Epidemiology

Smoke inhalation is common among the general population. The use of potentially toxic chemicals in industry continues to rise, and accidental spills, explosions, and fires can result in complex exposures, with little known of the health consequences. The potential health effects produced by inhaled toxins in the United States may be tremendous. More than 500,000 workers risk occupational exposure to ammonia (NH₃) and other gases such as sulfur dioxide (SO₂). More than 100,000 individuals have potential exposure to hydrogen sulfide (H₂S). Tens of thousands risk smoke inhalation from household fires. The number of people environmentally exposed to potentially hazardous levels of air pollutants such as ozone can be estimated in the tens of millions. The threat of biologic and other weaponized agents increases inhalational exposure risks. Also, the World Trade Center collapse showed that firefighters and other rescue workers who respond to emergencies form an additional class of patients at risk from exposures to complex mixtures of dust, fumes, and gas.

Etiology and Risk Factors

Major risk factors for inhalational exposure and injury are related to the environment and not to the individual. Exposures occur randomly in the general environment, such as when a chemical spill occurs on a highway or railroad, carbon monoxide (CO) leaks in a home, or a person incorrectly mixes household chemicals together and releases a gas or aerosol. Smoke that comprises the pyrolysis products of synthetic materials is a common cause of injury to the respiratory tract, as well as a cause of pulmonary insufficiency and death from fires.

Occupational injuries more often occur when workers handle chemicals, work in areas that are inadequately ventilated, or enter exposed areas with improper protective equipment. Table 56-2 lists sources of occupational exposure to major chemical causes of irritant lung injury and asphyxiation.

Table 56-2 Inhalational Toxins and Source of Exposure

Factors that influence the acute effects of toxic chemicals include solubility, particle size, concentration, duration of exposure, chemical properties, and individual factors such as minute ventilation. The more water-soluble compounds dissolve in the upper respiratory tract and airways, whereas the less water-soluble agents tend to bypass the upper airway and affect peripheral airways and pulmonary parenchyma (Figure 56-1).

Figure 56-1 Distribution of gases and particulate matter in the respiratory tract influences the site of toxic injury.

Pathology

In general, the upper airway can be affected by most inhaled toxins, which result in edema of the nasal passage, posterior oropharynx, and larynx. In severe cases, mucous membrane ulceration and hemorrhage ensue. Toxins of low water solubility may reach the lung parenchyma without necessarily producing upper airway lesions. If breath holding, laryngospasm, and normal “scrubbing” activities of the nasopharynx fail to contain the exposure, lesions develop in the trachea and bronchi (e.g., paralysis of cilia, increased mucus production, goblet cell hyperplasia, injury to airway epithelium, epithelial denudation, exudation, submucosal hemorrhage, edema). Pseudomembranes may form along the trachea and bronchi, causing various degrees of bronchiolitis, bronchiolitis obliterans (Figure 56-2), and organizing pneumonia (Figure 56-3). Bronchiolitis has been associated with exposures to oxides of nitrogen—nitric oxide (NO), nitrogen dioxide (NO₂), and nitrogen peroxide (N₂O₄)—as well as sulfur dioxide, ammonia, chlorine (Cl₂), phosgene, fly ash that contains trichloroethylene (C₂HCl₃), ozone (O₃), hydrogen sulfide, hydrogen fluoride (HF), metal oxide fumes, dusts (e.g., asbestos, silica, talc, grain dust), free-base cocaine, tobacco smoke, and fire smoke.

Figure 56-2 Histologic appearance of bronchiolitis obliterans caused by inhalation of oxides of nitrogen in silo filler.

Figure 56-3 Histopathologic features of organizing pneumonia after sulfur dioxide inhalation.

Parenchymal injury is less common than airway damage. When alveolar or interstitial injury occurs, both epithelial damage and endothelial damage are observed, resulting in alveolocapillary leak and the pathologic changes of adult respiratory distress syndrome (ARDS). Diffuse alveolar damage (DAD) is a common histologic pattern in acute interstitial lung disease caused by inhaled toxins. It is characterized by widespread, diffuse edema, epithelial necrosis and cell sloughing (with exudates that fill the alveolar spaces), and formation of hyaline membranes (Figure 56-4). Later, DAD may organize, which leads to proliferation of type II pneumonocytes, resorption of the hyaline membranes and exudates, and fibroblast proliferation. Long-term survivors of such parenchymal injury may fully recover or may have various degrees of permanent interstitial fibrosis.

Figure 56-4 Diffuse alveolar damage caused by anhydrous ammonia inhalation. An agricultural worker inhaled the gas when a hose broke during the transfer of this fertilizing agent.

Pathogenesis

Asphyxiants, such as methane (CH₄) and carbon dioxide (CO₂), displace oxygen (O₂) from the air or, in the case of CO, interfere with normal oxidative metabolism and O₂ transport. Typically, the more soluble gases produce greater injury in the upper airway, whereas less soluble gases injure distal airways and parenchyma. Some of the irritant gases produce direct cellular injury because they are alkalis (e.g., ammonia) or acids (e.g., phosgene). Others, such as ozone and oxides of nitrogen, form oxygen free radicals that cause respiratory tract injury. These gases may also produce smooth muscle bronchoconstriction and stimulate afferent parasympathetic receptors, which explain some of their ability to induce airway hyperreactivity and bronchoconstriction.

Chronic lower-level exposures to various toxic gases (e.g., SO₂, Cl₂) can induce copious mucus secretion, cough, bronchoconstriction, and bronchitis as a physiologic response to the inhalational exposure. Chronic bronchitis is common among workers exposed to relatively low levels of irritants and may increase their risk for development of chronic airflow obstruction and accelerated longitudinal decline in forced expiratory volume in 1 second (FEV₁). In some cases, nonspecific airway hyperreactivity is induced by persistent, nonspecific irritant exposures.

Clinical Features and Diagnosis

Diagnosis should focus on the nature of the compound inhaled, the magnitude and duration of exposure, and the water solubility of the inhaled agent. Inhalational injury is suspected in those who have facial burns or inflamed nares. Headache and dizziness, along with chest pains and emesis, suggest systemic poisons (e.g., cyanide, H₂S). Unconscious victims found in confined spaces are assumed to have received longer inhalational exposures than conscious ones because of the unprotected airways and concentrated exposures. Evidence of hoarseness, upper airway stridor, wheezing or rales, cough, and sputum production is assessed. Chest radiographs may show pulmonary edema, atelectasis, or infiltrates (Figure 56-5), although they are often negative early after exposure. Flow-volume loops are the most sensitive noninvasive indicators of upper and lower airway obstruction. Hypoxemia in the face of a normal arterial partial pressure of oxygen (PaO₂) suggests CO toxicity. Carboxyhemoglobin levels are obtained for all fire and explosion victims. Metabolic acidosis may indicate cyanide or H₂S intoxication.

Figure 56-5 Radiographic changes produced by diffuse alveolar damage. Chest radiograph of the same patient as in Figure 56-4 shows acute, diffuse alveolar and interstitial infiltrates.

In patients who have persistent symptoms months after exposure, bronchial provocation tests with methacholine may help assess whether the patient has reactive airway dysfunction syndrome. Computed tomography (CT) may help determine if permanent fibrotic changes have developed.