Constrictive pericarditis in a patient with fiberglass lung disease: a case report.

BACKGROUND: Fiberglass has a larger aerodynamic diameter and is less likely to be inhaled into the lungs. Further, it will be cleared even if it is mechanically broken into smaller pieces and inhaled into the lungs. Fiberglass lung disease has been well documented if long term exposure but was thought reversible and would not cause severe diseases. The diagnosis of fiberglass lung disease depends on exposure history and histopathological findings. However, the exact occupational exposure history is often difficult to identify because mixed substance exposure often occurs and fiberglass disease is not as well-known as asbestosis. CASE PRESENTATION: A 66-year-old man had unexplained transudative pericardial effusion requiring pleural pericardial window operation twice at another medical center where asbestosis was told because of his self-reported long-term asbestosis exposure and the histopathological finding of a ferruginous body in his lung. Constrictive pericarditis developed two years later and resulted in congestive heart failure. Radical pericardiectomy combined with lung biopsy was performed following chest computed tomography imaging and the transudative nature of pericardial effusion not compatible with asbestosis. However, the histopathologic findings of his lung and pericardium at our hospital only showed chronic fibrosis without any asbestosis body. The patient's lung was found to be extremely fragile during a lung biopsy; histopathologic specimens were reviewed, and various fragments of fiberglass were found in the lung and pericardium. The patient's occupational exposure was carefully reevaluated, and he restated that he was only exposed to asbestosis for 1-2 years but was heavily exposed to fiberglass for more than 40 years. This misleading exposure history was mainly because he was only familiar with the dangers of asbestos. Since most fiberglass lung diseases are reversible and the symptoms of heart failure resolve soon after surgery, only observation was needed. Ten months after radical pericardiectomy, his symptoms, pleural effusion, and impaired pulmonary function eventually resolved. CONCLUSION: Fiberglass could cause inflammation of the pericardium, resulting in pericardial effusion and constrictive pericarditis, which could be severe and require radical pericardiectomy. Exact exposure history and histopathological examinations are the key to diagnosis.

[Asbestos: detection and characterization in tissue]. / Asbest: Nachweis und Charakterisierung im Gewebe.

BACKGROUND: When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of an asbestos-related disease. OBJECTIVES: The aim of this review is to present methods to detect asbestos bodies in lung tissue, the development of diagnostic criteria and to discuss pros and cons of different methods. MATERIALS AND METHODS: Observations and evaluations from the German Mesothelioma Register, along with relevant literature review and expert recommendations in guidelines are presented. RESULTS: Assessing asbestos-related diseases requires recognition of the person's occupational history, the asbestos fiber burden in the lungs, and determining fiber types. Various methods have been developed and validated, including light microscopy techniques such as bright-field microscopy, phase-contrast microscopy, polarization microscopy, and differential interference microscopy, as well as electron microscopy techniques like field-emission-scanning electron microscopy (e.g., FE-SEM) and transmission electron microscopy (TEM). CONCLUSION: The use of asbestos has been heavily restricted worldwide, even completely banned in Europe. Thus, patients' exposure to asbestos is decreasing. However, asbestos exposure during renovations, demolitions, or through unconscious handling of asbestos-containing materials remains a concern.

The diagnosis of asbestosis in the 21st century: a clinicopathological correlation of 102 cases.

Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21st century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001. 102 cases were identified, with a median age of 75 years (range: 45-89). There were 100 men and 2 women. The women were from Turkey and Brazil (none from the United States). Malignancies were present in 78 cases, including 38 lung cancers, 29 pleural mesotheliomas, and 8 peritoneal mesotheliomas. The grade of asbestosis was available in 88 cases (median severity of 2; scale: 1-4). Pleural plaque was present in 94% of cases. The most common exposure categories were insulators (39), shipyard workers (16), asbestos manufacturing (9), boiler workers (8) and pipefitter/welders (6). The median duration of exposure was 33 years (range: 2-49 years). Lung fiber burden analysis was performed in 34 cases, with amosite being the predominant fiber type. Results were compared with similar information for 475 cases diagnosed prior to 1/1/2001.

