The Encyclopedia of Occupational Health and Safety of the International Labour Organization (ILO) defines pneumoconiosis as “the accumulation of dust in the lungs and the tissue reactions to its presence.” The main reaction to mineral dust in the lungs is fibrosis. Not included in the definition of pneumoconiosis are conditions such as asthma, chronic obstructive pulmonary disease (COPD), and hypersensitivity pneumonitis, which do not require dust to accumulate in the lungs.
Accumulation of Dust in the Lung and Tissue Reactions
The deposition of dust in the lungs depends on the size and geometric and aerodynamic properties of the particles. Particle clearance is determined by the mucociliary escalator and cellular mechanisms, in particular, the macrophage (see Chapter 12 ). Dust accumulation in the lungs is determined by deposition and clearance. The biologic response depends on the amount and duration of the accumulation and the nature of the dust. Tissue responses to inorganic dusts depend on particle size and the biologic activity of the dust, which in turn depends on its surface chemical and physical properties. Some dusts, such as coal, are relatively inert and may accumulate in considerable amounts with minimal tissue response; others, in particular silica and asbestos, have potent biologic effects. Parenchymal responses include nodular fibrosis (the classic example is the silicotic nodule), diffuse fibrosis (the classic example is asbestosis), and macule formation with focal emphysema (the classic example is the coal dust macule). Irregular and mixed fibrotic patterns have been described as a consequence of mixed exposures involving other mineral dusts or fibers in addition to silica dust exposure. For any given dust exposure, the severity of the tissue reaction appears to be related to the cumulative lung dust burden.
In epidemiologic studies, the dust burden in the lung can be assessed only indirectly. However, at an individual level, exposure can be estimated more directly from the job history, from the engineering history of the plant, including the efficiency of dust control, and from environmental measurements.
The demonstration of exposure-response relationships has implications for clinical practice. For instance, a clinical diagnosis of pneumoconiosis is strengthened greatly when there has been exposure to dust levels known to be associated with an increased risk of disease. Although exposure-response relationships generally describe the events in a work force, there may be heavily exposed individuals who remain unaffected and lightly exposed individuals with disease. Thus, environmental standards such as threshold limit values set by the American Conference of Government and Industrial Hygienists (ACGIH) are levels that if respected throughout an individual’s working life, are unlikely to be associated with disease. However, dust sampling may be problematic and even in a workplace where average dust concentrations are below the threshold limit value, nearly half the samples exceed this value. Thus, a clinician should not reject the diagnosis of pneumoconiosis solely on the grounds that exposure was too remote, too short, or in a workplace where the threshold limit value was maintained. The subject in question may be unusually susceptible, may have had an unusual exposure profile, or may retain more dust than others similarly exposed.
The ILO standard films for the descriptive interpretation of the radiologic appearance of diffuse parenchymal lung disease were originally developed for epidemiologic studies of occupational lung disease but may also be used for clinical interpretation. The 2011 ILO guidelines accommodate the use of digital images, and a set of standard digital images is available. Apart from improving consistency in the reading of parenchymal disease, which is notoriously subject to reader variability, they enable the clinician to set an individual case in the context of the available epidemiologic information. Small opacities in the parenchyma are classified by shape and size: p, q, or r for rounded opacities (diameter, <1.5 mm, 1.5 to 3 mm, or >3 mm, respectively) and s, t, or u for irregular opacities (width, <1.5 mm, 1.5 to 3 mm, or >3 mm, respectively). Profusion category (or concentration) is read on a 12-point scale (0/−, 0/0, 0/1, up to 3/2, 3/3, and 3/+) in comparison with the standard radiographs. Large opacities are classified as category A (for one or more such opacities with a diameter > 1 cm but not exceeding a combined diameter of 5 cm), category B (one or more opacities > 5 cm in diameter and whose combined area does not exceed one upper zone), and category C (>B). Provision is made to grade pleural thickening for width ( a ≤ 5 mm, b > 5 mm but < 10 mm, and c ≥ 10 mm) and extent ( 1 = up to one quarter, 2 = one quarter to one half, and 3 = over one half of the lateral chest wall). The extent of pleural calcification is also graded, and there are provisions for comment on other features.
In the United States, the National Institute of Occupational Safety and Health (NIOSH) administers the National Coal Workers’ Health Surveillance Program, which provides coal miners with the opportunity of a periodic medical examination. The program incorporates quality control in terms of radiographic technique and reading procedures using the ILO classification and reader training. This involves training seminars for physicians who may qualify as “A” readers (i.e., attended the seminars) or “B” readers, who passed a comprehensive examination on the basis of 120 radiographs read into the ILO classification.
Conventional chest radiographs or digital images are the cornerstone of surveillance for pneumoconiosis in the workplace. Computed tomography (CT) and high-resolution computed tomography (HRCT) have revolutionized clinical case evaluation. CT and HRCT are able to characterize lung and pleural lesions, as well as their extent and confluence, and are considerably more sensitive than the conventional chest radiograph. The role of magnetic resonance imaging in the diagnosis of pneumoconiosis is limited, but the technique has been used to differentiate between pleural plaques and mesothelioma. Positron emission tomography (PET) scans have been used to detect pulmonary neoplasms in the presence of pneumoconiosis, but increased metabolic activity in lesions of progressive massive fibrosis, in benign lung nodules in coal workers’ pneumoconiosis, and in mediastinal nodes in patients with pneumoconiosis limit the usefulness of the technique. The chest radiograph remains the accepted method for surveillance and assessment because of its wide availability, acceptable cost and radiation dose, and the standardization of its reading.
Clinical Issues, Lung Function, and Principles of Management
The clinician is faced with two main tasks when evaluating a case of suspected pneumoconiosis. First, the clinician must assess the nature of the disease process, including its site (airways or pulmonary parenchyma or pleura) and its extent, as well as to determine whether it has decreased the individual’s performance in particular for his or her current job (evidence of impairment or disability). Assessment of impairment is based on symptoms and measurements of pulmonary function at rest and during exercise where indicated (see Chapters 25 and 26 ). Pneumoconiosis may be associated with apparently normal lung function or with a predominantly obstructive, restrictive, or mixed pattern of dysfunction. In the individual case, interpretation of results in terms of lung function profiles is usually done by the use of reference or predicted values. These may, however, be misleading given that those who undertake dusty occupations on average have higher initial spirometry and lung volumes than the general population, on whom most predicted values are based. Thus, it is not appropriate to minimize the functional significance of pneumoconiosis on the grounds of apparently normal lung function. Assessment of disability is made in the wider context of whether the subject is fit for his or her job and, thus, requires expert knowledge of the job content.
