Military Service is a Vulnerable Occupation: Lung Disease as a - PDF document

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 1 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 Nerve Anti‐ Solvents Orange Agent Malarial Dust & Fuels Pesticides Radiation Sand Depleted Oil Well Vaccines Burn Pits Uranium Fires

Mean PM 2.5 Concentration (06‐07) 15μg/m 3 35μg/m 3 Redrawn from: Engelbrecht et al. 2008 Non‐Inhalational Exposure Figure from Cernak and Noble‐Haeusslein 2010, J Cereb Blood Flow Metab

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 3.50% 25000 3.00% 20000 2.50% No. of Veterans Prevalence (%) 15000 2.00% 1.50% 10000 1.00% 5000 0.50% 0.00% 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 Asthma Asthma COPD COPD ILD ILD Redrawn from: Pugh et al. 2016 Mil Med

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 % Preserved Spirometry 100% Morris et al. 95% Krefft et al. (n=50), 84% (n=28), 82% 90% Falvo et al. 85% (n=143), 75% 80% 75% 70% Butzko et al. Holley et al. 65% (n=178), 72% (n=267), 64% 60% 55% 50% National VA Post‐Deployment Health Resource (Public Law 105‐368)

WRIISC  AHBPCE • Increased reports of airborne hazards exposure 2007 and concerns (Helmer et al. 2007) • Working Group at National Jewish publishes 2010 recommendations (Rose et al. 2010) 2011 • Full PFTs on all referrals • Expanded cardiopulmonary evaluations for Veterans with primary respiratory complaints 2013 • Airborne Hazards and Burn Pits Center of 2018 Excellence NJ WRIISC Referral Cohort 110.00 Post‐9/11 100.00 Pre‐9/11 90.00 FEV 1 /FVC 80.00 70.00 60.00 50.00 n = 485 40.00 6.8 0.8 16.5 Normal Obstructed N = 485 Restricted Mixed 74.9

Preserved Spirometry Age Sex 46.0 (37.0, 50.0) yrs 86.3% male n = 364 Post‐Deploy Tobacco Pack Length Years 12.8 (7.3, 23.4) yrs 0.0 (0.0, 10.0) Deployment‐Related Exposures 120 100 80 60 40 20 0 Burn Pits Air Pollution Sand/Dust Petrochem Blast Exposed Concerned Lower Respiratory Symptoms (≥ 2d∙wk⁻¹) Cough Wheeze Short of Breath 2+ Symp 0 10 20 30 40 50 60

BD Reversibility 25.00 20.00 FEV 1 BD %change 15.00 +12% 10.00 5.00 0.00 ‐5.00 ‐10.00 ‐15.00 n = 357 Isolated ↓ DLCO 150 130 DL CO (%predicted) 110 90 70 50 n = 349 30 HgB corrected; Miller et al. 1983 predicted • N = 123 * – Preserved spirometry – Current smokers excluded • Low DL CO – DL CO ≤ LLN – Miller ’83 – HgB corrected Falvo et al. 2018 Clin Resp J

Forced Oscillation Technique (FOT) 20 Hz 5 Hz Figure from: Brashier & Salvi 2015 Resistance (Rrs) Reactance (Xrs) R5 R20 �� � ��� �� � ��� � ��% ��5 � �20� � ��5 � �20� � 100 ��5� Figures from: Brashier & Salvi 2015 • 75% (93/124) demonstrate distal airway dysfunction Butzko et al. 2019 Respir Physiol Neurobiol

Butzko et al. 2019 Respir Physiol Neurobiol BD Reversibility for R4 80.00 60.00 40.00 R4 Δ (% Change) 20.00 0.00 ‐20.00 ‐40.00 ‐60.00 ‐80.00 BD Reversibility for AX4 40.00 20.00 AX4 Δ (% Change) 0.00 ‐20.00 ‐40.00 ‐60.00 ‐80.00 ‐100.00

MMRC Dyspnea Severe 100 yards 15 min When hurrying Not troubled 0 10 20 30 40 50 Borg Breathlessness at Peak Maximal 1.00% 5.10% 8.10% Very Severe 13.10% 15.20% Severe 20.20% 27.30% Moderate 8.10% 2.00% Very Slight 0.00% 0.00% n = 99 Nothing at all 0.00% CPET Patterns for Exertional Dyspnea VE/VCO2 Slope Peak VO2 (%) etCO2 (mmHg) VE/MVV < 30 ≥ 100% Rest 36‐42 < 0.80 30.0 ‐ 35.9 75 ‐ 99% 3‐8 ↑ ex 36.0 ‐ 44.9 50 ‐ 75% Rest < 36 ≥ 0.80 ≥ 45.0 < 50% < 3 ↑ ex 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 No sustained arrhythmias, ectopic foci, and/or No Δ in SpO2 from VO2) ST segment changes during CPET or recovery baseline Altered rhythm, foci, and/or ST ‐ but did not ↔ or ↓ SBP during CPET, or lead to test termination >5% ↓in SpO2 from excessive ↑ SBP (≥ 20 mmHg/3.5 Altered rhythm, foci, and/or ST ‐ led to test baseline mL O2·kg·min VO2) termination Adapted from: EACPR/AHA Statemen; Guazzi et al. 2012 Circ

CPET Pattern Results VE/VCO2 Slope Peak VO2 (%) etCO2 (mmHg) VE/MVV 50.5% 18.2% < 30 ≥ 100% Rest 36‐42 58.1% < 0.80 53.2% 3‐8 ↑ ex 30.0 ‐ 35.9 35.3% 75 ‐ 99% 50.5% 12.1% 27.2% 36.0 ‐ 44.9 50 ‐ 75% Rest < 36 41.9% ≥ 0.80 46.8% < 3 ↑ ex ≥ 45.0 2.0% < 50% 4.0% 29.7 (27.4, 32.8) 83.8 (71.0, 95.5) 32.2 (30.2, 34.4) 0.77 (0.63, 0.96) Post‐Exercise Spirometry No Δ FEV1, PEF post‐CPET (84.9%) ≥ 15% ↓ in FEV1, PEF post‐CPET (15.1%) Hemodynamics ECG Pulse Oximetry ↑ SBP (10 mmHg/3.5 mL O2·kg·min No sustained arrhythmias, ectopic foci, and/or No Δ in SpO2 from VO2) ST segment changes during CPET or recovery baseline Altered rhythm, foci, and/or ST ‐ but did not ↔ or ↓ SBP during CPET, or lead to test termination >5% ↓in SpO2 from excessive ↑ SBP (≥ 20 mmHg/3.5 Altered rhythm, foci, and/or ST ‐ led to test baseline (9.1%) mL O2·kg·min VO2) (1‐2%) termination (1‐2%) 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)

Questions 34 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

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