Heavy metal worker's pneumonoconiosis with lung parenchymal damage and Peripheral neuropathy: case report.

Heavy metals even at low concentrations can damage all systems in the human body from the cellular level by causing disruptions in DNA repair mechanisms, cell division and apoptosis. A 49-year-old man who had been working in the sanding and deburring department of a factory producing underground water pipes for 15 years, presented with complaints of effort dyspnea, cough and loss of strength in his left hand. Computed tomography of the lung revealed diffuse micronodular appearance in all zones in both lungs, subpleural nodule and bronchial dilatation. All serological tests for autoimmune disease were negative. Neurological examination of the patient revealed signs of 2nd motor neuron involvement only in one upper extremity. All of the tests that were studied for the differential diagnosis of multifocal motor neuropathy were found negative. Open lung biopsy with videothoracoscopy was practiced and interstitial changes were observed in the lung parenchyma with intense iron accumulation with Prussian blue stain. The patient was diagnosed with hard metal lung disease (HMLD) and toxic neuropathy (TN) with peripheral nerve involvement due to exposure to metal dust in the working environment. Although the patient had no loss of lung function, he was removed from the working environment, because of function loss in the left hand and is still being followed up.

Interstitial lung disease related to occupational hard metal exposure: two case reports.

BACKGROUND: Hard metal lung disease (HMLD) is a relatively less known occupational interstitial lung disease, and instances of HMLD resulting from para-occupational exposure are rarely reported. CASE PRESENTATION: This paper presents two cases of interstitial lung disease caused by exposure to hard metal. The first case involves a 37-year-old Taiwanese man who had worked at a grinder station for hard metal materials for 12 years without respiratory protective equipment. He experienced a dry cough and exertional dyspnea, and his chest imaging and pathology findings were consistent with the features of usual interstitial pneumonia. Analysis of his lung tissue revealed the presence of tungsten and cobalt. The second case involves a 68-year-old Taiwanese woman, the mother of the first patient, who had hand-washed her son's workwear. She experienced a dry cough and had similar imaging findings to her son. After her son left his job, they both exhibited improved symptoms and lung functions with nintedanib treatment. These findings suggest a diagnosis of HMLD and interstitial lung disease resulting from para-occupational exposure to hard metal dust. CONCLUSIONS: The diagnosis of HMLD relies on obtaining a detailed occupational exposure history. If HMLD is diagnosed, discontinuing exposing to hard metal dusts can lead to improved lung function.

The effect of different drugs on hard metal lung disease in a rat model.

Hard metal lung disease (HMLD) drugs include dexamethasone sodium phosphate (Dex), methylprednisolone (MP) injection, N-acetylcysteine injection (NAC), and a mix of Dex, MP, and NAC (MIX). In this study, we compared the effects of these drugs on different cytokines of hard metal lung disease in a rat model. Thirty-six adult female Sprague Dawley rats were distributed equally into the control group, hard metal (HM) group, Dex group, MP group, NAC group, and MIX group. HM powder (0.5 mL, 20 mg/mL; one time) was administered by intraperitoneal injection to the HM group through the pulmonary endotracheal tube, while the control group received normal saline (0.5 mL, 20 mg/mL; one time). After 4 weeks, the drugs were administered to the experimental groups (0.5 mL, 20 mg/mL; one time). After 8 weeks, bronchoalveolar lavage fluid (BALF) and serum were examined for cytokine levels. Biochemical analysis indicated that the Dex, MP, NAC, and MIX did not improve TGF-ß1, TGF-ß2, KL-6, and MMP-1 in the BALF, while MIX increased TIMP-1 in BALF. In addition, the NAC treatment significantly increased the expression levels of TGF-ß1, TGF-ß2, KL-6, and MMP-1. The MIX treatment significantly increased the expression levels of TGF-ß1, TGF-ß2, and KL-6. The MP treatment significantly increased the expression levels of KL-6, and MMP-1. The Dex treatment significantly increased the expression levels of TGF-ß1, KL-6, and MMP-1. This study demonstrated that administered with NAC and MIX could improve TGF-ß1, TGF-ß2, and KL-6 in serum of hard metal lung disease in a rat model. Therefore, NAC injection may be considered a useful candidate in the development of a preventive agent against HMLD.

PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis.

Prolonged exposure to hard metal dust results in hard metal lung disease (HMLD) characterized by respiratory symptoms. Understanding the pathogenesis and pathological process of HMLD would be helpful for its early diagnosis and treatment. In this study, we established a mouse model of hard metal-induced acute lung injury through one-time intratracheal instillation of WC-Co dust suspension. We found that WC-Co treatment damaged the lungs of mice, leading to increased production of IL-1ß, TNF-α, IL-6 and IL-18, inflammatory cells infiltration and apoptosis. In vitro, WC-Co induced cytotoxicity, inflammatory response and apoptosis in macrophages (PMA-treated THP-1) and epithelial cells (A549) in a dose-dependent manner. Moreover, RNA-sequence and validation experiments verified that Pentraxin 3 (PTX3), an important mediator in the regulation of inflammation, was elevated both in vivo and in vitro induced by WC-Co. Functional experiments confirmed the PTX3, which was located on the membrane of apoptotic cells, promoted macrophage efferocytosis efficiently. This progress could help block the lung inflammation and contribute to the rapid recovery of WC-Co-induced acute lung injury. These observations provide a further understanding of the molecular mechanism of WC-Co-induced pulmonary injury and disclose PTX3 as a new potential therapeutic approach to relieve WC-Co-induced acute lung injury via efferocytosis.

