682

A variety of chemicals, when liberated into the atmosphere as gases, fumes, or mist, can cause irritant lung injury or asphyxi­ation. As summarized in Table 56-1, any level of the respiratory tract can be the target for toxins, which produce a wide range of disorders, from tracheitis and bronchitis to pulmonary edema.

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 mono x­ide (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.

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 water­soluble compounds dissolve in the

upper respiratory tract and airways, whereas the less water­soluble agents tend to bypass the upper airway and affect peripheral airways and pulmonary parenchyma (Figure 56-1).

PathologyIn 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), free­base cocaine, tobacco smoke, and fire smoke.

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. Long­term survivors of such parenchymal injury may fully recover or may have various degrees of permanent interstitial fibrosis.

PathogenesisAsphyxiants, 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

Chapter 56

Toxic Inhalational Lung InjuryLee S. Newman l Kathryn G. Bird

Section 8PARENCHYMAL LUNG DISEASES