Second, the clinician needs to determine whether there has been environmental or occupational exposure of duration, intensity, and character sufficient to account in full or in part for the patient’s present condition. For this task, the key tool is the occupational history, which can be completed with the addition of the often extensive knowledge that the worker can provide concerning his or her occupations, the materials handled, and the processes involved. Because pneumoconiosis is a reaction to retained dust, it may appear and progress after exposure has ceased ; hence, the importance of a complete exposure history, including student summer jobs, military service, and short-term jobs. In addition, in industrialized countries, between 25% and 60% of men and up to 30% of women report exposure to dust or fumes at work, further testimony to the fact that an occupational history is as essential as the smoking history in the practice of respiratory medicine. On occasions, it may be necessary to establish occupational exposure on the basis of analysis of biologic material (sputum, bronchoalveolar lavage [BAL], transbronchial or open-lung biopsy specimen) for the putative dust or its breakdown products. This is particularly so in cases in which the exposure is remote and the exposure history incomplete or unreliable. Figure 73-1 presents examples of cases in which the putative dust was demonstrated in the pathologic specimens. The case record described in the legend for Figure 73-9 is an example of the use of lung dust burden measurements in establishing attributability.
Tuberculosis was a common complication of pneumoconiosis in the early part of the 20th century. Although now relatively rare in industrialized countries, tuberculosis remains an important issue in industrializing countries and has increased dramatically, especially in South Africa, in response to the human immunodeficiency virus (HIV) epidemic.
Pneumoconiosis does not regress and may appear and progress only after work exposure ceases. In general, the worker with pneumoconiosis should have no further occupational dust exposure.
The physician has the legal responsibility to report all cases of pneumoconiosis. The diagnosis of pneumoconiosis reflects a failure of environmental controls in the workplace that may require intervention by an appropriate authority. There are differences in disease notification practice and compensation legislation among states and among countries, and physicians should be aware of the appropriate procedures in the location of their practice.
Epidemiology and Implications for Clinical Practice
Information on the distribution of these diseases within and between work forces and the factors that influence distribution provides the scientific base that the physician uses to reach a diagnosis, set prognosis, and plan management. Thus, knowledge of pneumoconiosis rates in the industries located in the local area assists the physician in diagnosis. Likewise, determining prognosis depends on work force–based information, on knowing which factors influence disease progression favorably and unfavorably, and the likely effect of further exposure even at low levels.
In the discussion that follows, the various types of pneumoconioses are considered separately with respect to occupations at risk, pathophysiology and epidemiology, as well as the clinical issues of diagnosis, prognosis, and management. On all continents and in many countries, a substantial proportion of individuals is exposed to dust at work and therefore potentially at risk for pneumoconiosis. Lists of occupations and jobs at risk are never exhaustive ( Table 73-1 ) but are a guide for use in general office practice. For those in occupational health or occupational medicine practice, reference should be made to one of the more specialized texts that describe the occupations at risk in greater detail.
|Industries with Examples||Occupations Implicated|
|MINING, TUNNELING, AND EXCAVATING|
|Underground: gold, copper, iron, tin, uranium, civil engineering projects||Miner, driller, tunneler, developer, stoper *|
|Surface: coal, iron, excavation of foundations||Mobile rig drill operator|
|Granite, sandstone, slate, sand, chinastone/clay||Driller, hammerer, digger|
|Granite sheds, monumental masonry||Cutter, dresser, driller, polisher, grinder, mason|
|Ferrous and nonferrous metals||Molder, knockout man, fettler, † coremaker, caster|
|Production: silica flour, metal polish, and sandpapers, fillers in paint, rubber, and plastics||Crusher, pulverizer, and mixer; workers in the manufacture of abrasives|
|Sandblasting: oil rigs, tombstones, denim||Operators of high-speed jets|
|Manufacture of pottery, stoneware, refractory bricks for ovens and kilns||Workers at any stage of process if products are dry|
|Glass making, boiler scaling, traditional crafts, stone grinders, gemstone workers, dental technicians, concrete reconstruction|
Silicosis is a fibrotic lung disease attributable to the inhalation of crystalline silica usually in the form of quartz and, less commonly, as cristobalite and tridymite. Amorphous silica is relatively nontoxic; silicates such as asbestos, mica, and talc evoke a different type of pulmonary response and are considered separately.
Industries and Occupations Still at Risk
Silicosis is an ancient disease that continues to be a major disease worldwide in men and women exposed to silica dust in a variety of occupations. Table 73-1 provides some common examples of industries in which workers are at risk for silica exposure. Construction, surface, and underground rock drilling have all been subjects of Alert documents from NIOSH. Foundries are also a main source of silica dust. More recent reports have shown a silicosis risk for workers involved with the repair, rehabilitation, or demolition of concrete structures including roads. Less common occupations associated with silicosis include workers producing stressed denim by sandblasting, stone carvers, granite countertop manufacturers, dental technicians, and jewelers using chalk molds. Many of the current cases of silicosis come from industries using relatively new technology that, if unaccompanied by modern controls, may result in exposures to finer dust particles than in traditional industries and jobs. Many “new” types of pneumoconiosis often turn out to be silicosis in an industry not previously thought to be at risk or a mixed dust pneumoconiosis in which silica is implicated with other dusts.
Silicosis is often the result of exposure in the remote past and not in the current workplace. The risks for silicosis depend on the levels of exposure and, although this can be controlled, there is evidence that dust levels may be monitored inappropriately and that the sampling accuracy may be poor in many workplaces.
Outbreaks of silicosis and death from the disease continue to be reported worldwide, even in countries with developed legislative systems and environmental surveillance programs, such as the United States, Canada, Europe, and South Africa. U.S. data show that the rate of decline in deaths from silicosis has lessened after 1995 with an increased proportion of deaths in the age group younger than 45 years. These data indicate “that intense overexposures to respirable crystalline silica continue to occur despite the existence of legally enforceable limits.” In China 23 million workers are exposed to silica, while in the United States, NIOSH has estimated that at least 1.7 million workers are exposed to silica, of whom between 1500 and 2360 will develop silicosis each year. Cases of silicosis have also been reported following general environmental exposure and in agricultural workers.
Three clinicopathologic types of silicosis have been described: chronic silicosis, which typically follows exposure, measured in decades rather than years, to respirable dust usually containing less than 30% quartz; accelerated silicosis, which follows shorter, heavier exposure; and acute silicosis (silicoproteinosis), which follows intense exposure to fine dust of high silica content, such as that found in sandblasting industries, for periods measured in months rather than years.
Chronic silicosis is the most common form of the disease. The hallmark of chronic silicosis is the silicotic nodule, one of the few agent-specific lesions in pathology ( Fig. 73-2A and B ; eFig. 73-1 ). Silicotic nodules develop first in the hilar lymph nodes and may be confined to this area; they may become encased in calcification and impinge on or erode into airways. The disease process next involves the lung parenchyma. It is usually bilateral, predominantly involving the upper zones.
In accelerated silicosis, the changes are similar to those seen in chronic silicosis. However, the nodules develop sooner (after 3 to 10 years of exposure), may be more widely distributed in the lung, and are more cellular than fibrotic.
With disease progression in both chronic and accelerated silicosis, the nodules may become confluent, leading to the development of progressive massive fibrosis (PMF) (see Fig. 73-2C ), also known as complicated silicosis. These lesions, which are at least 1 cm in diameter (and often larger), usually involve the upper lobes. They tend to obliterate lung structure and may cavitate, which may be an indication of tuberculosis. Rheumatoid nodules may also develop in the setting of silicosis and may be seen in subjects with rheumatoid arthritis or high levels of circulating rheumatoid factor. There may be silicotic nodules in the background. Rheumatoid nodules are less frequently associated with silica than with coal dust exposure (see subsequent discussion).
