Environmental Lung Disease: Introduction

Environmental Lung Disease: Introduction

This chapter provides perspectives on ways to assess pulmonary diseases for which environmental or occupational causes are suspected. This assessment is important because removal of the patient from harmful exposure is often the only intervention that might prevent further significant deterioration or lead to improvement in a patient's condition. Furthermore, the identification of an environment-associated disease in a single patient may lead to primary preventive strategies affecting other similarly exposed people who have not yet developed disease.

The exact magnitude of the problem is unknown, but there is no question that large numbers of individuals are at risk for developing serious respiratory disease as a result of occupational or environmental exposures. For example, for the populations over age 15, 15–20% of the burden of asthma and chronic obstructive pulmonary disease (COPD) has been estimated to be due to occupational factors.

History and Physical Examination

The patient's history is of paramount importance in assessing any potential occupational or environmental exposure. Inquiry into specific work practices should include questions about specific contaminants involved, the availability and use of personal respiratory protection devices, the size and ventilation of workspaces, and whether co-workers have similar complaints. The temporal association of exposure at work and symptoms may provide clues to occupation-related disease. In addition, the patient must be questioned about alternative sources for exposure to potentially toxic agents, including hobbies, home characteristics, exposure to secondhand smoke, and proximity to traffic or industrial facilities. Short-term and long-term exposures to potential toxic agents in the distant past must also be considered.

Many employees are aware of the potential hazards in their workplaces, and many states require that employees be informed about potentially hazardous exposures. These requirements include the provision of specific information about potential hazardous agents in products being used (Material Safety Data Sheets) and training in personal protective equipment and environmental control procedures. Reminders posted in the workplace may warn workers about hazardous substances. Protective clothing, lockers, and shower facilities may be considered necessary parts of the job. However, the introduction of new processes and/or new chemical compounds may change exposure significantly, and often only the employee on the production line is aware of the change. For the physician who regularly sees patients from a particular industry, a visit to the work site can be very instructive. Alternatively, physicians can request inspections by appropriate federal and/or state authorities.

The physical examination of patients with environment-related lung diseases may help to determine the nature and severity of the pulmonary condition. Unfortunately, these findings do not typically point to the specific causative agent, and other types of information must be used to arrive at an etiologic diagnosis.

Pulmonary Function Tests and Chest Imaging

Many mineral dusts produce characteristic alterations in the mechanics of breathing and lung volumes that clearly indicate a restrictive pattern (Chap. 246). Similarly, exposures to a number of organic dusts or chemical agents may result in occupational asthma or COPD. Measurement of change in forced expiratory volume (FEV1) before and after a working shift can be used to detect an acute bronchoconstrictive or inflammatory response. For example, an acute decrement of FEV1 over the first work shift of the week is a characteristic feature of cotton textile workers with byssinosis (an obstructive airway disorder with features of both asthma and chronic bronchitis).

The chest radiograph is useful in detecting and monitoring the pulmonary response to mineral dusts, certain metals, and organic dusts capable of inducing hypersensitivity pneumonitis. The International Labour Organisation (ILO) International Classification of Radiographs of Pneumoconioses classifies chest radiographs according to the nature and size of opacities seen and the extent of involvement of the parenchyma. In general, small rounded opacities are seen in silicosis or coal worker's pneumoconiosis and small, linear opacities are seen in asbestosis. The profusion of such opacities is rated using a 12-point scheme. Although useful for epidemiologic studies and screening large numbers of workers, the ILO system can be problematic when applied to an individual worker's chest radiograph. With dusts causing rounded opacities, the degree of involvement on the chest radiograph may be extensive, while pulmonary function may be only minimally impaired. In contrast, in pneumoconiosis causing linear, irregular opacities like those seen in asbestosis, the radiograph may lead to underestimation of the severity of the impairment until relatively late in the disease. For the individual patient with a history of exposure, conventional CT and high-resolution CT (HRCT) have improved the sensitivity of identifying diffuse parenchymal abnormalities of the lung as well as pleural thickening characteristic of asbestos exposure.

Other procedures that may be of use in identifying the role of environment exposures in causing lung disease include evaluation of heavy metal concentrations in urine (cadmium in battery plant workers); skin prick testing or specific IgE antibody titers for evidence of immediate hypersensitivity to agents capable of inducing occupational asthma (flour antigens in bakery workers); specific IgG precipitating antibody titers for agents capable of causing hypersensitivity pneumonitis (pigeon antigens in bird handlers); or assays for specific cell-mediated immune responses (beryllium lymphocyte proliferation testing in nuclear workers or tuberculin skin testing in health care workers). Sometimes, a bronchoscopy to obtain bronchoalveolar lavage fluid and transbronchial biopsy of lung tissue may be required for histologic diagnosis (chronic beryllium disease). Rarely, video-assisted thoracoscopic surgery to obtain a larger sample of lung tissue may be required to determine the specific diagnosis of environment-induced lung disease (hypersensitivity pneumonitis or giant cell interstitial pneumonitis due to cobalt exposure).

Measurement of Exposure

If reliable environmental sampling data are available, this information should be used in assessing a patient's exposure. Since many of the chronic diseases result from exposure over many years, current environmental measurements should be combined with work histories to arrive at estimates of past exposure.