The relationship between respiratory health and hard metal dust exposure: A cross-sectional study.

The frequency and severity of respiratory disorders among workers exposed to hard metal dust is not well known.The objective of this cross-sectional study is to report the prevalence of respiratory symptoms, functional status, and radiological findings in hard metal-exposed workers in Türkiye.Among 139 workers, 96 were machining workers, and 43 were industrial tool sharpening workers. Radiographic abnormalities compatible with pneumoconiosis were found 39% of the workers and were more in machining workers statistically significant.Also, in machining workers group, percentage of expected values of FVC was lower than industrial tool sharpening workers group. The prevalence of respiratory symptoms was 14.3%, and there was not a statistically significant difference in working groups. The study reveals that pulmonary symptoms, functional abnormalities, and radiological findings are mild. Assuming that reversibility may develop with avoidance from exposure when detected at this stage, early diagnosis of lung damage is essential.

Cobalt-related interstitial lung disease or hard metal lung disease: A case series of Chinese workers.

Hard metal lung disease (HMLD) is rarely diagnosed and is caused by the occupational inhalation of hard metal dust, mainly cobalt. The diagnosis of HMLD is based on a thorough occupational dust exposure combined with clinical-radiological-histological findings. We present a series of four Chinese workers who had occupational exposure to cobalt acid lithium or cobalt and tungsten dust. Four patients all complained of intermittent cough, chest tightness, or shortness of breath on exertion. High-resolution computed tomography scans presented bilateral ground-glass attenuation, consolidations, and/or reticular opacities with diffuse small nodules. Histologic findings showed that interstitial inflammation and fibrotic lesions distributed peribronchioles. The infiltrations by macrophages as well as visible multinucleated giant cells indicated giant cell interstitial pneumonia (GIP). Cobalt was detectable in the lung tissues of two patients measured by inductively-coupled plasma mass spectrometry. The first patient was diagnosed with cobalt-related interstitial lung disease (ILD), while the others were HMLD. GIP is the classic pathology of cobalt-related ILD or HMLD. One of the patients showed spontaneous remission after the cessation of exposure, while the other three recovered within 6-32 weeks after avoiding occupational exposure and using corticosteroids. At follow-up, all four patients showed no recurrence. A multidisciplinary diagnostic panel including occupational cobalt exposure evaluation is beneficial to recognize cobalt-related ILD or HMLD and to indicate the necessity of prevention.

Hard Metal Lung Disease with Favorable Response to Corticosteroid Treatment: A Case Report and Literature Review.

Hard metal lung disease (HMLD) is a pneumoconiosis caused by occupational exposure to hard metals such as tungsten carbide and cobalt, but the treatment strategies for HMLD have not been well established. A 68-year-old Japanese man with occupational history as a grinder of hard metals for 18 years referred to our hospital because of dry cough and dyspnea. A chest computed tomography (CT) on admission revealed centrilobular micronodules, ground-glass opacities, and reticular opacities in the peripheral zone of both lungs. Mineralogic analyses of lung tissues detected components of hard metals, such as tungsten, titanium and iron, and the same metals were also detected in the sample of the dust of his workplace. Thus, the patient was diagnosed as having HMLD based on occupational exposure history and radiologic and mineralogic analyses of the lung. Corticosteroid therapy was initiated, which resulted in partial improvements in his symptoms, radiological and pulmonary functional findings. In a review of the 18 case reports of HMLD treated with corticosteroids, including our case, the majority of patients (77.8%) showed favorable responses to corticosteroid treatment. Furthermore, the presence of fibrotic changes, such as reticular opacity, in radiological examinations was associated with the resistance to corticosteroids. In conclusion, the majority of patients with HMLD are expected to favorable response to corticosteroid treatment, whereas chest CT findings such as fibrotic changes may be predictive of the resistance of corticosteroid treatment. Lastly, proper prevention of hard metal exposure is most important as the first step.

Study of lung toxicity in rats exposed to silica powder with different hard metal constituents.

The objective of this study was to assess the lung toxicity induced by the inhalation of different hard metal constituents and silica powder and screen for potential toxicity biomarkers. Rats were randomly divided into saline, cobalt, tungsten carbide, silica, and hard metal (HM) groups and were administered a single 10-mg dose of the respective treatments. After 8 weeks, the lung tissue structure in the HM group was deformed, numerous nucleated giant and epithelial-like cells appeared in the stroma, and the computed tomography scanning images appeared abnormal. Krebs von den Lungen-6 (KL-6), transforming growth factor (TGF)-ß1, and TGF-ß2 expression in bronchoalveolar lavage fluid (BALF) significantly differed between the groups ( p < 0.05). Serum KL-6 and TGF-ß1, but not TGF-ß2, levels significantly differed between some groups ( p < 0.05). We observed multinucleated giant cells in the rat lung tissue. While the serum and BALF levels of KL-6 and TGF-ß2 are not highly specific, TGF-ß1 may be a valuable reference diagnostic marker in HM lung disease.

