Objectives

1. Review the diagnostic criteria for silicosis.
2. Review the classification schemes for the radiographic diagnosis of silicosis.
3. Summarize the relationship between silica exposure and mycobacterial disease.
4. Outline the relationship between silica exposure and the increased rate of FEV₁ decline.
5. Address the relationship between silica exposure and lung cancer.

Key words: lung cancer; obstructive lung disease; silica; silicosis

Abbreviations: PEL = permissible exposure limit; PMF = progressive massive fibrosis; PPD = purified protein derivative

Introduction

The prevalence of silicosis peaked in the last half of the 19th century and the early part of the 20th century. A series of epidemics of silicosis occurred in the United States over this period of time, with some occurring in the same industries years apart (Table 1). The result has been the premature death of many workers.

With the initiation of effective dust control measures and compliance with these measures, the prevalence of silicosis has decreased dramatically. However, workers in many occupations are exposed to silica and are at risk for silica-related adverse health effects. For example, miners of some ores or minerals and drillers exploring for oil or natural gas are at risk for excessive silica exposure as they drill through siliceous rock. In some mines and quarries, compliance with the permissible exposure limit (PEL) has been achieved simply by instituting wetting techniques; however, workers in many disparate industries remain at risk (Table 2). The common thread among occupations where silica-related lung disease occurs is the manipulation of the silica particle by making it smaller (eg, sandblasting, drilling into siliceous rock, or exposure to finely milled silica [silica flour]). Without changing the silica particle so that it becomes a respirable size (an aerodynamic diameter of <10 μm), the particle is trapped by the upper airway defenses. Particles <1 μm in diameter are the most fibrogenic. Depending on the distribution of particle sizes, up to 80% of the dust deposited in the alveoli can be quickly cleared.¹ It is the small fraction of retained particles that initiates and perpetuates the fibrosis.

In addition to the clinical disease of silicosis, silica exposure also is associated with an increased risk for mycobacterial infection, the development of obstructive lung disease, and an increased risk for lung cancer.

Silicosis: The Clinical Illness

There are three requisites for the diagnosis of silicosis. The worker must first provide a history of silica exposure that is thought by the physician to be sufficient to cause this illness. Knowledge of the length of employment and the specific job(s) performed by the worker is important. Information regarding dust levels in the workplace can provide important information, yet this approach cannot be guaranteed to represent the complete picture. Cases of acute silicosis in surface coal mine drillers using dry techniques have been reported where the measured dust levels were within the PEL.² The results were not representative of the overwhelming number of dust exposures that induce very aggressive silicosis, and there were no measurements of the percentage of free crystalline silica in the measured mine dust. It is essential to understand the conditions in which the samples were collected and have confidence that these results accurately represent the workplace environment. Sometimes, this can only happen by going to the workplace and observing how the work is performed.

Although the best solution for avoiding excessive dust exposure is engineering control of the exposure, respiratory protective devices are sometimes needed. Respiratory protection devices may be protective, but their effectiveness may be highly variable.³ Silicosis can occur in workers even though they use personal respiratory protection.

The second requisite for the diagnosis of silicosis is that the chest radiograph must show opacities consistent with silicosis, which typically present as small, rounded opacities in the upper lung zones.

The third requisite is that there are no underlying illnesses that mimic silicosis. These illnesses might include a miliary distribution of mycobacterial or fungal organisms, rheumatoid nodules (referred to as Caplan syndrome when occurring in the presence of pneumoconiosis), malignancy (most often considered when the coalesced lesions of progressive massive fibrosis are unilateral or asymmetric), or sarcoidosis. Although the diagnosis of silicosis is nearly always made on a clinical basis, histologic examination of lung tissue is occasionally necessary. Finally, although respiratory symptoms and lung function impairment are commonly present, neither is necessary for the diagnosis.

It is important to mention that the silicotic nodule, the histologic hallmark of silicosis, may begin de novo or continue to enlarge even after exposure has ceased. For this reason, the physician’s initial response to the diagnosis of silicosis should be to recommend that the worker cease exposure to silica. Yet, even if the worker ceases exposure, it does not guarantee that the disease will not progress.

Silicosis can be categorized in two ways. In the first scheme, the disease is categorized by the extent of profusion of opacities on the chest radiograph and described as either simple silicosis or conglomerate silicosis or progressive massive fibrosis (PMF). On the chest radiograph, simple silicosis is recognized as a profusion of small (<1 cm in diameter) rounded opacities (nodules) predominant in the upper lung zones. In some patients, these small opacities gradually enlarge and coalesce to form larger, typically bilateral, upper zone opacities of similar sizes (>1 cm in diameter), recognized as conglomerate silicosis or PMF.

