Silicosis is a fibrotic disease of the lungs caused by the inhalation, retention and pulmonary reaction to crystalline silica. Despite knowledge of the cause of this disorder—respiratory exposures to silica containing dusts—this serious and potentially fatal occupational lung disease remains prevalent throughout the world. Silica, or silicon dioxide, is the predominant component of the earth’s crust. Occupational exposure to silica particles of respirable size (aerodynamic diameter of 0.5 to 5μm) is associated with mining, quarrying, drilling, tunnelling and abrasive blasting with quartz containing materials (sandblasting). Silica exposure also poses a hazard to stonecutters, and pottery, foundry, ground silica and refractory workers. Because crystalline silica exposure is so widespread and silica sand is an inexpensive and versatile component of many manufacturing processes, millions of workers throughout the world are at risk of the disease. The true prevalence of the disease is unknown.
Silicosis is an occupational lung disease attributable to the inhalation of silicon dioxide, commonly known as silica, in crystalline forms, usually as quartz, but also as other important crystalline forms of silica, for example, cristobalite and tridymite. These forms are also called “free silica” to distinguish them from the silicates. The silica content in different rock formations, such as sandstone, granite and slate, varies from 20 to nearly 100%.
Workers in High-Risk Occupations and Industries
Although silicosis is an ancient disease, new cases are still reported in both the developed and developing world. In the early part of this century, silicosis was a major cause of morbidity and mortality. Contemporary workers are still exposed to silica dust in a variety of occupations—and when new technology lacks adequate dust control, exposures may be to more hazardous dust levels and particles than in non-mechanized work settings. Whenever the earth’s crust is disturbed and silica-containing rock or sand is used or processed, there are potential respiratory risks for workers. Reports continue of silicosis from industries and work settings not previously recognized to be at risk, reflecting the nearly ubiquitous presence of silica. Indeed, due to the latency and chronicity of this disorder, including the development and progression of silicosis after exposure has ceased, some workers with current exposures may not manifest disease until the next century. In many countries throughout the world, mining, quarrying, tunnelling, abrasive blasting and foundry work continue to present major risks for silica exposure, and epidemics of silicosis continue to occur, even in developed nations.
Forms of Silicosis—Exposure History and Clinicopathologic Descriptions
Chronic, accelerated and acute forms of silicosis are commonly described. These clinical and pathologic expressions of the disease reflect differing exposure intensities, latency periods and natural histories. The chronic or classic form usually follows one or more decades of exposure to respirable dust containing quartz, and this may progress to progressive massive fibrosis (PMF). The accelerated form follows shorter and heavier exposures and progresses more rapidly. The acute form may occur after short-term, intense exposures to high levels of respirable dust with high silica content for periods that may be measured in months rather than years.
Chronic (or classic) silicosis may be asymptomatic or result in insidiously progressive exertional dyspnoea or cough (often mistakenly attributed to the ageing process). It presents as a radiographic abnormality with small (<10 mm), rounded opacities predominantly in the upper lobes. A history of 15 years or more since onset of exposure is common. The pathologic hallmark of the chronic form is the silicotic nodule. The lesion is characterized by a cell-free central area of concentrically arranged, whorled hyalinized collagen fibers, surrounded by cellular connective tissue with reticulin fibers. Chronic silicosis may progress to PMF (sometimes referred to as complicated silicosis), even after exposure to silica-containing dust has ceased.
Progressive massive fibrosis is more likely to present with exertional dyspnoea. This form of disease is characterized by nodular opacities greater than 1 cm on chest radiograph and commonly will involve reduced carbon monoxide diffusing capacity, reduced arterial oxygen tension at rest or with exercise, and marked restriction on spirometry or lung volume measurement. Distortion of the bronchial tree may also lead to airway obstruction and productive cough. Recurrent bacterial infection not unlike that seen in bronchiectasis may occur. Weight loss and cavitation of the large opacities should prompt concern for tuberculosis or other mycobacterial infection. Pneumothorax may be a life-threatening complication, since the fibrotic lung may be difficult to re-expand. Hypoxaemic respiratory failure with cor pulmonale is a common terminal event.
