Silicosis Workup

Updated: Dec 05, 2019
  • Author: Bathmapriya Balakrishnan, MBBS, BMedSc(Melb); Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Approach Considerations

The diagnosis of silicosis is based on a history of exposure, chest radiographic appearance consistent with silicosis, and an absence of other diagnoses that simulate the radiographic abnormalities of silicosis. Clinical manifestations, symptoms, and physical examination findings provide evidence to support the diagnosis.


Laboratory Studies

Although various serologic abnormalities have been noted in patients with silicosis, they are not diagnostic of the disease, and tests to detect these abnormalities are not indicated routinely. Humoral immune system abnormalities observed in silicosis include an increased incidence and titer of rheumatoid factor, antinuclear antibodies, and immune complexes. No consistent abnormality is noted in the cell-mediated immune system.

Some of the markers being considered for utilization in the evaluation of silicosis are discussed below.

Serum coppper (Cu)

The primary pathologic changes in silicosis are fibrosis in the lungs. Studies conducted on Cu levels in blood serum indicate that Cu plays a very important role in the progress of lung fibrosis, and it has a direct relationship with serum Cu levels. Ren and Jiang confirmed that an increase in ceruloplasmin levels in the silicosis group is one of the factors for elevated Cu. [42]  Each ceruloplasmin molecule contains eight Cu atoms, and the Cu level in blood serum is maintained by ceruloplasmin. The Cu increase may therefore be explained by an increase in the ceruloplasmin level in blood serum. Thus, fibrosis of lungs due to silicosis is accompanied by increases in ceruloplasmin as well as Cu levels in blood serum. Tiwari et a conducted an important study involving 134 workers in quartz stone crushing units to assess serum Cu activity and concluded the following [43] :

  • There was no significant difference among different categories of workers when mean serum Cu levels were compared according to duration of exposure.
  • When workers were categorized according to the presence or absence of respiratory diseases, those having respiratory diseases and exposed for at least 1 year had significantly higher levels of serum Cu compared to those with a similar duration of exposure but who were disease free.
  • Smokers had significantly higher serum Cu values relative to nonsmokers.
  • When pulmonary function tests were categorized according to respiratory morbidity, serum Cu levels were higher among those with respiratory disorders compared to those free from disease.

Clara cell protein (CC16)

CC16 is a 16-kDa protein secreted by nonciliated cells of the tracheobronchial tree. It has been proposed as a peripheral marker of respiratory epithelial injury. Broeckaert and Bernard [44]  and Bernard et al [45]  found that Clara cells are one of the most multifunctional and heterogeneous cell types in the mammalian lung, with their main function being protection of the respiratory tract. The highest concentrations of CC16 are in sputum and bronchoalveolar lavage fluid, reflecting intense secretion of the protein in the airways. [45]  The protein also occurs, but in smaller concentrations, in other fluids such as urine, amniotic fluid, and semen. 

In a study that measured the concentration of CC16 in the serum of 86 miners exposed to silica-rich dust in a quarry (average exposure: 15.2 months) and 86 control subjects matched for age, body mass index, and smoking status, no appreciable difference could be detected between exposed and control workers with regard to respiratory symptoms, chest radiograph findings, or lung function tests. [45] However, the concentration of CC16 in serum decreased in silica-exposed workers (geometric mean 12.3 μg/L) compared to control subjects (16.3 μg/L). The decrease was found both in lifelong nonsmokers (14.7 vs 21.9) and current smokers (11.3 vs 14.5). Tobacco smoking caused a decrease in serum CC16 that was further lowered after silica exposure. [45] These serum concentrations of CC16 probably reflect the very early toxic effects of silica particles on the respiratory epithelium. This reinforces the view that serum CC16 is a sensitive marker, which might improve our ability to detect exposure to chemicals potentially harmful to the respiratory tract.

Heme oxygenase-1 (HO-1)

HO-1, a rate-limiting enzyme in heme catabolism, has antioxidative, anti-apoptotic and anti-inflammatory activities. Studies indicate that crystalline silica induces the production of reactive oxygen species (ROS), which play a key role in the development of silicosis.

HO-1 is present in the lungs of humans and mice with silicosis, especially at sites of silica particle deposition. In mice, silica exposure is associated with acute leukocyte infiltration, leading to the development of silicotic lung lesions. Inflammation has been shown to be suppressed by treatment with hemin, an inducer of HO-1, and enhanced by zinc protoporphyrin, an inhibitor of HO-1. Pulmonary HO-1 expression is increased in silicosis.

HO-1 suppresses ROS activity and subsequent pathologic changes, thereby attenuating disease progression. A study by Sato et al showed that HO-1 is persistently expressed in lung lesions of patients with silicosis. [46]  This appears to reflect ROS induction by silica, leading to elevation in serum HO-1 levels. The increased HO-1 can protect the host by suppressing silica-induced ROS activity. Thus, regulation of HO-1 may represent a novel strategy for treatment of silicosis.

