Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Nitrogen Dioxide Toxicity Clinical Presentation

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

History

New-onset asthma or COPD in an otherwise previously healthy nonsmoker should immediately raise suspicion for potential nitrogen dioxide (NO2) or other toxic gaseous exposure. One should first rule out common infectious etiologies for symptoms. Recent sick contacts, flulike or viral symptoms, any history of exposure to pulmonary mycoses, and other factors should all be considered prior to a diagnosis of NO2 toxicity.

A thorough social history is then essential to identifying potential NO2 exposures. Inquire about occupation. Welders, firefighters, military and aerospace personnel, traffic personnel, individuals working with explosives, and farmers generally have higher risk of exposure than those in other occupations. Additionally, those working with poor air ventilation are at much higher risk. Inquire about living situations. Individuals living in large urban centers or near congested roadways, highways, or airports may are at increased risk of long-term exposure. Inquire about household burners, smoking history, and second-hand smoke exposure.

Attempt to establish the duration of exposure. Short-term and low-dose NO2 exposures are generally less pathogenic.[19] Timing of potential exposures may also be important with respect to seasonal and diurnal variations in air quality.[20, 21] Silo filler’s disease is prevalent primarily during harvest seasons.

In acute exposure, symptoms may range from mild cough to mucous membrane irritation to sudden fatality. Suspect methemoglobinemia in patients exposed to NO2 who exhibit cyanosis or dyspnea. The initial absence of significant symptoms does not exclude a subsequent development of serious disease. If a patient presents immediately postexposure, the full injury may not be appreciated; effects may occur up to 24 hours after the event.

Acute symptoms

Common symptoms are as follows:

  • Cough
  • Light-headedness
  • Dyspnea
  • Chest tightness
  • Choking
  • Diaphoresis
  • Loss of consciousness (at very high concentrations or in very susceptible individuals)

Coughing is the most common symptom; however, it may not occur in all patients. Wheezing, chest pain, weakness, throat and ocular irritation, and nausea are less common symptoms with pure NO2 exposure. NO2 is not as soluble as other gases (eg, chlorine); consequently, mucous membrane irritation is not common. However, NO2 may often be found in association with other harmful gases that do produce these effects, so NO2 toxicity cannot be excluded.

Following a delay of 2-48 hours, patients exposed to NO2 may develop the following signs and symptoms:

  • Dyspnea
  • Cough
  • Chest pain
  • Clinical manifestations of noncardiogenic pulmonary edema

Subacute signs and symptoms

The following may develop 2-6 weeks after initial exposure:

  • Bronchiolitis obliterans, manifested as fever, cough, and dyspnea
  • Diffuse reticulonodular or miliary pattern on chest radiography

Chronic, persistent, or delayed symptoms

These may present with symptoms similar to asthma or COPD exacerbations and may appear days or even weeks later after both short- and long-term exposures. They include the following:

  • Dyspnea
  • Cough
  • Chest pain
  • Rapid breathing
  • Chest tightness
  • Headache
  • Fever
  • Insomnia
  • Wheezing
  • Chills
  • Light-headedness
  • Myalgias
  • Nausea
  • Hemoptysis
  • Palpitations
  • Blue lips
  • Weakness
  • Fatigue
Next

Physical Examination

Initial physical findings are generally mild but, depending on the severity of exposure, may progress quickly to life-threatening respiratory distress. Findings may be difficult to distinguish from severe asthma or COPD exacerbations. Pulmonary signs are the most common manifestation of nitrogen dioxide (NO2) toxicity and include the following:

  • Tachypnea
  • Wheezing
  • Rales
  • Rhonchi
  • Decreased breath sounds
  • Stridor
  • Tripod breathing or use of accessory muscles

Other signs include the following:

  • Tachycardia
  • Irritation or erythema of mucous membranes
  • Conjunctival injection
  • Decreased strength
  • Skin burns, in cases of liquid N 2 O 4 exposure
  • Cyanosis, particularly of lips or distal extremities
Previous
 
 
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.

References
  1. [Guideline] World Health Organization. WHO Air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide. Available at http://whqlibdoc.who.int/hq/2006/WHO_SDE_PHE_OEH_06.02_eng.pdf. Accessed: November 12, 2013.

  2. Andersen ZJ, Kristiansen LC, Andersen KK, et al. Stroke and long-term exposure to outdoor air pollution from nitrogen dioxide: a cohort study. Stroke. 2012 Feb. 43(2):320-5. [Medline].

  3. Chen R, Samoli E, Wong CM, Huang W, Wang Z, Chen B, et al. Associations between short-term exposure to nitrogen dioxide and mortality in 17 Chinese cities: the China Air Pollution and Health Effects Study (CAPES). Environ Int. 2012 Sep 15. 45:32-8. [Medline].

  4. Environmental Protection Agency. Nitrogen Dioxide. Available at http://www.epa.gov/air/nitrogenoxides/health.html. Accessed: November 12, 2013.

  5. Environmental Protection Agency. An Introduction to Indoor Air Quality (IAQ) - Nitrogen Dioxide (NO2). Available at http://www.epa.gov/iaq/no2.html. Accessed: November 12, 2013.

  6. Stieb DM, Szyszkowicz M, Rowe BH, Leech JA. Air pollution and emergency department visits for cardiac and respiratory conditions: a multi-city time-series analysis. Environ Health. 2009 Jun 10. 8:25. [Medline]. [Full Text].