In situations where individual exposure to specific agents—either in a work setting or via ambient air pollutants—has been determined, the chemical and physical characteristics of these agents affect both inhaled dose and site of deposition in the respiratory tract. Water-soluble gases such as ammonia or sulfur dioxide are absorbed in the lining fluid of the upper and proximal airways and thus tend to produce irritative and bronchoconstrictive responses. In contrast, nitrogen dioxide and phosgene, which are less soluble, may penetrate to the bronchioles and alveoli in sufficient quantities to produce acute chemical pneumonitis that can be life-threatening (acute respiratory distress syndrome with noncardiogenic pulmonary edema).

Particle size of air contaminants must also be considered. Particles >10–15 m in diameter, because of their settling velocities in air, do not penetrate beyond the upper airways. Particles <10 m in size are deposited below the larynx and are primarily created by the burning of fossil fuels or high-temperature industrial processes resulting in condensation products from gases, fumes, or vapors. These particles are divided into three size fractions on the basis of their size characteristics and sources. Particles of ~2.5–10 m (coarse-mode fraction) contain crustal elements, such as silica, aluminum, and iron. These particles mostly deposit relatively high in the tracheobronchial tree. Although the total mass of an ambient sample is dominated by these larger respirable particles, the number of particles, and therefore the surface area on which potential toxic agents can deposit and be carried to the lower airways, is dominated by particles <2.5 m (fine-mode fraction). The smallest particles, those <0.1 m in size, represent the ultrafine fraction and make up the largest number of particles, which tend to remain in the airstream and deposit in the lung only on a random basis as they come into contact with the alveolar walls. Besides the size characteristics of particles and the solubility of gases, the actual chemical composition, mechanical properties, and immunogenicity or infectivity of inhaled material determine in large part the nature of the diseases found among exposed persons.

Categories

Table 250-1 provides broad categories of exposure in the workplace and diseases associated with chronic exposure in these industries.

Table 250-1 Categories of Occupational Exposure and Associated Respiratory Conditions



Occupational Exposures Nature of Respiratory Responses Comment
Inorganic Dusts

Asbestos: mining, processing, construction, ship repair Fibrosis (asbestosis), pleural disease, cancer, mesothelioma Virtually all new mining and construction with asbestos done in developing countries
Silica: mining, stone cutting, sandblasting, quarrying Fibrosis (silicosis), PMF, cancer, silicotuberculosis, COPD Improved protection in United States, persistent risk in developing countries
Coal dust: mining Fibrosis (coal workers' pneumoconiosis), PMF, COPD Risk dropping in United States, increasing where new mines open
Beryllium: processing alloys for high-tech industries Acute pneumonitis, chronic granulomatous disease, lung cancer (highly suspect) Risk in high-tech industries persists
Other metals: aluminum, chromium, cobalt, nickel, titanium, tungsten carbide, or "hard metal" (contains cobalt) Wide variety of conditions from acute pneumonitis to lung cancer and asthma New diseases appear with new process development
Organic Dusts

Cotton dust: milling, processing Byssinosis (an asthma-like syndrome), chronic bronchitis, COPD Increasing risk in developing countries with drop in United States as jobs shift overseas
Grain dust: elevator agents, dock workers, milling, bakers Asthma, chronic bronchitis, COPD Risk shifting more to migrant labor pool
Other agricultural dusts: fungal spores, vegetable products, insect fragments, animal dander, bird and rodent feces, endotoxins, microorganisms, pollens Hypersensitivity pneumonitis (farmers' lung), asthma, chronic bronchitis Important in migrant labor pool but also resulting from in-home exposures
Toxic chemicals: wide variety of industries, see Table 250-2 Chronic bronchitis, COPD, hypersensitivity pneumonitis, pneumoconiosis, and cancer Reduced risk with recognized hazards; increasing risk for developing countries where controlled labor practices are less stringent
Other respiratory environmental agents (proven or highly suspect): uranium and radon daughters, environmental tobacco smoke, polycyclic hydrocarbons, biomass fuels, diesel exhaust, welding fumes, woods or wood finishing products Estimates vary from ~3 to 10% of all lung cancers; in addition chronic bronchitis, COPD, and fibrosis In-home exposures important, in developing countries disease rates as high or higher in females compared to males




Asbestos-Related Diseases

Asbestos is a generic term for several different mineral silicates, including chrysolite, amosite, anthophyllite, and crocidolite. In addition to workers involved in the production of asbestos products (mining, milling, and manufacturing), many workers in the ship-building and construction trades, including pipe fitters and boilermakers, were occupationally exposed because asbestos was widely used for its thermal and electrical insulation properties. Asbestos also was used in the manufacture of fire-smothering blankets and safety garments, as filler for plastic materials, in cement and floor tiles, and in friction materials, such as brake and clutch linings.

Exposure to asbestos is not limited to persons who directly handle the material. Cases of asbestos-related diseases have been encountered in individuals with only bystander exposure, such as the painter or electrician who worked alongside the insulation worker in a shipyard. Community exposure resulted from the use of asbestos-containing mine or mill tailings as landfill, road surface, and playground material. Finally, exposure can also occur from the disturbance of naturally occurring asbestos (e.g., from increasing residential development in the foothills of the Sierra Mountains in California).

Asbestos was first used extensively in the 1930s. Starting in 1975 it was mostly replaced with synthetic mineral fibers, such as fiberglass or slag wool, but it continues to be used increasingly in the developing world. Despite current regulations mandating adequate training for any worker potentially exposed to asbestos, exposure continues among inadequately trained and protected demolition workers. The major health effects from exposure to asbestos are pleural and pulmonary fibrosis and cancers of the respiratory tract, the pleura, and (in rare cases) the peritoneum.