Recognizing the pleura in asbestos-related pleuropulmonary disease: Known and new manifestations of pleural fibrosis.

Pleural thickening (PT) is a major consequence of exposure to all fiber types of asbestos. In recent decades, it is more prevalent than parenchymal asbestosis. Its manifestations occupy a full clinical and radiographic spectrum. Six major manifestations can be identified: (a) acute pleuritis generally with effusion; (b) diffuse PT or fibrous pleuritis; (c) rounded atelectasis; (d) circumscribed PT or plaques; (e) chronic pleuritic pain; and (f) mesothelioma. Review of the experience of workers and community members in Libby, MT to asbestiform fibers in vermiculite has confirmed the appearance of these previously known benign and malignant asbestos-related diseases as well as a unique pleuropulmonary disease characterized as lamellar PT and associated with progressive decline in pulmonary function and pleuritic pain. Despite previous literature asserting that PT represents a marker for asbestos exposure without significant effect on pulmonary function and physiology, the experience of Libby amphibole (LA) disease, along with other studies, indicates that PT plays a role in declining vital capacity in those with prolonged or unusual exposures such as those arising from LA.

Closing the knowledge gap on the composition of the asbestos bodies.

Asbestos bodies (AB) form in the lungs as a result of a biomineralization process initiated by the alveolar macrophages in the attempt to remove asbestos. During this process, organic and inorganic material deposit on the foreign fibers forming a Fe-rich coating. The AB start to form in months, thus quickly becoming the actual interface between asbestos and the lung tissue. Therefore, revealing their composition, and, in particular, the chemical form of Fe, which is the major component of the AB, is essential to assess their possible role in the pathogenesis of asbestos-related diseases. In this work we report the result of the first x-ray diffraction measurements performed on single AB embedded in the lung tissue samples of former asbestos plant workers. The combination with x-ray absorption spectroscopy data allowed to unambiguously reveal that Fe is present in the AB in the form of two Fe-oxy(hydroxides): ferrihydrite and goethite. The presence of goethite, which can be explained in terms of the transformation of ferrihydrite (a metastable phase) due to the acidic conditions induced by the alveolar macrophages in their attempt to phagocytose the fibers, has toxicological implications that are discussed in the paper.

Asbestos-associated pulmonary disease.

PURPOSE OF REVIEW: Exposure to asbestos can cause both benign and malignant, pulmonary and pleural diseases. In the current era of low asbestos exposure, it is critical to be aware of complications from asbestos exposure; as they often arise after decades of exposure, asbestos-related pulmonary complications include asbestosis, pleural plaques, diffuse pleural thickening, benign asbestos-related pleural effusions and malignant pleural mesothelioma. RECENT FINDINGS: Multiple recent studies are featured in this review, including a study evaluating imaging characteristics of asbestos with other fibrotic lung diseases, a study that quantified pleural plaques on computed tomography imaging and its impact on pulmonary function, a study that examined the risk of lung cancer with pleural plaques among two large cohorts and a review of nonasbestos causes of malignant mesothelioma. SUMMARY: Asbestos-related pulmonary and pleural diseases continue to cause significant morbidity and mortality. This review summarizes the current advances in this field and highlights areas that need additional research.

Characteristics of asbestos fibers in lung tissue from occupational and environmental asbestos exposure of lung cancer patients in Busan, Korea.