Acute silicosis shows all the features of pulmonary alveolar proteinosis (see Chapter 70 ). Silica particles and various biomarkers of tissue reaction can be identified in the proteinaceous material from the alveolar spaces and in lavage material.
The lungs of exposed individuals, whether or not they show silicosis, also may demonstrate the features of other diseases associated with occupational dust exposure, such as chronic bronchitis and emphysema. The pathologic features are similar whether associated with occupational exposure to dusts and fumes encountered in the workplace or with exposure to tobacco smoke. Small airway abnormalities, including fibrosis and pigmentation of respiratory bronchioles (see Fig. 73-2D ), are seen in association with exposures to a variety of mineral dusts including those responsible for silicosis.
Silicotic nodules may also develop in the cervical and abdominal lymph nodes and, occasionally, in the liver, spleen, and bone marrow.
The pathogenicity of silica dust is dependent on the physical, mechanical, and chemical properties of the particles. A review of this topic summarizes the processes whereby silica produces inflammation and fibrogenesis in the lung. However, the cellular mechanisms that initiate and drive the process of inflammation and fibrosis are not fully understood. There is agreement that freshly fractured silica, such as that generated during sandblasting, is more toxic to the alveolar macrophages than is “aged” silica, presumably because of its increased redox potential. Other minerals, particularly clay components, may adhere to the surfaces of silica particles, producing “coated” silica that is less toxic than uncoated silica dust. This may explain the relatively nonfibrogenic response to silica in coal and hematite miners and the observation that the incidence of silicosis is decreased by concomitant exposure to other dusts. Silica particles smaller than 5 µm reach the lower respiratory tract and may enter the alveoli. The intensity of the exposure determines the nature of the lung injury.
Tumor necrosis factor-α (TNF-α) and interleukin 1 (IL-1) play an important role in the initiation of silicosis, and experimental inhibition of these cytokines has been shown to prevent silicosis. Growth factors, including transforming growth factor-β (TGF-β), are important in fibrogenesis (and also have been implicated in carcinogenesis) in association with silica. A review describes the immune response to silica in more detail and the role of innate and adaptive immunity. Although the major determinant of silicosis is the level of exposure to silica-containing dust, individual susceptibility to the disease may play a role in its development and severity.
Epidemiology: Secular Trends and Their Implications for the Clinician
Over the course of the 20th century, silicosis changed from a rapidly fatal disease to an indolent and disabling disorder. Reasons include improved environmental controls, falling rates of tuberculosis, and the advent of drug therapy for tuberculosis. Nevertheless, there is still well-warranted concern that this avoidable disease will remain a significant cause of morbidity and mortality in the 21st century. The prevalence of silicosis is difficult to estimate, given the large number of industries at risk (see Table 73-1 ), the transient labor force in industrializing and industrialized countries, and the frequent appearance (and progression) of disease after the worker has left the work force. Despite the progress made, silicosis has been reported in workers from a variety of industries in persons starting work after 1970, and reported cases have been estimated to underrepresent the total cases of silicosis substantially. In calculating an individual’s risk for silicosis, duration and intensity of exposure are of primary interest but peak exposure also may be important. The physician should never dismiss the diagnosis of silicosis when that diagnosis is suggested by clinical and radiologic features, even when exposure appears to have been insignificant or in an occupation not known to be associated with silicosis.
The association between silicosis and tuberculosis has long been recognized. Rates for active tuberculosis in silicotic subjects range from two- to thirty-fold more than those in the same workforce without silicosis. Factors that influence the development of tuberculosis in the subject with silicosis include the severity and type of disease (the risk is considerably higher in patients with acute and accelerated silicosis), the prevalence of tuberculosis in the population from which the work force was drawn, as well as their age, general health, and HIV status. Exposure to silica, without silicosis, may also predispose individuals to tuberculosis.
Tuberculosis is characterized by necrotizing epithelioid granulomas. These are never seen with silicosis alone. Although Mycobacterium tuberculosis is the usual organism, nontuberculous mycobacteria account for a large proportion of the mycobacterial disease in populations in which nontuberculosis mycobacterial disease is common. Smoking has been shown to increase the risk for the development of tuberculosis in those with silicosis. There is some evidence to suggest that those with silicosis are also at risk for fungal infections.
Airflow Obstruction and Chronic Bronchitis
COPD and chronic bronchitis are common manifestations of long-term occupational exposure to environments contaminated by silica dust and can develop in silica-exposed individuals with or without silicosis. Small airway abnormalities, including fibrosis and pigmentation of respiratory bronchioles (see Fig. 73-2D ), are also seen in association with exposures to a variety of mineral dusts including silica. In South African gold miners, the estimated additional loss of lung function attributable to mine dust exposure without invoking silicosis or tuberculosis is an average of 208 mL of forced vital capacity over a 30-year working life (in excess of the expected loss of 400 to 500 mL over 30 years in normal men with age). In a study of adolescents and young adults working in a stone-crushing plant, lung function changes were interpreted as evidence for impaired lung growth that was attributed to their high respirable crystalline silica exposure. Smoking can potentiate the effect of silica dust on airflow obstruction.
Connective Tissue Diseases, Renal Disease, and Cardiovascular Disease
Associations have been reported between exposure to silica and certain connective tissue diseases including progressive systemic sclerosis, systemic lupus erythematosus, and as previously mentioned, rheumatoid arthritis. Epidemiologic evidence indicates that the prevalence of rheumatoid arthritis is increased in those with exposure to silica and in those with silicosis. Systemic sclerosis has been shown to be associated with silicosis but may also be associated with silica dust exposure without silicosis. The evidence for an association between lupus erythematosus and silicosis is strongest for acute or accelerated silicosis but is inconclusive for chronic silicosis.
Renal disease has been reported in silica-exposed workers. Some studies have implicated an immune complex glomerulitis or a direct toxic effect of silica. Silicosis has been linked with antineutrophil cytoplasmic antibody (ANCA) positivity and possibly with vasculitis.
Cardiovascular disease may also be associated with silica exposure. A recent report of a cohort of 74,040 silica-exposed workers found an increased mortality compared with nonexposed workers; cardiovascular disease was the major cause of death.
The association between silicosis and lung cancer has been difficult to establish because of the high prevalence of smoking in silica-exposed workers and because of frequent concomitant radon exposure. Studies of non–radon-exposed, nonsmoking workers with silicosis suggest a clear relationship between silicosis and lung cancer, but there remains some doubt as to whether silica exposure, in the absence of silicosis, carries an increased risk for lung cancer.
The symptoms and signs of chronic silicosis may be minimal. The main symptom is breathlessness but, in chronic silicosis, in the absence of other respiratory disease, even this symptom may be absent. It is not unusual for a patient with chronic silicosis to present without symptoms for assessment of an abnormal chest radiograph. The appearance of breathlessness may mark the development of a complication such as PMF or tuberculosis or may reflect associated airway disease. Cough and sputum production are common symptoms and usually relate to chronic bronchitis but may reflect the development of tuberculosis or lung cancer. Chest pain is not a feature of silicosis nor are systemic symptoms such as fever and weight loss, which should be attributed to tuberculosis or lung cancer until proved otherwise. Clubbing is also not a feature of silicosis and should raise concern about lung cancer.