Asbestosis is a diffuse interstitial fibrosing disease of the lung that is directly related to the intensity and duration of exposure. The disease resembles other forms of diffuse interstitial fibrosis (Chap. 255). Usually, moderate to severe exposure has taken place for at least 10 years before the disease becomes manifest and may occur following exposure to any of the asbestiform fiber types.

Physiologic studies reveal a restrictive pattern with a decrease in both lung volumes and diffusing capacity. There may also be evidence of mild airflow obstruction (due to peribronchiolar fibrosis).

The fibrotic lesions are the end result of oxidative injury due to the generation of reactive oxygen species by the transition metals on the surface of the fibers as well as from cells engaged in phagocytosis.

Diagnosis

The chest radiograph can be used to detect a number of manifestations of asbestos exposure. Past exposure is specifically indicated by pleural plaques, which are characterized by either thickening or calcification along the parietal pleura, particularly along the lower lung fields, the diaphragm, and the cardiac border. Without additional manifestations, pleural plaques imply only exposure, not pulmonary impairment. Benign pleural effusions may also occur. The fluid is typically a serous or bloody exudate. The effusion may be slowly progressive or may resolve spontaneously. Irregular or linear opacities, usually first noted in the lower lung fields and spreading into the middle and upper lung fields, occur as the disease progresses. An indistinct heart border or a "ground glass" appearance in the lung fields is seen in some cases. In cases in which the x-ray changes are less obvious, HRCT may show distinct changes of subpleural curvilinear lines 5–10 mm in length that appear to be parallel to the pleural surface (Fig. 250-1).

Figure 250-1





Asbestosis: A. Frontal chest radiograph shows bilateral calcified pleural plaques consistent with asbestos-related pleural disease. Poorly defined linear and reticular abnormalities are seen in the lower lobes bilaterally. B. Axial high-resolution CT of the thorax obtained through the lung bases shows bilateral, subpleural reticulation (black arrows), representing fibrotic lung disease due to asbestosis. Subpleural lines are also present (arrowheads), characteristic of, though not specific for, asbestosis. Calcified pleural plaques representing asbestos-related pleural disease (white arrows) are also evident.



No specific therapy is available for the management of patients with asbestosis. The supportive care is the same as that given to any patient with diffuse interstitial fibrosis from any cause. In general, newly diagnosed cases will have resulted from exposure levels that were present many years before and, in spite of the patients' having left the industry, are attributable to that former exposure. Since the patient may be eligible for compensation within a specific time frame after the diagnosis of an asbestos-related disease is made, the physician making the diagnosis should be certain to inform the patient promptly. On occasion, the physician may have reason to suspect ongoing exposure from a patient's current job description. Such a patient needs to wear appropriate respiratory protective gear according to federal regulation. Casual, nonoccupational exposure to undisturbed sources of asbestos-containing materials—e.g., in walls of schools or other buildings—represents virtually no hazard of asbestosis.

Lung cancer (Chap. 85) is the most frequent cancer associated with asbestos exposure. The excess frequency of lung cancer (all histologic types) in asbestos workers is associated with a minimum latency of 15–19 years between first exposure and development of the disease. Persons with more exposure are at greater risk of disease. In addition, there is a significant multiplicative effect of smoking and asbestos exposure than would be expected from the additive effect of each factor. The use of HRCT in such at-risk individuals to detect lung cancer at an earlier stage is currently under investigation.

Mesotheliomas (Chap. 257), both pleural and peritoneal, are also associated with asbestos exposure. In contrast to lung cancers, these tumors do not appear to be associated with smoking. Relatively short-term asbestos exposures of 1–2 years or less, occurring up to 40 years in the past, have been associated with the development of mesotheliomas (an observation that emphasizes the importance of obtaining a complete environmental exposure history). While the risk of mesothelioma is much less than for lung cancer among asbestos-exposed workers, over 2,000 cases were reported in the U.S. per year at the start of the 21st century.

Although ~50% of mesotheliomas metastasize, the tumor generally is locally invasive, and death usually results from local extension. Most patients present with effusions that may obscure the underlying pleural tumor. In contrast to the findings in effusion due to other causes, because of the restriction placed on the chest wall, no shift of mediastinal structures toward the opposite side of the chest will be seen. The major diagnostic problem is differentiation from peripherally spreading pulmonary adenocarcinoma or from adenocarcinoma metastasized to pleura from an extrathoracic primary site. Although cytologic examination of pleural fluid may suggest the diagnosis, biopsy of pleural tissue, generally with video-assisted thoracic surgery, and special immunohistochemical staining is usually required. There is no effective therapy.

Since epidemiologic studies have shown that >80% of mesotheliomas may be associated with asbestos exposure, documented mesothelioma in a patient with occupational or environmental exposure to asbestos may be compensable.

Silicosis

In spite of the technical adequacy of existing protective equipment, free silica (SiO2), or crystalline quartz, is still a major occupational hazard. The major occupational exposures include: mining; stonecutting; employment in abrasive industries, such as stone, clay, glass, and cement manufacturing; foundry work; packing of silica flour; and quarrying, particularly of granite. Most often, pulmonary fibrosis due to silica exposure (silicosis) occurs in a dose-response fashion after many years of exposure.

