Several small studies have been published by Alzheimer disease Update 2010 individual researchers using the "AO exposed" Metabolic syndrome Update 2006 variable in VA medical records without Paternally mediated effects on health of offspring Update 2006 explanation of its derivation.
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From page 911... ...
era Veterans Health Study to investigate the relationship between herbicide exposure during the Vietnam War and morbidity from hypertension and COPD in ACC veterans [results have not yet been reported]
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From page 912... ...
Study the potential for paternally mediated effects on health outcomes in Update 2006 No known follow-up offspring. Comprehensive longitudinal analysis of the AFHS data collected in the Update 2008 No known follow-up six intensive medical-cycle examinations (particularly concerning medical interventions, cancer incidence, mortality, birth defects in veterans' offspring)
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From page 913... ...
The IOM committee's final report, Disposition Retain and maintain AFHS medical records and biological samples with VAO of the Air Force Health Study, concluded that the oversight that could be established for future use and research, while respecting medical records, data, and biological specimens the privacy of participants. collected in the study, which closed on September Dedicated funding is required so that focused analyses can be carried out by Update 2008 30, 2006, were a trove of valuable research material.
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From page 914... ...
National Institute for Occupational Safety and Health (NIOSH) Conduct epidemiologic studies -- with adequate sample size to detect elevated VAO No known follow-up associations -- of the reproductive history of individuals with occupational or environmental exposure to herbicides and dioxin.
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From page 915... ...
.] Additional studies of the COIs and conditions that have been noted to be of Update 2006 No known follow-up special interest but on which the current evidence is inadequate or insufficient (such as COPD, brain cancer, breast cancer, tonsil cancer, melanoma, amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer disease)
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From page 916... ...
Exposure ESTIMATION A non-governmental organization with appropriate experience in historical VAO Stellman model developed reconstruction should be commissioned to develop and test models of herbicide exposure for use in studies of Vietnam veterans. If it is determined that a valid exposure reconstruction model is feasible, then the VA and other government agencies should facilitate additional epidemiologic studies of veterans.
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From page 917... ...
NOTE: ACC, US Army Chemical Corps; AFHS, Air Force Health Study; AHS, Agricultural Health Study; AO, Agent Orange; COI, chemical of interest; COPD, chronic obstructive pulmonary disease; DOD, US Department of Defense; EMR, electronic medical record; HT, hypertension; IARC, International Agency for Research on Cancer; IOM, Institute of Medicine; NIOSH, National Institute for Occupational Safety and Health; NVVLS, National Vietnam Veterans Longitudinal Study; NVVRS, National Vietnam Veterans Readjustment Study; PBPK model, physiologically based pharmacokinetic model; PD, Parkinson disease; PTSD, posttraumatic stress disorder; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; VA, Veterans Administration; VAO, Veterans and Agent Orange: VV, Vietnam veteran.
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From page 918... ...
EPIDEMIOLOGIC STUDIES Air Force Health Study (AFHS) Comprehensive longitudinal analysis of the AFHS data collected in the six intensive medical cycle examinations (particularly concerning medical interventions, cancer incidence, mortality, birth defects in veterans' offspring)
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From page 919... ...
VAO committees have been gratified by some of the responses to their encouragement of following up on established cohorts of Vietnam veterans, as embodied by additional epidemiology studies of female Vietnam veterans and the Army Chemical Corps. For example, the committee for Update 2010 placed a high priority on research to address COPD from a morbidity perspective with an appropriate functional diagnosis of COPD and a collection of data to permit adjustments for smoking and other relevant confounders.
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From page 920... ...
Although the committee asked repeatedly about the status of this effort, it was not until a terse summary of the findings of the National Vietnam Veterans Longitudinal Study appeared in the Summer 2015 issue of VA's erratically published Agent Orange Newsletter, it became evident that this advice had not been incorporated into the experimental design. In retrospect, it appears that the implementation of some of these suggestions was not feasible.
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From page 921... ...
(Of course, numerous points concerning the appointment of members and other procedural matters would need to be addressed in advance.) More specifically, before committing extensive resources to ameliorating adverse health consequences in the descendants of veterans, both male and female, it would be appropriate to conduct a very careful review of evidence concerning whether paternal exposure to any toxicant has definitively been demonstrated to result in abnormalities in even the first generation of offspring.
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From page 922... ...
In addition, VA should establish an external advisory group to identify effective mechanisms for mining VA medical database information and to establish guidelines for the creation of a grants program focused on proposals for the conduct of analytic studies related to specific health outcomes of interest. Epidemiologic Studies The committee notes that future analyses of health outcomes in any future epidemiology studies should be as specific as possible because generic findings, such as those for "all respiratory outcomes," are not useful in determining associations of herbicide exposures with specific health conditions.
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From page 923... ...
Recently, VA launched the ACC Vietnam-Era Veterans Health Study to investigate the relationship between herbicide exposure during the Vietnam War and hypertension and COPD in ACC veterans. Information garnered from the study could benefit VA and future VAO committees as potential associations between exposure to the chemicals of interest and respiratory outcomes are evaluated.
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From page 924... ...
Exposure–response relationship for Data only dioxin and cancer and non-cancer health outcomes in the Air Force Health Study cohort using physiologically based pharmacokinetic modeling of exposure and updated mortality Knafl University of North Effects of dioxin exposure for male Air Data only Carolina at Chapel Hill Force Vietnam veterans on reproductive outcomes Mandel Exponent, Inc. The reanalysis of the Ranch Hand data Data only Mazur Syracuse University Testosterone changes Data only Mitchell Emory University and Identifying novel biomarkers of Data and Atlanta VA Medical vulnerable coronary artery disease: The biospecimens Center Air Force Health Study Ramosc University of Louisville Detection of L1 protein in Ranch Hand Data and biospecimens biospecimens Rossc Pacific Health Research Parkinson's disease and pre-motor Data only and Education Institute, features of Parkinson's disease in the VA Air Force Health Study Rothc VA San Diego Caveolin's role during healthy aging Data and Healthcare System biospecimens Seldinc Boston University Incidence of abnormal free light Data and chains and other markers of light chain biospecimens amyloidosis in veterans exposed to Agent Orange: A pilot study Shimv Centers for Disease Monoclonal gammopathy of Data and Control and Prevention undetermined significance (MGUS)
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From page 925... ...
VAO committees have been monitoring studies of morphologic birth defects and cancers in the offspring of exposed individuals, but systematic review of defined clinical health conditions that are manifested later in the offspring's lives remains difficult because most studies report on physiologic biomarkers that might or might not predict the potential for disease development later in life, rather than investigating specific diseases. A longstanding major concern is the possible association between the exposure of male Vietnam veterans to the chemicals of interest and health problems in their offspring, but there are few epidemiology studies of these endpoints that have addressed paternal exposure in the absence of maternal exposure.
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From page 926... ...
The rapidly expanding field of epigenetics is revealing the molecular mechanisms by which environmental agents can modify gene expression without changing DNA sequence long after exposure occurs, even in later generations -- at least in the case of maternal exposure to some chemicals. Animal studies of the mechanisms of inhibition of fetal growth, particularly in male offspring, after maternal exposure could help to elucidate findings seen in some epidemiologic studies that examined maternal exposure to the chemicals of interest and birth weight.
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