Postservice Mortality of US Air Force Veterans Occupationally Exposed to Herbicides in Vietnam: 15-Year Follow-up
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American Journal of Epidemiology Vol. 148, No. 8
Copyright © 1998 by The Johns Hopkins University School of Hygiene and Public Health Printed in U.S.A.
All rights reserved
Postservice Mortality of US Air Force Veterans Occupationally Exposed to
Herbicides in Vietnam: 15-Year Follow-up
Joel E. Michalek,1 Norma S. Ketchum,1 and Fatema Z. Akhtar2
The US Air Force continues to assess the mortality of veterans of Operation Ranch Hand, the unit
responsible for aerially spraying herbicides in Vietnam. The authors of this study found that the cumulative
all-cause mortality experience of these veterans was not different from that expected (standardized mortality
ratio (SMR) = 1.0). Overall, cause-specific mortality did not differ from that expected regarding deaths from
accidents, cancer, or circulatory system diseases, but the authors found that there was an increased number
of deaths due to digestive diseases (SMR = 1.7, 95% confidence interval (Cl) 0.9-3.2). When analyzing by
military occupation, they found an increase in the number of deaths caused by circulatory system diseases
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(SMR = 1.5, 95% Cl 1.0-2.2) among enlisted ground personnel, the subgroup with the highest dioxin levels.
Most of the increase in the number of deaths from digestive diseases was caused by chronic liver disease and
cirrhosis, and more than half of the increase in the number of deaths from circulatory system diseases was a
result of atherosclerotic heart disease. In the subgroup of Ranch Hand veterans who had survived more than
20 years since their military service in Southeast Asia, the authors found no significant increase in the risk of
death due to cancer at all sites (SMR = 1.1) and a nonsignificant increase in the number of deaths due to
cancers of the bronchus and lung (SMR = 1.3). Am J Epidemiol 1998;148:786-92.
dioxins; herbicides; mortality
Debate is ongoing concerning the susceptibility of sarcoma and cancer of the respiratory system (9).
humans to the toxic effects of 2,3,7,8-tetrachlorodibenzo- However, a study of workers who were exposed as a
p-dioxin (dioxin), the contaminant found in Agent result of a trichlorophenol process accident found no
Orange and other herbicides sprayed during the Viet- association between dioxin exposure and cancer mor-
nam War. Several studies have examined the post- tality (11). A study of workers at a herbicide-producing
service mortality experience of Vietnam veterans ( 1 - plant in Hamburg, Germany, reported a dose-dependent
7). A study of US Army Chemical Corps veterans (2) relation between dioxin exposure and mortality caused
and a study of Australian Army veterans (4) reported by cancer and ischemic heart disease (12).
an increased risk of death due to accidents and diges- The Air Force Health Study is a 20-year prospective
tive diseases but no increase due to cancer; however, a study of the health (13, 14), mortality (15), and repro-
study of women veterans (3) found an increased risk of ductive outcomes (16-18) of veterans of Operation
deaths caused by specific cancers. Ranch Hand, the unit responsible for the 1962-1971
aerial spraying of herbicides in Vietnam. The study
The relation between dioxin exposure and mortality
began in 1982 and will conclude in 2002. This paper
has been studied in industrial populations (8-12). A updates our first report (15) by summarizing current
study of US chemical workers who were exposed to all-cause and cause-specific postservice mortality
dioxin reported an increased cancer mortality and, in among veterans of Operation Ranch Hand.
workers who survived more than 20 years since their
exposure, an increased mortality due to soft-tissue
MATERIALS AND METHODS
Received for publication January 31, 1998, and accepted for
publication March 25, 1998. Population definition and the process by which mor-
Abbreviations: Cl, confidence interval; ICD-9, International Clas- tality was determined are discussed elsewhere (15).
sification of Diseases, Ninth Revision; SMR, standardized mortality
ratio. Briefly, we contrast cumulative Ranch Hand (n =
1
2
Air Force Research Laboratory, Brooks Air Force Base, TX. 1,261) mortality through December 31, 1993 (verified
Vista Technologies, Inc., San Antonio, TX. as of December 1995) with that expected on the basis
Reprint requests to Dr. Joel E. Michalek, AFRL/HEDB, 2606
Doolittle Road, Building 807, Brooks Air Force Base, TX 78235- of the mortality of a comparison population of 19,080
5250. US Air Force veterans who flew or serviced C-130
786Mortality in Veterans Exposed to Herbicides 787
cargo aircraft in Southeast Asia during the same time contributed the time, in years, between the date on
that the Ranch Hand unit was active in Vietnam which they entered follow-up (the date they began
(1962-1971). Comparison veterans were not involved their service in Southeast Asia) and the cutoff date;
in spraying herbicides in Vietnam but are demograph- those known to have died before the cutoff date con-
ically similar to Ranch Hand veterans. tributed the time, in years, between the date on which
This report updates our previous analysis (15), for they entered follow-up and their date of death. We
which the dates of military service in Southeast Asia computed the standardized mortality ratio, the ratio of
were unavailable for 179 comparison subjects. Rather the observed to the expected number of deaths (20).