The Asbestos Injury Relief Act in Korea requires that asbestos exposure be assessed through clinical examination and chest computed tomography (CT). However, a more specific measurement of asbestos characteristics in the lung tissue may be appropriate. We aimed to investigate the asbestos burden and characterize asbestos fibers in patients with lung cancer and ultimately assess the relationship between occupational and environmental asbestos exposure and lung cancer in Korea. We evaluated 37 lung cancer patients (LCPs) from Busan. The factors affecting asbestos burden in LCPs were analyzed using a multiple regression analysis. History of asbestos exposure (environmental/occupational), male sex, and old age were the main factors affecting asbestos burden in lung tissues of LCPs. These factors had an approximate 37% adjusted coefficient of determination. There was a significant difference in the length of asbestos fibers (4.06-37.6 µm vs. 4.26-91.7 µm) and aspect ratio (4.5-151.9 vs. 5.6-735.6) between those who were occupationally exposed to asbestos and those who were environmentally exposed (P < 0.01). Therefore, both environmental/occupational exposure to asbestos should be strongly managed to reduce the risk of lung cancer, and exposure should be assessed according to the characteristics of asbestos fibers in the lung tissue.

Mitochondrial 8-oxoguanine DNA glycosylase mitigates alveolar epithelial cell PINK1 deficiency, mitochondrial DNA damage, apoptosis, and lung fibrosis.

Alveolar epithelial cell (AEC) apoptosis, arising from mitochondrial dysfunction and mitophagy defects, is important in mediating idiopathic pulmonary fibrosis (IPF). Our group established a role for the mitochondrial (mt) DNA base excision repair enzyme, 8-oxoguanine-DNA glycosylase 1 (mtOGG1), in preventing oxidant-induced AEC mtDNA damage and apoptosis and showed that OGG1-deficient mice have increased lung fibrosis. Herein, we determined whether mice overexpressing the mtOGG1 transgene (mtOgg1tg) are protected against lung fibrosis and whether AEC mtOGG1 preservation of mtDNA integrity mitigates phosphatase and tensin homolog-induced putative kinase 1 (PINK1) deficiency and apoptosis. Compared with wild type (WT), mtOgg1tg mice have diminished asbestos- and bleomycin-induced pulmonary fibrosis that was accompanied by reduced lung and AEC mtDNA damage and apoptosis. Asbestos and H2O2 promote the MLE-12 cell PINK1 deficiency, as assessed by reductions in the expression of PINK1 mRNA and mitochondrial protein expression. Compared with WT, Pink1-knockout (Pink1-KO) mice are more susceptible to asbestos-induced lung fibrosis and have increased lung and alveolar type II (AT2) cell mtDNA damage and apoptosis. AT2 cells from Pink1-KO mice and PINK1-silenced (siRNA) MLE-12 cells have increased mtDNA damage that is augmented by oxidative stress. Interestingly, mtOGG1 overexpression attenuates oxidant-induced MLE-12 cell mtDNA damage and apoptosis despite PINK1 silencing. mtDNA damage is increased in the lungs of patients with IPF as compared with controls. Collectively, these findings suggest that mtOGG1 maintenance of AEC mtDNA is crucial for preventing PINK1 deficiency that promotes apoptosis and lung fibrosis. Given the key role of AEC apoptosis in pulmonary fibrosis, strategies aimed at preserving AT2 cell mtDNA integrity may be an innovative target.

A case of hypersensitivity pneumonitis in a worker exposed to terephthalic acid in the production of polyethylene terephthalate.

Occupational hypersensitivity pneumonitis (OHP) is an interstitial lung disease caused by sensitization to an inhaled antigen. Polyethylene terephthalate (PET) is mainly used for disposable beverage bottles. A clinical case of hypersensitivity pneumonitis (HP) in a 66-year-old patient in the follow-up as a worker formerly exposed to asbestos is presented. At the first visit in 2012 a diagnosis of asbestosis and pleural plaques was formulated. In 2017 the high resolution computed tomography was performed demonstrating a slight progression of the pulmonary fibrosis, while physical examinations revealed inspiratory crackles on auscultation, and lung function tests showed a decreased diffusing capacity for carbon monoxide. The radiological and histological pictures were compatible with HP. From 1992 to 2013 the patient worked in a chemical company that produced PET for disposable beverage bottles. A diagnosis of OHP was made, and the most likely causative agents were terephthalic acid and dimethyl terephthalate. To the best of the authors' knowledge, this is the first report of an OHP case in PET production. Int J Occup Med Environ Health. 2020;33(1):119-23.