Accelerated silicosis may appear after more intense exposures of shorter (5 to 10 years) duration. Symptoms, radiographic findings and physiological measurements are similar to those seen in the chronic form. Deterioration in lung function is more rapid, and many workers with accelerated disease may develop mycobacterial infection. Auto-immune disease, including scleroderma or systemic sclerosis, is seen with silicosis, often of the accelerated type. The progression of radiographic abnormalities and functional impairment can be very rapid when auto-immune disease is associated with silicosis.
Acute silicosis may develop within a few months to 2 years of massive silica exposure. Dramatic dyspnoea, weakness, and weight loss are often presenting symptoms. The radiographic findings of diffuse alveolar filling differ from those in the more chronic forms of silicosis. Histologic findings similar to pulmonary alveolar proteinosis have been described, and extrapulmonary (renal and hepatic) abnormalities are occasionally reported. Rapid progression to severe hypoxaemic ventilatory failure is the usual course.
Tuberculosis may complicate all forms of silicosis, but people with acute and accelerated disease may be at highest risk. Silica exposure alone, even without silicosis may also predispose to this infection. M. tuberculosis is the usual organism, but atypical mycobacteria are also seen.
Even in the absence of radiographic silicosis, silica-exposed workers may also have other diseases associated with occupational dust exposure, such as chronic bronchitis and the associated emphysema. These abnormalities are associated with many occupational mineral dust exposures, including dusts containing silica.
Pathogenesis and the Association with Tuberculosis
The precise pathogenesis of silicosis is uncertain, but an abundance of evidence implicates the interaction between the pulmonary alveolar macrophage and silica particles deposited in the lung. Surface properties of the silica particle appear to promote macrophage activation. These cells then release chemotactic factors and inflammatory mediators that result in a further cellular response by polymorphonuclear leukocytes, lymphocytes and additional macrophages. Fibroblast-stimulating factors are released that promote hyalinization and collagen deposition. The resulting pathologic silicotic lesion is the hyaline nodule, containing a central acellular zone with free silica surrounded by whorls of collagen and fibroblasts, and an active peripheral zone composed of macrophages, fibroblasts, plasma cells, and additional free silica as shown in figure 1.
Figure 1. Typical silicotic nodule, microscopic section. Courtesy of Dr. V. Vallyathan.
The precise properties of silica particles that evoke the pulmonary response described above are not known, but surface characteristics may be important. The nature and the extent of the biological response are in general related to the intensity of the exposure; however, there is growing evidence that freshly fractured silica may be more toxic than aged dust containing silica, an effect perhaps related to reactive radical groups on the cleavage planes of freshly fractured silica. This may offer a pathogenic explanation for the observation of cases of advanced disease in both sandblasters and rock drillers where exposures to recently fractured silica are particularly intense.
The initiating toxic insult may occur with minimal immunological reaction; however, a sustained immunological response to the insult may be important in some of the chronic manifestations of silicosis. For example, antinuclear antibodies may occur in accelerated silicosis and scleroderma, as well as other collagen diseases in workers who have been exposed to silica. The susceptibility of silicotic workers to infections, such as tuberculosis and Nocardia asteroides, is likely related to the toxic effect of silica on pulmonary macrophages.
The link between silicosis and tuberculosis has been recognized for nearly a century. Active tuberculosis in silicotic workers may exceed 20% when community prevalence of tuberculosis is high. Again, people with acute silicosis appear to be at considerably higher risk.
Clinical Picture of Silicosis
The primary symptom is usually dyspnoea, first noted with activity or exercise and later at rest as the pulmonary reserve of the lung is lost. However, in the absence of other respiratory disease, shortness of breath may be absent and the presentation may be an asymptomatic worker with an abnormal chest radiograph. The radiograph may at times show quite advanced disease with only minimal symptoms. The appearance or progression of dyspnoea may herald the development of complications including tuberculosis, airways obstruction or PMF. Cough is often present secondary to chronic bronchitis from occupational dust exposure, tobacco use, or both. Cough may at times also be attributed to pressure from large masses of silicotic lymph nodes on the trachea or mainstem bronchi.
Other chest symptoms are less common than dyspnoea and cough. Haemoptysis is rare and should raise concern for complicating disorders. Wheeze and chest tightness may occur usually as part of associated obstructive airways disease or bronchitis. Chest pain and finger clubbing are not features of silicosis. Systemic symptoms, such as fever and weight loss, suggest complicating infection or neoplastic disease. Advanced forms of silicosis are associated with progressive respiratory failure with or without cor pulmonale. Few physical signs may be noted unless complications are present.
