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Air Force Health Study Update 10 June 2005. Presenter: Joel Michalek, PhD Air Force Research Laboratory Brooks City-Base, Texas. Contents. Overview of the 2002 report Research Diabetes Cancer Reported sleep abnormalities Interactions with the IOM. Overview of the 2002 Report. Methods.

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Air force health study update 10 june 2005 l.jpg

Air Force Health Study Update10 June 2005

Presenter:

Joel Michalek, PhD

Air Force Research Laboratory

Brooks City-Base, Texas


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Contents

  • Overview of the 2002 report

  • Research

    • Diabetes

    • Cancer

    • Reported sleep abnormalities

  • Interactions with the IOM



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Methods

  • Summarized health conditions observed at the 2002 AFHS physical examination (N=1951, Ranch Hand: 777, Comparison: 1174)

  • Main effects linear, logistic, and proportional hazards models with covariate adjustment

  • Data sources

    • Laboratory

    • Questionnaire

    • Physical examination

    • Medical records


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Results

  • General health

    • Body mass index increased with 1987 dioxin

  • Neoplasia

    • A mixed pattern of associations with no suggestion of internal or external consistency

  • Neurology

    • The risks of abnormal pin prick (not bilateral) and absent patellar reflex were increased in the High dioxin category


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Summary

  • Psychology

    • No outcome measures were associated with herbicide or dioxin exposure

  • Gastrointestinal

    • The risk of abnormally high triglycerides was increased in Ranch Hand enlisted ground crew and the High dioxin category


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Summary

  • Dermatology

    • The frequency and occurrence of reported acne after service in SEA was increased in Ranch Hand enlisted ground crew, and in the Background, Low, and High dioxin categories

    • The duration of reported acne after service in SEA increased with 1987 dioxin

    • The frequency of acneiform lesions was increased only in the Background dioxin category

    • Secondary skin lesions were not associated with herbicide or dioxin exposure


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Summary

  • Cardiovascular

    • Associations observed were not consistent or clinically interpretable as adverse

  • Hematology

    • Associations observed did not suggest an adverse relation between herbicide or dioxin exposure and any hematological diagnosis

  • Renal

    • The few associations observed did not indicate an adverse relation between renal function and herbicide or dioxin exposure


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  • Endocrine

    • The risk of diabetes requiring insulin control was increased in the High dioxin category

    • Fasting insulin and the risk of diabetes requiring insulin control increased and time to diabetes onset decreased with initial dioxin

    • The risk of diabetes requiring oral hypoglycemic or insulin control and the risk of diabetes requiring insulin increased with 1987 dioxin

    • The risk of abnormally high hemoglobin A1c increased with dioxin


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  • Endocrine

    • Associations between herbicide or dioxin exposure and measures of thyroid function or gonadotropins did not appear consistent or clinically important

    • The adverse associations between type 2 diabetes and dioxin exposure were consistent with findings at previous physical examinations


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  • Immunology

    • There was no consistent or interpretable association between any measure of immune function and herbicide or dioxin exposure

  • Pulmonary

    • The associations observed did not suggest an adverse relation between respiratory health and herbicide or dioxin exposure


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Diabetes, Dioxin, Calendar Period of Service, and Days of Spraying

Another Look at the Check Mark Pattern


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Diabetes

  • Background

    • Diabetes risk increased, time to diabetes onset decreased, and diabetes severity increased with dioxin (Henriksen et al, Epidemiology 1997;8(3):252-258)

    • Dioxin category analysis produced a “check mark” pattern

    • Statistical modeling of the check mark pattern was attempted but not published


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Diabetes

  • New analyses of dioxin and diabetes were conducted with adjustment for

    • Days of spraying

    • Calendar period of spraying

  • Two rounds of analyses were conducted

    • Cycle 5

    • Cycle 6

  • Time to diabetes onset measured from end of qualifying tour


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Cumulative Days of Spraying by Last Ranch Hand Year


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Sample Reduction*

*Up to and including cycle 5


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Demographics by Calendar Period1

1. Up to and including cycle 5. 2. During or prior to 1968



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Ranch Hand Dioxin by Calendar Period of Service

  • 1. During or prior to 1969, 2. Log units, 3. Yes-No, 4. Adjusted for age, BMI at tour, last year in Vietnam.


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Ranch Hand Dioxin by Spray Category

  • 1. High:≥90 d, 2. Log units, 3. Yes-No, 4. Adjusted for age, BMI at tour, last year in Vietnam.