Workers heavily exposed through sandblasting in confined spaces, tunneling through rock with high quartz content (15–25%), or the manufacture of abrasive soaps may develop acute silicosis with as little as 10 months' exposure. The clinical and pathological features of acute silicosis are similar to those of pulmonary alveolar proteinosis (Chap. 255). The chest radiograph may show profuse miliary infiltration or consolidation and there is a characteristic HRCT pattern known as "crazy paving" (Fig. 250-2). The disease may be quite severe and progressive, despite the discontinuation of exposure. Whole-lung lavage may provide symptomatic relief and slow progression.

Figure 250-2




Acute silicosis. The high-resolution CT scan shows multiple small nodules consistent with silicosis but also diffuse ground-glass densities with thickened intralobular and interlobular septa, producing polygonal shapes. This has been referred to as "crazy paving."




With long-term, less intense exposure, small rounded opacities in the upper lobes may appear on the chest radiograph after 15–20 years of exposure (simple silicosis). Calcification of hilar nodes may occur in as many as 20% of cases and produces a characteristic "eggshell" pattern. Silicotic nodules may be identified more readily by HCRT (Fig. 250-3). The nodular fibrosis may be progressive in the absence of further exposure, with coalescence and formation of nonsegmental conglomerates of irregular masses >1 cm in diameter (complicated silicosis). These masses can become quite large and when this occurs the term progressive massive fibrosis (PMF) is applied. Significant functional impairment with both restrictive and obstructive components may be associated with this form of silicosis.

Figure 250-3





Chronic silicosis. A. Frontal chest radiograph in a patient with silicosis shows variably sized, poorly defined nodules (arrows) predominating in the upper lobes, B. Axial thoracic CT image through the lung apices shows numerous small nodules, more pronounced in the right upper lobe. A number of the nodules are subpleural in location (arrows).



Because silica is cytotoxic to alveolar macrophages, patients with silicosis are at greater risk of acquiring lung infections that involve these cells as a primary defense (Mycobacterium tuberculosis , atypical mycobacteria and fungi). Because of the increased risk of active tuberculosis, the recommended treatment of latent tuberculosis in these patients is longer. Another potential clinical complication of silicosis is autoimmune connective tissue disorders such as rheumatoid arthritis or scleroderma. In addition, there are sufficient epidemiologic data that the International Agency for Research on Cancer lists silica as a probable lung carcinogen.

Other less hazardous silicates include Fuller's earth, kaolin, mica, diatomaceous earths, silica gel, soapstone, carbonate dusts, and cement dusts. The production of fibrosis in workers exposed to these agents is believed to be related either to the free silica content of these dusts or, for substances that contain no free silica, to the potentially large dust loads to which these workers may be exposed.

Other silicates, including talc dusts, may be contaminated with asbestos and/or free silica. Fibrosis and/or pleural or lung cancer have been associated with chronic exposure to commercial talc.

Coal Worker's Pneumoconiosis (CWP)

Occupational exposure to coal dust can lead to CWP, which has enormous social, economic, and medical significance in every nation in which coal mining is an important industry. Simple radiographically identified CWP is seen in ~10% of all coal miners and in as many as 50% of anthracite miners with more than 20 years' work on the coal face. The prevalence of disease is lower in workers in bituminous coal mines. Since much western U.S. coal is bituminous, CWP is less prevalent in that region.

With prolonged exposure to coal dust (i.e., 15–20 years), small, rounded opacities similar to those of silicosis may develop. As in silicosis, the presence of these nodules (simple CWP) is not usually associated with pulmonary impairment. Much of the symptomatology associated with simple CWP appears to be due to the effects of coal dust on the development of chronic bronchitis and COPD (Chap. 254). The effects of coal dust are additive to those of cigarette smoking.

Complicated CWP is manifested by the appearance on the chest radiograph of nodules ranging from 1 cm in diameter to the size of an entire lobe, generally confined to the upper half of the lungs. As in silicosis, this condition can progress to PMF which is accompanied by severe lung function deficits and associated with premature mortality.

Caplan's syndrome (Chap. 314), first described in coal miners but subsequently found in patients with silicosis, includes seropositive rheumatoid arthritis with characteristic pneumoconiotic nodules. Silica has immunoadjuvant properties and is often present in anthracitic coal dust.

Chronic Beryllium Disease

Beryllium is a light-weight metal with tensile strength, has good electrical conductivity, and is valuable in the control of nuclear reactions through its ability to quench neutrons. Although beryllium may produce an acute pneumonitis, it is far more commonly associated with a chronic granulomatous inflammatory disease that is similar to sarcoidosis (Chap. 322). Unless one inquires specifically about occupational exposures to beryllium in the manufacture of alloys, ceramics, or high-technology electronics in a patient with sarcoidosis, one may miss entirely the etiologic relationship to the occupational exposure. What distinguishes chronic beryllium disease (CBD) from sarcoidosis is evidence of a specific cell-mediated immune response (i.e., delayed hypersensitivity) to beryllium.

The test that usually provides this evidence is the beryllium lymphocyte proliferation test (BeLPT). The BeLPT uses the in vitro proliferation of lymphocytes from blood or bronchoalveolar lavage in the presence of beryllium salts as compared to that of unstimulated cells. Proliferation is usually measured by lymphocyte uptake of radiolabeled thymidine.

Chest imaging findings are similar to those of sarcoidosis (nodules along septal lines) except that hilar adenopathy is somewhat less common. Like sarcoidosis, pulmonary function test results may show restrictive and/or obstructive ventilatory deficits and decreased diffusing capacity. With early disease, both chest imaging studies and pulmonary function tests may be normal. Fiberoptic bronchoscopy with transbronchial lung biopsy is usually required to make the diagnosis of CBD. In a beryllium-sensitized individual, the presence of noncaseating granulomas or monocytic infiltration in lung tissue establishes the diagnosis. Accumulation of beryllium-specific CD4+ T cells occurs in the granulomatous inflammation seen on lung biopsy.