than exclude those veterans, we replaced the missing We adjusted this ratio by stratifying on age (in 5-year
dates with randomly generated dates. By using this intervals), follow-up time (in 5-year intervals), and
method, we were able to include all comparison vet- military occupation and by summing the observed and
erans in our previous report (15). Since then, we expected numbers of deaths across strata. The ex-
retrieved the actual service dates for 148 of these 179 pected number of deaths within each stratum was the
veterans from military personnel records but were product of the number of Ranch Hand person-years
unable to find dates for 31 veterans because the and the comparison death rate. We used the Mid-P
records were missing; therefore, we excluded those method derived from a Poisson model to compute
veterans from this report. Additionally, we excluded confidence intervals for the standardized mortality ra-
one comparison veteran who was erroneously included tio (21). Although the confidence interval formula was
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in our last report and added 11 comparison veterans based on the assumption that the comparison death
whom we found and verified since our last report. rates were constants, the comparison rates were sub-
Therefore, the total number of comparison subjects is ject to random variation; therefore, the widths of our
now 19,080, 21 fewer than reported previously (15). confidence intervals were slightly understated. In
All Ranch Hand and comparison veterans are male. some tables in this report, because of small numbers of
The number of veterans at risk and the number of veterans, we combined the data on pilots, navigators,
person-years are summarized in table 1 by military and administrative officers into a single occupational
occupation (pilots and navigators, administrative of- category called "officers." We were not able to adjust
ficers, enlisted flight engineers, and enlisted ground for race because too few blacks (6.1 percent) were
personnel). All pilots and navigators were officers. We included.
used military occupation as a surrogate to adjust for We tabulated the number of observed and expected
differences in socioeconomic characteristics and in- cancer deaths by length of survival time since military
ferred dioxin exposure among Ranch Hand veterans. service in Southeast Asia (20 years since their first tour in Vietnam.
veterans, ground personnel were more heavily ex- All veterans were included in the788 Michalek et al.
detecting a relative risk of 1.5 for all-cause mortality. table 4 by military occupation. Within-stratum relative
Regarding deaths caused by cancer, the power to de- risks of death from any cause ranged from 0.7 to 1.1,
tect a relative risk of 1.5 and 2.0 was 77.4 and 99.6 and there were no significant stratum-specific differ-
percent, respectively. This study had no power to ences between the observed and the expected numbers
detect small or moderate increases in Ranch Hand of deaths. The risk of death from cancer was not
death rates specific to rare cancers, such as soft-tissue increased among pilots and navigators (SMR = 0.9),
sarcoma and lymphoma. enlisted flight engineers (SMR = 1.0), or enlisted
ground personnel (SMR = 0.8). The risk of death
RESULTS caused by diseases of the circulatory system was in-
creased among Ranch Hand enlisted ground personnel
Demographic characteristics of all veterans are pre- (SMR = 1.5, 95 percent CI 1.0-2.2).
sented in table 2. Birth year and race were similar for
Ranch Hand and comparison veterans. On a percent- Data on cancer mortality by survival time since
age basis, more Ranch Hand veterans (35.0 percent) service in Southeast Asia (Mortality in Veterans Exposed to Herbicides 789
TABLE 3. Cause-specific and all-cause mortality of US Air Force veterans exposed to herbicides in
Vietnam: Air Force Health Study
Cause No. of deaths
ICD-9*
of SMR* 95% Cl*,t
death codes Observed Expected
Infectious or parasitic
diseases 001-139 2 1.3 1.5
Cancer 140-208, 230-234 30 33.2 0.9 0.6-1.3
Endocrine diseases 240-279 1 1.1 0.9
Circulatory diseases 390-459 39 39.6 1.0 0.7-1.3
Respiratory diseases 460-519 2 4.1 0.5
Digestive diseases 520-579 9 5.1 1.7 0.9-3.2
Ill-defined or unknown 780-799 3 2.4 1.2
Accident 800-949 26 22.3 1.2 0.8-1.7
Suicide 950-959 4 5.8 0.7
Homicide 960-969 2 1.7 1.2
All causes 001-969 118 120.U 1.0 0.8-1.2
* ICD-9, International Classification of Diseases, Ninth Revision; SMR, standardized mortality ratio; Cl, con-
fidence interval.
t Confidence intervals were not computed when the observed number of deaths was790 Michalek et al.
