Veterans and Agent Orange Update 11 (2018) (2018) / Chapter Skim
Currently Skimming:
11 Other Chronic Health Outcomes
11 Other Chronic Health Outcomes
Pages 515-558
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 515... ...
) and other chronic, non-malignant outcomes including respiratory disorders, gastrointestinal and digestive diseases, adverse effects on thyroid homeostasis, kidney and urinary disorders, chronic skin conditions, eye problems, and bone conditions.
|
From page 516... ...
The categories of association and the committee's approach to categorizing the health outcomes are discussed in Chapter 3. NON-CANCEROUS RESPIRATORY DISORDERS For the purposes of this report, "non-cancerous respiratory disorders" are defined as all acute and chronic lung diseases other than cancers; the variety of conditions are described by the International Classification of Diseases (ICD)
|
From page 517... ...
. The causes of death from respiratory diseases, especially chronic diseases, are often misclassified on death certificates (Mieno et al.
|
From page 518... ...
However, the majority of these studies were not able to control for major risk factors, such as smoking or tobacco use. Mortality from respiratory diseases was not found to be higher than expected in the Centers for Disease Control and Prevention's Vietnam Experience Study (Boehmer et al., 2004)
|
From page 519... ...
did not find an association between exposure to the COIs and deaths from all non-malignant respiratory diseases; no association with COPD deaths was found for the subgroup exposed to both TCDD and PCP. Updated mortality data on workers in two chlorphenoxy herbicide plants in the Netherlands were reanalyzed by Boers et al.
|
From page 520... ...
There also remains inadequate or insufficient evidence of an association between exposure to the COIs and the prevalence of respiratory diseases, such as wheeze or asthma, COPD, and farmer's lung. Update of the Epidemiologic Literature This section summarizes the results of the relevant studies on respiratory disorders and exposures to the COIs.
|
From page 521... ...
, cigarette smoking status, allergy status based on self-reports of doctor-diagnosed hay fever or eczema, and adult onset of asthma based on onset at >20 years of age. No association with an elevated odds of asthma exacerbation was found for either 2,4-D (OR = 0.8; 95% CI 0.5–1.3)
|
From page 522... ...
For 111 participants, a neurological examination was conducted. Associations between exposure and health outcomes were assessed using logistic regression models that controlled for age, gender, smoking, BMI, and ethnicity using two different methods of exposure: having worked in a TCDD-exposed job (based on occupational records)
|
From page 523... ...
Other Identified Studies Five other studies of non-malignant respiratory diseases were identified, but all lacked sufficient exposure specificity to be included as contributing to the evidence base of the potential effect of the COIs. One study of U.S.
|
From page 524... ...
In Ahr knockout mouse lung fibroblasts and human lung adenoma cells that were deficient in AHR expression and exposed to cigarette smoke extract, they found increased
|
From page 525... ...
Therefore, the prior assessment cannot be altered since the new findings are mixed, and the study designs have limitations. Conclusion On the basis of the evidence reviewed here and in previous VAO reports, the committee concludes that there is inadequate or insufficient evidence of an association between exposure to the COIs and mortality from all non-cancerous respiratory diseases or from COPD specifically.
|
From page 526... ...
Other risk factors include genetic predisposition (such as some blood and human leukocyte antigen types) , cigarette smoking, and psychologic factors (chronic anxiety and stress)
|
From page 527... ...
Cirrhosis is the most commonly reported liver disease in epidemiologic studies of herbicide or TCDD exposure. Cirrhosis is an irreversible chronic injury of the liver with extensive scarring and a resulting loss of function.
|
From page 528... ...
Deaths from alcoholic liver disease were also statistically significantly elevated in the more highly exposed veterans. Most of the analyses of occupational or environmental cohorts have had insufficient numbers of cases to support confident conclusions.
|
From page 529... ...
Age-specific hospitalization rates were calculated using the total number of annual hospitalizations published by the Ministry of Health and the average annual resident population. Standardized hospitalization rates and 99% CIs were calculated for the veteran cohort and the general population and reported for 14 conditions related to gastrointestinal and hepatobiliary outcomes.
|
From page 530... ...
Exposure to the COIs was not validated and was assumed based on deployment to Vietnam. Moreover, the analysis did not control for smoking or ethnicity or other potentially important risk factors.
|
From page 531... ...
