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Nitrogen Dioxide Toxicity

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

Practice Essentials

Signs and symptoms

The diagnosis of nitrogen dioxide (NO2) toxicity largely depends on the history of exposure. If possible, inquire about exposure and occupation. Welders, firefighters, military and aerospace personnel, individuals working with explosives, traffic personnel, and farmers generally have higher risk of short-term exposure than those in other occupations. Additionally, individuals living in particular urban areas or near congested highways may have increased risk of long-term low-level exposure.

NO2 is a mucous membrane irritant commonly associated with other toxic products of combustion. Symptoms most commonly range from mild cough and mucous membrane irritation to severe exacerbations of underlying pulmonary diseases like COPD or asthma and, in extreme cases, death. 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.

Common symptoms are as follows:

  • New or worsening cough and/or wheezing (most common)
  • Eye, nose or throat irritation
  • Light-headedness or headache
  • Dyspnea (shortness of breath)
  • Chest tightness
  • Choking
  • Chest pain
  • Diaphoresis (sweating)

In addition, the following signs and symptoms may appear acutely or persist for days to weeks, and may indicate severe or worsening disease:

  • Severe shortness of breath
  • Turning blue in the lips, fingers, or toes
  • Rapid breathing
  • Rapid heart rate
  • Fever
  • More frequent use of inhalers

See Clinical Presentation for more detail.

Diagnosis

No laboratory studies that are specific to the diagnosis of NO2 -induced illness have been reported. However, the following blood studies can be helpful in excluding other causes of the symptoms:

  • Arterial blood gas (ABG) levels
  • Lactate level
  • Methemoglobin (MHb) level
  • Complete blood cell count (CBC) with peripheral smear
  • Glucose levels

Other studies are as follows:

  • ECG can rule out cardiac events
  • Chest radiography findings range from normal to noncardiogenic pulmonary edema to that of soft reticulonodular infiltrates (see the image below)
    Noncardiogenic pulmonary edema following exposure Noncardiogenic pulmonary edema following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
  • Pulmonary function tests (PFTs) should be performed as soon as possible, to establish a baseline

See Workup for more detail.

Management

Treatment varies with the severity of symptoms, as follows:

  • If no initial symptoms are present, observe the patient for at least 12 hours for hypoxemia
  • Hospitalize the patient for 12-24 hours for observation or longer if gas exchange is compromised
  • Administer oxygen to hypoxemic patients
  • Consider high-dose steroids for patients with pulmonary manifestations
  • Intubation and mechanical ventilation may be necessary if gas exchange is severely impaired
  • Administer volume expanders cautiously
  • Transfer to a tertiary care center for further diagnostic evaluation and ventilator support may be necessary
  • Bronchiolitis obliterans, which may develop 2-6 weeks after NO2 exposure, may require 6-12 months of corticosteroid therapy
  • Inhaled sympathomimetics (eg, albuterol), anticholinergics (eg, ipratropium bromide), and steroids (eg, fluticasone propionate) may be indicated if the patient develops symptoms of reactive airway disease

See Treatment and Medication for more detail.

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Background

Harmful effects of nitrogen dioxide (NO2) often occur from either high-level short-term or low-level long-term exposures. In an era founded largely on the success and availability of fossil fuels, the realization of the harmful effects of fossil fuel byproducts has become an increasing public health concern. Clean air is recognized as a basic requirement for human health and well-being, alongside access to clean water and sanitation.[1] NO2 in particular is among the most commonly recognized components of air pollution. NO2 and the other pollutants it consorts with are increasingly associated with worsening lung function, increased risk of ischemic heart disease and stroke, increased rates of hospital admissions, and even increased rates of mortality.[2, 3, 4]

NO2 is a reddish-brown gas that has a sharp, harsh odor at higher concentrations, but it may be clear and odorless at lower, but still harmful, concentrations. Registry numbers for NO2 include the following:

  • American Chemical Society's Chemical Abstract Service (CAS): CAS #10102-44-0
  • United Nations/Department of Transportation: UN#1067
  • National Institute of Occupational Safety and Health (NIOSH) Registry of Toxic Effects of Chemical Substances (RTECS): QW 9800000

