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Bronchiolitis Obliterans in a Survivor of a Chemical Weapons Attack
To the Editor: Bronchiolitis obliterans develops when an injury of small conducting airways leads to the proliferation of granulation tissue and obliteration of the airway lumen. The histological pattern is nonspecific and can result from multiple etiologies. The clinical presentation is divided into 5 categories: toxic fume inhalation, postinfectious, connective tissue disease–associated, localized, and idiopathic.1 Several substances have been reported to cause bronchiolitis obliterans through inhalation of toxic fumes. The distribution of these agents in the lung is determined by the size of the molecule, the duration of exposure, and the solubility of the agent.2
The inhalation of mustard gas has been reported to cause chronic bronchitis, airway hyperactivity, bronchiectasis, and pulmonary fibrosis,3-6 but there are no reports of the occurrence of bronchiolitis obliterans. We report a patient with confirmed bronchiolitis obliterans several years after likely exposure to mustard gas in Iraq.
Report of a Case
In August 2001, we evaluated a 37-year-old male Iraqi Kurd for possible lung transplantation. He reported that he had been present on March 16, 1988, when Iraqi fighter jets dropped multiple warheads on the northeastern Iraqi city of Halabja. (The Halabja attack has been extensively documented elsewhere.7-8) He and his family initially feared direct physical harm and fled to the basement of their home, but oppressive heat and poor air circulation forced them from this enclosed space. As they ran outside, the patient noted a noxious odor similar to rotten fruit. He reported that the intense smell lasted for 5 hours, during which time 15 members of the patient's family died on the street.
Six hours after his initial exposure, our patient reported experiencing eye pain, copious tearing, cough, and dyspnea. He then developed complete blindness, a condition that lasted for 20 days. The Red Crescent service of Iran transported him to the United States for ophthalmologic care and he recovered with treatment (records unavailable). His cough, dyspnea, and production of sputum progressed over the next 14 years, eventually limiting his ability to perform activities of daily living. The patient reported that his parents also complain of similar but less severe lung-related symptoms, including the daily production of purulent sputum. Neither the patient nor any members of his family have any history of tobacco use. He denied having had a history of pneumonia or significant occupational or environmental exposures before 1988.
The patient's ambulatory room air oxygen saturation was 87%. Pertinent physical findings included decreased bilateral breath sounds and an increased anteroposterior diameter. A posterior-anterior chest radiograph displayed hyperinflation and basilar bullae (Figure 1), and pulmonary function testing revealed a severe obstructive pattern with no airflow reversibility. There was no evidence of a connective tissue disorder or  1-antitrypsin deficiency on laboratory evaluation. Subsequent studies included a high-resolution computed tomography scan of his chest (Figure 2) and transbronchial lung biopsies (Figure 3), which revealed bronchiolitis obliterans.
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Figure 1. Posterior-Anterior Chest Radiograph of Patient With Bronchiolitis Obliterans
Radiograph shows hyperinflation and basilar bullae.
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Figure 2. Computed Tomography Scan of the Chest of Patient With Bronchiolitis Obliterans
Scan performed using intravenous contrast demonstrates a ground-glass, mosaic pattern with sharply demarcated borders and surrounding hypodense pulmonary parenchyma, consistent with small airway disease.
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Figure 3. Transbronchial Lung Biopsy Specimen From Patient With Bronchiolitis Obliterans
Low-power view showing 2 obliterated airways, one with chronic inflammatory infiltrate (black arrowhead) and one with fibrosis alone (white arrowhead) (Mason Trichrome stain, original magnification x25).
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Treatment included high doses of prednisone (1 mg/kg of body weight) for 6 months, followed by tapering to his current dose of 10 mg/d.9 His symptoms have substantially improved, his spirometry remains stable, and he has not yet required listing for lung transplantation.
Comment
Investigations have revealed that mustard gas and the nerve gases sarin, VX, and Tabun were used in the Halabja attack.7-8 Mustard gas is a vesicant that damages cells through alkylation of DNA and through a secondary, cytokine-mediated inflammatory response.10 This occurs at areas of contact between the gas and human tissue (ie, the eyes and respiratory tract). Eye pain, excessive lacrimation, and blindness occur within 1 to 12 hours of exposure, while edema of the tracheobronchial tree occurs between 4 and 12 hours. High concentrations induce pseudomembranous changes in the airways, and may result in airway necrosis. The clinical course is frequently complicated by secondary bacterial pneumonias. Our patient's initial ophthalmic and ongoing pulmonary symptoms are consistent with exposure to a vesicant such as mustard gas.
The majority of medical reports regarding exposure to mustard gas describe the respiratory symptoms of soldiers involved in various military conflicts, including World War I and the Iran-Iraq war.3-4,6 None of these reports, however, has described bronchiolitis obliterans resulting from exposure to mustard gas or among civilian populations specifically targeted by chemical warfare. We suggest that bronchiolitis obliterans should be considered in patients with respiratory symptoms who have a history of possible exposure to mustard gas.
Funding/Support: This work was supported by grant HL 07123 from the National Heart, Lung, and Blood Institute, National Institutes of Health.
Acknowledgment: We thank Joyce Johnson, MD, and Stephen Dummer, MD.
Jason W. W. Thomason, MD;
Todd W. Rice, MD;
Aaron P. Milstone, MD
Division of Allergy, Pulmonary, and Critical Care Medicine
Vanderbilt University School of Medicine
Nashville, Tenn
1. Epler GR, Colby TV. The spectrum of bronchiolitis obliterans. Chest. 1983;83:161-162.
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2. Greenfield RA, Brown BR, Hutchins JB. Microbiological, biological, and chemical weapons of warfare and terrorism. Am J Med Sci. 2002;323:326-340.
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3. Bijani K, Moghadamnia AA. Long-term effects of chemical weapons on respiratory tract in Iraq-Iran war victims living in Babol (North of Iran). Ecotoxicol Environ Saf. 2002;53:422-424.
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4. Emad A, Rezainan GR. The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure. Chest. 1997;112:734-738.
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5. Freitag L, Firusian N, Stamatis G. The role of bronchoscopy in pulmonary complications due to mustard gas inhalation. Chest. 1991;100:1436-1441.
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6. Gilchrist HL, Matz PB. The residual effects of warfare gases: the use of phosgene gas, with report of cases. Med Bull Vet Adm. 1933;10:1-37.
7. Rubin J. US Statement on Twelfth Anniversary of the Halabja Massacre. 2000. Available at: http://www.usis.it/file2000_03/alia/a0031711.htm. Accessibility verified July 7, 2003.
8. Gosden CM. The 1988 chemical weapons attack on Halabja, Iraq. In: Alexander Y, Hoening M, eds. Super Terrorism: Biological, Chemical, and Nuclear. Ardsley, NY: Transnational Publishers Inc; 2001.
9. Lazarus SC. Disorders of intrathoracic airways. In: Murray J, Nadel J, eds. Textbook of Respiratory Medicine. 3rd ed. St Louis, Mo: WB Saunders Co; 2000.
10. Urbanetti JS. Battlefield chemical inhalation injury. In: Loke J, ed. Pathophysiology and Treatment of Inhalation Injuries. New York, NY: Marcel Dekker; 1998:281-346. Lung Biology in Health and Disease; vol 34.
Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.
JAMA. 2003;290:598-599.
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