A major limitation of all these studies is that they were conducted in a lateral dimension over a small time period and within a group population, which gives only statistical and probabilistic results with respect to an individual subject. Therefore, a more conclusive finding may be obtained when the observations from these biomarkers are monitored in a cohort or for a specific subject over a long period and the data are interpreted with a time scale. Although such studies may take longer (in years) to provide any meaningful changes in the characteristics' values, they will be more conclusive and have a more definite prognostic value with respect to the health status of the subjects under monitoring.


Imaging Studies

Over the last seven decades the International Labour Organization (ILO) has published a series of guidelines on how to classify chest radiographs of persons with pneumoconioses. The goals have been to standardize classification methods and facilitate international comparisons of data on pneumoconioses, epidemiologic investigations, and research reports. The 2011 ILO guidelines accommodate the use of digital images, and a set of standards for digital images is available. [47] Apart from improving consistency in the reading of parenchymal disease, which is notoriously subject to reader variability, these guidelines 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 ≥1 such opacities with a diameter > 1 cm but not exceeding a combined diameter of 5 cm), category B (≥1 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.

Quality control in terms of radiographic technique and reading procedures using the ILO classification and reader training is incorporated. This involves training seminars for physicians who may qualify as “A” readers (ie, attended the seminars) or “B” readers, who passed a comprehensive examination on the basis of 120 radiographs read into the ILO classification.

Uncomplicated silicosis is characterized by the presence of small rounded opacities on the chest radiograph as graded in the ILO classification. 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 in advanced silicosis determined by histology, no chest radiographic changes may be apparent.

Silicotic nodules are usually symmetrically distributed and tend to appear first in the upper zones, later, although not invariably, involving other zones. 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.

Progressive massive fibrosis is characterized by the coalescence of small rounded opacities to form larger lesions; they are graded on the ILO scale according to size and extent (categories A to C). Computed tomography (CT) assessment is superior to the chest radiograph in not only assessing the presence and extent of silicotic nodulation but also in revealing early conglomeration. With time, the mass lesions tend to contract, usually to the upper lobes, leaving hypertranslucent zones at their margins 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.

Acute silicosis is characterized radiologically by diffuse changes that usually display an air space and interstitial pattern rather than the usual nodularity.


Other Tests

The lung function profile is determined by the extent of the silicosis, as well as the associated or concomitant airway and vascular changes. In chronic silicosis, spirometric tests (forced expiratory volume in 1 second [FEV1 ], FEV1 / forced vital capacity [FVC]) usually reflect airflow limitation. Reduction in the diffusing capacity of carbon monoxide (DLCO) is generally apparent in more advanced chronic silicosis and reflects associated emphysema. In the accelerated and acute forms of silicosis, 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.

Either interferon-gamma release assays (IGRA) or the Mantoux tuberculin skin test (TST) should be used to test for latent tuberculosis infection (LTBI). In individuals who have a positive skin test result, sputum samples should be examined for acid-fast bacilli (AFB) by microscopy and cultured for AFB to identify active disease.




Silicosis is diagnosed based on a history of exposure and the characteristic radiographic changes. Problems arise when the history of exposure is remote, forgotten, or missed, or it has taken place outside a recognized occupation.  

Although bronchoscopy is not required for the diagnosis of silicosis, it is useful to exclude other conditions. Bronchoalveolar lavage (BAL) fluid may demonstrate lymphocytosis (20%, compared to 6% in healthy controls) or neutrophilia (10%, compared to 0% in healthy controls) in acute silicosis; however, these findings are nonspecific and are noted in other radiologically similar diseases, such as sarcoidosis and pulmonary fibrosis. [5]

BAL from patients with acute silicoproteinosis has classically been reported to be a milky effluent with positive periodic-acid Schiff stain; however, cases from more recent outbreaks rarely describe this finding. [5]


Histologic Findings

Examination of lung tissue is seldom warranted in cases of silicosis. Lung biopsy is typically pursued to distinguish progressive massive fibrosis or other atypical features from lung cancer and tuberculosis. 

The characteristic histopathologic finding is the silicotic nodule mostly located near the respiratory bronchiole. The nodule is composed of refractile particles of silica surrounded by whorled collagen in concentric layers, with macrophages, lymphocytes, and fibroblasts in the periphery. Emphysematous blebs surround the silicotic nodule, especially in the subpleural area. Birefringent crystals of silica in the center of a silicotic nodule may be identified by polarized light microscopy. For definitive identification, scanning electron microscopy combined with x-ray spectroscopy may be needed.

Acute silicosis is seldom seen. The histology is similar to pulmonary alveolar proteinosis, in which the alveoli are filled with proteinaceous material that stains with periodic acid-Schiff stain.