NO2 is one of several pollutants formed as a byproduct of burning fuel or combustion. Common sources include cars, trucks, buses, power plants, and diesel-powered heavy engines, but smaller significant sources also include kerosene burners, gas space heaters, and tobacco smoke.[5] Thus, common occupations at risk include arc welders, firefighters, military and aerospace personnel, traffic personnel, and those working with explosives.[6] In addition, individuals who spend significant amounts of time near major roadways or in traffic may be at considerably increased risk of long-term exposure.[4]

Finally, NO2 can also form from noncombustion sources. When farm silos are filled with fresh organic material (eg, corn, other grains), anaerobic fermentation of the crops results in NO2 production. Within a few hours, high levels of NO2 develop on top of the silage. This may also occur with silage bags, but this risk is lower given natural outdoor ventilation. In either case, farmers who enter silos, work with silage bags, or remain near open silo hatches during the first 10 days after filling may experience NO2 toxicity in a phenomenon known as silo filler’s disease.

NO2 is poorly soluble in water. As a result, when inhaled, it easily bypasses the moist oral mucosa and upper airways and penetrates deep into the lower respiratory tract. Toxicity depends largely on the concentration and duration of exposure, as well as an individual’s baseline pulmonary function. Elderly individuals or individuals with COPD or asthma are at much higher risk of adverse events, are more susceptible to developing infections, and may experience more severe symptoms than healthy individuals with normal pulmonary function.

Currently, the WHO recommends limiting exposures to less than 40 µg/mL (approximately 20 parts per billion [ppb]) annual average for long-term exposures and less than 200 µg/mL (approximately 100 ppb) per hour for short-term exposure. These values are based on using NO2 as a general marker for the complex mixture of pollutants generated by combustion. The recommended values were also based on values shown to have direct effects on the pulmonary function of asthmatic people.[1]

In the United States, current Environmental Protection Agency (EPA) standards are set at less than 100 ppb for 1-hour exposures and less than 53 ppb annual average for long-term exposure.[7] States such as California may have more stringent state regulations. Specific regions, including the Northeast corridor, Chicago, and Los Angeles have historically high levels of NO2.[8] See the EPA’s National Trends in Nitrogen Dioxide levels for specific NO2 level trends in a particular national region.[9] Also see the graph below.

Nitrogen dioxide air quality from 1980 to 2012. CoNitrogen dioxide air quality from 1980 to 2012. Courtesy of the US Environmental Protection Agency.

Some studies suggest that chronic exposure to NO2 may predispose individuals to the development of chronic lung diseases, including infection and COPD, and particularly asthma in children. In a study of 728 children with active asthma, children in households with gas stoves (which increase the levels of NO2) had an increased likelihood of wheezing, shortness of breath, and chest tightness.[10]

Recent literature on NO2 focuses on its association with nitrous acid (HONO), a molecule that can be formed as a primary product of gas combustion or by the reaction of NO2 with surface water.[11, 12, 13, 14] Although early data are inconclusive, some studies suggest that HONO may contribute to the adverse health outcomes previously attributed to NO2.

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Pathophysiology

In the lung, nitrogen dioxide (NO2) hydrolyzes to nitrous (HNO2) and nitric (HNO3) acid, which can then cause chemical pneumonitis and pulmonary edema. Because NO2 is poorly water soluble, it hydrolyzes more slowly than other water-soluble gases, resulting in deep lung injury in the bronchioles and alveoli. Type I pneumocytes and ciliated airway cells are primarily affected, but damage also occurs from free radical generation, which results in protein oxidation, lipid peroxidation, and cell membrane damage. A proposed pathway involves oxidation of mitochondrial cytochrome c,[15] which can result in electron transport chain decoupling and cellular apoptosis.

The chemical irritation of the alveoli and bronchioles results in rapid destruction of the epithelial cells and breakdown of the pulmonary capillary bed. The subsequent release of fluid results in pulmonary edema.