In accelerated and acute silicosis, the time scale of symptom evolution is in years or months rather than in decades. In acute silicosis, breathlessness may become disabling within months, followed by impaired gas exchange and respiratory failure.
Uncomplicated silicosis is characterized by the presence of small rounded opacities on the chest radiograph, as graded in the ILO classification (as described previously). In general, there is a good correlation among dust exposure, the amount of dust in the lungs, the lung pathology, and the chest radiograph. However, occasionally, even advanced silicosis, determined by histology, may not be apparent on a chest radiograph.
Silicotic nodules are usually symmetrically distributed and tend to appear first in the upper zones ( Fig. 73-3 ), later, although not invariably, involving other zones ( eFig. 73-2 ). Enlargement of the hilar nodes may precede the development of the parenchymal lesions. Eggshell calcification, when present, is strongly suggestive, although not pathognomonic, of silicosis ( Fig. 73-4 ; see also Fig. 73-3 , eFig. 73-3 ).
PMF is characterized by the coalescence of small rounded opacities to form larger lesions ( eFig. 73-4A ); they are graded on the ILO scale according to size and extent (categories A to C). CT assessment is superior to the chest radiograph in not only assessing the presence and extent of silicotic nodulation but also revealing early conglomeration ( eFig. 73-4-E ; ). With time, the mass lesions tend to contract, usually to the upper lobes, leaving hypertranslucent zones at their margins ( eFigs. 73-5 and 73-6 ) and often at the lung bases. In this process, small rounded opacities, previously evident, may disappear, resulting in a picture that must be distinguished from tuberculosis. The rapid development of several large lesions suggests rheumatoid silicosis, but new lesions, especially if cavitated, should be regarded as evidence of mycobacterial disease. Acute silicosis is characterized radiologically by diffuse changes that usually display an air space and interstitial pattern rather than the usual nodularity.
The lung function profile is determined by the extent of silicosis, as well as associated or concomitant airway and vascular changes. In chronic silicosis, spirometric tests ( forced expiratory volume in 1 second [FEV 1 ], FEV 1 / forced vital capacity [FVC]) usually reflect airflow limitation. Reduction in diffusing capacity of carbon monoxide (D l CO ) is generally apparent in more advanced chronic silicosis and probably reflects associated emphysema.
In the accelerated and acute forms, functional changes are more marked and progression is more rapid. In acute silicosis, lung function shows a restrictive defect and impairment of gas exchange, which leads to respiratory failure.
Diagnosis and Complications
Silicosis is diagnosed on the basis of a history of exposure and the characteristic radiographic changes. Problems arise when the history of exposure is remote, forgotten, or missed or has taken place outside a recognized occupation. Occasionally, the radiologic features are unusual; examples include the presence of hilar lymphadenopathy or of large lung opacities in the absence of typical small nodules. Detection of silica in BAL material may suggest the diagnosis. Lung biopsy may be necessary to distinguish progressive massive fibrosis or other atypical features from lung cancer, tuberculosis, and other diagnoses. Biopsy material should be submitted for microanalysis for dust including silica.
Less common complications include cor pulmonale, spontaneous pneumothorax, broncholithiasis, and tracheobronchial obstruction from enlarged calcified hilar nodes. The diagnosis of active tuberculosis in the silicotic subject may be more difficult than in the nonsilicotic subject but, in general, a good sample of sputum or sputum induced by nebulized hypertonic saline sent for mycobacterial culture provides the diagnosis. The presence of cough, hemoptysis, weight loss, fever, or any new radiologic feature ( eFig. 73-7 ) should be pursued with culture of sputum or BAL fluid or with culture and histologic examination of tissue. In many instances, it is the chest imaging rather than the clinical features that gives the first indication of tuberculosis in the presence of silicosis (see eFig. 73-7 , ), but it should be noted that those with silicosis are also at risk for extrapulmonary tuberculosis.
Management and Control
Once established, the fibrotic process of chronic silicosis is thought to be irreversible. Management of the individual case is thus directed toward preventing progression and the development of complicated disease. A change in occupation to an environment free of silica-containing dust should be advised. The disease will generally progress even without further exposure, but the rate of deterioration may be reduced.
Interventions to interrupt the inflammatory process that leads to chronic silicosis including the inhalation of aluminum or polyvinylpyridine- N -oxide and oral tetrandrine have not been shown to be successful. There is currently interest in the use of lung lavage to remove silica from the lung, but a favorable impact on progression of acute or chronic silicosis has not been demonstrated. Treatment of all forms of silicosis should be directed toward control of mycobacterial disease. This is especially true for acute and accelerated silicosis and silicosis in workers with HIV infection. All subjects with silicosis should have a tuberculin skin test or an interferon -γ (IFN-γ) release assay and, if positive in the absence of evidence of tuberculosis, be offered treatment for latent tuberculosis infection (see Chapter 35 ).
The interaction between silica exposure and smoking in the development of COPD, tuberculosis, and lung cancer makes it important to implement smoking-cessation programs in the workplace.
Because acute and accelerated silicosis carry such a poor prognosis and tend to arise in younger subjects, consideration should be given for lung transplantation in such cases (see Chapter 106 ).
The most important aspect of the management of silicosis relates to its prevention. To achieve this, a sustained effort must be made to increase awareness of silicosis. Recent deaths from silicosis in younger subjects in the United States have been reported after exposure in the construction and manufacturing sectors, with none from mining. Deaths of young people sandblasting denim are a reminder that there is often a lack of awareness of the hazards of silica outside the traditional occupations associated with silicosis.
Coal Workers’ Pneumoconiosis
Definition and Occupations at Risk
Coal workers’ pneumoconiosis (CWP) is a distinct pathologic entity resulting from the deposition of coal dust in the lungs. The tissue reactions to deposits of dust include the coal macule and coal nodule (simple CWP) and PMF (complicated CWP) ( Fig. 73-5 ).
The main occupation at risk for CWP is coal mining, an industry that in the 1970s employed approximately 250,000 people in the United Kingdom and a comparable number in Western Europe. Approximately 175,000 coal miners were employed in the United States in 1986; since then, there had been a steady decrease in the number to approximately 80,000 in 1999 but, in 2011, the number increased to 143,437. It has been estimated that there are 6 million coal miners in China. Coal is also mined in Eastern Europe, India, and on the African, Australian, and South American continents. With mechanization, output and potential for dust exposure have increased. Former and current coal workers are likely to continue to be seen with CWP. Surface coal miners are also at risk for pneumoconiosis but are not always included in surveillance programs.
Coal mine dust contains a variable amount of quartz depending on the nature of ore-bearing rock, the size of the coal seam, and the processes used to mine the seam (including the degree of mechanization). Coal miners may also develop silicotic nodules when the coal seams are in hard rock. Silicosis is more common in mines with a high grade or rank of coal (see later in “ Pathogenesis ”) and in workers such as roof bolters who work outside of the coal seams. Current evidence shows that coal mining, even in the absence of CWP, is associated with chronic bronchitis, chronic airflow limitation, and emphysema.
