Poster produced by Faculty & Curriculum Support (FACS), Georgetown University Medical Center

Bronchiolitis from inhalational exposure in IraqWilliam Bender, MD, MPH1; Maria Romero, MD2; LTC Stuart A. Roop, MD, FACP, FCCP3; Eric D. Anderson MD, FCCP4

1Department of Medicine, Georgetown University Hospital, Washington, DC, 2Department of Pathology, Georgetown University Hospital, Washington, DC, 3Pulmonary Critical Care Medicine Service, Walter Reed Army Medical Center/National Naval Medical Center, Washington DC,

4Division of Pulmonary, Critical Care & Sleep Medicine, Georgetown University Hospital, Washington, DC,

Introduction

Pathology

Conclusion

References

AcknowledgmentsThe patient and his family for the time spent reviewing details and providing information.

1. Ryu JH, Myers JL, Swensen SJ. Bronchiolar disorders. Am J Respir Crit Care Med 2003; 168: 1277.

2. Visscher DW, Myers JL. Bronchiolitis: the pathologist’s perspective. Proc Am Thorac Soc 2006; 3: 41.

3. Pipavath SJ, Lynch DA, Cool C, et al. Radiologic and pathologic features of bronchiolitis. AJR Am J Roentgenol 2005; 185: 354.

4. U.S. Senate Committee on Veterans’ Affairs. VA/DOD Response to Certain Military Exposures. Hearing, October 8, 2009. Available at: http://veterans.senate.gov/hearings.cfm?action=release.display&release_id=8e6c9acc-ae05-41de-a5f6-484ea25a52bc; Accessed 4/14/10.

5. King MS, Miller R, Johnson J, et al. Bronchiolitis in solidiers with inhalational exposures in the Iraq War. Am J Respir Crit Care Med 2008;177: A885.

Bronchiolitis refers to a nonspecific inflammatory injury to the bronchioles, which are defined as airways that do not contain cartilage within their walls and are less than 2mm in diameter. Bronchiolitis can be classified as either primary, with the injury occurring as a direct result of insult to the bronchioles, or secondary, with the injury occurring as a result of parenchymal or large airway disease. There are a number of different types of primary bronchiolitis including constrictive, acute, diffuse panbronchiolitis, respiratory bronchiolitis, mineral dust airway disease and follicular bronchiolitis.1,2 These subtypes are often delineated from each other by a combination of histopathological characteristics such as fibrous tissue proliferation resulting in airway narrowing, radiological findings such as mosaic attentuation and air trapping on CT scan and clinical presentation.

A number of causes of primary bronchiolitis have been demonstrated including inhalational injury, infections, connective tissue disorders, hypersensitivity pneumonitis, organ transplantation and medications.1,3 With regards to inhalational injury, a variety of substances including nitrogen dioxide, sulfur dioxide, ammonia, chlorine, phosgene, cigarette smoke, volatile flavoring agents and fly ash have all been implicated as bronchiolitis inducing agents. The most common clinical presentation associated with these entities is a complaint of shortness of breath. A subsequent work-up usually entails a thorough history and physical, imaging studies and pulmonary function tests at which point a diagnosis is then rendered.

Recently, a number of previously healthy soldiers stationed at Fort Campbell, Kentucky and returning from active duty in Iraq have come forward with complaints of shortness of breath on exertion with a resulting inability to pass physical fitness testing.4 While a number of these soldiers had been exposed to the sulfur dioxide fires at the Mishraq Sulfur Mine near Mosul, Iraq in June 2003, approximately one-quarter of them had not had this exposure. In fact, they reported no inhalational exposures other than those associated with day-to-day service in Iraq. Subsequent respiratory evaluations, including chest x-rays, CT scans and pulmonary function testing, were all normal and were unable to explain the soliders’ new-onset limitations.

Surgical lung biopsy was ultimately performed on 45 of the soldiers with findings consistent with some form of bronchiolitis. While this was not overly surprising for those exposed to the sulfur dioxide fires at Mishraq, it was for those who had not suffered this exposure. These findings certainly raise the possibility of there being other toxic inhalants associated with duty in Iraq that are able to produce duty-limiting bronchiolitis.

We report the case of an Army colonel who has developed limiting dyspnea of exertion after serving in Iraq both during 2005 and 2009 and without any exposure to sulfur dioxide fires.

