1

Air Force Interaction with IOM

Karen Fox, Col, USAF, MC

Principal Investigator

Brooks City-Base TX

2

Air Force Interactions with IOM

• February 2005, briefing by Dr Michalek

• May 2005, visit to Brooks City-Base

• Responded to questions

• Scanned and provided data upon request

• Documented all laboratory test across all 6 cycles

3

TEST DESCRIPTION CYCLE: 1 2 3 4 5 6

HEMATOLOGY

CELL COUNT/INDICIES X X X X X X

WBC X X X X X X

RBC X X X X X X

RDW X X X X

Hgb X X X X X X

Hct (%) X X X X X X

MCV (Cu microns) X X X X X X

MCH (ug) X X X X X X

MCHC (gm/dl) X X X X X X

Plt (Thou/cumm) X X X X X X

DIFFERENTIAL X X X X X X

NEUTROPHILS X X X X X X

LYMPH X X X X X X

MONO X X X X X X

EOS X X X X X X

BANDS X X X X X X

BASO X X X X X X

BLAST X X X X X X

4

CHEMISTRY MISCELLANEOUS 1 2 3 4 5 6

FSH X X X X X X

LH X X X X X X

TESTOSTERONE, FREE X X X

TESTOSTERONE, TOTAL X X X X X X

SEX HORMONE BINDING GLOBULIN X

ESTRADIOL X X X

T4, FREE X

T4, RIA X X X X X

T3, FREE X

T3,UPTAKE X X X

TSH X X X X X X

FTI X

PSA X X X

INSULIN,FASTING X

5

AFHS Viability Study

SpecPro Inc.

San Antonio, TX, USA

Dr. Marian Pavuk

6

AFHS Viability Study

• Purpose: To examine the viability of AFHS

archived biological specimen

– Over 70,000 samples stored

– Some stored for over 20 years

7

Viability Study Objectives

We want to assess whether:

• The MAP technologies can be applied to assay biochemical parameters in AFHS frozen specimens

• AFHS frozen samples are viable for use in future studies by other investigators

8

Viability StudyMethods

• We randomly selected five AFHS veterans who

participated at the 1982, 1985, 1987, 1992, and

1997 physical examinations and had multiple

serum samples stored

• One sample per examination per participant was

selected

• Total of 25 serum samples to be analyzed

9

Viability StudyTechnology

• Multi-Analyte Profile (MAP) testing by the Rules

Based Medicine laboratory (Austin, TX) to analysis

samples

• MAPs are high-density, quantitative immunoassays

panels that allow identification of biomarker

patterns

• MAPs provide a comprehensive evaluation of protein

expression patterns indicative of response to

disease, drugs, or environment

10

AFHS Viability Study

• Each serum specimen to be analyzed for 78

specific serum antigens, 43 autoimmune serologies

and 56 infection disease serologies for a total of

177 analytes

• One complex analytical procedure

• Serum requirements: 100 µl

11

Rules-Based Medicine Technology

• Rules-Based Medicine's MAP

technology employs bioassays,

dyed microspheres, high speed

fluidics, and digital signal

processing

• Specific dyes permeate the

polystyrene microspheres

12

Rules-Based Medicine Technology

• Each microsphere set is covered

with capture antibodies that react

with the target protein

• After the assay is complete, the

microspheres pass single file past

two lasers

13

Viability StudyCurrent Status

• Samples selected and ready to ship to laboratory

• Awaiting completion of contract activities

14

15

Air Force Health StudyClosure Activities

• RIF of civil servants

• Hard copy and electronic materials

• Specimens

16

17

Air Force Health Study

• AFHS history

– White House letter

– Participant selection, location

– Dioxin testing

18

Air Force Health Study

• Comprehensive study

– Formerly called the longitudinal or summary study

– Purpose: To document significant AFHS findings

• Physical examination reports

• Air Force technical reports

• Publications

– Open to RHAC comments

19

20

Program Management Update

Mr. Richard OgershokHSG/PSP

Brooks City-Base TX

21

Air Force Health Study

• 6 Oct 05, House & Senate Veterans Affairs Committee

– 2002 Follow-up Examination Results

– Publications

– Presentations at scientific meetings

– Ranch Hand Advisory Committee meetings

– Interactions with the Institute of Medicine

– Planned research activities

• 8 Oct 05, Ranch Hand Reunion

22

Air Force Health Study 2002 Follow-up Physical Examination

Report

• Released 8 Jul 2005

• Responded to numerous email inquiries

• Available on AFHS website:

– http://www.brooks.af.mil/AFRL/HED/hedb/default.html

23

Air Force Health StudyFY06 Activities Overview

• Air Force history

• Comprehensive study

• Collaborations

• Compliance study

• Relational database

• Publication support

• In-house Research

• Dioxin congeners with CDC

24

Air Force Health Study FY06 Activities

• External Collaborations

– New guidelines for collaborations: past and present

– CDC and dioxin congeners

– UC Davis

– Texas Tech University Health Science Center

• Metabolic syndrome and dioxin

• Insomnia and dioxin

• Metabolic syndrome/chronic sleep loss: nested case-control study

25

Air Force Health StudyFY06 Activities

• Compliance study

– Factors that impacted study subjects participation in the six follow-up physical examinations

26

Air Force Health Study FY06 Activities

• Relational database

• Publication Support

– Nerve velocity conduction

– Dioxin and memory

– Dioxin and hepatic function

27

Air Force Health Study FY06 Activities

• In-house research

– Mortality

– Collaborations

– Viability study

28

Dioxins, Dibenzofurans, and Polychlorinated Biphenyls in 106

Participants of 2002 AFHS Physical Examination

Dr. Marian Pavuk

SpecPro Inc.

San Antonio, TX, USA

29

Organochlorines Study Goal

• To measure levels of dibenzo-p-dioxins (PCDDs),

dibenzofurans (PCDFs), mono-ortho and non-ortho

substituted polychlorinated biphenyls (PCBs) in

participants of the 2002 physical examination who

did not have a previous valid TCDD measurement

30

Methods

• 94 Comparison veterans who participated at 2002

examination did not have a TCDD measurement

- 61 did not attend any previous physical examination

- 33 did not have a valid previous measurement

• 12 Ranch Hand veterans without TCDD

measurement also included in the study

31

Methods

• High-resolution gas chromatography high-resolution mass spectrometry used to analyze dioxin-like compounds

• CDC dioxin laboratory performed the analyses

• Lipid adjusted measurements presented in pg/g of

lipid or parts per trillion (ppt) for all congeners

except mono-ortho PCBs in ng/g of lipid or parts per

billion (ppb)

• WHO TEF used to calculated PCDDs, PCDFs, and

PCBs TEQs, and total (sum) TEQ in pg/g of lipid or ppt

32

Demographic Characteristics of US Air Force Veterans

Comparison

(N=96)

Ranch Hand

(N=12)

Age at qual. tour (yr), Mean (SD)

Year at birth, Mean (SD)

2002 BMI, Mean (SD)

2002 Alcohol (drink-yrs)

2002 Pack years of smoking

Officer (%)

Enlisted Flyer (%)

Enlisted Ground (%)

31 (7.4)

1939 (7.6)

28.9 (4.3)

46 (107)

16.4 (21.5)

33 (35.1)

20 (21.3)

41 (43.6)

30.2 (8.7)

1938 (7.6)

28.7 (4.7)

68 (83)

13.8 (23.2)

6 (50)

2 (16.7)

4 (33.3)

33

PCDDs in Comparisons and Ranch Hands (ppt)

% Dt.

Comp

MeanMin- Max % Dt.

RH

Mean Min- Max

2,3,7,8-TCDD 36 1.74 0.42-11.7 42 5.46 0.42-34

1,2,3,7,8-PnCDD

1,2,3,4,7,8-HxCDD

1,2,3,6,7,8-HxCDD

1,2,3,7,8,9-HxCDD

1,2,3,4,6,7,8-HpCDD

OCDD

60

43

99

19

100

99

4.97

3.61

48.2

2.64

47

369

0.49-21.7

0.64-14.3

1.62-107

0.64-13

5.7-129

43-900

75

50

83

75

100

92

5.27

3.87

37.9

4.73

39.8

261

0.42-11.3

0.78-8.4

1.41-67.2

0.85-11.1

6.8-74.9

52.8-529

% Dt. - % above the limit of detection

34

PCDFs in Comparisons and Ranch Hands (ppt)

% Dt.

Comp

Mean

Min- Max % Dt.

RH

Mean Min- Max

2,3,7,8-TCDF

1,2,3,7,8-PnCDF

2,3,4,7,8-PnCDF

1,2,3,4,7,8-HxCDF

1,2,3,6,7,8-HxCDF

2,3,4,6,7,8-HxCDF

1,2,3,7,8,9-HxCDF

1,2,3,4,6,7,8-HpCDF

1,2,3,4,7,8,9-HpCDF

OCDF

2.1

1.0

88

97

95

0

50

100

0

--

0.73

0.77

7.54

5.56

5.46

0.79

1.54

12.6

0.9

--

0.42-1.91

0.42-2.26

0.57-23.2

0.49-14.5

0.84-15.7

0.42-2.19

0.57-4.7

3.7-36.5

0.42-2.33

--

0

0

83

100

75

0

8.3

92

0

--

0.88

0.91

6.49

5.33

4.04

1

1.42

8.91

1.08

--

0.28-4.74

0.35-4.53

0.71-18.4

1.9-10.8

0.49-8

0.42-5.02

0.49-4.88

4.74-16.7

0.49-4.74

--

35

Non-ortho PCBs in Comparisons and Ranch Hands (ppt)

% Dt.