Associations between exposure and health outcomes were assessed using logistic regression models that controlled for age, gender, smoking, BMI, and ethnicity using two different methods of exposure: having worked in a TCDD-exposed job (based on occupational records) and having serum TCDD concentration ≥10 pg/g lipid (18%)
|
From page 532... ...
(2016) studied a mouse model of liver injury and found that TCDD exposure increased
|
From page 533... ...
However, the available animal data do not support a plausible link between herbicide exposure and gastrointestinal toxicity in Vietnam veterans. Synthesis Previous updates indicated that there have been inconsistent findings for the COIs and gastrointestinal and liver disease and that interpreting individual studies is difficult because of a lack of information on alcohol consumption (especially for liver cirrhosis)
|
From page 534... ...
Conclusion On the basis of the evidence reviewed here and in previous VAO reports, the committee concludes that there is inadequate or insufficient evidence to determine whether there is an association between exposure to the COIs and gastrointestinal and digestive diseases. KIDNEY AND URINARY DISORDERS Update 2014 was the first update for which the literature search identified studies reporting results concerning a possible association between exposure to the COIs and kidney diseases (ICD-9 580–589; ICD-10 N00–N29)
|
From page 535... ...
Age-specific hospitalization rates were calculated using the total number of annual hospitalizations published by the Ministry of Health and the average annual resident population. Standardized hospitalization rates and 99% CIs were calculated for the veteran cohort and the general population and the two rates were used to calculate an SHR for several conditions including kidney and urinary outcomes.
|
From page 536... ...
The plant produced 2,4,5-T, and the workers were potentially exposed to 2,4,5-T, the intermediates of TCP and other chlorophenols, as well as to TCDD. Workers had previously been recruited and examined as part of the international cohort of producers of phenoxy herbicides led by IARC (Kogevinas et al., 1997)
|
From page 537... ...
Associations between exposure and health outcomes were assessed using logistic regression models that controlled for age, gender, smoking, BMI, and ethnicity using two different methods of exposure: having worked in a TCDD-exposed job (based on occupational records) and having serum TCDD concentration ≥10 pg/g lipid (18%)
|
From page 538... ...
. After adjustment for PCDD/Fs, gender, mercury, metabolic syndrome, age, fasting glucose, insulin, and uric acid, a high dioxin level was found to be significantly associated with chronic kidney disease (OR = 1.74, 95% CI 1.02–2.97)
|
From page 539... ...
and various factors, including uric acid, glomerular filtration rates, and hyperuricemia risk. Hyperuricemia is a measure of disturbed metabolism, not a health outcome, and therefore this study was not considered relevant to the committee's task.
|
From page 540... ...
evaluated the association of the blood levels of three chlorinated dibenzo-p-dioxins, one chlorinated dibenzofuran, and four dioxin-like PCBs with nephropathy among 1,505 adolescents and young adults and found that dioxin-like chemicals were associated with nephropathy among young females, but not males, although the effect estimates were very imprecise. An environmental exposure study of Taiwanese residents living in close proximity to a former PCP-producing factory found that those who had high serum dioxin levels had a statistically significantly elevated risk of chronic kidney disease (Huang et al., 2016)
|
From page 541... ...
In particular, clinical disruptions of thyroid function are grouped as ICD-9 240–246 or as ICD-10 E00–E07, E20–21, while the remaining endocrine disorders are grouped as ICD-9 252–259 or as ICD-10 E22–E35. Thyroid homeostasis in humans was first addressed with respect to the COIs by the committee for Update 2002.
|
From page 542... ...
After consideration of several new studies and because of the consistent observations of exposures to the COIs being related to perturbations of thyroid function -- and to clinical hypothyroidism in particular -- the committee for Update 2014 considered the body of epidemiologic data, in combination with strong biologic plausibility, to represent limited or suggestive evidence of an association between exposure to the COIs and hypothyroidism. Additional endocrine effects have been observed in conjunction with exposure to the COIs in both humans and animals, but the evidence is inadequate or insufficient to establish an association with herbicide exposure for them.
|
From page 543... ...
The results from several environmental studies have also been reviewed by update committees, and no evidence was found of effects on thyroid function or disease in women exposed to pesticides (Chevrier et al., 2008) or, among women in the AHS, exposed to phenoxy herbicides (Goldner et al., 2010)
|
From page 544... ...
