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1 Military Service is a Vulnerable Occupation: Lung Disease as a Paradigm Michael J. Falvo, PhD Research Physiologist, VA War Related Illness & Injury Study Center – Airborne Hazards and Burn Pits Center of Excellence Assistant Professor, Rutgers New Jersey Medical School Disclosure I have nothing to disclose Contents of this presentation do not represent the views of the U.S. Department of Veterans Affairs or the United States Government Deployment‐Related Exposures Agent Orange Nerve Agent Solvents Anti‐ Malarial Dust & Sand Fuels Pesticides Radiation Depleted Uranium Vaccines Oil Well Fires Burn Pits

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Page 1: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

1

Military Service is a Vulnerable Occupation: Lung Disease as a 

Paradigm

Michael J. Falvo, PhDResearch Physiologist, VA War Related Illness & Injury Study Center –

Airborne Hazards and Burn Pits Center of Excellence

Assistant Professor, Rutgers New Jersey Medical School

Disclosure

• I have nothing to disclose

• Contents of this presentation do not represent the views of the U.S. Department of Veterans Affairs or the United States Government

Deployment‐Related Exposures

Agent Orange

Nerve Agent

SolventsAnti‐

Malarial

Dust & Sand

Fuels Pesticides Radiation

Depleted Uranium

VaccinesOil Well Fires

Burn Pits

Page 2: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

Mean PM2.5 Concentration (06‐07)

Redrawn from: Engelbrecht et al. 2008

15μg/m3

35μg/m3

Non‐Inhalational Exposure

Figure from Cernak and Noble‐Haeusslein 2010, J Cereb Blood Flow Metab

Page 3: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

Uniquely Vulnerable, Susceptible?

Falvo et al., 2015, Epidemiologic Rev

Epidemiologic Findings

• 15 epidemiologic studies (2005 – present)

• Relationship to deployment?

– Respiratory Symptoms: 9 studies, favorable

– Asthma: 10 studies, mixed results

– COPD: 7 studies, largely null

– Other Outcomes: 6 studies, inconclusive

• Limitations

↑ Chronic Lung Disease

0

5000

10000

15000

20000

25000

0.00%

0.50%

1.00%

1.50%

2.00%

2.50%

3.00%

3.50%

2003 2004 2005 2006 2007 2008 2009 2010 2011

No. o

f Veterans

Prevalence (%)

Redrawn from: Pugh et al. 2016 Mil Med

AsthmaAsthma

COPDCOPD

ILDILD

Page 4: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

Clinical Findings

• 18 clinical studies (2004 – present)

– 4 Case reports/series

– 5 Retrospective chart reviews

– 2 Pre‐deployment evaluations

– 6 Post‐deployment evaluations

– 1 Pre‐ and post‐deployment evaluation

• Main findings

– Dyspnea….still complicated

Morris et al. (n=50), 84%

Butzko et al. (n=178), 72%

Krefft et al. (n=28), 82%

Falvo et al. (n=143), 75%

Holley et al. (n=267), 64%

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

% Preserved Spirometry

National VA Post‐Deployment Health Resource (Public Law 105‐368) 

Page 5: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

WRIISC  AHBPCE

2007• Increased reports of airborne hazards exposure and concerns (Helmer et al. 2007)

2010• Working Group at National Jewish publishes recommendations (Rose et al. 2010)

2011• Full PFTs on all referrals

2013• Expanded cardiopulmonary evaluations for Veterans with primary respiratory complaints

2018• Airborne Hazards and Burn Pits Center of Excellence

NJ WRIISC Referral Cohort

40.00

50.00

60.00

70.00

80.00

90.00

100.00

110.00

FEV1/FVC

n = 485

Post‐9/11

Pre‐9/11

74.9

16.5

6.8 0.8

Normal

Obstructed

Restricted

Mixed

N = 485

Page 6: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

Preserved Spirometry

Age

46.0 (37.0, 50.0) yrs

Sex

86.3% male

Post‐Deploy Length

12.8 (7.3, 23.4) yrs

Tobacco Pack Years

0.0 (0.0, 10.0)

n = 364

0

20

40

60

80

100

120

Burn Pits Air Pollution Sand/Dust Petrochem Blast

Deployment‐Related Exposures

Exposed Concerned

0 10 20 30 40 50 60

2+ Symp

Short of Breath

Wheeze

Cough

Lower Respiratory Symptoms (≥ 2d∙wk⁻¹)

Page 7: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

BD Reversibility

‐15.00

‐10.00

‐5.00

0.00

5.00

10.00

15.00

20.00

25.00

FEV1BD %chan

ge

n = 357

+12%

30

50

70

90

110

130

150

DL C

O(%

predicted)

Isolated ↓ DLCO

HgB corrected; Miller et al. 1983 predicted

n = 349

*

Falvo et al. 2018 Clin Resp J

• N = 123

– Preserved spirometry

– Current smokers excluded

• Low DLCO– DLCO ≤ LLN

–Miller ’83

– HgB corrected

Page 8: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

Forced Oscillation Technique (FOT)

20 Hz 5 Hz

Figure from: Brashier & Salvi 2015

Resistance (Rrs) Reactance (Xrs)