In some workers with lesser silica exposure, silica deposited on the alveolar surface is relatively efficiently cleared from the alveolar spaces into the regional chest lymph nodes. In such an instance, the chest radiograph reveals peripheral calcification of the hilar lymph nodes, and sometimes mediastinal lymph nodes, with only a minimal background or no background of small, rounded opacities.

The final radiographic presentation occurs rarely and is referred to as acute silicosis. It is the result of an overwhelming exposure over only several years. The effect of this excessive exposure may potentiate its fibrogenic effect by the fact that this "freshly" fractured silica possesses considerably more free radical oxygen species than "stale" or "old" fractured silica.⁴ In some patients with acute silicosis, the chest radiograph appears as a basilar alveolar filling pattern (identical to that seen in pulmonary alveolar proteinosis, hence the term "silicoproteinosis"⁵) without rounded opacities or lymph node calcifications. With time, these features progress to large masses of coalesced parenchymal tissue, typically bilateral but not always symmetrical, in the mid- and lower zones. In other patients with very excessive silica exposures, the radiographic features are those of simple silicosis that progress to conglomerate silicosis in a very short time frame, which is consistent with acute silicosis. The explanation for the very different radiographic response of an alveolar filling pattern vs a very aggressive nodular silicosis in the face of an overwhelming silica exposure is not known, but it might reflect important differences in an individual’s pulmonary lymphatic drainage.⁶

In the second scheme, silicosis is categorized by the duration from initial exposure to the recognition of the disease. The time frames are imprecise, but this approach is useful because of its relevance to prognosis. Classic silicosis develops slowly. Usually, 10 to 30 years, which is considered to be a working lifetime, are required from the beginning of exposure to the recognition of radiographic manifestations. In a minority of patients, the nodules of simple silicosis coalesce to become PMF. Accelerated silicosis occurs infrequently and appears radiographically as simple silicosis that develops after <10 years of excessive silica exposure. The development of silicosis after such a short time signals that a worker is at great risk for the immunologic sequelae of silicosis, such as scleroderma-like skin changes or kidney disease,⁷ and for the development of PMF. Finally, acute silicosis occurs over a fewer number of years and is associated with an inexorable progression toward a rapid respiratory death.

Mycobacterial Infection

Silica exposure also is associated with the development of mycobacterial infection with ensuing respiratory impairment, even in the absence of silicosis.⁸ In some workers exposed to silica, silicotic nodules are present, but they are of an inadequate profusion to allow for a radiographic diagnosis of silicosis. However, the mechanisms of fibrogenesis are underway. Cellular and humoral features that alter immunologic mechanisms and may be a result of silica-induced immunologic impairment are present. Mycobacterial infection in a person with silicosis has the very great potential to hasten respiratory impairment and shorten the person’s life. In an individual with silicosis, progression of the disease shown radiographically over a relatively short time period indicates a superimposed mycobacterial infection until proven otherwise. A new infiltrate, coalescence of nodules in the upper lung fields, an acute chest illness, or cavitation of a preexisting lesion are reasons for great concern and demand an aggressive search for mycobacterial organisms.

Although not studied in a systematic fashion, authors have suggested that it is clinically reasonable to administer yearly chest radiographs and a purified protein derivative (PPD) skin test in patients with silicosis. This may or may not be the case. The incidence of mycobacterial infections in patients with silicosis varies with the prevalence of this infection in the general population. For example, in a population of South African miners, performing a PPD just once a year may not be frequent enough to identify new infection. In other developed countries where the risk for tuberculosis is low, the yearly administration of a PPD skin test may be more frequent than needed.

In a patient with silicosis with negative acid-fast bacilli smears and a positive tuberculin test, 6 months of isoniazid therapy reduced the incidence of silicotuberculosis by one-half.⁹ The American Thoracic Society (ATS) and the Centers for Disease Control and Prevention recommend treatment with 300 mg of isoniazid daily for a year or a 4-month course of a multidrug regimen in this setting.^10-12 Anecdotal reports¹³ have advocated longer, even lifelong, multiple-drug, antituberculous prophylactic therapy. Active tuberculosis is treated with four-drug therapy, and, once the drug sensitivities are known, two drugs are likely to be effective.

Obstructive Pulmonary Disease

In the general population, cigarette smoking accounts for the overwhelming proportion of patients with severe airways obstruction. However, since most smokers show relatively little excess loss of lung function (smokers average a 10 to 20 mL/y excess rate of FEV₁ decline), which often returns toward normal when the individual ceases smoking, and just 10 to 15% of the smoking population severely affected, it is clear that there is a very wide range of individual susceptibility. The explanation for this individual susceptibility remains elusive, and the "apparent randomness" of severe adverse effects induced by cigarette smoke inhalation may explain why many individuals begin smoking and continue to smoke. Zay and colleagues¹⁴ suggested that the mechanism for silica-induced emphysema is similar to that of cigarette-induced emphysema, ie, the release of proteolytic enzymes from dust-evoked inflammatory cells, particularly neutrophils and macrophages, and inactivation of α₁-antitrypsin by the dust-catalyzed formation of oxidants.