Nitrogen oxides can alter immune function and macrophage activity, leading to an impaired resistance to infection. Viral illnesses such as the flu are commonly associated infections. Significant exposure can also result in methemoglobinemia. NO2 binds to hemoglobin with great affinity, forming nitrosyl hemoglobin, which is readily oxidized to methemoglobin. Methemoglobin results in a leftward shift of the oxygen disassociation curve, which impairs the oxygen delivery and compounds the already present hypoxia.

In untreated cases, fibrous granulation tissue may develop within small airways and alveolar ducts resulting in bronchiolitis obliterans. As its name suggests, bronchiolitis obliterans refers to an inflammatory process that results in the progressive partial or complete obliteration of the small airways. This results in obstructive lung disease. (Please see Medscape article Constrictive Bronchiolitis Obliterans: The Fibrotic Airway Disorder.)

Briefly, bronchiolitis obliterans is classified in two subtypes: proliferative and constrictive. Proliferative bronchiolitis is more common and is characterized by the development of steroid-reversible intraluminal polyps that obstruct the small airways. By contrast, constrictive bronchiolitis is a more diffuse and chronic process characterized by concentric thickening and destruction of bronchioli. While fumes containing sulfur or ammonia have been associated with constrictive bronchiolitis, proliferative bronchiolitis is more common with nitrogen dioxide toxicity.

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Etiology

Occupational risk for nitrogen dioxide (NO2) exposure is high for the following workers:

  • Farmers, particularly those who work near silos
  • Firefighters
  • Arc welders
  • Military personnel, particularly those working with explosives or in regions with poor air-quality control
  • Aerospace workers (missile fuel)
  • Traffic officers, particularly those standing at high-volume intersections
  • Miners

In addition, workers in any occupation that involves the production, transportation, or use of nitric acid are at risk. Gas- and kerosene-fired household appliances and motor vehicle exhaust all pose significant risk of exposure. For example, there are multiple reports of nitrogen dioxide exposure occurring in ice skating rinks secondary to poor ventilation and exhaust from ice resurfacing machines[16] and exposures in mines where poor ventilation results in exposure to fumes from diesel engine equipment or explosives.

Silo filler’s disease

Silos filled with freshly cut corn, oats, grass, alfalfa, or other plant material generates oxides of nitrogen within hours. Maximum concentrations of NO2 are reached within 1-2 days, and then the levels begin to fall after 10-14 days. In well-sealed silos, NO2 can be present for weeks. Silage that is heavily fertilized, has experienced drought, or is derived from immature plants produces much higher concentrations of nitrogen oxides within the silo. The same phenomenon occurs with silage bags, but because of better natural ventilation, the hazard is lower.

During storage, NO2, which is 1.5 times heavier than air, can remain in deep depressions of the silage material. Exposure can develop while attempting to level the silage without proper ventilation or breathing apparatus. One documented case occurred in an individual who traversed the ladder at the opening of a silo. The heavier-than-air NO2 flowed down the side of the silo, exposing the worker to toxic levels of gas.

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Epidemiology

In the United States, manufactured sources of nitrogen oxides primarily from burned fuels exceed 19.4 million metric tons. The US Environmental Protection Agency (EPA) has regulations for monitoring nitrogen dioxide (NO2) concentrations and has historically found outdoor ambient air concentrations highest in large urban regions such as the New York metropolitan area, Chicago, and Los Angeles.[8]

In the 2006 World Health Organization (WHO) air quality global update, it was estimated that more than 2 million premature deaths occur each year secondary to the effects of both indoor and outdoor air pollution. While more than half of this disease burden was in developing countries, the effect in developed countries in not negligible.[1] In the United States, the EPA estimates that 16% of US housing units are located within 100 yards of a major highway, railroad, or airport. This translates to roughly 48 million people at increased risk of exposure. In addition, this population likely includes an increased proportion of lower-income individuals and minorities.[4]

Individuals at increased risk of adverse effects include those with underlying asthma or COPD, those with other pulmonary diseases with poor pulmonary function (eg, interstitial lung disease, pulmonary fibrosis, pulmonary hypertension), and those with existing cardiovascular disease and low oxygen reserve. Elderly persons and children are also at increased risk of respiratory infections or asthma exacerbations, respectively.