Chronic beryllium disease is one of the best studied examples of gene-environment interaction. Susceptibility to CBD is highly associated with HLA-DP alleles possessing a glutamic acid in position 69 of the chain. In addition, there is also evidence that a polymorphism in position 308 of the promoter region of tumor necrosis factor is involved in mediating the severity of the inflammatory response in patients with CBD.

Other metals, including aluminum and titanium dioxide, have been rarely associated with a sarcoid-like reaction in lung tissue. Exposure to dust containing tungsten carbide, also known as "hard metal," may produce giant cell interstitial pneumonitis. Cobalt is a constituent of tungsten carbide and is the likely etiologic agent of both the interstitial pneumonitis and the occupational asthma that may occur. The most common exposures to tungsten carbide occur in tool and dye, saw blade, and drill bit manufacture. Diamond polishing may also involve exposure to cobalt dust. The same Glu69 polymorphism of the HLA-DP chain that confers increased risk of CBD also appears to increase risk of cobalt-induced giant cell interstitial pneumonitis.

In patients with interstitial lung disease, one should always inquire about exposure to metal fumes and/or dusts. Especially when sarcoidosis appears to be the diagnosis, one should always consider possible CBD.

Other Inorganic Dusts

Most of the inorganic dusts discussed thus far are associated with the production of either dust macules or interstitial fibrotic changes in the lung. Other inorganic and organic dusts (see categories in Table 250-1), along with some of the dusts previously discussed, are associated with chronic mucous hypersecretion (chronic bronchitis), with or without reduction of expiratory flow rates. Cigarette smoking is the major cause of these conditions and any effort to attribute some component of the disease to occupational and environmental exposures must take cigarette smoking into account. Most studies suggest an additive effect of dust exposure and smoking. The pattern of the irritant dust effect is similar to that of cigarette smoking, suggesting that small airway inflammation may be the initial site of pathologic response in those cases and continued exposure may lead to chronic bronchitis and COPD.

Organic Dusts

Some of the specific diseases associated with organic dusts are discussed in detail in the chapters on asthma (Chap. 248) and hypersensitivity pneumonitis (Chap. 249). Many of these diseases are named for the specific setting in which they are found, e.g., farmer's lung, malt worker's disease, or mushroom worker's disease. Often the temporal relation of symptoms to exposure furnishes the best evidence for the diagnosis. Three occupational groups are singled out for discussion because they represent the largest proportion of people affected by the diseases resulting from organic dusts.

Cotton Dust (Byssinosis)

Many persons are exposed occupationally to cotton, flax, or hemp in the production of yarns for cotton, linen, and rope making. Although this discussion focuses on cotton, the same syndrome—albeit somewhat less severe—has been reported in association with exposure to flax, hemp, and jute.

Exposure occurs throughout the manufacturing process but is most pronounced in those portions of the factory involved with the treatment of the cotton prior to spinning—i.e., blowing, mixing, and carding (straightening of fibers). Risk of byssinosis is associated with both cotton dust and endotoxin levels in the workplace environment. Attempts to control dust levels by use of exhaust hoods, general increases in ventilation, and wetting procedures in some settings have been highly successful. However, respiratory protective equipment appears to be required during certain operations to prevent workers from being exposed to levels of cotton dust that exceed the current U.S. permissible exposure level.

Byssinosis is characterized clinically as occasional (early stage) and then regular (late stage) chest tightness toward the end of the first day of the workweek ("Monday chest tightness"). In epidemiologic studies, depending on the level of exposure via the carding room air, up to 80% of employees may show a significant drop in their FEV1 over the course of a Monday shift.

Initially the symptoms do not recur on subsequent days of the week. However, in 10–25% of workers, the disease may be progressive, with chest tightness recurring or persisting throughout the workweek. After >10 years of exposure, workers with recurrent symptoms are more likely to have an obstructive pattern on pulmonary function testing. The highest grades of impairment are generally seen in smokers.

Reduction of dust exposure is of primary importance to the management of byssinosis. All workers with persistent symptoms or significantly reduced levels of pulmonary function should be moved to areas of lower risk of exposure. Regular surveillance of pulmonary function in cotton dust–exposed workers using spirometry before and after the workshift is required by the Occupational Safety and Health Administration (OSHA) of the U.S. government.

Grain Dust

Although the exact number of workers at risk in the United States is not known, at least 500,000 people work in grain elevators, and >2 million farmers are potentially exposed to grain dust. The presentation of obstructive airway disease in grain dust-exposed workers is virtually identical to the characteristic findings in cigarette smokers, i.e., persistent cough, mucous hypersecretion, wheeze and dyspnea on exertion, and reduced FEV1 and FEV1/FVC ratio (Chap. 246).

Dust concentrations in grain elevators vary greatly but appear to be >10,000 g/m3; approximately one-third of the particles, by weight, are in the respirable range. The effect of grain dust exposure is additive to that of cigarette smoking, with ~50% of workers who smoke having symptoms. Among nonsmoking grain elevator operators, approximately one-quarter have mucous hypersecretion, about five times the number that would be expected in unexposed nonsmokers. Smoking grain dust–exposed workers are more likely to have obstructive ventilatory deficits on pulmonary function testing. As in byssinosis, endotoxin may play a role in grain dust–induced chronic bronchitis and COPD.