[Asbestos and its effects on health of Icelanders - review].

Asbestos are crystallized silicate minerals that form fibers with different structures and characteristics. Asbestos fibers are very durable and can tolerate very high temperatures. Therefore it was common to use asbestos as a fire retardants, heat insulation and where high temperature is used. Asbestos has been banned in Iceland from 1983 but can still be found in large amounts in buildings, ships and hot water pipes. Large amounts of asbestos were imported in the years before the ban but diminished soon to almost nothing today. Needle or filamentous shaped dust is released when working with asbestos. It is this dust that is dangerous for health. The latent time from exposure to disease can be up to forty years. Asbestos reaches the lungs via inhalation and can cause asbestosis that is a form of lung fibrosis with slow progression. Asbestos can also cause benign pleural effusions, pleural plaques and diffuse pleural thickening. Asbestos is a carcinogen. Lung cancer is most common but asbestos is also a risk factor for cancers of other organs. Mesothelioma is most common in the pleura but can be seen in other membranes. The incidence of these tumors is high in Iceland and is still increasing among males. Of all the European countries mortality is highest in Iceland. It is important for physicians to include asbestos exposure in the differential diagnosis of lung diseases and when lung cancer is diagnosed.

Bronchoalveolar cell differential count and the number of asbestos bodies correlate with survival in patients with asbestosis.

OBJECTIVES: To determine cell differential counts and the number of asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid obtained from patients with asbestosis, and to correlate the results with their survival. METHODS: The BAL cell differential counts and ABs from 91 patients with asbestosis were determined. The BAL cell differential counts were analysed in relation to smoking status. BAL cell differential counts and the number of ABs were correlated with the patients' survivals. RESULTS: A neutrophilic cell pattern was observed independently of smoking habits with both Papanicolau (8.4%) and May-Grunwald-Giemsa (6.5%) staining. Smoking and a high number of ABs (>2 AB/mL) were associated with high total cell counts and high macrophage and low lymphocyte differential counts. The median survival of the patients was 131.8 months. Shortened survival was associated with high numbers of ABs (78 vs 165 months; p=0.042) and low lymphocyte (77 vs 179 months; p=0.005), high neutrophil (102 vs 180 months; p=0.016) and high eosinophil (104 vs170 months; p=0.007) differential counts. CONCLUSION: A neutrophilic cell pattern was evident in BAL from patients with asbestosis. Smoking and ABs both affected the total cell count and the macrophage and lymphocyte differential counts. Several BAL parameters associated with patient survival, suggesting that BAL cell count analyses could be used in the estimation of the prognosis of patients with asbestosis.

Grade 4 asbestosis does not extend directly from the respiratory bronchiole to the peripheral lung.

AIMS: To confirm whether or not grade 4 asbestosis progresses from the respiratory bronchiole to the peripheral lung. METHODS AND RESULTS: We examined retrospectively the autopsy or lobectomy specimens from 31 cases (29 males; mean age 64 years) satisfying the pathological criteria of grade 4 asbestosis. Asbestos bodies (ABs) were quantified in samples of dissolved lung and in tissue preparations on glass slides. Respiratory bronchiolar lesions were graded as 0, 1 and ≥2. Grade 4 asbestosis was subdivided into an atelectatic induration (AI) and usual interstitial pneumonia pattern (UIP pattern). Five, 10, and 16 cases had grades 0, 1 or ≥2 lesions, respectively, with mean respective numbers of ABs in dissolved lung of 117 000/g dry lung, 468 000/g and 968 000/g; and in specimens on glass slides of seven ABs/cm2 of tissue slice, 34 ABs /cm2 and 195 ABs /cm2 . The differences were significant. Fifteen and 16 cases showed AI and UIP patterns, respectively, with mean respective numbers of ABs in dissolved lung of 1 006 000/g dry lung and 354 000/g, and 186 and 56 ABs/cm2 on glass slides. The differences were significant. AI patterns originated in subpleural lobules or subpleural zonal areas and UIP patterns originated in subpleural, peripheral lobules. CONCLUSIONS: Grade 4 asbestosis does not start in the respiratory bronchiole. The presence of a grade 1 lesion is not required for the diagnosis of grade 4 asbestosis.