Radiographic Patterns and Functional Pulmonary Abnormalities
The earliest radiographic signs of uncomplicated silicosis are generally small rounded opacities. These can be described by the ILO International Classification of Radiographs of Pneumoconioses by size, shape and profusion category. In silicosis, “q” and “r” type opacities dominate. Other patterns including linear or irregular shadows have also been described. The opacities seen on the radiograph represent the summation of pathologic silicotic nodules. They are usually found predominantly in the upper zones and may later progress to involve other zones. Hilar lymphadenopathy is also noted sometimes in advance of nodular parenchymal shadows. Egg shell calcification is strongly suggestive of silicosis, although this feature is seen infrequently. PMF is characterized by the formation of large opacities. These large lesions can be described by size using the ILO classification as categories A, B or C. Large opacities or PMF lesions tend to contract, usually to the upper lobes, leaving areas of compensatory emphysema at their margins and often in the lung bases. As a result, previously evident small rounded opacities may disappear at times or be less prominent. Pleural abnormalities may occur but are not a frequent radiographic feature in silicosis. Large opacities may also pose concern regarding neoplasm and radiographic distinction in the absence of old films may be difficult. All lesions that cavitate or change rapidly should be evaluated for active tuberculosis. Acute silicosis may present with a radiologic alveolar filling pattern with rapid development of PMF or complicated mass lesions. See figures 2 and 3.
Figure 2. Chest radiograph, acute silico-proteinosis in a surface coal mine driller. Courtesy of Dr. NL Lapp and Dr. DE Banks.
Pulmonary function tests, such as spirometry and diffusing capacity, are helpful for the clinical evaluation of people with suspected silicosis. Spirometry may also be of value in early recognition of the health effects from occupational dust exposures, as it may detect physiologic abnormalities that may precede radiologic changes. No solely characteristic pattern of ventilatory impairment is present in silicosis. Spirometry may be normal, or when abnormal, the tracings may show obstruction, restriction or a mixed pattern. Obstruction may indeed be the more common finding. These changes tend to be more marked with advanced radiologic categories. However, poor correlation exists between radiographic abnormalities and ventilatory impairment. In acute and accelerated silicosis, functional changes are more marked and progression is more rapid. In acute silicosis, radiologic progression is accompanied by increasing ventilatory impairment and gas exchange abnormalities, which leads to respiratory failure and eventually to death from intractable hypoxaemia.
Complications and Special Diagnostic Issues
With a history of exposure and a characteristic radiograph, the diagnosis of silicosis is generally not difficult to establish. Challenges arise only when the radiologic features are unusual or the history of exposure is not recognized. Lung biopsy is rarely required to establish the diagnosis. However, tissue samples are helpful in some clinical settings when complications are present or the differential diagnosis includes tuberculosis, neoplasm or PMF. Biopsy material should be sent for culture, and in research settings, dust analysis may be a useful additional measure. When tissue is required, open lung biopsy is generally necessary for adequate material for examination.
Vigilance for infectious complications, especially tuberculosis, cannot be overemphasized, and symptoms of change in cough or hemoptysis, and fever or weight loss should trigger a work-up to exclude this treatable problem.
Substantial concern and interest about the relationship between silica exposure, silicosis and cancer of the lung continues to stimulate debate and further research. In October of 1996, a committere of The International Agency for Research on Cancer (IARC) classified crystalline silica as a Group I carcinogen, reaching this conclusion based on “sufficient evidence of carcinogenicity in humans”. Uncertainty over the pathogenic mechanisms for the development of lung cancer in silica-exposed populations exists, and the possible relationship between silicosis (or lung fibrosis) and cancer in exposed workers continues to be studied. Regardless of the mechanism that may be responsible for neoplastic events, the known association between silica exposures and silicosis dictates controlling and reducing exposures to workers at risk for this disease.
Prevention of Silicosis
Prevention remains the cornerstone of eliminating this occupational lung disease. The use of improved ventilation and local exhaust, process enclosure, wet techniques, personal protection including the proper selection of respirators, and where possible, industrial substitution of agents less hazardous than silica all reduce exposure. The education of workers and employers regarding the hazards of silica dust exposure and measures to control exposure is also important.