Other occupations at risk for exposure to coal or carbon dust include coal trimming (which involves loading and stowing coal in stores or ships’ holds), the mining and milling of graphite in carbon plants, the manufacture of carbon electrodes, and the manufacture and use of carbon black.
The primary lesion in CWP is the coal macule, which can be seen (although not palpated) on macroscopic examination as a small (≤4 mm) pigmented lesion, distributed initially in the upper lobes, although the lower lobes may subsequently become involved. On microscopic examination, the coal macule consists of a stellate aggregation of dust and dust-laden macrophages around respiratory bronchioles, with reticulin fibers and a variable amount of collagen (see Fig. 73-5 ). Focal emphysema, a form of centriacinar emphysema, forms within and around the coal macule, and together they form the characteristic lesion of CWP. The coal nodule is a palpable lesion that, in addition to dust-laden macrophages and reticulin, contains a substantial number of haphazardly arranged collagen fibers. Coal nodules, which result from exposure to coal dust admixed with silica, are usually present in association with coal macules. Classic silicotic lesions are seen in approximately 12% of U.S. coal miners and form when lung dust residue contains 18% or more quartz. Other features include subpleural dust deposits, enlargement of the hilar and mediastinal nodes and, on occasion, tattooing of the parietal pleural lymphatic channels by coal dust.
PMF (complicated CWP) is defined as a fibrotic pneumoconiotic lesion 1 cm or greater in diameter. These bulky, often irregular, well-defined, heavily pigmented rubbery black tissue masses usually appear in a background of severe simple CWP. PMF usually develops in the posterior segment of the upper lobes or apical segments of the lower lobes and is typically bilateral ( Figs. 73-6 and 73-7 ). Microscopically, the lesions contain the same elements as the coal nodule (see Fig. 73-5C ). They may impinge on and obliterate airways and vessels and cross interlobar fissures. Cavitation is not uncommon, probably as a consequence of ischemic necrosis, given that vascular obliteration is common within areas of PMF.
Rheumatoid pneumoconiosis, one variant of which is called Caplan syndrome, is a form of CWP associated with rheumatoid arthritis or a rheumatoid diathesis. It is characterized by nodules that are larger than coal nodules and have smoother borders. Pigmentation is arranged in concentric laminations and, relative to PMF lesions, they contain little dust. These lesions may cavitate or calcify. The microscopic features are similar to those described for the rheumatoid silicotic lesion (see earlier discussion under the “ Pathology ” of “ Silicosis ”). Active areas in the nodules contain dust-laden macrophages, lymphocytes, polymorphonuclear leukocytes, and plasma cells. When activity ceases, they may collapse or calcify. Rheumatoid pneumoconiosis lesions were originally described in Welsh coal miners and are reported in Belgian coal miners but are uncommon in North American coal miners.
Diffuse interstitial fibrosis has also been reported in coal miners; the fibrosis may contain black carbon pigment and may appear similar to the usual interstitial pneumonia (UIP) pattern. However, it has a relatively benign clinical course compared with that of the same condition in the general population.
The risk for CWP increases with the intensity and duration of exposure to coal dust. The effect of coal on the lung is also related to its rank, a measure of the degree of metamorphosis and which is based on its carbon content. Anthracite ranks highest (93% carbon), followed by bituminous, sub bituminous, and lignite, with the lowest carbon content (60% to 70%). In epidemiologic studies, CWP is more common in mines of high-rank coal than in those of low-rank coal. This may relate to the greater relative surface area of the coal dust particles, higher surface free radicals, and more frequent presence of silica in the high-rank, rather than the low-rank, coal. The coal dust macule and nodule are ascribed to the accumulation of large amounts of relatively inert dust in the lung. As the lung burden of dust increases, alveolar macrophages are activated and reactive oxygen species are released. These in turn trigger the release of cytokines, including interleukins and TNF, which set in motion the processes of inflammation and fibrogenesis that are responsible for the development of pneumoconiosis and also trigger the release of proteases, which contribute to the associated emphysema. The fibrosis, however, is considerably less intense and extensive than that evoked by the more bioactive dusts, such as silica and asbestos.
Although the exact pathogenic mechanisms underlying the development of PMF remain in doubt, these lesions are thought to relate to the amount of coal dust accumulated in the lung, the proportion of inhaled silica in the dust and its surface bioactivity, individual immunologic and genetic factors, and whether tuberculosis is present. Of these factors, the total dust burden appears to be the most important. In addition, there are striking differences in rates of simple pneumoconiosis and PMF among different coal pits, mining areas, and countries, suggesting that other characteristics of the dust particles, including their shape, size, composition, bioactivity, and durability in lung tissue, also contribute to the risk of developing CWP and PMF.
Epidemiology and Natural History
Early studies of coal miners suggested that the occupation of coal mining and even the presence of CWP were not associated with higher mortality rates. These studies probably did not take the healthy worker effect into account, and more recent studies have shown that exposure to coal dust is associated with increased mortality. Overall, in the United States, the mortality associated with CWP decreased by 36% from 1982 to 2000 compared with 1968 to 1981, but more recent data showed an increase in years of potential life lost before the age of 65 years since 2002.
Although the rates of CWP had been falling steadily in the United States and Europe, new cases continue to be detected and the diseases associated with coal dust have shown an increase since 1995 notwithstanding apparent adherence to the current dust standard. The presence of PMF is associated with more severe adverse effects on the health and life expectancy of coal miners than those of simple CWP, and recent data show a sharp increase in the finding of PMF in U.S. underground coal miners. Risk factors for PMF include the presence and stage of CWP, the intensity of dust exposure, and the age of the subject. The role of silica in the development of PMF is controversial but is generally believed to be important. A study of coal miners with rapidly progressive CWP suggests that silica exposure might be a marker for the development of PMF. Risk factors for rapid progression of CWP included working at the face in smaller mines, younger age, and mining in eastern Kentucky and western Virgina.
Rheumatoid pneumoconiosis (Caplan syndrome) was originally described as a variant of PMF in coal workers on the basis of its distinctive radiologic features. Active arthritis or circulating rheumatoid factor were commonly associated with rheumatoid pneumoconiosis. At present, most evidence suggests that the presence of rheumatoid arthritis, a predisposition to rheumatoid disease, or both is a host factor that modifies the response of an individual to coal mine dust exposure. Conversely, dust exposure does not appear to be a risk factor for rheumatoid arthritis. CWP does not appear to have an association with other connective tissue disorders.
Role of Silica
Although it is recognized that silica does not play a primary role in the causation of CWP, coal miners, especially those mining anthracite, may develop the lesions of silicosis. When present, silicosis is usually associated with CWP. Although combined exposure to silica and coal dust may produce less silicosis than would a similar pure exposure to silica, silica exposure is nevertheless thought to contribute to the risk of developing PMF.
Airflow Obstruction and Chronic Bronchitis
The association between coal mining and obstructive lung disease has now been confirmed by several longitudinal studies that show that airflow can be limited from coal dust exposure independently from CWP and that the effect becomes comparable with that of smoking at exposure levels at which there is a risk for CWP.