Farmer's Lung

This condition results from exposure to moldy hay containing spores of thermophilic actinomycetes that produce a hypersensitivity pneumonitis (Chap. 249). There are few good population-based estimates of the frequency of occurrence of this condition in the United States. However, among farmers in Great Britain, the rate of disease ranges from approximately 10–50 per 1000. The prevalence of disease varies in association with rainfall, which determines the amount of fungal growth, and with differences in agricultural practices related to turning and stacking hay.

The patient with acute farmer's lung presents 4–8 h after exposure with fever, chills, malaise, cough, and dyspnea without wheezing. The history of exposure is obviously essential to distinguish this disease from influenza or pneumonia with similar symptoms. In the chronic form of the disease, the history of repeated attacks after similar exposure is important in differentiating this syndrome from other causes of patchy fibrosis (e.g., sarcoidosis).

A wide variety of other organic dusts are associated with the occurrence of hypersensitivity pneumonitis (Chap. 249). For those patients who present with hypersensitivity pneumonitis, specific and careful inquiry about occupations, hobbies, or other home environmental exposures is necessary to uncover the source of the etiologic agent.

Toxic Chemicals

Exposure to toxic chemicals affecting the lung generally involves gases and vapors. A common accident is one in which the victim is trapped in a confined space where the chemicals have accumulated to toxic levels. In addition to the specific toxic effects of the chemical, the victim will often sustain considerable anoxia, which can play a dominant role in determining whether the individual survives.

Table 250-2 lists a variety of toxic agents that can produce acute and sometimes life-threatening reactions in the lung. All these agents in sufficient concentrations have been demonstrated, at least in animal studies, to affect the lower airways and disrupt alveolar architecture, either acutely or as a result of chronic exposure. Some of these agents may be generated acutely in the environment (see below).

Table 250-2 Selected Common Toxic Chemical Agents Affecting the Lung



Agent(s) Selected Exposures Acute Effects from High or Accidental Exposure Chronic Effects from Relatively Low Exposure
Acid fumes: H2SO4, HNO3
Manufacture of fertilizers, chlorinated organic compounds, dyes, explosives, rubber products, metal etching, plastics Mucous membrane irritation, followed by chemical pneumonitis 2–3 days later Bronchitis and suggestion of mildly reduced pulmonary function in children with lifelong residential exposure to high levels; clinical significance unknown
Acrolein and other aldehydes By-product of burning plastics, woods, tobacco smoke Mucous membrane irritant, decrease in lung function Mutagen in animals, no human data
Ammonia Refrigeration; petroleum refining; manufacture of fertilizers, explosives, plastics, and other chemicals Same as for acid fumes Chronic bronchitis
Anhydrides Manufacture of resin esters, polyester resins, thermoactivated adhesives Nasal irritation, cough Asthma, chronic bronchitis, hypersensitivity pneumonitis
Cadmium fumes Smelting, soldering, battery production Mucous membrane irritant, acute respiratory distress syndrome (ARDS) COPD
Formaldehyde Manufacture of resins, leathers, rubber, metals, and woods; laboratory workers, embalmers; emission from urethane foam insulation Same as for acid fumes Cancers in one species; no data on humans
Halides and acid salts (Cl, Br, F) Bleaching in pulp, paper, textile industry; manufacture of chemical compounds; synthetic rubber, plastics, disinfectant, rocket fuel, gasoline Mucous membrane irritation, pulmonary edema; possible reduced FVC 1–2 yrs after exposure Dryness of mucous membrane, epistaxis, dental fluorosis, tracheobronchitis
Hydrogen sulfide By-product of many industrial processes, oil, other petroleum processes and storage Increase in respiratory rate followed by respiratory arrest, lactic acidosis, pulmonary edema, death Conjunctival irritation, chronic bronchitis, recurrent pneumonitis
Isocyanates (TDI, HDI, MDI) Production of polyurethane foams, plastics, adhesives, surface coatings Mucous membrane irritation, dyspnea, cough, wheeze, pulmonary edema Upper respiratory tract irritation, cough, asthma, allergic alveolitis
Nitrogen dioxide Silage, metal etching, explosives, rocket fuels, welding, by-product of burning fossil fuels Cough, dyspnea, pulmonary edema may be delayed 4–12 h; possible result from acute exposure: bronchiolitis obliterans in 2–6 wks Emphysema in animals, ?chronic bronchitis, associated with reduced lung function in children with lifelong residential exposure, clinical significance unknown
Ozone Arc welding, flour bleaching, deodorizing, emissions from copying equipment, photochemical air pollutant Mucous membrane irritant, pulmonary hemorrhage and edema, reduced pulmonary function transiently in children and adults, and increased hospitalization with exposure to summer haze Chronic eye irritation and slight excess in cardiopulmonary mortality in susceptible individuals
Phosgene Organic compound, metallurgy, volatilization of chlorine-containing compounds Delayed onset of bronchiolitis and pulmonary edema Chronic bronchitis
Sulfur dioxide Manufacture of sulfuric acid, bleaches, coating of nonferrous metals, food processing, refrigerant, burning of fossil fuels, wood pulp industry Mucous membrane irritant, epistaxis ?Chronic bronchitis




Firefighters and fire victims are at risk of smoke inhalation, a numerically important cause of acute cardiorespiratory failure. Smoke inhalation kills more fire victims than does thermal injury. Carbon monoxide poisoning with resulting significant hypoxemia can be life-threatening (Chap. e35). The use of synthetic materials (plastic, polyurethanes), which, when burned, may release a variety of other toxic agents (such as cyanide or hydrochloric acid), must be considered when evaluating smoke inhalation victims. Exposed victims may suffer some degree of lower respiratory tract inflammation and/or pulmonary edema.