HPI• The patient is a 56 year old male who initially presented with dyspnea on exertion beginning in June of 2009.• Was previously able to walk and run long distances without any difficulty but at the beginning of June, began to notice increasing difficulty climbing stairs. His dyspnea progressed to the point where he could barely complete a flight of stairs without having to stop and rest.• He denied any chest pain, cough, hemoptysis or wheezing but did note some intermittent chest tightness associated with his dyspnea.• Initial evaluation at Walter Reed Army Medical Center notable for:

• Negative cardiac work-up• Mild decrease in total lung capacity on pulmonary function testing• Normal six minute walk test• Chest x-ray with very mild interstitial lung disease• High resolution chest CT scan with subpleural posteriorly located right lower lobe air space disease.

• VATS open lung biopsy in October 2009• Second opinion sought at Georgetown University Hospital in January of 2010 given persistent dyspnea.

Past Medical/Surgical History• Obstructive Sleep Apnea (on home CPAP), Post Traumatic Stress Disorder, Peripheral Neuropathy, Post-vaccine encephalitis• VATS open lung biopsy – October 2009

Social History• Cardiothoracic surgeon and currently active duty colonel in the US Army• Served in field hospitals in Saudia Arabia and UAE during the first Gulf War • Served 1 month at Balad USAF Hospital in Balad, Iraq in 2005• Served 3 months at 345th Combat Support Hospital in Tikrit, Iraq in 2008-09• No history of tobacco use, alcohol use, drug use

Physical ExamVS – 36.8 135/79 85 20 95% RAHeight – 72 inchesWeight/BMI – 300lbs / 40.33Gen – Well developed, In no acute distress, obeseHEENT - No lymphadenopathy or thyromegaly notedChest/Pulmonary – Well healed VATS scar, Clear to auscultation bilaterally.CVS - Normal S1/S2 noted, No M/R/G noted, Normal rate and regular rhythm.Abd - Soft, Nontender, nondistended, No hepatosplenomegaly noted.Ext – Warm, dry, 1+ pretibial edema noted, No clubbing/cyanosis

High resolution CT scan showing mild patchy groundglass opacities within the peripheral posterior aspect of the lungs

Bronchiolitis should be on the differential diagnosis for any soldier that served in Iraq and is presenting with dyspnea on exertion. Further research is needed for the development of appropriate diagnostic and preventive measures as well as the long term outcomes associated with this newly recognized problem.

Left lung biopsy showing mild chronic inflammation of the small airways with bronchiolectasia and mild peribronchial fibrosis

Case Description Radiology

Pulmonary Function StudiesPulmonary Function Tests

Measured % PredictedFVC 3.82 (L) 82FEV1 3.15 (L) 86

FEV1/FVC 82% -TLC 5.49 (L) 79

DLCO 24.1 (mL/min/mmHg) 79

Cardiopulmonary Exercise TestingMeasured % Predicted

VO2 Max 22.8 (ml/kg/min) 78

Discussion• While it is entirely possible that this patient’s dyspnea on exertion is a result of his obesity and deconditioning, it would not explain the findings seen on his CT scan or in his tissue sectioning. Also, it is clear that inhalation of a variety of toxic substances has the potential to cause bronchiolitis and an injury pattern similar to the one exhibited by this patient.

• Given the relatively similar pattern of findings exhibited by the soldiers deployed from Fort Campbell, specifically those without sulfur dioxide exposure, it seems very likely that this particular patient has developed bronchiolitis due to inhalational exposure while serving in Iraq.

• It is not clear at this point in time what particular agent caused these findings but given the variety of exposures associated with the intense combat environment within Iraq, including its desert location, burn pits, burning human waste, weapon operation and diesel exhaust, any number of potential agents could be implicated.1

• At the same time, given the large number of troops deployed during the Iraq War, and the sparse documentation thus far of these cases, the potential definitely exists for a growing patient population with a similar presentation and more importantly, with similar duty-limiting and life-limiting capabilities.5

• It seems imperative then, that further research as well as a standardized approach to these patients should be developed, with emphasis not only on awareness, but also on diagnosis as well as the long term outcomes and implications associated with these exposures. At the same time, preventive measures should be fully explored as well, including the potential use of respirators in combat or other high risk environments.

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