Mucus hypersecretion (chronic bronchitis) is common in coal workers but does not appear to play a direct role in their development of COPD. Mucus hypersecretion will generally resolve after withdrawal from dust exposure as it does after smoking cessation. Bronchial hyperresponsiveness appears to predispose coal workers to develop COPD.
Tuberculosis and Cancer
Mycobacterial infection, either by M. tuberculosis (see eFig. 73-7 ) or nontuberculous mycobacteria, has not been demonstrated to be more common in association with CWP in the absence of silicosis. Most evidence suggests that the occupation of coal mining is not associated with lung cancer; however, two recent studies have reported an association between lung cancer and coal mining. An increased risk of stomach cancer has been documented, but this was not apparent in a 23-year follow-up study of 8899 coal miners.
Simple CWP is regarded as a disease state without symptoms or physical signs. The diagnosis is based on the radiologic features. The symptoms of cough and sputum reported by most coal miners are likely to be the consequence of dust-induced chronic bronchitis. Breathlessness on effort is usually caused by associated chronic airflow limitation or by the development of PMF. Respiratory impairment and disability develop as PMF progresses, although patients with category A PMF (lesions 1 to 5 cm in diameter) may be asymptomatic. Lesions of PMF that impinge on airways may cause abnormal breath sounds. Large or bilateral PMF lesions may be associated with hypoxemia and right heart failure. The presence of new lung lesions with rheumatoid arthritis, subcutaneous rheumatoid nodules, or positive rheumatoid factor raises the possibility of rheumatoid pneumoconiosis. The lung lesions may or may not develop concomitantly with joint disease.
The hallmark of simple CWP on the chest radiograph is the presence of small rounded opacities in the lung parenchyma ( eFig. 73-8 ). (See the discussion of chest radiographs in the “Introduction” to this chapter.) Coal macules are usually associated with small (<1.5 mm) p nodules on the chest radiograph, but the radiograph may show no nodularity with mild to moderate grades of CWP. Large amounts of coal dust in the lungs are found in association with small, rounded p nodules. When the larger q and r nodules are visible radiologically, this usually reflects the presence of coal nodules and a higher proportion of quartz in the lungs.
Because the chest radiograph has been shown to be insensitive to the presence of macules and nodules, in individual cases, CT may be useful. Small rounded opacities are usually seen first in the upper zones and involve the other zones at a later stage. The nodule profusion is closely related to the lung dust content at autopsy. Small irregular opacities also appear in a profusion up to 1/0 in association with increasing age and smoking and, in coal workers, may relate to coexisting fibrosis and emphysema. Small rounded opacities probably never regress, but the presence of emphysema appears to reduce the reading of profusion on the chest radiograph. Some enlargement of hilar nodes is usual, but eggshell calcification is unusual. In a recent report, the presence of small irregular shadows indicating the presence of interstitial fibrosis has been described as a feature in those with exposure to coal dust and the same report disputes the conventional view that nodular opacities in CWP are predominantly in the upper lung zones.
PMF is diagnosed radiologically when the parenchymal opacities exceed 1 cm in diameter, a cutoff point that is arbitrary in what is obviously a continuous process, as shown by the pathologic demonstration of PMF without associated radiologic features. Conversely, approximately one third of cases diagnosed as PMF on the radiograph have been shown, at autopsy, to represent other lesions, including tumors, rheumatoid nodules, or tuberculosis scars. PMF lesions are more common in the upper lobes, are situated posteriorly, and are usually well demarcated from the adjacent lung. As PMF becomes more advanced, the lesions are nearly always bilateral (see Figs. 73-6 and 73-7 ). They may take on bizarre shapes, cavitate, or calcify. As the lesions shrink toward the hilum or to the apex, bullous lesions may be seen in the surrounding lung.
Lesions seen on the chest radiograph in rheumatoid pneumoconiosis are similar to those of PMF but are usually multiple and peripherally located. The lesions, which range in diameter from 0.5 to 5.0 cm, may appear within weeks. These lesions generally appear in the presence of lesser degrees of nodule profusion than are usual for PMF. They may cavitate, contain fluid levels, and show some calcification surrounding the cavity. In some cases, the lesions disappear, often completely, but may be followed at a later date by a fresh crop of lesions. The ILO classification of radiographs provides a special notation for lesions thought to be rheumatoid pneumoconiosis.
The controversy regarding the association between simple CWP and abnormal lung function has persisted largely because coal dust has been shown to cause both obstructive lung disease and pneumoconiosis. In general, it is probably true that simple CWP is a condition with little demonstrable effect on lung function. In part, this may be due to the health selection effect into a dusty job. Small irregular opacities and PMF have each been shown to be associated with abnormal lung function. Lung function deficits in complicated CWP include reduction in FVC and FEV 1 , increased total lung capacity (TLC) and residual volume, and decreased D l CO (particularly in the presence of mixed rounded and irregular opacities). Similar changes have also been noted in nonsmoking coal miners without CWP. Pulmonary hypertension may develop in proportion to the reduction of the vascular bed associated with advanced PMF.
Diagnosis, Complications, and Management
A history of occupational exposure to coal and a chest radiograph are the fundamental elements in the diagnosis of CWP. A CT scan of the chest may be used to demonstrate evidence of CWP when the features on the radiograph are inconclusive.
There are no data to suggest that CWP alone carries an increased risk for mycobacterial infection, either tuberculous or nontuberculous, but treatment of latent tuberculosis infection should be considered for coal workers who are thought to have had significant silica dust exposure or who have evidence of silicosis. Other complications include rheumatoid nodules, which are associated more commonly with coal mining than with gold mining exposure, and scleroderma, in which the opposite is true. Most evidence suggests that the occupation of coal mining is not associated with a risk of lung cancer, but some data suggest and some data refute an increased risk of stomach cancer.
The principles of management are those summarized in the “Introduction” to this chapter and elaborated in the section on “Silicosis.” Subjects with radiologic disease of profusion category 1 or greater should be advised to change their occupation to one in which they are no longer exposed to dust because of their risk of developing PMF. Management of other dust-related, smoking-related, or dust- and smoking-related diseases, such as chronic bronchitis and emphysema, is less straightforward. Smoking-cessation counseling should be given on general principles. Although there are no data to show any interaction between smoking and CWP, both coal mining and smoking have the capacity to cause COPD.
ASBESTOS-Related Fibrosis of the Lungs (Asbestosis) and Pleura
History and Uses
Asbestos is an ancient mineral exploited by humans from prehistoric times because of its durability and heat resistance and its fibrous nature, which enabled it to be spun. Commercial use of asbestos grew with mechanization; growth was exponential between the two world wars. Annual production peaked over 5 million tons in 1976 and stabilized at approximately 4 million tons in the early 1980s. Production began to fall in Europe and North America only in the late 1980s, when the ill health effects of exposure became a matter of increasing public concern. In 2010, the world consumption of asbestos, mainly chrysotile, was estimated to have been 2 million tons. By contrast, annual world production of the nonasbestos mineral silicates is approximately 30 million tons. The use of substitutes has increased proportionately as the use of asbestos has been restricted or banned, although in 2012, only 54 countries had banned or severely restricted the use of asbestos. On the African, Asian, and South American continents, asbestos continues to be in demand as a cheap, durable material for use in water reticulation and in housing projects for their rapidly urbanizing populations, and in many countries, the consumption of asbestos remains high and is increasing.