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Diabetes by Groupwithout Stratifying

  • Adjusted for BMI at blood draw, pk-yr82, fh diab, BMI tour, yob, last year, VNdays/SEAdays, occupation


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Diabetes by Dioxin Categorywithout Stratifying

  • Adjusted for BMI at blood draw, pk-yr82, fh diab, BMI tour, yob, last year, VNdays/SEAdays, occupation


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Diabetes by Groupand Calendar Period of Service

  • Adjusted for BMI at blood draw, pk-yr82, fh diab, BMI tour, yob, last year, VNdays/SEAdays, occupation


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Diabetes by Groupand Spray Category

  • Adjusted for BMI at blood draw, pk-yr82, fh diab, BMI tour, yob, last year, VNdays/SEAdays, occupation


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Diabetes by Dioxin Categoryand Calendar Period of Service

  • Adjusted for BMI at blood draw, pk-yr82, fh diab, BMI tour, yob, last year, VNdays/SEAdays, occupation


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Diabetes by Dioxin Categoryand Spray Category

  • Adjusted for BMI at blood draw, pk-yr82, fh diab, BMI tour, yob, last year, VNdays/SEAdays, occupation


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Diabetes by Dioxin Categoryand Calendar and Spray Category

  • Adjusted for BMI at blood draw, pk-yr82, fh diab, BMI tour, yob, last year, VNdays/SEAdays, occupation


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Conclusions

  • These data support the hypothesis that herbicides were more heavily contaminated with dioxin early in the war

  • Days of spraying and calendar year of service are “effect modifiers” in the association between dioxin and diabetes

  • The check mark pattern is an artifact of lack of adjustment

  • Other unknown factors may be important


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Cancer, Dioxin, Calendar Year of Service, and Days of Spraying

Adjusting for Additional

Operational Factors


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Background Spraying

  • Associations between cancer and dioxin are not evident in simple main effects models

  • Years of service in Southeast Asia is a risk factor for cancer in Comparisons

  • Cancer vs dioxin associations were revealed in Ranch Hands after stratification by

    • Years of service in SEA

    • The proportion of time spent in Vietnam

  • Calendar period of service and days are spraying are considered here


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Methods Spraying

  • Cancer determined through 30 September 2004

  • Onset to the first diagnosis of SEER cancer measured from 1 January 1982

  • Time to onset for veterans without cancer was the date of last physical plus 2 years or date of death

  • Cancer was determined by review of medical records and death certificates

  • Proportional hazards models for time to cancer onset adjusted for year of birth, military occupation, skin reaction to sunlight, eye color, smoking history from baseline (pack-years), years served in Southeast Asia


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Methods Spraying

  • Veterans compliant to at least one physical examination were included


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Sample Reduction Spraying

  • Fully or partially compliant to any physical examination

  • Not fully compliant to at least one physical examination


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Cumulative Days of Spraying Sprayingby Last Ranch Hand Year


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Strata Spraying

  • Early service and increased spraying

    • Ranch Hand: Service in the Ranch Hand Operation during or prior to 1968 and at least 30 days of spraying during or prior to 1967

    • Comparison: Service in Southeast Asia during or prior to 1968

  • Served at most 2 years in Southeast Asia


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Analysis Sample Sizes Spraying1

  • White. Pre-baseline cancer, Ranch Hands with missing dioxin

  • Excluded (N=2262).


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Demographics SprayingEarly Service and Increased Spraying


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Demographics SprayingComplement Stratum


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Demographics SprayingEarly Service and Increased Spraying


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Demographics SprayingComplement Stratum


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Ranch Hand Dioxin Sprayingby Calendar Period of Service

  • 1. During or prior to 1968 and ≥30 pre 67 spray days , 2. Log units, 3. Yes-No, 4. Adjusted for age, BMI at tour, last year in Vietnam.


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Ranch Hand Dioxin Sprayingby Spray Category

1. Adjusted for age at tour, BMI at tour, last year of Rand Hand service


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SEER Cancer: Unrestricted, White Spraying

  • Adjusted for year of birth, military occupation, smoking history (pack-years),

  • skin reaction to sun, eye color, years in SEA


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SEER Cancer: Spraying≥30 pre-1967 spray days, Service≤1968, White

1. Adjusted for year of birth, military occupation, smoking history (pack-years),

skin reaction to sun (burns painfully or freckles with no tan, burns or tans

mildly, tans deep brown) , eye color (brown, hazel/green and gray/blue), years in SEA


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SEER Cancer: Complement, SprayingWhite

1. Adjusted for year of birth, military occupation, smoking history (pack-years),

skin reaction to sun, eye color, years in SEA


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SEER Cancer: Spraying≤2 Years in SEA, White

1. Adjusted for year of birth, military occupation, smoking history (pack-years),

skin reaction to sun, eye color, years in SEA


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SEER Cancer: Spraying≥30 pre-1967 SprayDays, Service≤1968, ≤2 Years in SEA, White

1. Adjusted for year of birth, military occupation, smoking history (pack-years),

skin reaction to sun, eye color, years in SEA


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SEER Cancer by Spray Category, White Spraying

1. Adjusted for year of birth, military occupation, smoking history (pack-years),

skin reaction to sun, eye color, years in SEA


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SEER Cancer vs Spray: Spraying≥30 pre-1967 SprayDays, Service≤1968, ≤2 Years in SEA, White

1. Adjusted for year of birth, military occupation, smoking history (pack-years),

skin reaction to sun, eye color, years in SEA


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Conclusions Spraying

  • These data are consistent with the hypothesis that herbicides were more heavily contaminated with dioxin in the early years of the war

  • The number of spray days correlates with dioxin in Ranch Hand veterans

  • Calendar period of service correlates with dioxin in Ranch Hand veterans

  • Calendar period of service, spray days, and years served in SEA are effect modifiers of the relation between dioxin and SEER cancer


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Reported Sleep Disorders and Dioxin in Veterans of Operation Ranch Hand

Liu1 Y, Michalek2 JE, Lian1 M,

Dickerson1 RL, Frame1 LT

Texas Tech University, Lubbock, Texas

Air Force Research Laboratory, San Antonio, Texas


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Background Ranch Hand

  • Sleep disruption is one of the most common complaints cited by chemical plant workers with occupational exposure to dioxin

  • Sleep deprivation is associated with glucose intolerance, type 2 diabetes, cardiovascular disease, and memory deficits

  • This is the first epidemiological study of reported sleep quality and serum dioxin measurements


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Methods Ranch Hand

  • Reported sleep problems were obtained during interviews in 1987 and 1992

  • Each participant was asked 11 questions to assess sleep quality, based on a study of the prevalence of sleep disorders conducted in Los Angeles in 1979

  • Veterans compliant to the 1987 or 1992 AFHS physical examinations were included

  • Statistical analysis was based on contrasts of Ranch Hands in the Background, Low, and High dioxin categories with Comparisons


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Methods Ranch Hand

  • Insomnia was defined by the occurrence of at least one of

    • Having trouble falling asleep

    • Waking up during the night

    • Waking up too early and cannot go back to sleep

    • Waking up unrefreshed


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Methods Ranch Hand

  • Parasomnia was defined by the occurrence of at least one of

    • Frightening dreams

    • Sleep talking

    • Sleep walking

    • Abnormal movement or activity during the night


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Methods Ranch Hand

  • Main effects logistic regression models were used, adjusted

    • Age

    • Race (black, non-black)

    • Education (high school, college)

    • Total household income (0-55k, >55k)

    • Marital status (yes, no)

    • Alcohol consumption (drink-years) (0,0-40,>40)

    • Cigarette smoking (pack-years) (0,0-10,>10)

    • Body mass index at the time of service in Southeast Asia


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Sample Reduction Ranch Hand


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Dioxin Categories Ranch Hand


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1987 Demographics Ranch Hand


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Sleep Complaints in 1987 and 1992 Ranch Hand

1. Significantly increased relative to Comparisons (p<0.05)


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1987 Sleep Disturbances (%) Ranch Hand

1. OR=3.1, 95% CI 1.6-6.0


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1992 Sleep Disturbances (%) Ranch Hand

1. OR=1.4, 95% CI 1.1-1.8


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1987 Sleep Disturbances Ranch Handand Dioxin Category (%)

  • OR=3.5, 95% CI 1.6-7.8

  • OR=2.9, 95% CI 1.3-6.3


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1992 Sleep Disturbances Ranch Handand Dioxin Category (%)

1. OR=1.4, 95% CI 1.01-1.90


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Insomnia Trajectories Ranch Hand

1. Significantly different from Comparisons (p<0.05)


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Other findings Ranch Hand

  • The odds of any sleep problem in 1987 were increased in Low and High Ranch Hands relative to Background Ranch Hands

  • The odds of any sleep complaint in 1992 were increased in Ranch Hand Low and High category relative to Comparisons

  • Odds of snoring and disabling daytime fatigue increased with dioxin in Ranch Hands in 1987 but not 1992


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Conclusions Ranch Hand

  • The increased odds of snoring and disabling fatigue and the persistence of insomnia in Ranch Hands with elevated dioxin suggest that low-dose dioxin exposure targets systems of arousal regulation

  • The increased risk of snoring and disabling fatigue may account for diminished sleep quality among Ranch Hands with elevated dioxin


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Interactions with the IOM Ranch Hand

  • We briefed the IOM committee in February on

    • Study history

    • Study design

    • Methods of analysis

    • Materials

    • Ongoing research

  • An IOM subcommittee will visit the Air Force Health Study facilities on 27 May 2005


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