If silicosis is recognized in a worker, removal from continuing exposure is advisable. Unfortunately, the disease may progress even without further silica exposure. Additionally, finding a case of silicosis, especially the acute or accelerated form, should prompt a workplace evaluation to protect other workers also at risk.
Screening and Surveillance
Silica and other mineral-dust exposed workers should have periodic screening for adverse health effects as a supplement to, but not a substitute for, dust exposure control. Such screening commonly includes evaluations for respiratory symptoms, lung function abnormalities, and neoplastic disease. Evaluations for tuberculosis infection should also be performed. In addition to individual worker screening, data from groups of workers should be collected for surveillance and prevention activities. Guidance for these types of studies is included in the list of suggested readings.
Therapy, Management of Complications and Control of Silicosis
When prevention has been unsuccessful and silicosis has developed, therapy is directed largely at complications of the disease. Therapeutic measures are similar to those commonly used in the management of airway obstruction, infection, pneumothorax, hypoxaemia, and respiratory failure complicating other pulmonary disease. Historically, the inhalation of aerosolized aluminium has been unsuccessful as a specific therapy for silicosis. Polyvinyl pyridine-N-oxide, a polymer that has protected experiment animals, is not available for use in humans. Recent laboratory work with tetrandrine has shown in vivo reduction in fibrosis and collagen synthesis in silica exposed animals treated with this drug. However, strong evidence of human efficacy is currently lacking, and there are concerns about the potential toxicity, including the mutagenicity, of this drug. Because of the high prevalence of disease in some countries, investigations of combinations of drugs and other interventions continue. Currently, no successful approach has emerged, and the search for a specific therapy for silicosis to date has been unrewarding.
Further exposure is undesirable, and advice on leaving or changing the current job should be given with information about past and present exposure conditions.
In the medical management of silicosis, vigilance for complicating infection, especially tuberculosis, is critical. The use of BCG in the tuberculin-negative silicotic patient is not recommended, but the use of preventive isoniazid (INH) therapy in the tuberculin-positive silicotic subject is advised in countries where the prevalence of tuberculosis is low. The diagnosis of active tuberculosis infection in patients with silicosis can be difficult. Clinical symptoms of weight loss, fever, sweats and malaise should prompt radiographic evaluation and sputum acid-fast bacilli strains and cultures. Radiographic changes, including enlargement or cavitation in conglomerate lesions or nodular opacities, are of particular concern. Bacteriological studies on expectorated sputum may not always be reliable in silicotuberculosis. Fiberoptic bronchoscopy for additional specimens for culture and study may often be helpful in establishing a diagnosis of active disease. The use of multidrug therapy for suspected active disease in silicotics is justified at a lower level of suspicion than in the non-silicotic subject, due to the difficulty in firmly establishing evidence for active infection. Rifampin therapy appears to have enhanced the success rate of treatment of silicosis complicated by tuberculosis, and in some recent studies response to short-term therapy was comparable in cases of silicotuberculosis to that in matched cases of primary tuberculosis.
Ventilatory support for respiratory failure is indicated when precipitated by a treatable complication. Pneumothorax, spontaneous and ventilator-related, is usually treated by chest tube insertion. Bronchopleural fistula may develop, and surgical consultation and management should be considered.
Acute silicosis may rapidly progress to respiratory failure. When this disease resembles pulmonary alveolar proteinosis and severe hypoxaemia is present, aggressive therapy has included massive whole-lung lavage with the patient under general anaesthesia in an attempt to improve gas exchange and remove alveolar debris. Although appealing in concept, the efficacy of whole lung lavage has not been established. Glucocorticoid therapy has also been used for acute silicosis; however, it is still of unproven benefit.
Some young patients with end-stage silicosis may be considered candidates for lung or heart-lung transplantation by centres experienced with this expensive and high-risk procedure. Early referral and evaluation for this intervention may be offered to selected patients.
The discussion of an aggressive and high-technology therapeutic intervention such as transplantation serves dramatically to underscore the serious and potentially fatal nature of silicosis, as well as to emphasize the crucial role for primary prevention. The control of silicosis ultimately depends upon the reduction and control of workplace dust exposures. This is accomplished by rigorous and conscientious application of fundamental occupational hygiene and engineering principles, with a commitment to the preservation of worker health.