The association between chronic dust exposure and loss of lung function in an obstructive pattern (the rate of FEV₁ decline exceeds the rate of FVC decline), even in the absence of simple pneumoconiosis, began to find acceptance in the 1980s. Dust exposures may adversely alter lung function by inducing industrial bronchitis or worsening smoking-induced bronchitis. What is not generally agreed upon is the degree of lung function decline, with or without cigarette smoking, that is attributable to dust exposure alone, and whether occupational dust exposure alone can cause "clinically important" airways obstruction and disabling impairment.¹⁵

The basis for the effects of airways obstruction, as it relates to silica, is formed in large part by epidemiologic studies of South African gold miners. For the most part, investigators of these populations have found an association between silica dose and an accelerated rate of FEV₁ decline in workers exposed to silica dust. Gold mine dust contains roughly 30% free silica. As with other dusts, chronic bronchitis can develop and be associated with a decline in flow rates. The particles have an impact on the bifurcations of the terminal conducting airways, leading to small airway wall (peribronchiolar) fibrosis and thickening. These pathologic changes adversely affect small airway flow rates.¹⁶ Silica particles are engulfed by alveolar macrophages, which release proteolytic enzymes and toxic-free radical species. These cells have the potential to destroy alveolar walls and cause histologic change that may eventually lead not only to fibrosis, but also to emphysema.¹⁷ However, it should be noted that a description of emphysema in silicosis is conspicuously absent in other reports.¹⁸

A metaanalysis by Oxman and colleagues¹⁹ found occupational dust to be an important cause of COPD. The risk appears to be greater for gold miners, with silica exposure as their primary fibrogenic dust exposure, than for coal miners. Studies conducted between 1966 and 1991 were reviewed. In these studies, dust measurements were available and the relationship between dust exposure and outcome was determined while controlling for age and smoking. Although 13 studies were available, they encompassed only four different cohorts. Three of the cohorts were coal miners and one cohort consisted of gold miners. All of the studies found a statistically significant association between the loss of lung function and cumulative respirable dust exposure. One possible explanation of the greater risk among gold miners compared with other dust-exposed populations is the higher silica content in gold mine dust.

There is a statistically significant relationship between FEV₁ decline and dust exposure.²⁰ In a population of dust-exposed workers, it appears that a small proportion of workers may develop a clinically significant decline in FEV₁. In the population of workers who develop declines in FEV₁, processes such as asthma, bronchospasm, bronchiectasis, chronic bronchitis, airway responsiveness, and emphysema also may play a role and occur independently from dust exposure.

There are several cautions in interpreting attributing airways obstruction in dust-exposed populations. Chronic bronchitis occurs frequently in dust-exposed workers, so it is often likely to be responsible for FEV₁ declines.²¹ Further studies of the outcome of chronic bronchitis in those who leave dust exposure conditions would help us better understand the role of chronic bronchitis and changes in lung function. Although reports of the statistically expected number of workers with "clinically significant" declines in FEV₁ exist in populations with dust exposure, the number of declines thought to be attributable to dust has not been frequently reported.²² The number of declines also has not been reported among "blue collar" workers where dust exposure is absent.

Emphysema can be found in silica-exposed nonsmokers without silicosis. Silica dust may trigger air space enlargement; however, the relationship between the histologic features of emphysema, the clinical features of dust-induced chronic bronchitis, and the rate of lung function decline in a dust-exposed population is not clear. The relationship between silica dust exposure and silica-induced emphysema appears to be stronger when silicosis is present.

Attributing a decline in FEV₁ to dust exposure in any individual worker may not be reasonable unless specific information regarding the worker’s overall health is available. For example, in a epidemiologic study of a population of steel workers with dust exposure who underwent yearly spirometry testing twice or more over a decade, 3 of 203 (1.5%) and 17 of the remaining 200 (8.5%) steel workers who never smoked had final FEV₁ values <65% or between 65% and 80% predicted, respectively.²³ Of the three workers with FEV₁ values <65% predicted, one was morbidly obese (BMI of 39.6 kg/m²), with an FEV₁/FVC of 70%; the second had a history of a crush injury with fractured ribs, arm, and pelvis, and a diaphragmatic hernia, and an FEV₁/FVC of 88%; and the third had an FEV₁ of 64% and FVC of 59% (FEV₁/FVC of 89%). In this case, the explanation for this apparent restriction was unclear. In the 17 workers with FEV₁ values between 65% and 80% predicted, one chart was unavailable for review, 1 worker had chest trauma, 1 worker was obese with asthma, 7 were obese, 3 had asthma, and 2 had hay fever. Medical conditions that might explain the decline in FEV₁ in the remaining two workers were not apparent. When one looks at the rate of FEV₁ decline in a population, it may not be obvious that the decrease is associated with obstructive or restrictive impairment. In addition, the explanation for this decline is not always apparent.

