Overview of Exposures of Concern: A Clinical Perspective- What We Have Seen in the Literature and at the WRIISC

1. Overview of Exposures of Concern: A Clinical Perspective- What We Have Seen in the Literature and at the WRIISC Caring for Veterans: Moving Forward in Providing Quality Care August 9-10, 2011 Ron Teichman, MD, MPH, FACP, FACOEM Associate Director – Clinical, Education and Risk Communication Services War Related Illness and Injury Study Center East Orange, NJ

2. Disclaimer • The views expressed in this presentation are those of the author and do not necessarily represent the position of the Department of Veterans Affairs or the United States Government • I have no known conflicts of interest other than that I work for the Department of Veterans Affairs

3. Environmental Exposure Concerns of Veterans • Exposure concerns of Veterans are not new, but … • Are exposure concerns of Veterans common? • What combat and military exposures are Veterans concerned about? • What does the literature say about these?

4. Prevalence (%) of exposure concerns common to Vietnam, Persian Gulf and Bosnia-Kosovo From Schneiderman, Lincoln, Wargo, et. al., APHA, 12-14-05

5. Percentage of OEF/OIF service members who endorsed Exposure Concerns on PDHA and PDHRA (9/07-10/08) • Active component • Pre-Deployment n=245,378 0.0% • Post-Deployment n=224,511 16.2% • Reassessment n=189,933 21.2% • Reserve component • Pre-Deployment n=85,843 0.0% • Post-Deployment n=75,174 24.9% • Reassessment n=96,886 34.8% • Frequency of exposure concerns rise after 3-6 months MSMR Vol. 15 / No. 7 – Sept. 2008

6. Top ten environmental exposures of concern: Gulf War • Protective gear/alarms (82.5%) • Diesel, kerosene, other petrochems (80.6%) • Oil well fire smoke (66.9%) • Local food (64.5%) • Insect bites (63.7%) • Harsh weather (62.5%) • Smoke from burning trash or feces (61.4%) • Within 1 mile of missile warfare (59.9%) • Repellants and pesticides (47.5%) • Paint, solvents (36.5%) From Schneiderman, Lincoln, Wargo, et. al., APHA, 12-14-05

7. 30.0 30.0 Reserve Reserve Active Active 25.0 25.0 20.0 20.0 Percent Percent 15.0 15.0 10.0 10.0 5.0 5.0 0.0 0.0 Noise Sand Noise Sand Solvents Solvents JP8 or Fuel JP8 or Fuel DEET on skin DEET on skin Vehicle exhaust Vehicle exhaust Smoke from trash Smoke from oil fire Industrial pollution Industrial pollution Smoke from trash Excessive vibration Smoke from oil fire Excessive vibration Blast / Vehicle accident Pesticide treated uniform Blast / Vehicle accident Pesticide treated uniform Frequency of OEF/OIF service member exposure concern reported on the PDHRA (9/05-8/06) MSMR Vol. 12 / No. 8 – Nov. 2006

8. Top ten environmental exposures of concern: OEF/OIF • Smoke from burning trash or feces (44.6%)-7 • Sand and dust storms (41.5%)-6 • Gasoline, Jet Fuel, Diesel Fuel (21.1%)-2 • Depleted Uranium (19.0%) • Paint, solvents, other petrochems (15.2%)-10 • Oil well fire smoke (14.9%)-3 • Contaminated food and water (14.4%)-4 • Anthrax Vaccine (14.2%) • Multiple Vaccinations (13.9%) [8+9>3] • Vehicular Exhaust (10.3%) Seen at NJ WRIISC, n=612. 1889 concerns, range 0-15

9. Environmental Exposure Concerns of Veterans • Combat and military exposures are not new. • Exposure concerns are common in Veterans. • Many of the exposures that Veterans are concerned about are the same from conflict to conflict, but some exposures are unique to a particular conflict. • What have we found at the WRIISC?