TABLE 5. Cancer mortality, by number of years since service in Southeast Asia and military occupation,
among US Air Force veterans exposed to herbicides in Vietnam: Air Force Health Study
20 years
Military No. of deaths No. of deaths
occupation SMR* 95%CI*,t SMR 95% Cl
Observed Expected Observed Expected
Officers 5 6.5 0.8 0.3-1.7 6 5.4 1.1 0.5-2.3
Enlisted flight engineers 2 2.9 0.7 6 4.9 1.2 0.5-2.6
Enlisted ground personnel 4 5.8 0.7 7 7.5 0.9 0.4-1.9
All personnel 11 15.2 0.7 0.4-1.3 19 17.7 1.1 0.7-1.6
* SMR, standardized mortality ratio; Cl, confidence interval.
t Confidence intervals were not computed when the observed number of deaths wasMortality in Veterans Exposed to Herbicides 791
Among all Ranch Hand veterans, the risk of death the Ranch Hand group and a complete determination
from diseases of the circulatory system was not in- of the mortality status of all subjects. As a group, the
creased (SMR = 1.0); however, among enlisted Ranch Hand veterans were probably among the most
ground personnel, we found a nonsignificant excess herbicide-exposed cohorts of Vietnam veterans. Thus,
(SMR = 1.5), and nearly half of the increase was due our study offers the best available opportunity to ad-
to atherosclerotic heart disease (SMR = 1.4). As a dress a hypothetical relation between dioxin exposure
group, these personnel have the highest current dioxin and mortality in Vietnam veterans.
levels, and those levels correlate with skin contact Our analysis of deaths caused by diseases of the
with herbicides in Vietnam (22). The increased risk of circulatory system was limited by our inability to
death caused by diseases of the circulatory system is adjust for smoking and for family history of circula-
consistent with the findings from three studies and tory system diseases, and our analysis of digestive
inconsistent with two others. A study of Australian disease mortality was limited by our inability to adjust
Army veterans (4) found increased circulatory system for alcohol consumption. Available information for
disease mortality in Vietnam veterans. A study of the the subgroup of Ranch Hand and comparison veterans
Seveso, Italy, population after a chemical plant acci- who participated in the physical examinations that
dent (23) reported an increased number of deaths from were given as part of this study (13, 14) suggests that
diseases of the circulatory system in the most contam- Ranch Hand veterans do not differ substantially from
inated area, and a study of exposed workers at a comparison subjects in terms of smoking or alcohol
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Hamburg, Germany, plant found a dose-related in- consumption. Our analysis of deaths caused by cancer
creased risk of death caused by ischemic heart disease before 20 years or after 20 years since military service
(12). Two studies of US Army veterans found fewer in Southeast Asia was limited because we could not
than the expected number of deaths caused by circu- examine risks that might occur after a longer delay.
latory system diseases (1, 2). The suggested increased Exposure misclassification was also a potential
risk of death from circulatory system diseases among weakness. Serum dioxin measurements in the sub-
Ranch Hand enlisted ground personnel should be in- group of Ranch Hand veterans who have been exam-
terpreted cautiously, because we were unable to adjust ined revealed that 40 percent of them have background
for known risk factors, such as smoking and family levels similar to those of comparison veterans (22).
history. We are uncertain about the exposure status of Ranch
The number of Ranch Hand deaths caused by diges- Hand veterans with low dioxin levels; some could
tive diseases was small (observed number = 9) but have had elevated dioxin levels in Vietnam but their
borderline significantly increased (SMR = 1.7). Seven body burden decayed to background levels in the
of these deaths were caused by chronic liver disease intervening time period, and some may not have had
and cirrhosis. As with the increased risk of death due elevated levels during their service in the Ranch Hand
to circulatory diseases, this finding should be inter- unit. A study of skin exposure to herbicides in Ranch
preted with caution, because we were unable to adjust Hand enlisted veterans (23) showed that veterans as-
for known risk factors, such as alcohol consumption. signed to administrative duties and those reporting no
This increase in the number of deaths caused by di- skin exposure had the lowest dioxin levels (approxi-
gestive diseases is consistent with the results of the mately 60 percent had background levels) and that
Australian Army study (4), which also found elevated more than 75 percent of those reporting high levels of
digestive system disease mortality in Vietnam veter- skin exposure had above-background levels of dioxin.
ans, mainly related to alcohol consumption. However, Thus, it seems that some Ranch Hand veterans were
a study of US Army veterans (1) found no significant probably unexposed or received minimal exposure to
difference between Vietnam veterans and non-Vietnam herbicides in Vietnam. More specific statements about
veterans regarding digestive disease mortality. More Ranch Hand exposure are not possible based on avail-
recently, a study of a Taiwan population poisoned by able data.
cooking oil that was contaminated with heat-degraded Our last mortality report (15), which assessed cu-
polychlorinated biphenyls (PCBs) reported an in- mulative Ranch Hand mortality as of December 31,
creased mortality from chronic liver disease and cir- 1987, also found no difference between observed and
rhosis (24). A study of pentachlorophenol manufactur- expected mortality from all causes combined (SMR =
ing workers found an increased mortality from 1.0, 95 percent CI 0.8-1.2). In this report, we did not
cirrhosis of the liver among the most exposed sub- analyze deaths among enlisted ground personnel. By
group (25). using the cutoff date from that report (December 31,
The strengths of our study include a large compar- 1987) with the current data, we found a nonsignificant
ison population that was demographically similar to increased risk of death caused by diseases of the
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