Time-series studies on ozone (formed by the oxidation of NO2 in ambient air) reported by the WHO suggested a 1-2% increase in attributable daily deaths when ozone concentrations exceeded 100 µg/mL (approximately 47.3 ppb). Levels above 160 µg/mL (approximately 75.7 ppb) were associated with an estimated 3-5% increase in daily mortality, even in purportedly healthy individuals. Levels above 240 µg/mL (approximately 114 ppb) were associated with a 5-9% increase. All numbers of daily mortality are relative to background levels of ozone at 70 µg/mL (33.1 ppb).

Silo filler's disease is prevalent during the harvest months of September and October. An estimated annual incidence of 5 cases per 100,000 silo-associated farm workers per year was reported in New York.[17, 18] Silo filler's disease is likely significantly underreported.

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Prognosis

Overall, the long-term prognosis is good for patients who survive the initial exposure to nitrogen dioxide (NO2). Some cases of NO2 toxicity resolve with no persistent or delayed symptoms. The long-term prognosis for an individual patient can be determined by conducting follow-up pulmonary function tests.

In patients with lung damage from NO2, improvement in pulmonary function may take weeks or months. Permanent mild dysfunction, likely due to bronchiolitis obliterans, may occur. This manifests as the following:

  • Mild hyperinflation
  • Abnormal flow at 50% or 75% of vital capacity (Vmax50, Vmax75)
  • Reduction in forced expiratory flow from 25-75% of vital capacity (FEF25-75)
  • Increased respiratory resistance
  • Airway obstruction

The lungs clear quickly with steroid treatment, and the chest radiograph may reveal no evidence of residual lung damage. Deconditioning can be treated with a pulmonary rehabilitation program.

Complications

Complications include secondary infection and bronchiolitis obliterans. Infection (eg, pneumonia) is possible because of the mucosal injury caused by pulmonary edema and the inhibition of immune function by NO2. Bronchiolitis obliterans consists of fibrous granulation tissue that develops within small airways and alveolar ducts. It occurs weeks or months after the initial incident.

Mortality/morbidity

NO2 poisoning may result in mortality or short-term and long-term morbidity. Manifestations of NO2 toxicity are related to the concentration inhaled, duration of exposure, and time since exposure.

Illness from acute exposure is usually mild and self-limiting; however, some exposure results in pulmonary edema, bronchiolitis obliterans, or rapid asphyxiation. In one study, approximately one third of people with severe exposures died. Death can result from bronchiolar spasm, laryngeal spasm, reflex respiratory arrest, or asphyxia. If sufficiently high, NO2 can displace oxygen and cause fatal asphyxiation. High concentrations can render a person helpless within 2-3 minutes.

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Patient Education

In general, patients should be taught to recognize the signs and symptoms of worsening pulmonary or cardiovascular function.

Educate farm workers at risk for exposure and development of silo filler's disease. Offer the following preventive advice:

  • Stay out of the silos during the 2-week danger period after the initial filling
  • Close all doors before putting in the silage
  • Go up the outside ladder to the level of silage
  • If the silo is not completely full, remove the doors that lead down to the silage
  • Enter the silo only with a complete oxygen support system (ie, air supply, self-contained breathing apparatus)
  • Ventilate the silo by opening the cover flaps and running the silo blower for 24-48 hours before entering
  • Never enter the silo alone or without a lifeline for rescue during the danger period.
  • If it is necessary to enter a silo during filling, enter immediately after the last load

Advise patients who have had a significant exposure to nitrogen dioxide (NO2) to avoid other pulmonary toxins. They should wear appropriate personal protective equipment in the workplace.

Advise patients that delayed symptoms, including life-threatening pulmonary edema and dyspnea caused by bronchiolitis obliterans, may result. Therefore, patients should be followed for a minimum of 2-3 months after exposure to monitor possible development of bronchiolitis obliterans.

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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.

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.

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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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