10. NJ WRIISC Non-specific symptom severity (PHQ-15) at post-deployment for those exposed to a given environmental hazard versus not exposed to a hazard at post-deployment. Exposure Non-Specific Symptom Severity at Post-deployment   Exposed Not Exposed Biological warfare agents 14.0 7.5* Nerve agents/gas 11.8 7.6 Pesticides 9.8 6.6* Pyridostigmine bromide 10.9 7.7 Insect repellant sprays for several hours 9.0 7.4* Insect repellant flea collars x several hrs 11.2 7.4* Depleted Uranium 10.8 7.3* *p≤.05 Unpublished data from HEROES project

11. NJ WRIISC Level of symptom burden (PHQ-15) for those exposed to an environmental hazard versus those not exposed to a hazard. Exposure Mean Symptom Burden for Mean Symptom Burden for Those Exposed Those Not Exposed Herbicide 15.55 10.90* Biological warfare 15.04 10.76* Chemical weapons 14.24 10.82* Depleted Uranium 13.16 10.44* Chemical gear/tablets 13.32 10.22* Contaminated food/water 12.87 9.97* Insect repellant 12.20 8.67* Insect bites 11.75 8.75* Petrochemicals 11.75 7.76* Chemicals used on job 11.71 9.98* Air pollution-specific (e.g. burn pit) 11.46 8.63* Air pollution-general (e.g. sand storm) 11.29 7.90* * = p≤ 0.05 Unpublished data

12. Hottest Exposure Issues? Pulmonary effects of deployment to SW Asia Inhalational exposures of Veterans of SW Asia

13. Let’s talk about two particular inhalation exposures that have created a lot of concern and have been, and continue to be, heavily studied: • Burn Pits • Sand Storms

14. Sandstorms • What is this substance? • Extremely fine sand, comparable to our dust. Wind blowing across large areas of flat terrain picks up the sand and creates sandstorms. • Microscopically this is a matrix that can carry a variety of metals, chemicals, bacteria, viruses, fungi, etc. • How might a Veteran have been exposed? • Anyone that has been through a sandstorm will know it. The sky typically darkens, the dust in the air becomes thick, visibility drops significantly and every mucous membrane may become irritated.

15. Sandstorms

16. Sandstorms • What are the known health effects? • Very limited data regarding direct health effects. • Reasonably good evidence that individuals with chronic pulmonary and/or cardiac disease are at increased risk of exacerbation during or shortly after exposure to sandstorms. • There is anecdotal evidence of the development of reactive airway disease following exposure to sandstorms, with a variable time to onset. Additional investigations are continuing.

17. Burn Pits • What is this Substance? • Military burns all waste, including paper, wood, metal, chemical, vegetable, human, etc. many burn pits operated 24/7. As large as 100 acres. • Sampling reveals multiple contaminants in very low levels*. • How might a Veteran have been exposed? • Working or being billeted downwind • Most actual operators were/are contractors • Regulations about what should not be burned, but…

19. Burn Pits • What are the known health effects? • Very limited data regarding direct health effects. • Reasonably good evidence that individuals with chronic pulmonary and/or cardiac disease are at increased risk of exacerbation during or shortly after exposure to sandstorms. • There is anecdotal evidence of the development of reactive airway disease following exposure to sandstorms, with a variable time to onset. Additional investigations are continuing.

20. Particulate Size • From an occupational and environmental health point of view, dust is classified by size into three primary categories: • Respirable Dust • Inhalable Dust • Total Dust

21. Particulate Size • Respirable Dust • Dust particles that are small enough to penetrate the nose and upper respiratory system and deep into the lungs. These are generally beyond the body's natural clearance mechanisms of cilia and mucous and are more likely to be retained. • In a mixed size sample, the percent of particles by size that is respirable is:

23. Particulate Size • Inhalable Dust • The EPA describes inhalable dust as that size fraction of dust which enters the body, but is trapped in the nose, throat, and upper respiratory tract. The median aerodynamic diameter of this dust is about 10 µm. • Total Dust • Total dust includes all airborne particles, regardless of their size or composition.