Histological findings and lung dust analysis as the basis for occupational disease compensation in asbestos-related lung cancer in Germany.

OBJECTIVES: This study has researched the significance of histologically raised findings and lung dust analyses in the context of claiming the recognition of and thus compensation for an asbestos-associated occupational disease. MATERIAL AND METHODS: For this approach, all findings from the German Mesothelioma Register in 2015 that included lung dust analyses were evaluated and were compared with information on asbestos fiber exposure at work based on fiber years, and with the results of radiological findings. RESULTS: For 68 insured persons, recognition of an asbestos-induced lung disease according to Section 4104 of the German Ordinance on Occupational Diseases (Berufskrankheitenverordnung - BKV) could be recommended solely on the basis of the histological examinations of lung tissues and complementary lung dust analyses. Neither did the calculation of the cumulative asbestos dust exposure at work yield 25 fiber years, nor could bridge findings (e.g., plaques) be identified. In addition, the autopsies of 12 patients revealed plaques that had not been diagnosed during radiological examinations. These results show that - irrespective of the prescribed working techniques and radiological diagnosis - pathological/anatomical and histological diagnostics are often the only way for the insureds to demonstrate the causal connection between asbestos and their disease. Even after long intervals of up to 40 years post last exposure, the asbestos fibers would still be easily detectable in the lung tissues evaluated. CONCLUSIONS: Whenever suitable tissue is available, it should be examined for mild asbestosis with the aid of a lung dust analysis. Otherwise there is a risk that an occupational disease is wrongfully rejected. In the context of health insurance, the lung dust analysis and the resulting proof of the presence of asbestosis often constitute one option of providing evidence of an occupational disease. Int J Occup Med Environ Health 2018;31(3):293-305.

A clinical assessment and lung tissue burden from an individual who worked as a Libby vermiculite miner.

During its days of operation (1920s-1990), the world's largest source of vermiculite was extracted from a mine located near Libby, Montana. The material mined at this site was shipped for various commercial applications to numerous sites in the United States. There was a "fibrous" component with toxic potential within the vermiculite deposit that has resulted in "asbestos-like" diseases/deaths being reported in numerous studies involving miners as well as residents of the town of Libby. The present case involves the clinical assessments of an individual who worked at the mine from 1969 to 1990. He had no other known occupational exposures to fibrous materials. He developed a clinical picture that included "asbestos-like" pathological features and eventually an adenocarcinoma. The clinical assessment including radiographic features will be presented. The evaluation will also include the analytical evaluation of the fibrous/ferruginous body composition of the lung tissue. This is to our knowledge the first time such an extensive evaluation has been conducted in a vermiculite miner from Libby, Montana.

MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study.

BACKGROUND: The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression. AIMS: To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients. METHODS: miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients. CONCLUSIONS: All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.

State-of-the-art nanopathological diagnostics.