R5 R20

Figures from: Brashier & Salvi 2015

5 205 20

5100

%

• 75% (93/124) demonstrate distal airway dysfunction

Butzko et al. 2019 Respir Physiol Neurobiol

Page 9: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

Butzko et al. 2019 Respir Physiol Neurobiol

‐80.00

‐60.00

‐40.00

‐20.00

0.00

20.00

40.00

60.00

80.00

R4 Δ (% Chan

ge)

BD Reversibility for R4

‐100.00

‐80.00

‐60.00

‐40.00

‐20.00

0.00

20.00

40.00

AX4 Δ (% Chan

ge)

BD Reversibility for AX4

Page 10: 07 Falvo MilitaryService - UCSF CME•Airborne Hazards and Burn Pits Center of Excellence NJ WRIISC Referral Cohort 40.00 50.00 60.00 70.00 80.00 90.00 100.00 110.00 FEV 1 /FVC n =

0 10 20 30 40 50

Not troubled

When hurrying

15 min

100 yards

Severe

MMRC Dyspnea

0.00%

0.00%

0.00%

2.00%

8.10%

27.30%

20.20%

15.20%

13.10%

8.10%

5.10%

1.00%

Nothing at all

Very Slight

Moderate

Severe

Very Severe

Maximal

Borg Breathlessness at Peak

n = 99

CPET Patterns for Exertional Dyspnea

< 0.80

≥ 0.80Rest < 36            

< 3 ↑ ex

Rest 36‐42           

3‐8 ↑ ex

< 50%

50 ‐ 75%

VE/VCO2 Slope Peak VO2 (%) etCO2 (mmHg) VE/MVV

75 ‐ 99%

≥ 100%

30.0 ‐ 35.9

< 30

36.0 ‐ 44.9

≥ 45.0

Post‐Exercise Spirometry

No Δ FEV1 or PEF post‐CPET ≥ 15% reduction in FEV1 or PEF post‐CPET

Hemodynamics ECG Pulse Oximetry↑ SBP (10 mmHg/3.5 mL O2·kg·min 

VO2)No sustained arrhythmias, ectopic foci, and/or ST segment changes during CPET or recovery

No Δ in SpO2 from baseline

↔ or ↓ SBP during CPET, or excessive ↑ SBP (≥ 20 mmHg/3.5 

mL O2·kg·min VO2)

Altered rhythm, foci, and/or ST ‐ but did not lead to test termination >5% ↓in SpO2 from 

baselineAltered rhythm, foci, and/or ST ‐ led to test termination

Adapted from: EACPR/AHA Statemen; Guazzi et al. 2012 Circ

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CPET Pattern Results

Hemodynamics ECG Pulse Oximetry↑ SBP (10 mmHg/3.5 mL O2·kg·min 

VO2)No sustained arrhythmias, ectopic foci, and/or ST segment changes during CPET or recovery

No Δ in SpO2 from baseline

↔ or ↓ SBP during CPET, or excessive ↑ SBP (≥ 20 mmHg/3.5 

mL O2·kg·min VO2)  (1‐2%)

Altered rhythm, foci, and/or ST ‐ but did not lead to test termination >5% ↓in SpO2 from 

baseline (9.1%)Altered rhythm, foci, and/or ST ‐ led to test 

termination (1‐2%)

VE/VCO2 Slope Peak VO2 (%) etCO2 (mmHg) VE/MVV< 30 50.5% ≥ 100% 18.2% Rest 36‐42      

3‐8 ↑ ex58.1% < 0.80 53.2%

30.0 ‐ 35.9 35.3% 75 ‐ 99% 50.5%

36.0 ‐ 44.9 12.1% 50 ‐ 75% 27.2% Rest < 36       < 3 ↑ ex

41.9% ≥ 0.80 46.8%≥ 45.0 2.0% < 50% 4.0%

Post‐Exercise Spirometry

No Δ FEV1, PEF post‐CPET (84.9%) ≥ 15% ↓ in FEV1, PEF post‐CPET (15.1%)

83.8 (71.0, 95.5)29.7 (27.4, 32.8) 32.2 (30.2, 34.4) 0.77 (0.63, 0.96)

Conclusions

• Beyond spirometry

• DLCO, FOT, CPET…

Acknowledgements

• Drew Helmer, MD

• Anays Sotolongo, MD

• WRIISC/AHBPCE Clinical, Research, Edu Teams

• VA Post‐Deployment Health Service 

• Funding– VA (1I01CX001329, 1I01CX001515)

– DoD (W81XWH‐16‐1‐0663, W81XWH‐17‐1‐0575)

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34

Questions

Q1. Which of the following deployment‐related exposures are NOT relevant for the 

Veteran with dyspnea on exertion?

a) Smoke from open burn pits

b)Blast overpressure waves from IEDs

c) Aircraft/military truck engine exhaust

d)Multiple anthrax vaccinations

Q2. Which of the following conditions is NOT increasing in prevalence among post‐9/11 Veterans receiving care at VA Medical 

Centers?

a) Constrictive bronchiolitis

b)Asthma

c) COPD

d) Interstitial lung disease

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Q3. Which pulmonary function assessment is most sensitive for assessing the small 

airways?

a) Fractional exhaled nitric oxide

b)Forced oscillation technique

c) Diffusing capacity of the lung for carbon monoxide

d)Exercise flow‐volume loop