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Considerable attention has recently been paid to the biomarkers in the prevention of occupational diseases, in form of scientific literature. Different categories of biomarkers are used to (1) assess exposure, (2) identify early changes or effects of this exposure, (3) identify the initiation of pathological changes prior to development of disease state, and (4) predict underlying susceptibility of persons to disease, still the usage is not precedent.
What is a Biomarker?
The term “biomarker”, a portmanteau of “biological marker”, which refers to a broad subcategory of medical signs – which can be measured accurately and reproducibly. Medical signs stand in contrast to medical symptoms, which are limited to those indications of health or illness perceived by patients themselves[1].
A joint venture on chemical safety, the International Programme on Chemical Safety, led by the World Health Organization (WHO) and in coordination with the United Nations (UN) and the International Labor Organization (ILO), has defined a biomarker as “any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease”[2].
Club cell protein 16[3] – According to the paper published by ICMR, patients with silicosis are prone to develop pulmonary tuberculosis (i.e., silicotuberculosis), probably due to destruction of alveolar macrophages. The club cell protein 16 (formerly known as Clara cell protein) aka (CC16) is one of the potentially immunosuppressive or anti-inflammatory proteins secreted from non-ciliated epithelial cells of bronchoalveolar epithelium which is being used in the study. Though the exact physiological mechanism of CC16 was unknown, the study suggests significant reduction of CC16 in silica dust-exposed workers. With no change in respiratory symptoms, normal chest X-ray and lung function tests indicates that CC16 could be an early asymptomatic detection tool for silicosis and silica-exposed population at risk.
Age and occupational silica dust exposure history of both the non-smoker and smoker groups were taken separately before running the tests for better results. Long-term exposure to silica dust may result in a reduction in CC16 levels in serum and can be used as a blood serum biomarker for higher accuracy in the diagnosis of silicosis[4].
Importance of Biomarkers in Silicosis diseases – An important aspect of the control of occupational disease is early detection, so that treatment can be given while the disease is still reversible. Occupational diseases are usually severe, and disabling. However, two factors make them easily preventable: first, the causal agents of these diseases can be identified, measured, and controlled; second, the populations at risk are usually easily accessible and can be regularly supervised and treated[5]. Furthermore, the initial changes are often reversible if treated promptly and effectively. Differential diagnosis is difficult unless the physician is proficient and aware of the occupational dust (silica) exposure history of the workers, which is very subjective in nature. Hence, with the help of biomarkers, early diagnosis or prediction may become very useful to control the disease.
Clinical detection of silicosis is dependent on the detection of radiological abnormalities, which are sometimes late (5 to 10 year following exposure) and are mostly irreversible manifestation of disease. Exposition of the mechanisms of action of crystalline silica-induced fibrosis has contributed greatly to the identification of a number of biological responses that are involved in the pathogenesis of silicosis[6].
Long-term exposure to respirable dust containing silica leads to silicosis. The disease is irreversible and incurable. Silicosis is histologically characterized by hyalinized and fibrotic pulmonary nodules, accumulation of lymphocytes and alveolar macrophages, and thickening of pulmonary alveolar interstitium[7]. The diseases caused by continuous inhalation of the silica dust (crystalline silica, SiO2 (Silicon dioxide)) with marked inflammation and irreversible scarring[8] of the lungs with nodules in the upper lobes.
Some other Identified Biomarkers for Silicosis
- Neopterin. – regarded as an early biomarker of the cellular immune response. The increased serum neopterin concentration could be used as a marker for silicosis[9].
- Serum selenium – Serum Se (Selenoprotein P) concentrations were found to be at inadequate levels in patients with silicosis, and decreased significantly with the severity of the disease[10].
- Angiotensin-converting enzyme – The serum activity of ACE in pulmonary diseases is of interest owing to its principal localization in the large capillary bed of the lungs[11].
- Serum Cu – as the primary pathologic changes in silicosis include fibrosis and the proliferation of collagen tissue in the lungs there could be possible association with raised levels of serum Cu as copper has a fibrogenic property. But this is not certain if the person is yet to develop the disease[12].
- Heme oxygenase-1 – Pulmonary HO-1 expression is increased in case of silicosis[13].
- Fas ligand (FasL) – Fas/ FasL expression in silicosis patients to be significantly higher than those in healthy controls which are associated to immunological abnormalities[14].
Conclusion –
Even though there are several biomarkers which has been studied till date, but there is no such biomarker which can be both absolute precise and cost effective. The CC16 being the recent research have proved to be rationale, but the study lacks the descriptive cost analysis. Tests like ELISA as used in these studies are expensive (Rs 13500 – Rs 70000 per kit) and cannot be afforded in general. Moreover these groups of workers (stone quarries/industries or coal mines) are some of the poorest with minimum wages and hence such expensive tests will be unaffordable even if near-specific with early diagnosis.
Thus to infer, it can be stated that though many investigations have been tried to develop a suitable biomarker for silicosis, further studies are needed to establish a cost effective biomarker of the disease so that the early prediction of silicosis in exposed workers and its prevention can be effectively done.
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