The nanopathological diagnostics (ND) is an ultra-specialized branch of pathological anatomy aimed to identify the nanoparticles of metallic, semimetallic, or nonmetallic elements in the inorganic particulate matter present inside pathological tissues, even on the nanometer scale. ND exploits an environmental scanning electron microscope, connected to an X-ray microprobe mounted on an energy-dispersive spectrometer. The searching of nanoparticles can be performed on paraffin-embedded material, omitting emissions of black overlay and plating procedures. The technique is highly sensitive and specific, reproducible and rapid, covering an entire operating cycle in few hours. Nowadays, ND finds many applications: (I) intratumor detection of heavy metals and endocrine metal disruptors; (II) identification of pathogenic nanoparticles in medical or veterinary drugs and devices, cosmetics, household products, and foodstuffs; (III) differential diagnosis of sarcoid-type granulomas (berylliosis, baritosis) and foreign body granulomas (prosthetic, iatrogenic); (IV) attestation of occupational disease correlating the datum with the occupational risk (anthracosis, asbestosis, bauxite fibrosis, byssinosis, chalicosis, siderosis, silicosis, stannosis, talcosis); and (V) forensic investigations to ascertain a causal link between disease and environmental, military, or work exposure. In addition to filling a knowledge gap, ND offers to the pathologist a current research field, with particular reference to the impact of occupational and environmental pollution on the human health and cancer.

First Identification of Pulmonary Asbestos Fibres in a Spanish Population.

INTRODUCTION: This study aimed to characterize, for the first time in Spain, the type of asbestos fibres (AF) in the lungs of exposed and non-exposed populations. MATERIALS AND METHODS: Lung samples from 38 subjects living in Barcelona and Ferrol, Spain, were studied, which were divided into three groups: Group A-five subjects without known respiratory disease; Group B-20 ex-shipyard workers and Group C-13 patients with lung cancer. After eliminating the organic material, the inorganic residue was analysed using electronic microscopy (EM). To identify the type of fibre, the samples were analysed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). RESULTS: All the fibres identified corresponded to amphiboles (crocidolite 45%, anthophyllite 22%, tremolite 16%, amosite 15% and actinolite 3%). In 14 patients (37%), a single type of asbestos was found in the lungs (amosite in two, actinolite in one, anthophyllite in four, crocidolite in five and tremolite in two). Forty-six percent of the AF analysed had a length > 5 µm and a diameter < 0.2 µm. CONCLUSIONS: The results of this study provide the first data on the type of asbestos retained in the lung of Spanish population. A particularly striking finding is the exclusive retention of amphiboles, which suggests that chrysotile is eliminated after inhalation. Our findings support estimations considering Spain and other southern European countries with similar asbestos imports and consumption at a high risk to develop asbestos-related diseases in the years to come.

[Analysis of changes in radiographic lung image and lung ventilation disorders in workers occupationally exposed to chrysotile in the past]. / Analiza zmian w obrazie radiologicznym pluc i zaburzen czynnosci wentylacyjnej pluc u pracowników zawodowo narazonych na azbest chryzotylowy w przeszlosci.

BACKGROUND: The adverse health effects of occupational exposure to asbestos dust may occur several years after first exposure. The objective of the study was to assess the relationship between lesions in the respiratory system and the factors contributing to occupational exposure to asbestos described in the first medical examination as well as to analyze the factors responsible for the progression of these changes in further medical tests. MATERIAL AND METHODS: The study group comprised 591 former workers of asbestos processing plant "Gambit" in Lubawka. The results of medical examinations carried out in 2001-2012 were assessed. Statistical inference was performed based on bilateral significance tests at the 0.05 level of significance. RESULTS: A higher risk of interstitial lung changes along with an increase in the cumulative concentration of asbestos was indicated; for the employees with the highest exposure, the adjusted odds ratio (OR) was 1.63 (95% confidence interval (CI): 0.99-2.71), while for changes with the severity degree qualifying for asbestosis diagnosis, the risk was significantly increased, over fivefold higher, compared to subjects employed in the lowest exposure. The analysis of the relationship between the progression of interstitial changes and the exposure to asbestos dust showed a fourfold higher risk of the progression in workers employed in the highest exposure. Mean values of FEV1 (forced expiratory volume in 1 s), FVC (forced vital capacity), FEV1/FVC (forced expiratory volume in 1 s to forced vital capacity) were significantly lower in the subjects working in a higher asbestos exposure. The effect of tobacco smoking on the occurrence of interstitial lung changes and their progression was also confirmed. CONCLUSIONS: The results of prophylactic medical examinations of the health status of workers formerly employed in the plants using chrysotile indicate the importance andthe need for a long-term clinical follow-up and the promotion of anti-smoking prevention in this group of former employees. Med Pr 2017;68(2):247-258.