Exposure to certain highly reactive, low-molecular-weight agents used in the manufacture of synthetic polymers, paints, and coatings (diisocyanates in polyurethanes; aromatic amines and acid anhydrides in epoxies) are associated with a high risk of occupational asthma. Although this occupational asthma manifests clinically as if sensitization has occurred, there is little evidence that an IgE antibody–mediated mechanism is involved. Hypersensitivity pneumonitis–like reactions also have been described in diisocyanate and acid anhydride–exposed workers.

Fluoropolymers, such as Teflon, which at normal temperatures produce no reaction, upon heating become volatilized. The inhaled agents cause a characteristic syndrome of fever, chills, malaise, and occasionally mild wheezing leading to the diagnosis of polymer fume fever. A similar self-limited, influenza-like syndrome—metal fume fever—results from acute exposure to fumes or smoke containing zinc oxide. The syndrome may begin several hours after work and resolves within 24 h, only to return on repeated exposure. Welding of galvanized steel is the most common exposure leading to metal fume fever.

Two other agents have been recently associated with potentially severe interstitial lung disease. Occupational exposure to nylon flock has been shown to induce a lymphocytic bronchiolitis, and workers exposed to diacetyl used to provide "butter" flavor in the manufacture of microwave popcorn have developed bronchiolitis obliterans (Chap. 255).

World Trade Center Disaster

A consequence of the attack on the World Trade Center (WTC) on September 11, 2001, was relatively heavy exposure of a large number of firefighters and other rescue workers to the dust generated by the collapse of the buildings. Environmental monitoring and chemical characterization of WTC dust has revealed a wide variety of potentially toxic constituents, although much of the dust was pulverized cement. Possibly because of the high alkalinity of WTC dust significant cough, wheeze, and phlegm production occurred among firefighters and clean-up crews. New cough and wheeze syndromes also occurred among local residents. Initial longitudinal follow-up of New York firefighters suggests that heavier exposure to WTC dust is associated with accelerated decline of lung function.

Environmental Respiratory Carcinogens

In addition to asbestos exposures, other occupational exposures associated with either proven or suspected respiratory carcinogens include those to acrylonitrile, arsenic compounds, beryllium, bis(chloromethyl) ether, chromium (hexavalent), formaldehyde (nasal), isopropyl oil (nasal sinuses), mustard gas, the various ores used to produce pure nickel, polyaromatic hydrocarbons (coke oven emissions and diesel exhaust), secondhand tobacco smoke, silica (both mining and processing), talc (possible asbestos contamination in both mining and milling), vinyl chloride (sarcomas), wood (nasal cancer only), and uranium. The occurrence of excess cancers in uranium miners raises the possibility that a large number of workers are at risk by virtue of exposure to similar radiation hazards. This number includes not only workers involved in processing uranium but also workers exposed in underground mining operations where radon daughters may be emitted from rock formations.

Assessment of Disability

Patients who have lung disease may have difficulty continuing to work in their usual jobs because of respiratory symptoms. Such patients frequently seek assistance from their physicians in obtaining compensation for loss of income. Disability is the term used to describe the decreased ability to work due to the effects of a medical condition. Physicians are generally able to assess physiologic dysfunction, or impairment, but the rating of disability also involves non-medical factors such as the education and employability of the individual. The disability rating scheme differs with the compensation-granting agency. For example, the U.S. Social Security Administration requires that an individual be unable to do any work (i.e., total disability) before he/she will receive income replacement payments. Many state workers' compensation systems allow for payments for partial disability. In the Social Security scheme no determination of cause is done, while work-relatedness must be established in workers' compensation systems.

Most commonly the need for disability assessment comes about because of the patient's complaint of shortness of breath. It is important to remember that dyspnea may result from cardiac, hematologic, or neuromuscular diseases in addition to respiratory diseases. For respiratory disability, resting pulmonary function tests (spirometry and diffusing capacity) are used as the initial assessment tool, with cardiopulmonary exercise testing (to assess maximal oxygen consumption) used if the results of the resting tests do not correlate with the patient's symptoms. Methacholine challenge (to assess airways reactivity) can also be useful in patients with asthma who have normal spirometry when evaluated. Some compensation agencies (e.g., Social Security) have proscribed disability classification schemes based on pulmonary function test results. When no specific scheme is proscribed, the Guidelines of the American Medical Association should be used.

Evaluating relation to work exposure requires a detailed work history, as previously discussed in this chapter. Occasionally, as with some cases of suspected occupational asthma, challenge to the putative agent in the work environment with repeated pulmonary function measures may be required.

Outdoor Air Pollution

In 1971, the U.S. government established national air quality standards for several pollutants believed to be responsible for excess cardiorespiratory diseases. Primary standards regulated by the Environmental Protection Agency (EPA) designed to protect the public health with an adequate margin of safety exist for sulfur dioxide, particulates matter, nitrogen dioxide, ozone, lead, and carbon monoxide. Standards for each of these pollutants are updated regularly through an extensive review process conducted by the EPA. (For details on current standards—http://www.epa.gov/air/criteria.html.)