  7. Environmental Protection Agency. National Ambient Air Quality Standards (NAAQS). Available at http://www.epa.gov/air/criteria.html. Accessed: November 12, 2013.

  8. American Lung Association. Nitrogen Dioxide. Available at http://www.lung.org/healthy-air/outdoor/resources/nitrogen-dioxide.html. Accessed: November 12, 2013.

  9. Environmental Protection Agency. National Trends in Nitrogen Dioxide Levels. Available at http://www.epa.gov/airtrends/nitrogen.html. Accessed: November 12, 2013.

  10. Belanger K, Gent JF, Triche EW, Bracken MB, Leaderer BP. Association of indoor nitrogen dioxide exposure with respiratory symptoms in children with asthma. Am J Respir Crit Care Med. 2006 Feb 1. 173(3):297-303. [Medline]. [Full Text].

  11. Jarvis DL, Leaderer BP, Chinn S, Burney PG. Indoor nitrous acid and respiratory symptoms and lung function in adults. Thorax. 2005 Jun. 60(6):474-9. [Medline]. [Full Text].

  12. Jones GR, Proudfoot AT, Hall JI. Pulmonary effects of acute exposure to nitrous fumes. Thorax. 1973 Jan. 28(1):61-5. [Medline]. [Full Text].

  13. Lee K, Xue J, Geyh AS, Ozkaynak H, Leaderer BP, Weschler CJ, et al. Nitrous acid, nitrogen dioxide, and ozone concentrations in residential environments. Environ Health Perspect. 2002 Feb. 110(2):145-50. [Medline]. [Full Text].

  14. van Strien RT, Gent JF, Belanger K, Triche E, Bracken MB, Leaderer BP. Exposure to NO2 and nitrous acid and respiratory symptoms in the first year of life. Epidemiology. 2004 Jul. 15(4):471-8. [Medline].

  15. Silkstone RS, Mason MG, Nicholls P, Cooper CE. Nitrogen dioxide oxidizes mitochondrial cytochrome c. Free Radic Biol Med. 2012 Jan 1. 52(1):80-7. [Medline]. [Full Text].

  16. Kahan ES, Martin UJ, Spungen S, Ciccolella D, Criner GJ. Chronic cough and dyspnea in ice hockey players after an acute exposure to combustion products of a faulty ice resurfacer. Lung. 2007 Jan-Feb. 185(1):47-54. [Medline].

  17. Centers for Disease Control and Prevention. Silo-Filler's disease in rural New York. MMWR Morb Mortal Wkly Rep. 1982 Jul 23. 31(28):389-91. [Medline].

  18. Zwemer FL Jr, Pratt DS, May JJ. Silo filler's disease in New York State. Am Rev Respir Dis. 1992 Sep. 146(3):650-3. [Medline].

  19. Hesterberg TW, Bunn WB, McClellan RO, Hamade AK, Long CM, Valberg PA. Critical review of the human data on short-term nitrogen dioxide (NO2) exposures: evidence for NO2 no-effect levels. Crit Rev Toxicol. 2009. 39(9):743-81. [Medline].

  20. Kimbrough ES, Baldauf RW, Watkins N. Seasonal and diurnal analysis of NO2 concentrations from a long-duration study conducted in Las Vegas, Nevada. J Air Waste Manag Assoc. 2013 Aug. 63(8):934-42. [Medline].

  21. Baldauf R, Thoma E, Hays M, et al. Traffic and meteorological impacts on near-road air quality: summary of methods and trends from the Raleigh Near-Road Study. J Air Waste Manag Assoc. 2008 Jul. 58(7):865-78. [Medline].

  22. Ichinose F, Roberts JD Jr, Zapol WM. Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential. Circulation. 2004 Jun 29. 109(25):3106-11. [Medline].

  23. Takizawa H. Impact of air pollution on allergic diseases. Korean J Intern Med. 2011 Sep. 26(3):262-73. [Medline]. [Full Text].

  24. Romieu I, Sienra-Monge JJ, Ramírez-Aguilar M, Moreno-Macías H, Reyes-Ruiz NI, Estela del Río-Navarro B, et al. Genetic polymorphism of GSTM1 and antioxidant supplementation influence lung function in relation to ozone exposure in asthmatic children in Mexico City. Thorax. 2004 Jan. 59(1):8-10. [Medline]. [Full Text].

  25. Gilliland FD. Outdoor air pollution, genetic susceptibility, and asthma management: opportunities for intervention to reduce the burden of asthma. Pediatrics. 2009 Mar. 123 Suppl 3:S168-73. [Medline]. [Full Text].

  26. Dries DJ, Endorf FW. Inhalation injury: epidemiology, pathology, treatment strategies. Scand J Trauma Resusc Emerg Med. 2013 Apr 19. 21:31. [Medline]. [Full Text].

  27. Mushtaq N, Ezzati M, Hall L, et al. Adhesion of Streptococcus pneumoniae to human airway epithelial cells exposed to urban particulate matter. J Allergy Clin Immunol. 2011 May. 127(5):1236-42.e2. [Medline].

  28. Neupane B, Jerrett M, Burnett RT, Marrie T, Arain A, Loeb M. Long-term exposure to ambient air pollution and risk of hospitalization with community-acquired pneumonia in older adults. Am J Respir Crit Care Med. 2010 Jan 1. 181(1):47-53. [Medline].

  29. US Food and Drug Administration. FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. Available at http://www.fda.gov/Drugs/DrugSafety/ucm263190.htm. Accessed: July 27, 2011.

 
Previous
Next
 
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.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.