24. Characterizing mineral dusts and other aerosols from the Middle East--Part 1: ambient sampling • Engelbrecht JP, et al. Inhalational Toxicology 2009 Feb;21(4):297-326 • The purpose of the Enhanced Particulate Matter Surveillance Program was to provide scientifically founded information on the chemical and physical properties of dust collected over a period of approximately 1 year in Djibouti, Afghanistan, Qatar, United Arab Emirates, Iraq, and Kuwait. • This study shows the three main air pollutant types to be geological dust, smoke from burn pits, and heavy metal condensates (possibly from metals smelting and battery manufacturing facilities). Non- storm events resulted in elevated trace metal concentrations.

25. The Occurrence, Recrudescence, and Worsening of Asthma in a Population of Young Adults: Impact of Varying Types of Occupation • Katz I, et al. Chest 1999:116;614-618 (http://chestjournals.org/cgi/content/abstract/116/3/614) • Service in Combat Units (CUs) was associated with an increased frequency of exacerbation of asthma among recruits with previous disease and with the appearance of disease de novo. “Normal” conscripts with a history of childhood asthma are at a higher risk of developing overt asthma when compared to subjects with no such history. We found a 25% relative excess of incident cases of asthma in soldiers posted in Maintenance Units (MUs) compared to those performing clerical tasks (CTs) [(0.8 to 0.6%)/0.8%]. • Of a total of 59,058 recruits, 1.0% developed asthma during the 30 months of this study; of those in CUs, 1.2% developed asthma; of those in MUs, 0.8% developed asthma; and of those CTs, 0.6% developed asthma.

26. Newly reported respiratory symptoms and conditions among military personnel deployed to Iraq and Afghanistan: a prospective population-based study • Smith B, et al. American Journal of Epidemiology, 2009, Naval Health Research Center (NHRC) • Data on 46,077 Millennium Cohort Study participants who completed baseline (July 2001–June 2003) and follow-up (June2004–February 2006) • Questionnaires were used to investigate: • Respiratory symptoms (persistent or recurring cough or shortness of breath) • Chronic bronchitis or emphysema • Asthma

27. Smith et al. 2009 • Deployers had a higher rate of newly reported respiratory symptoms than nondeployers (14% vs. 10%) • Similar rates of (HCP diagnosed) chronic bronchitis or emphysema (1% vs. 1%) and asthma (1% vs. 1%) were observed • Deployment was associated with respiratory symptoms in both Army (adjusted odds ratio 1.73, 95% confidence interval: 1.57, 1.91) and Marine Corps (adjusted odds ratio 1.49, 95% confidence interval: 1.06, 2.08) personnel, independently of smoking status • Deployment length was linearly associated with increased symptom reporting in Army personnel (P < 0.0001).

28. Smith et al. 2009 • Among deployers, elevated odds of symptoms were associated with land-based deployment as compared with sea-based deployment. • Inconsistent correlation of respiratory symptom risk with cumulative exposure time suggests that specific exposures, rather than deployment in general, are determinants of post-deployment respiratory illness. • Significant associations seen with land-based deployment also imply that exposures related to ground combat may be important.

29. Navy researcher links toxins in war-zone dust to ailmentsUSA Today – May 14, 2011 • U.S. troops in Iraq, Afghanistan and Kuwait have inhaled microscopic dust particles laden with toxic metals, bacteria and fungi — a toxic stew that may explain everything from the undiagnosed Gulf War Syndrome symptoms lingering from the 1991 war against Iraq to high rates of respiratory, neurological and heart ailments encountered in the current wars, scientists say. • "From my research and that of others, I really think this may be the smoking gun," says Navy Capt. Mark Lyles, chair of medical sciences and biotechnology at the Center for Naval Warfare Studies at the Naval War College in Newport, R.I. "It fits everything — symptoms, timing, everything."