Pollutants are generated from both stationary sources (power plants and industrial complexes) and mobile sources (automobiles), and none of the pollutants occurs in isolation. Furthermore, pollutants may be changed by chemical reactions after being emitted. For example, reducing agents, such as sulfur dioxide and particulate matter from a power plant stack, may react in air to produce acid sulfates and aerosols, which can be transported long distances in the atmosphere. Oxidizing substances, such as oxides of nitrogen and oxidants from automobile exhaust, may react with sunlight to produce ozone. Although originally a problem confined to the southwestern part of the United States, in recent years, at least during the summertime, elevated ozone and acid aerosol levels have been documented throughout the United States. Both acute and chronic effects of these exposures have been documented in large population studies.

The symptoms and diseases associated with air pollution are the same as conditions commonly associated with cigarette smoking. In addition, respiratory illness in early childhood has been associated with chronic exposure to only modestly elevated levels of traffic-related gases and respirable particles. Multiple population-based time-series studies within cities have demonstrated excess cardiopulmonary hospitalizations and mortality. In addition, cohort studies comparing cities that have relatively high levels of particulate exposures with less polluted communities suggest excess morbidity and mortality from cardiorespiratory conditions in long-term residents of the former. These findings have led to stricter U.S. ambient air quality standards for particulate matter as well as greater emphasis on publicizing pollution alerts to encourage individuals with significant cardiopulmonary impairment to stay indoors during high pollution episodes.

Indoor Exposures

Environmental tobacco smoke (Chap. 390), radon gas, wood smoke, and other biologic agents generated indoors need to be considered. Several studies have shown that the respirable particulate load in any household is directly proportional to the number of cigarette smokers living in the home. Increases in prevalence of respiratory illnesses and reduced levels of pulmonary function measured with simple spirometry have been found in children of smoking parents in a number of studies. Recent meta-analyses for lung cancer, and cardiopulmonary diseases, combining data from the best of the environmental tobacco smoke exposure studies, suggest an ~25% increase in relative risk for each condition, even after adjustment for major potential confounders.

Radon gas is believed to be a risk factor for lung cancer. The main radon product (radon 222) is a gas that results from the decay series of uranium 238, with the immediate precursor being radium 226. The amount of radium in earth materials determines how much radon gas will be emitted. Outdoors, the concentrations are trivial. Indoors, levels are dependent on the sources, the ventilation rate of the space, and the size of the space into which the gas is emitted. Levels associated with excess lung cancer risk may be present in as many as 10% of the houses in the United States. When smokers reside in the household, the problem is potentially greater, since the molecular size of radon particles allows them to readily attach to smoke particles that are inhaled. Fortunately, technology is available for assessing and reducing the level of exposure.

Other indoor exposures associated with an increased risk of atopy and asthma include those to such specific recognized putative biologic agents as cockroach antigen, dust mites, and pet danders. Other indoor chemical agents include formaldehyde, perfumes, and latex particles. Nonspecific responses associated with "tight-building syndrome," in which no particular agent has been implicated, have included a wide variety of complaints, among them respiratory symptoms that are relieved only by avoiding exposure in the building in question. The degree to which "smells" or other sensory stimuli are involved in the triggering of potentially incapacitating psychological or physical responses has yet to be determined, and the long-term consequences of such environmental exposures are as yet unknown.

Portal of Entry

The lung is a primary point of entry into the body for a number of toxic agents that affect other organ systems. For example, the lung is a route of entry for benzene (bone marrow), carbon disulfide (cardiovascular and nervous systems), cadmium (kidney), and metallic mercury (kidney, central nervous system). Thus, in any disease state of obscure origin, it is important to consider the possibility of inhaled environmental agents. Such consideration can sometimes furnish the clue needed to identify a specific external cause for a disorder that might otherwise be labeled "idiopathic."

Global Considerations

Indoor exposure to biomass smoke (wood, dung, crop residues, charcoal) is estimated to be responsible for 2.7% of worldwide disability adjusted life-years (DALYs) lost, due to acute lower respiratory infections in children and COPD and lung cancer in women. This burden of disease places indoor exposure to biomass smoke as the second leading environmental hazard for poor health, just behind unsafe water, sanitation, and hygiene; and is 3.5 times larger than the burden attributed to outdoor air pollution.

More than one-half of the world's population uses biomass fuel for cooking, heating or baking. This occurs predominantly in the rural areas of developing countries. Because many families burn biomass fuels in open stoves, which are highly inefficient, and inside homes with poor ventilation, women and young children are exposed on a daily basis to high levels of smoke. In these homes, 24-h mean levels of fine particulate matter, a component of biomass smoke, have been reported to be 2–30 times higher than the National Ambient Air Quality Standards set by the U.S. EPA.

Epidemiologic studies have consistently shown associations between exposure to biomass smoke and both chronic bronchitis and COPD, with odds ratios ranging between 3 and 10 and increasing with longer exposures. In addition to the common occupational exposure to biomass smoke of women in developing countries, men from such countries may also be occupationally exposed. Because of increased migration to the United States from developing countries, clinicians need to be aware of the chronic respiratory effects of exposure to biomass smoke, which can also include interstitial lung disease (Fig. 250-4).

Figure 250-4




Histopathologic features of biomass smoke-induced interstitial lung disease. A. Anthracitic pigment is seen accumulating along alveolar septae (arrow heads) and within a pigmented dust macule (single arrow), B. A high-power photomicrograph contains a mixture of fibroblasts and carbon-laden macrophages.