Comp

Mean Min- Max % Dt.

RH

Mean Min- Max

TeCB 77

TeCB 81

PnCB 126

HxCB 169

--

32

96

100

--

4.3

48.3

33.3

--

0.1-23.5

1.2-1570

9.7-346

--

0

92

100

--

1.4

19

33.1

--

0.3-2.5

8.1-35.9

16.6-63.4

% Dt. - % above the limit of detection

36

Mono-ortho PCBs in Comparisons and Ranch Hands (ppb)

% Dt.

Comp

Mean Min- Max % Dt.

RH

Mean Min- Max

TeCB 118

PnCB 105

PnCB 167

HxCB 156

HxCB 157

91.5

21.3

6.4

90.4

4.3

22

3.9

3.2

10.6

2.6

2.3-395

0.2-82.5

0.6-34.4

2-50

0.5-13.8

91.7

8.3

0

0

8.3

14.4

2.9

2.7

12

2.6

3.6-67.7

0.7-16.1

1.4-5.4

5-24.3

1-5.4

% Dt. - % above the limit of detection

37

Sums of PCDDs, PCDFs, and non-ortho PCBs

60

35

206

22

33

445

102

54

797

1

10

100

1000

∑ PCDDs ∑ PCDFs ∑ no-PCBs

90% Mean 10%

ppt

56

34

99

16

27

247

71

43

689

1

10

100

1000

∑ PCDDs ∑ PCDFs ∑ no-PCBs

90% Mean 10%

Comparisons Ranch Hand

38

PCDDs, PCDFs, non-ortho and mono-ortho PCBs TEQs

1.7

12.6

5.4 5.2

9.2

32.4

5.5

15.5

4.62.2

9.1

31.4

0

5

10

15

20

25

30

35

Comparisons (n=94) Ranch Hands (n=12)

TCDD

∑ PCDDs*

∑ PCDFs

∑ no-PCBs

∑ mo-PCBs

Sum TEQ

ppt

* ∑ PCDDs includes values for TCDD

39

1987 and 2002 TCDD Levels

4.2

1.7

26.6

5.5

0

5

10

15

20

25

30

Comparisons Ranch Hands

1987

2002

n=1506n=94

n=1019

n=12

ppt

40

TEQ Levels in US and International General Population

12.6

5.4 5.2

13.5

5.9

12.2

8 8

3.2 3.54.1

0

2

4

6

8

10

12

14

Comparisons2002

Texas, USA2002

Germany2002

Australia 2002

∑ PCDDs

∑ PCDFs

∑ no-PCBs

ppt

N.A.

41

TEQs in US Vietnam War Veterans

15.5

4.62.2

9.1

19.5

7.2

13.5

50

0

5

10

15

20

25

30

35

40

45

50

Ranch Hand veterans 2002

Michigan Vietnam veterans1991-2

∑ PCDDs

∑ PCDFs

no-PCBs

mo-PCBs

n=12 n=50

ppt

42

Preliminary Results: PCDDs, PCDFs, non-ortho and mono-ortho PCBs TEQs

4

19.3

73.9

10.2

40.4

10.6

25.4

6.9

3.4

9

44.8

0

5

10

15

20

25

30

35

40

45

Comparisons (n=300) Ranch Hands (n=300)

TCDD

∑ PCDDs*

∑ PCDFs

∑ no-PCBs

∑ mo-PCBs

Total TEQ

ppt

* ∑ PCDDs includes values for TCDD

43

Conclusions

• Background organochlorines levels observed in the general population were found in both Ranch Hands and Comparisons in this study

• Mean TCDD levels decreased two to five times relative to the 1987 levels, consistent with decreases observed in the general population

44

Conclusions

• The mean 2002 TCDD level in Ranch Hands was about three times higher than in Comparison veterans (5.5 versus 1.7 ppt)

• Total TEQs were similar, 32.4 ppt and 31.4 ppt (10%-90%: Ranch Hands 15.1-48.4 ppt, Comparisons 15.9-45.7 ppt)

• Ranch Hands sample size was too small to make any definitive inferences about the total TEQs

45

Conclusions

• Additional 600 samples were analyzed by CDC for

PCDDs, PCDFs, PCBs, and organochlorine pesticides

• Statistical analysis of these data by the Air Force

and CDC is ongoing