Occupational hard metal lung disease: a case report / 中国职业医学

OBJECTIVE: To report the clinical manifestations,chest imaging,pathological changes,diagnosis and treatment on one case of hard metal lung disease( HMLD).METHODS: The occupational history,clinical manifestations,chest computed tomography and lung histopathological examinations of a case with pathologically confirmed HMLD were summarized.RESULTS: The patient began to cough and have dyspnea on exertion after 7 years of hard metal dust exposure of cobalt and tungsten, and pulmonary function test showed a restrictive ventilation dysfunction.Chest computed tomography showed bilateral areas of diffuse lesions,including ground-glass attenuation,areas of consolidation,diffuse small nodules, extensive reticular opacities and traction bronchiectasis.The lung histopathological changes include macrophage interstitial pneumonia,which is macrophages and a large number of multinucleated giant cells in the alveolar space.CONCLUSION: A clear history of hard metal dust exposure and the pathological examination of lung tissue are helpful for the diagnosis of HMLD.

Cobalt related interstitial lung disease.

Cobalt exposure in the hard metal and bonded diamond tool industry is a well-established cause of ILD. The primary theories regarding the underlying mechanism of cobalt related ILD include an immunologic mechanism and an oxidant injury mechanism. Cobalt related ILD may present in subacute and chronic forms and often has associated upper respiratory symptoms. The evaluation begins with a thorough occupational history and includes PFTs, HRCT, and bronchoalveolar lavage. HRCT findings are nonspecific and may resemble NSIP, UIP, sarcoidosis, or HP. The finding of cannibalistic multinucleated giant cells is diagnostic provided there is a history of exposure and appropriate changes on imaging; however, when these cells are not found on lavage, lung biopsy is required for diagnosis. Giant cell interstitial pneumonia is the classic pathologic pattern, but cobalt related ILD may also present with pathologic findings of UIP, DIP, or HP. When cobalt related ILD is suspected, removal from exposure is the most important step in treatment. Case reports suggest that treatment with steroids results in symptomatic, physiologic, and radiographic improvement.

Clinical analysis on hard metal lung disease / 中国职业医学

OBJECTIVE: To analyze the clinical features,and diagnostic and therapeutic method of hard metal lung disease( HMLD). METHODS: By using literature metrology method,the open published case reports associated with HMLD from January 1980 to October 2015 were searched using the China Hospital Knowledge Database,Wanfang Database and Pub Med Database. The data of patients with hard metal dust exposure history were collected and analyzed based on the inclusive and exclusive criteria. RESULTS: Thirty-six cases of HMLD were collected. The onset age of patients was 21. 0-63. 0( 37. 2 ± 11. 7) years old. The median exposure time was 6. 0( 0. 6-43. 0) years,and the major working type was hard metal grinder. The main clinical type of HMLD maily was giant cell interstitial pneumonia( GIP),hypersensitivity pneumonitis and occupational asthma were also seen. HMLD was lack of characteristic clinical manifestation. The clinical symptoms of HMLD mainly included dry cough,dyspnea on exertion,restrictive pulmonary ventilation,and diffuse pulmonary dysfunction. The imaging study showed ground-glass opacity,diffuse small nodule shadow and reticular opacity shadow,which were mainly seen in the lower lobes of both lungs. There were 24 cases( 66. 7%) showed GIP in the lung tissue in pathological examination. The tungsten and cobalt elements were detected in lung tissue and bronchoalveolar lavage fluid in some cases. Among 22 patients treated with glucocorticoid after keeping away from hard metal dust exposure,the treatment was effective in 19 patients. The clinical symptoms of 6 patients were improved by avoiding hard metal dust exposure. CONCLUSION: HMLD belongs to the interstitial lung disease and there is no specific clinical manifestation. Glucocorticoid therapy is effective in most of the patients. The history of exposure to hard metal dust has important significance in making the diagnosis.

Two cases of hard metal lung disease showing gradual improvement in pulmonary function after avoiding dust exposure.

We present herein two cases of hard metal lung disease (HMLD) with distinct pathological findings. Both cases showed gradual improvements in pulmonary function over a period of a few years (Case 1: 30 months; Case 2: 12 months) after the avoidance of dust exposure, while improvements on high-resolution computed tomography were modest. The increased lymphocytes and decreased CD4/CD8 ratio in BALF observed at initial diagnosis normalized after the avoidance of dust exposure in one case. To the best of our knowledge, this is the first report demonstrating continual follow-up of pulmonary function and radiographic findings, and a comparison of BALF findings before and after avoidance of hard metal dust exposure.

Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer.

Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases.