1 air force interaction with iom karen fox, col, usaf, mc principal investigator brooks city-base tx
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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
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