History
New-onset asthma or chronic obstructive pulmonary disease (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 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. [26] Timing of potential exposures may also be important with respect to seasonal and diurnal variations in air quality. [27, 28] 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 signs and symptoms are as follows:
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Cough
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Light-headedness
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Dyspnea
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Chest tightness
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Choking
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Diaphoresis
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Loss of consciousness (at very high concentrations or in very susceptible individuals)
Coughing is the most common manifestation; however, it may not occur in all patients. Wheezing, chest pain, weakness, throat and ocular irritation, and nausea are less common 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:
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Dyspnea
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Cough
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Chest pain
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Clinical manifestations of noncardiogenic pulmonary edema
Subacute signs and symptoms
The following may develop 2-6 weeks after initial exposure:
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Bronchiolitis obliterans, manifested as fever, cough, and dyspnea
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Diffuse reticulonodular or miliary pattern on chest radiography
Chronic, persistent, or delayed manifestations
These cases may resemble asthma or COPD exacerbations. Signs and symptoms may appear days or even weeks after both short- and long-term exposures. They include the following:
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Dyspnea
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Cough
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Chest pain
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Rapid breathing
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Chest tightness
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Headache
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Fever
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Insomnia
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Wheezing
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Chills
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Light-headedness
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Myalgias
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Nausea
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Hemoptysis
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Palpitations
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Blue lips
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Weakness
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Fatigue
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:
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Tachypnea
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Wheezing
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Rales
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Rhonchi
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Decreased breath sounds
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Stridor
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Tripod breathing or use of accessory muscles
Other signs include the following:
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Tachycardia
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Irritation or erythema of mucous membranes
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Conjunctival injection
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Decreased strength
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Skin burns, in cases of liquid N 2O 4 exposure
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Cyanosis, particularly of lips or distal extremities
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Bronchiolitis obliterans following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
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Noncardiogenic pulmonary edema following exposure to nitrogen dioxide. Courtesy of Dr. Ann Leung, Department of Radiology, Stanford University Hospital.
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Nitrogen dioxide air quality from 1980 to 2012. Courtesy of the Air Quality Analysis Group, US Environmental Protection Agency (EPA).
