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Air Force Health Study Update 10 June 2005






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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.
Air Force Health Study Update 10 June 2005

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Air force health study update 10 june 2005 l.jpgSlide 1

Air Force Health Study Update10 June 2005

Presenter:

Joel Michalek, PhD

Air Force Research Laboratory

Brooks City-Base, Texas

Contents l.jpgSlide 2

Contents

  • Overview of the 2002 report

  • Research

    • Diabetes

    • Cancer

    • Reported sleep abnormalities

  • Interactions with the IOM

Overview of the 2002 report l.jpgSlide 3

Overview of the 2002 Report

Methods l.jpgSlide 4

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

Results l.jpgSlide 5

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

Summary l.jpgSlide 6

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

Summary7 l.jpgSlide 7

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

Summary8 l.jpgSlide 8

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

Slide9 l.jpgSlide 9

  • 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

Slide10 l.jpgSlide 10

  • 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

Slide11 l.jpgSlide 11

  • 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

Diabetes dioxin calendar period of service and days of spraying l.jpgSlide 12

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

Another Look at the Check Mark Pattern

Diabetes l.jpgSlide 13

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

Diabetes14 l.jpgSlide 14

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

Cumulative days of spraying by last ranch hand year l.jpgSlide 15

Cumulative Days of Spraying by Last Ranch Hand Year

Sample reduction l.jpgSlide 16

Sample Reduction*

*Up to and including cycle 5

Demographics by calendar period 1 l.jpgSlide 17

Demographics by Calendar Period1

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

Demographics by spraying category l.jpgSlide 18

Demographics by Spraying Category

Ranch hand dioxin by calendar period of service l.jpgSlide 19

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.

Ranch hand dioxin by spray category l.jpgSlide 20

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.

Diabetes by group without stratifying l.jpgSlide 21

Diabetes by Groupwithout Stratifying

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

Diabetes by dioxin category without stratifying l.jpgSlide 22

Diabetes by Dioxin Categorywithout Stratifying

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

Diabetes by group and calendar period of service l.jpgSlide 23

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

Diabetes by group and spray category l.jpgSlide 24

Diabetes by Groupand Spray Category

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

Diabetes by dioxin category and calendar period of service l.jpgSlide 25

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

Diabetes by dioxin category and spray category l.jpgSlide 26

Diabetes by Dioxin Categoryand Spray Category

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

Diabetes by dioxin category and calendar and spray category l.jpgSlide 27

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

Conclusions l.jpgSlide 28

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

Cancer dioxin calendar year of service and days of spraying l.jpgSlide 29

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

Adjusting for Additional

Operational Factors

Background l.jpgSlide 30

Background

  • 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

Methods31 l.jpgSlide 31

Methods

  • 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

Methods32 l.jpgSlide 32

Methods

  • Veterans compliant to at least one physical examination were included

Sample reduction33 l.jpgSlide 33

Sample Reduction

  • Fully or partially compliant to any physical examination

  • Not fully compliant to at least one physical examination

Cumulative days of spraying by last ranch hand year34 l.jpgSlide 34

Cumulative Days of Spraying by Last Ranch Hand Year

Strata l.jpgSlide 35

Strata

  • 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

Analysis sample sizes 1 l.jpgSlide 36

Analysis Sample Sizes1

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

  • Excluded (N=2262).

Demographics early service and increased spraying l.jpgSlide 37

DemographicsEarly Service and Increased Spraying

Demographics complement stratum l.jpgSlide 38

DemographicsComplement Stratum

Demographics early service and increased spraying39 l.jpgSlide 39

DemographicsEarly Service and Increased Spraying

Demographics complement stratum40 l.jpgSlide 40

DemographicsComplement Stratum

Ranch hand dioxin by calendar period of service41 l.jpgSlide 41

Ranch Hand Dioxin by 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.

Ranch hand dioxin by spray category42 l.jpgSlide 42

Ranch Hand Dioxin by Spray Category

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

Seer cancer unrestricted white l.jpgSlide 43

SEER Cancer: Unrestricted, White

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

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

Seer cancer 30 pre 1967 spray days service 1968 white l.jpgSlide 44

SEER Cancer: ≥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

Seer cancer complement white l.jpgSlide 45

SEER Cancer: Complement,White

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

skin reaction to sun, eye color, years in SEA

Seer cancer 2 years in sea white l.jpgSlide 46

SEER Cancer: ≤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

Seer cancer 30 pre 1967 spray days service 1968 2 years in sea white l.jpgSlide 47

SEER Cancer: ≥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

Seer cancer by spray category white l.jpgSlide 48

SEER Cancer by Spray Category, White

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

skin reaction to sun, eye color, years in SEA

Seer cancer vs spray 30 pre 1967 spray days service 1968 2 years in sea white l.jpgSlide 49

SEER Cancer vs Spray: ≥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

Conclusions50 l.jpgSlide 50

Conclusions

  • 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

Reported sleep disorders and dioxin in veterans of operation ranch hand l.jpgSlide 51

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

Background52 l.jpgSlide 52

Background

  • 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

Methods53 l.jpgSlide 53

Methods

  • 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

Methods54 l.jpgSlide 54

Methods

  • 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

Methods55 l.jpgSlide 55

Methods

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

    • Frightening dreams

    • Sleep talking

    • Sleep walking

    • Abnormal movement or activity during the night

Methods56 l.jpgSlide 56

Methods

  • 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

Sample reduction57 l.jpgSlide 57

Sample Reduction

Dioxin categories l.jpgSlide 58

Dioxin Categories

1987 demographics l.jpgSlide 59

1987 Demographics

Sleep complaints in 1987 and 1992 l.jpgSlide 60

Sleep Complaints in 1987 and 1992

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

1987 sleep disturbances l.jpgSlide 61

1987 Sleep Disturbances (%)

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

1992 sleep disturbances l.jpgSlide 62

1992 Sleep Disturbances (%)

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

1987 sleep disturbances and dioxin category l.jpgSlide 63

1987 Sleep Disturbancesand Dioxin Category (%)

  • OR=3.5, 95% CI 1.6-7.8

  • OR=2.9, 95% CI 1.3-6.3

1992 sleep disturbances and dioxin category l.jpgSlide 64

1992 Sleep Disturbancesand Dioxin Category (%)

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

Insomnia trajectories l.jpgSlide 65

Insomnia Trajectories

1. Significantly different from Comparisons (p<0.05)

Other findings l.jpgSlide 66

Other findings

  • 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

Conclusions67 l.jpgSlide 67

Conclusions

  • 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

Interactions with the iom l.jpgSlide 68

Interactions with the IOM

  • 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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