The word asbestos (meaning “unquenchable” in Greek) is used currently as a collective term for naturally occurring mineral silicates of the serpentine and amphibole group. Despite different origins and physical and chemical properties, these silicates have in common a fibrous habit, that is, they form naturally in bundles from which fibers can be easily separated.
As a basis for standard setting, the Occupational Safety and Health Administration (OSHA) defines a fiber as a particle more than 5 µm in length with an aspect ratio equal to or greater than 3 : 1.
Table 73-2 lists some of the mineral silicates found in human lung tissue and gives a general indication of their commercial uses. From the point of view of health effects, the most important are asbestos fibers and man-made mineral fibers. Biologic potency (and disease-producing potential) depends in general on dose delivered to the target organ, fiber dimensions, and durability in the lung tissue. The role of each of these parameters may not be the same for all fibers and all disease entities. Nonfibrous particles greater than 10 µm seldom reach the lung parenchyma, whereas fibers up to 200 µm can be found in the lungs if their diameter is less than 3 µm.
|Mineral: Group and Form||Location of Major Deposits, Commercial or Other||Main Commercial Uses and/or Other Sources of Human Exposure|
|Chrysotile † (white asbestos)||Canada (Quebec, British Columbia, Yukon, Newfoundland ‡ ), Russia, China (Szechwan), Brazil, Mediterranean countries (Cyprus, Corsica, Greece, Italy), southern Africa (South Africa, Zimbabwe, Swaziland)||Brake lining, shipbuilding and repair, polishing of precious stones, stone cutting, whetstone cutting, foundry operations (mainly for insulation) |
Asbestos cement products (pipes, gutters, tiles, roofing); insulation, fireproofing, reinforced plastics (fan blades, electric switchgear); textiles; friction materials; paper products; filters, spray-on products
|Crocidolite (blue asbestos)||South Africa (Northwest Cape ‡ ), western Australia ‡||Used in combination, mostly in cement but also in some of the products listed above|
|Amosite (brown asbestos)||South Africa (Northern Province, former Transvaal)|
|Anthophyllite||Finland ‡||Filler in rubber and plastics|
|Tremolite||Contaminates ore in certain talc, iron, and vermiculite mines (e.g., Libby, MT); also found in some agricultural soils||May or may not be removed in processing; has rural domestic uses (e.g., stucco)|
|Cummington-grunerite||Contaminates ore in certain iron mines (often not fibrous)||No commercial use|
|NONASBESTOS MINERAL SILICATES|
|Clay minerals (usually fine-grained, powder-like) such as kaolin and montmorillonite (bentonite)||40 countries, including China, United States (Georgia, North Carolina), United Kingdom (Cornwall), Germany, Egypt, Japan||Functional filler in paper, plastic, bricks and cement, rubber, paint, etc.; fire clays, refractories, ceramics, lubricants|
|Attapulgite and sepiolite||United States (Georgia, Florida), Spain, Australia, South Africa||Oil absorbants; pesticide carriers; pet litter|
|Talcs (usually platelike but can roll into scrolls)||United States (Vermont, Montana, New York, California), Italy, Spain, Norway, China, Japan, Korea, Canada||Ceramics; paper making; cosmetics; pharmaceuticals; animal feed; fertilizer; anticaking; paints; varnishes; plastic reinforcer|
|Micas (Usually Flaky)|
|Muscovite||United States (North Carolina, Georgia, and other states), France, Spain, China, India, Italy||Filler in plastics, drill sites, special paints; refractories; semiconductors; insulation; anticorrosion materials; welding rods|
|Vermiculite (expands when heated)||South Africa, United States (Montana, Virginia), Australia, Kenya||Absorbents (horticulture); plasters; boards; insulation; fire resistance|
|Wollastonite (exists as needles or fibers in limestones)||United States (California, New York), Japan, former USSR, Finland, Mexico, Australia||Filler/flux in ceramic industry; used in latex and oil-based paint; in welding fluxes; asbestos substitute in hardboard, insulation, and brake linings|
|Zeolite (fibrous), e.g., Erionite §||Turkey (Cappadocia and Anatolia regions) § : noncommercial deposits||Houses constructed in erionite rock; soil-containing fibers mixed with tremolite; sepiolite used in stucco and plaster|
|Other (mainly nonfibrous)||Worldwide (in filling of lava cavities); mined in 16 countries, including several in Europe, the United States, and Japan||Pollutant and radioactive waste control; also used in catalysts, adsorbents, conditioners|
|MAN-MADE MINERAL FIBERS|
|Glass wool and filament, rock wool, slagwool, ceramic fiber||Production in factories around the world||Many uses previously reserved for asbestos: glass filament used in mats, lamination, yarns; glass-rock and slagwool used as insulation in buildings and in car and naval construction; ceramic fiber used in reinforced cloth, disks, brakes, gaskets, board, and paper; high-performance ceramic fiber used in jet engines, spacecraft|
* The list is not exhaustive, and the reader should consult other sources for further information. Asbestos minerals invariably exhibit the fibrous habit; nonasbestos mineral silicates also may do so. Most silicate deposits are mineralogically heterogeneous, as are most of the commercial forms of the minerals.
§ One of three epidemics of mesothelioma in Turkish villages implicated erionite; in the other two, tremolite and/or chrysotile were implicated. As of 2012, 54 countries have prohibited the use of asbestos or severely restricted its use, but in all countries, exemptions are allowed for certain uses. A prohibition decree was adopted to be enforced in the European Community in 2005.
Sources of Human Exposure
Table 73-2 gives a list of the more common sources for human exposure to asbestos. The discussion that follows deals mainly with exposure to asbestos fibers; the principles, however, apply equally to exposure to other fibers.
In industrialized countries, and increasingly in industrializing countries, human exposure is most likely to be occupational and may happen in mining, milling, transporting, manufacturing, and applying or using raw fiber or manufactured products. In World War II, a major source of exposure was in the naval shipbuilding, repair, or refitting industries; in the post–World War II period, major sources of exposure were in the construction and transport industries, although exposures in shipbuilding, repair, or refitting continued to pose risks. Asbestos-containing materials in post–World War II buildings include boards, panels, surfacing, insulation, tile and floor covering, roofing, and caulking. Workers are thus exposed in maintenance operations or demolition of plants and buildings in which asbestos-containing materials have been used. Other sources of human exposure are during the removal of asbestos lagging or insulation from ships or buildings and the disposal of industrial waste, such as the dumps of defunct asbestos plants. In most industrialized countries, these sources of exposure have diminished in response to heightened public awareness and control regulations. However, as recently as 2004, the U.S. Department of Labor estimated that 1.3 million workers remained exposed to asbestos in the workplace, notably in construction and general industry in the United States and, in a more recent report, ongoing asbestos exposure is also attributed to local and imported, asbestos-containing goods. Data do suggest that asbestos exposure has decreased, although a recent study from the United States comparing those examined between 1980 and 1992 and those examined between 1993 and 2005 found an unexplained increase in crocidolite fibers in the lungs from 819 subjects with lung cancer, malignant mesothelioma, and asbestosis.
Indirect occupational exposure, also called bystander exposure, describes the exposure of those whose trades require them to work in the vicinity of others who are working directly with asbestos or asbestos-containing materials. Examples are carpenters and welders who may work in close contact with insulators and laggers who mix asbestos on site, often in closed spaces. Workers were often indirectly exposed in the shipbuilding, repair, and refitting industries and the construction industries.
Domestic exposure happened primarily as a consequence of fiber-laden work clothes being brought home. Domestic exposure still accounts for a small proportion of cases of asbestos-related disease, mainly pleural, and is reported to have accounted for up to 15% of malignant mesothelioma in one U.K. study. Given the long incubation period of this tumor (from 20 to 40 years), domestic exposure is likely to be the source of cases presenting well into the 21st century.
Environmental and residential exposure takes place as a consequence of living in the neighborhood of asbestos mines, mills, or plants. This source of exposure was first dramatically brought to medical attention in 1960 in a report of a cluster of 31 cases of malignant mesothelioma among residents and crocidolite asbestos miners of the Northwest Cape, South Africa. New cases were reported from this area until 1995, and because occupational and environmental exposure continued until the 1970s, cases were expected to continue and to increase up to and beyond 2010. A cohort study comparing the mortality experience of more than 4500 women living in the vicinity of the Quebec chrysotile mines with that of 1.375 million women from 60 reference areas in the province found seven deaths from mesothelioma in women living in the asbestos mining area and none in the reference population. Vermiculite mined from Libby, Montana, and shipped around the country was found to be contaminated with asbestos fibers. Residents of Minneapolis who had lived near waste piles of Libby vermiculite and who had never worked in the vermiculite industry have been found to have a high prevalence of asbestos-related pleural disease, greater if they ever played in or had contact with the waste piles. Similar waste piles associated with the remote processing of Libby vermiculite are estimated to exist in 250 sites across the United States. A community-based study in Libby found that localized pleural abnormalities were associated with restrictive pulmonary function. Environmental exposures from nonindustrial sources have been documented among residents of rural areas in Eastern Europe where the soil is contaminated with various fibers. In addition, there have been epidemics of asbestos-related pleural disease, nonmalignant and malignant, among residents of Turkish villages whose homes were constructed in erionite tuff rock or who used erionite and tremolite in stucco and plaster and in Da-yao, southwestern China, where crocidolite is present in the soil. A major concern since the 1980s has been the potential risk of exposure to occupants of public (including schools), commercial, and residential buildings constructed during the post–World War II period, when asbestos-containing materials were widely used in construction. A health review mandated by the U.S. Congress concluded that exposure in buildings was less by an order of magnitude than that encountered in the workplace except for custodians and others responsible for building maintenance. The report also provided estimates of lifetime cancer risk (see “ Asbestosis, Asbestos Exposure, Lung Cancer, and Mesothelioma ” later).
Fate of Inhaled Fibers
Accumulation of fibers in the lung is the outcome of exposure, deposition, clearance, and retention, all processes that depend on fiber dimensions and the level, intensity, and profile of exposure. Clearance of fibers from the lung is greater for short and for chrysotile fibers than for long and amphibole fibers. Retention of fibers is inhomogeneous, with more fibers being found in the lung regions with shorter pathways and greater accumulations of longer fibers with asbestosis than in lungs in which only airway lesions have developed. Fibers equal to or less than 3 µm are phagocytosed by activated macrophages and then translocated to lymphatic channels. Longer fibers are incompletely phagocytosed, often by more than one macrophage, and become the core of what were originally called asbestos bodies because of their association with asbestos exposure. Although most coated fibers in human lungs have been shown to contain asbestos (usually amphibole) when subjected to radiographic diffraction analysis, the term ferruginous bodies has been suggested to underline the fact that other mineral fibers may undergo coating in human lungs. (For a discussion of the translocation of fibers to the pleural space, see Chapters 79 and 82 .)
In the lungs of exposed individuals, the number of uncoated, or bare, fibers (visible only on electron microscopy) exceeds the number of coated fibers ( asbestos or ferruginous bodies), visible by light microscopy, by 5- to 10,000-fold. For many years, the coated asbestos fiber, asbestos body, has been considered the hallmark of exposure, past or current, no doubt because of its distinctive structure and because it was readily visible under the light microscope. The presence of more than one coated fiber has been cited (and challenged) as a necessary criterion for the pathologic diagnosis of asbestosis even in a subject with an appropriate exposure history. Asbestos bodies may be found in sputum or in BAL fluid when lung tissue levels are high. They are also more commonly found when exposure has been recent and to amphibole rather than chrysotile fibers. BAL fluid may also show characteristic cellular, biochemical, and mineralogic features in workers exposed to asbestos and especially in those with asbestosis.
Exposure versus Dose-Response Relationships
Epidemiologic studies have consistently demonstrated exposure-response relationships for asbestos-related parenchymal lung fibrosis. There are differences in the exposure-response relationships between industrial sectors, which probably reflect the fiber size (smaller fibers causing more lung disease) and the nature of the fibers, their retention, and their biopersistence in lung tissue (amphiboles causing more disease than chrysotile). For asbestos-related pleural disease, exposure-response relationships can also usually be demonstrated, but the residence time of the dust in the lungs is more important than the cumulative exposure. Mineralogic analysis has also shown that the degree of fibrosis correlates with fiber concentration, both in chrysotile- and in amosite-exposed workers. The toxicity of mineral fibers is determined by their physical and aerodynamic properties, which determine deposition and retention. Also relevant in fibrogenesis and probably in carcinogenesis is the solubility of the fibers (which determines their survival in lung tissue), their surface properties and electrical charge (which may affect their toxicity for cell membranes and the formation of free radicals), and the length-to-width aspect ratio (which may affect cellular toxicity).
Asbestosis (Pulmonary Parenchymal Fibrosis)
Pathology and Pathogenesis
Asbestosis tends to be prominent in the lower lobes and subpleural areas. The lesions of mild asbestosis are found at scattered sites and usually consist of foci of peribronchiolar fibrosis with local chronic interstitial inflammation, accumulation of macrophages in the air spaces, and proliferation of type II pneumocytes. Second- and third-order bronchioles and alveolar ducts tend to be involved as the disease progresses and the fibrosis spreads to involve the alveolar interstitium ( Fig. 73-8A ). When disease is advanced, the lungs are small, streaks of fibrosis outline lobar and interlobar septa, and the visceral pleura is invariably thickened. Honeycombing may be prominent subpleurally and in the lower lobes. Unlike in silicosis, the tracheobronchial lymph nodes do not show characteristic changes and progressive massive fibrosis is unusual. Advanced asbestos-related fibrosis is distinguishable from advanced fibrosis due to any other cause only by the presence of asbestos bodies or uncoated asbestos fibers ( Fig. 73-8B ).