30. Medical Monday: Setting the Record Straight on Sand • Laraby P.DoD Live – May 23, 2011 • The Navy and Army Medical Departments have spent substantial time and resources researching the possibility that sand in the Middle East (specifically Iraq and Afghanistan) is harmful and to date have found no definitive basis to indicate that it is despite the claims by some military members outside the research community. • “The United States Army Public Health Command has been conducting surveillance of increased airborne particulate matter since 2005 and concluded it had a similar composition to other desert regions.  Additional published peer-reviewed research by Army infectious disease experts have failed to demonstrate a connection between bacteria in the soil and infections in service members.”

31. New-onset asthma among soldiers serving in Iraq and Afghanistan • Szema AM, et al. Allergy and Asthma Proceedings 2010 Sep;31(5):67-71. • Since June 4, 2004, asthma diagnosed and symptomatic after the age of 12 years has been an exclusion criterion for military enlistment unless exempted via medical waiver. • Retrospective review of asthma diagnoses among computerized charts revealed that out of 6233 patients who served between 2004 and 2007 and were followed at the Northport VAMC, 290 new-onset/prevalent asthma cases were identified. • Deployment to Iraq was associated with a significantly (50%) higher risk of asthma compared with stateside soldiers (6.6% versus 4.3%; with a crude odds ratio, 1.58; 95% CI, 1.18, 2.11). • Deployment to Iraq and Afghanistan is associated with new-onset asthma.

32. Troops in Mideast Face Breathing Ills - Burn Pits a Possible Factor as Data Show Higher Rate of Respiratory Woes Among Veterans of Afghanistan, IraqWall Street Journal - May 17, 2011 Debate Swirls Around Research Showing Lung Problems for Returned Troops New York Times – June 19, 2011 Lung problems for deployed veterans According to a soon-to-be-published study in the Journal of Occupational and Environmental Medicine, veterans from Iraq and Afghanistan are seven times more likely to report having lung problems compared with non-deployed vets. CBS News July 25, 2011 8:55 AM

33. Constrictive Bronchiolitis in Soldiers Returning from Iraq and Afghanistan • King MS, et al. New England Journal of Medicine 2011; 365:222-230 July 21, 2011 • (Most often referred to as the work of Dr. Robert Miller at Vanderbilt University) • Results: Of 49 soldiers who underwent lung biopsy, all biopsy samples were abnormal, with 38 soldiers having changes that were diagnostic of constrictive bronchiolitis. In the remaining 11 soldiers, other diagnoses that could explain the presenting dyspnea were established. All soldiers with constrictive bronchiolitis had normal results on chest radiography, but about one quarter were found to have mosaic air trapping or centrilobular nodules on chest CT. The results of pulmonary-function and cardiopulmonary-exercise testing were generally within normal population limits but were inferior to those of the military control subjects. • Conclusions: In 49 previously healthy soldiers with unexplained exertional dyspnea and diminished exercise tolerance after deployment, an analysis of biopsy samples showed diffuse constrictive bronchiolitis, which was possibly associated with inhalational exposure, in 38 soldiers.

34. Institute of Medicine Committee on Burn Pits • The IOM committee will determine the long-term health effects of exposure to burn pits in Iraq and Afghanistan • Will use the Balad Burn Pit in Iraq as an example • Will examine existing literature that has detailed the types of substances burned and their by-products • Will examine the feasibility and design issues for a possible epidemiology study of Veterans exposed to the Balad (and other) burn pit(s)

35. Inhalation Exposures Concerns of Veterans Who Served in SW Asia • Conclusions • Self –reports of respiratory diseases and symptoms are increased after deployment to the Persian Gulf. • Diagnosed disease and mortality from respiratory diseases is not (yet). • We are learning more about and increasingly studying: • The nature of the exposures • The pathophysiology of the symptoms • Diagnostic clarification of the disease process • We need more robust and well designed research.

36. Inhalation Exposures Concerns of Veterans Who Served in SW Asia • The bottom line: • We need to know much more.

37. Thank you NJ WRIISC 800-248-8005 www.warrelatedillness.va.gov