Although cumbersome, an assessment of the individual is necessary to understand the relationship between dust exposure, lung function decline, and other medical problems. The failure to identify these problems in individual workers may be a weakness of epidemiologic reports.

Cancer

Many animal and human epidemiologic studies have addressed the issue of whether exposure to crystalline silica plays a role in the development of pulmonary neoplasms. The issue is complex. Rats with silica injected into the pleural space develop malignant histiocytic lymphoma, and intratracheal instillation can result in respiratory neoplasms that resemble human bronchogenic carcinoma, yet autopsy findings from gold miners with silicosis have not shown an excess of lung cancer.²⁴

The question of silicosis and lung cancer was addressed by the International Agency for Research on Cancer (IARC) working group in 1987. The first report from this group on this subject concluded that there was sufficient evidence for the carcinogenicity of crystalline silica in experimental animals but only limited evidence in humans; a casual interpretation was credible, but chance, bias, and confounding could not be ruled out. Crystalline silica was classified as 2A—probably carcinogenic to humans.

In 1997, based on an increased amount of information to review, including nine additional cohort studies, the IARC concluded that there was sufficient evidence for the carcinogenicity of inhaled crystalline silica, and labeled silica as group 1A—definitely carcinogenic to humans. However, the IARC noted that carcinogenicity was not detected in all industrial circumstances and may be dependent on inherent characteristics of the crystalline silica or external factors affecting its biologic activity or distribution of its polymorphs. This unusual statement sparked considerable debate. Two reviews of these cohort studies and the process yielding the conclusion of carcinogenicity are available.^25,26

In 1988, Costello and Graham²⁷ reported mortality in a cohort of workers employed in the Vermont granite industry. Within this population, there was a high-exposure group of workers hired before 1940 and a low-exposure group of workers hired after 1940. Dust control measures by the Vermont State Health Department were implemented around 1938. Comparison of the mortality of the two groups showed the standardized mortality ratio (SMR) for lung cancer and cancer of the respiratory tract to be elevated in stone shed workers hired before 1930. However, it was not elevated in the entire cohort of workers, which included the quarrymen. Shed workers hired before 1940 with ≥40 years of latency and ≥30 years of tenure showed an increased SMR for lung cancer of 181.2 (P<0.01). This result was cited by the IARC as one of six studies considered to be relatively free of confounding factors, providing support for the hypothesis that granite dust exposure increases the risk of human lung cancer.

The Vermont granite mortality cohort study has been updated with conflicting conclusions. Attfield and Costello²⁸ assessed the quantitative exposure response for silica dust and lung cancer in this cohort group. Eight categories for quartz dust dose in individual workers were established using dust exposure measurements from 1924 to 1977. Work in this industry was translated into person-years of exposure. The results showed an increase of lung cancer with cumulative exposure, occurring at the lowest levels of exposure. The authors concluded that even the current recommended exposure limits by the National Institute for Occupational Safety and Health (half of the current PEL) might not be fully protective for workers exposed for a full working lifetime. Alternatively, Graham and colleagues²⁹ updated the mortality experience of this same Vermont granite cohort and compared mortality patterns between workers hired before and after 1940, when dust levels had been lowered by an estimated factor of 80 to 90%. The smoking history of workers who died of lung cancer also was examined. No worker who began employment after 1940 died of silicosis, although two died of TB. The cancer mortality findings did not support the IARC conclusions. There was an elevation in the SMR for lung cancer among quartz-exposed quarry workers hired before 1940, but when pre- and post-1940 hire groups were analyzed separately and compared, elevations in lung cancer SMRs were essentially the same in both groups, despite differences in quartz exposure. The authors concluded that if quartz is truly a carcinogen, the cancer incidence would be expected to be less in the low-exposure group. In addition, a second working group of knowledgeable investigators with an interest in silica-related diseases reported a lack of association between lung cancer and exposure to crystalline silica.³⁰

Nevertheless, the IARC, ATS, and NIOSH³¹ have concluded that lung cancer is associated with occupational exposures to crystalline silica.³² Metaanalyses of the epidemiologic studies of silica exposure and lung cancer in different exposed populations reported a summary relative risk of 1.3 for silica-exposed workers (a moderate increase in risk) and higher summary relative risks of 2.2 to 2.8 for workers with silicosis.^33,34 A recent metaanalysis³⁵ revealed that cigarette smoking strongly increased the lung cancer risk in patients with silicosis (relative risk, 4.47). The available data support the conclusion that silicosis produces an increased risk for bronchogenic carcinoma but are less clear as to whether silica exposure is associated with lung cancer in the absence of silicosis.

Conclusions

References

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