The plant produced 2,4,5-T, and workers were potentially exposed to 2,4,5-T, the intermediates of TCP and other chlorophenols, and TCDD. Workers had previously been recruited and examined as part of the international cohort of producers of phenoxy herbicides led by IARC (Kogevinas et al., 1997)
|
From page 545... ...
A blood sample was also collected at that time and analyzed for TCDD, lipids, thyroid hormones, and other substances. Associations between exposure and health outcomes were assessed using logistic regression models that controlled for age, gender, smoking, BMI, and ethnicity using two different methods of exposure: having worked in a TCDD-exposed job (based on occupational records)
|
From page 546... ...
However, the differences in hormone levels are not surrogate measures of a health outcome, and, therefore, this study was not considered relevant to the committee's charge. Biologic Plausibility The influence of TCDD on thyroid-hormone homeostasis has been measured in numerous animal studies, and TCDD exposure has been associated with changes in serum concentrations of T4, T3, and TSH.
|
From page 547... ...
There is inadequate or insufficient evidence for disruption of thyroid homeostasis or other endocrine disorders. CHRONIC SKIN DISORDERS In previous VAO reports, skin disorders such as chloracne were mentioned, but they were not consistently included as independent outcomes.
|
From page 548... ...
Although it is resistant to acne treatments, it usually regresses. The chronic skin conditions considered include skin infections, nuclear buds, karyolysis or karyorrhexis, comedones, scar formation, and skin pigmentation.
|
From page 549... ...
Age-specific hospitalization rates were calculated using the total number of annual hospitalizations published by the Ministry of Health and the average annual resident population. Standardized hospitalization rates and 99% CIs were calculated for the veteran cohort and for the general population for several noncancerous conditions, and an SHR was calculated using the two rates.
|
From page 550... ...
Associations between exposure and health outcomes were assessed using logistic regression models that controlled for age, gender, smoking, BMI, and ethnicity using two different methods of exposure: having worked in a TCDD-exposed job (based on occupational records) and having serum TCDD concentration ≥10 pg/g lipid (18%)
|
From page 551... ...
more evidence of DNA damage, as measured by comet tail length, micronuclei, binucleated cells, pycnosis, and condensed chromatin, was found among the agricultural workers who were exposed to pesticides than among the non-exposed workers, these differences are not tied to an observable health outcome, and the study was not considered further.
|
From page 552... ...
examined different outcomes and had varying exposure specificity, thereby limiting the comparisons that could be made. Although some differences between exposed and unexposed populations were noted, each study had several limitations that did not change the evidence of association with exposure to the COIs and chronic skin conditions.
|
From page 553... ...
On the basis of that one study, the committee for Update 2010 concluded that there was inadequate or insufficient evidence to determine whether there is an association between exposure to the COIs and eye conditions. No new epidemiologic studies of exposure to the COIs and eye problems had been published for review in Update 2012 and Update 2014.
|
From page 554... ...
Exposure was not validated through serum measurements and was assumed based on deployment to Vietnam. Biologic Plausibility There have been several recent reports of ocular activity associated with Ahr activation or TCDD exposure of rats (Sugamo et al., 2009)
|
From page 555... ...
. Other risk factors for the loss of bone mineral density include the use of long-acting benzodiazepine or anticonvulsant drugs, previous hyperthyroidism, excessive caffeine intake, and routinely standing for less than 4 hours per day (Lash et al., 2009)
|
From page 556... ...
Age-specific hospitalization rates were calculated using the total number of annual hospitalizations published by the Ministry of Health and the average annual resident population. Standardized hospitalization rates and 99% CIs were calculated for the veteran cohort and the general population, and an SHR was calculated using the two rates for conditions related to other joint
|
From page 557... ...
. In adult rats, TCDD exposure reduced trabecular bone cross-sectional area, but it significantly increased total bone mineral density; it was further noted that TCDD decreased the expression of the bone-formation marker procollagen type I N-terminal propeptide and increased the expression of the bone-resorption marker carboxy-terminal collagen cross-link, suggesting a net loss of bone tissue (Lind et al., 2009)
|
From page 558... ...
Conclusion There is inadequate or insufficient evidence of an association between expo sure to the COIs and clinical or overt adverse effects of osteoporosis, loss of bone mineral density, or other bone conditions.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.