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Nitrogen Dioxide Toxicity Workup

  • Author: Nader Kamangar, MD, FACP, FCCP, FCCM; Chief Editor: Ryland P Byrd, Jr, MD  more...
 
Updated: Apr 28, 2014
 

Approach Considerations

No laboratory studies that are specific to the diagnosis of nitrogen dioxide (NO2)–induced illness have been reported. However, in addition to a thorough history, the following blood studies can be helpful in excluding other causes of the symptoms and should be ordered based on clinical suspicion or history:

To assess severity of disease, request the following:

  • Arterial blood gas (ABG) or venous blood gas (VBG) levels
  • Lactate level
  • Methemoglobin (MHb) level

To help rule out infectious etiologies, request the following:

  • Sputum culture and Gram stain
  • Respiratory virus polymerase chain reaction (PCR) panel
  • Urine Legionella
  • Coccidioides immunoglobulin G and immunoglobulin M
  • Histoplasma enzyme immunoassay
  • Cryptococcal antigen

Other tests to possibly consider include the following:

  • Glucose levels
  • Complete blood cell (CBC) count
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Blood Studies

Significant nitrogen dioxide (NO2) exposure usually results in hypoxemia. Initial blood gas levels establish the presence and severity of gas exchange impairment, and are extremely important in deciding whether to intubate. Some literature supports obtaining serial ABG levels during follow-up visits to ascertain whether bronchiolitis obliterans is developing. Metabolic acidosis can occur by dissolution of nitrous oxide in body fluids, resulting in tissue hypoxemia and subsequent lactic acid formation.

Measure MHb to evaluate cyanosis that does not respond to oxygen administration. MHb is an inactive oxidized form of hemoglobin that does not contribute to oxygen transport; levels greater than 10-15% result in cyanosis. MHb levels may be increased after exposure to NO2. Although levels as high as 71% have been reported following exposure to nitrous fumes, welders exposed to NO2 at 4-5 ppm (4000-5000 ppb) were noted to have MHb levels of 2-3%. Methylene blue administration can affect this test result.

On the CBC count, leukocytosis is often present in patients who have been exposed to NO2. Peripheral eosinophilia may suggest an alternative cause of pulmonary inflammation more consistent with allergic or reactive airway disease.

Measure glucose levels to assure that anxiety and restlessness is not caused by concomitant hypoglycemia. Exposure to NO2 does not cause a primary hypoglycemia.

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Chest Radiography

Findings may be normal. During acute injury, the chest radiograph shows ill-defined, alveolar opacities, which are characteristic of pulmonary edema or acute respiratory distress syndrome (ARDS). Subacute injury reveals patchy, bilateral confluent woolly air-opacities. The small opacities can be mistaken for miliary tuberculosis. See the images below.

Bronchiolitis obliterans following exposure to nitBronchiolitis obliterans following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
Noncardiogenic pulmonary edema following exposure Noncardiogenic pulmonary edema following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
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Computed Tomography

High resolution CT presentations vary from patchy subpleural ground glass opacities to a diffuse hyperlucency.

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Pulmonary Function Testing

Pulmonary function tests (PFTs) should be performed as soon as possible to establish the extent of involvement. Repeat PFTs may be performed at regular intervals to chart progress and recovery. PFTs obtained late in the clinical course when bronchiolitis obliterans has developed may demonstrate presence of obstructive disease with prolonged forced expiratory volume at 1 second (FEV1).

Proliferative bronchiolitis is characterized by granulation tissue that primarily involves the bronchiolar lumen. It rarely involves alveolar spaces. In contrast constrictive bronchiolitis involves collagenous scarring of the lumen with proliferation of underlying smooth muscle and occasional luminal erosions.

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Histologic Findings

In patients who die quickly from nitrogen dioxide (NO2) toxicity, microscopic evaluation of lung tissue shows hemorrhagic edema and extensive damage of the respiratory epithelium. Complete shedding of the epithelium may occur in the small bronchi and bronchioles.

In patients who survive, small palpable nodules and hemorrhagic areas appear after several weeks. Generalized infiltration of the alveolar walls with lymphocytes (ie, numerous macrophages in alveolar spaces) occurs. Bronchiolitis obliterans occurs in various stages of organization and is responsible for the palpable nodules.

Proliferative bronchiolitis is characterized by granulation tissue that primarily involves the bronchiolar lumen. It rarely involves alveolar spaces. In contrast, constrictive bronchiolitis involves collagenous scarring of the lumen with proliferation of underlying smooth and occasional luminal erosions.

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Contributor Information and Disclosures
Author

Nader Kamangar, MD, FACP, FCCP, FCCM Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Medicine, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: Academy of Persian Physicians, American Academy of Sleep Medicine, American Association for Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Critical Care Medicine, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors, Association of Specialty Professors, California Sleep Society, California Thoracic Society, Clerkship Directors in Internal Medicine, Society of Critical Care Medicine, Trudeau Society of Los Angeles, World Association for Bronchology and Interventional Pulmonology

Disclosure: Nothing to disclose.

Coauthor(s)

Caleb Hsieh, MD, MS Department of Internal Medicine, Olive View-UCLA Medical Center

Caleb Hsieh, MD, MS is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

Rebecca Bascom, MD, MPH Professor of Medicine, Pennsylvania State College of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Charles B Cairns, MD Professor and Chair, Department of Emergency Medicine, University of North Carolina School of Medicine; Consulting Faculty, Department of Emergency Medicine, Duke University Medical School and Duke Clinical Research Institute

Charles B Cairns, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Emergency Physicians, American Heart Association, American Thoracic Society, American Trauma Society, European Respiratory Society, New York Academy of Sciences, Sigma Xi, Society for Academic Emergency Medicine, and Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.

Lex Chen, MD Resident Physician, Department of Internal Medicine, University of California Los Angeles, Olive View Medical Center

Lex Chen, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT Associate Clinical Professor, Department of Surgery/Emergency Medicine and Toxicology, University of Texas School of Medicine at San Antonio; Medical and Managing Director, South Texas Poison Center

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Clinical Toxicologists, American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, Society for Academic Emergency Medicine, and Texas Medical Association

Disclosure: Nothing to disclose.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP Director of Medical Toxicology, Allegheny General Hospital

Disclosure: Nothing to disclose.

Suzanne M Miller, MD Clinical Instructor, Emergency Medicine, George Washington University School of Medicine and Health Sciences; Attending Physician, Department of Emergency Medicine, INOVA Fairfax Hospital; Chief Executive Officer, MDadmit

Suzanne M Miller, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Jeffrey S Peterson, MD Clinical Assistant Professor of Surgery/Emergency Medicine, Stanford University School of Medicine, Stanford University Hospital; Founder and Sports Medicine Physician, Innovative Sports Medicine

Jeffrey S Peterson, MD, is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Sports Medicine, Massachusetts Medical Society, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Mark D Rasmussen, MD Staff Physician, Department of Anesthesia, Naval Medical Center San Diego

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Gregory Tino, MD Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital

Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

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Bronchiolitis obliterans following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
Noncardiogenic pulmonary edema following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
Nitrogen dioxide air quality from 1980 to 2012. Courtesy of the US Environmental Protection Agency.
 
 
 
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