New insights on the biomineralisation process developing in human lungs around inhaled asbestos fibres.

Once penetrated into the lungs of exposed people, asbestos induces an in vivo biomineralisation process that leads to the formation of a ferruginous coating embedding the fibres. The ensemble of the fibre and the coating is referred to as asbestos body and is believed to be responsible for the high toxicological outcome of asbestos. Lung tissue of two individuals subjected to prolonged occupational exposure to crocidolite asbestos was investigated using synchrotron radiation micro-probe tools. The distribution of K and of elements heavier than Fe (Zn, Cu, As, and Ba) in the asbestos bodies was observed for the first time. Elemental quantification, also reported for the first time, confirmed that the coating is highly enriched in Fe (~20% w/w), and x-ray absorption spectroscopy indicated that Fe is in the 3+ oxidation state and that it is present in the form of ferritin or hemosiderin. Comparison of the results obtained studying the asbestos bodies upon removing the biological tissue by chemical digestion and those embedded in histological sections, allowed unambiguously distinguishing the composition of the asbestos bodies, and understanding to what extent the digestion procedure altered their chemical composition. A speculative model is proposed to explain the observed distribution of Fe.

Dibutyryl-cAMP attenuates pulmonary fibrosis by blocking myofibroblast differentiation via PKA/CREB/CBP signaling in rats with silicosis.

BACKGROUND: Myofibroblasts play a major role in the synthesis of extracellular matrix (ECM) and the stimulation of these cells is thought to play an important role in the development of silicosis. The present study was undertaken to investigate the anti-fibrotic effects of dibutyryl-cAMP (db-cAMP) on rats induced by silica. METHODS: A HOPE MED 8050 exposure control apparatus was used to create the silicosis model. Rats were randomly divided into 4 groups: 1)controls for 16 w; 2)silicosis for 16 w; 3)db-cAMP pre-treatment; 4) db-cAMP post-treatment. Rat pulmonary fibroblasts were cultured in vitro and divided into 4 groups as follows: 1) controls; 2) 10-7mol/L angiotensin II (Ang II); 3) Ang II +10-4 mol/L db-cAMP; and 4) Ang II + db-cAMP+ 10-6 mol/L H89. Hematoxylin-eosin (HE), Van Gieson staining and immunohistochemistry (IHC) were performed to observe the histomorphology of lung tissue. The levels of cAMP were detected by enzyme immunoassay. Double-labeling for α-SMA with Gαi3, protein kinase A (PKA), phosphorylated cAMP-response element-binding protein (p-CREB), and p-Smad2/3 was identified by immunofluorescence staining. Protein levels were detected by Western blot analysis. The interaction between CREB-binding protein (CBP) and Smad2/3 and p-CREB were measured by co-immunoprecipitation (Co-IP). RESULTS: Db-cAMP treatment reduced the number and size of silicosis nodules, inhibited myofibroblast differentiation, and extracellular matrix deposition in vitro and in vivo. In addition, db-cAMP regulated Gαs protein and inhibited expression of Gαi protein, which increased endogenous cAMP. Db-cAMP increased phosphorylated cAMP-response element-binding protein (p-CREB) via protein kinase A (PKA) signaling, and decreased nuclear p-Smad2/3 binding with CREB binding protein (CBP), which reduced activation of p-Smads in fibroblasts induced by Ang II. CONCLUSIONS: This study showed an anti-silicotic effect of db-cAMP that was mediated via PKA/p-CREB/CBP signaling. Furthermore, the findings offer novel insight into the potential use of cAMP signaling for therapeutic strategies to treat silicosis.