Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice.

Silicosis is an occupational disease triggered by the inhalation of fine particles of crystalline silica and characterized by inflammation and scarring in the form of nodular lesions in the lungs. In spite of the therapeutic arsenal currently available, there is no specific treatment for the disease. Flunisolide is a potent corticosteroid shown to be effective for controlling chronic lung inflammatory diseases. In this study, the effect of flunisolide on silica-induced lung pathological changes in mice was investigated. Swiss-Webster mice were injected intranasally with silica particles and further treated with flunisolide from day 21 to 27 post-silica challenge. Lung function was assessed by whole body invasive plethysmography. Granuloma formation was evaluated morphometrically, collagen deposition by Picrus sirius staining and quantitated by Sircol. Chemokines and cytokines were evaluated using enzyme-linked immunosorbent assay. The sensitivity of lung fibroblasts was also examined in in vitro assays. Silica challenge led to increased leukocyte numbers (mononuclear cells and neutrophils) as well as production of the chemokine KC/CXCL-1 and the cytokines TNF-α and TGF-ß in the bronchoalveolar lavage. These alterations paralleled to progressive granuloma formation, collagen deposition and impairment of lung function. Therapeutic administration of intranasal flunisolide inhibited granuloma and fibrotic responses, noted 28 days after silica challenge. The upregulation of MIP-1α/CCL-3 and MIP-2/CXCL-2 and the cytokines TNF-α and TGF-ß, as well as deposition of collagen and airway hyper-reactivity to methacholine were shown to be clearly sensitive to flunisolide, as compared to silica-challenge untreated mice. Additionally, flunisolide effectively suppressed the responses of proliferation and MCP-1/CCL-2 production from IL-13 stimulated lung fibroblasts from silica- or saline-challenged mice. In conclusion, we report that intranasal treatment with the corticosteroid flunisolide showed protective properties on pathological features triggered by silica particles in mice, suggesting that the compound may constitute a promising strategy for the treatment of silicosis.

Enfermeiro do trabalho na prevenção da silicose: uma revisão integrativa / Enfermero de trabajo en prevención de la silicosis: una revisión integradora / Occupational health nurse in the prevention of silicosis: an integrative review

Objective: to investigate the spread of knowledge regarding silicosis and to identify the occupational health nurse course of action to prevent it. Method: It is an integrative review of the literature held in the databases: LILACS, SciELO, BDENF and PubMed. The employed keywords were “silicosis”, “occupational health nursing” and “pneumoconiosis”, published in Portuguese, Spanish and English, in the years of 2004 to 2014. Eight articles met the inclusion criteria were selected and answered the guiding questions. Results:The selected articles seek to deepen the knowledge on silicosis, to estimate its prevalence, to establish the patient’s profile, to describe the major symptoms, to identify the major risk factors associated with the disease and to evaluate the quality of living of those afflicted by it. Conclusion: Silicosis is a public health problem with high prevalence and which requires very specific strategies to its prevention and control, especially those developed in occupational health nursing.

Objetivo: averiguar a divulgação do conhecimento sobre silicose e identificar ações do enfermeiro do trabalho para sua prevenção. Métodos: Trata-se de uma revisão integrativa da literatura realizada nas bases dedados LILACS, SciELO, BDENF e PubMed, utilizando-se os descritores “silicose”, “enfermagem do trabalho” e “pneumoconiose”, nos idiomas português, inglês e espanhol, dos anos de 2004 a 2014. Foram selecionados oito artigos que atenderam aos critérios de inclusão e responderam as questões norteadoras. Resultados: Os artigos selecionados abordam a silicose, estimam sua prevalência, delineiam o perfil dos portadores, descrevem os principais sintomas, identificam fatores de risco associados e avaliam a qualidade de vida dos acometidos. Conclusão: A silicose é um problema de saúde pública com alta prevalência, que necessita de estratégias específicas para seu controle e prevenção, especialmente aquelas desenvolvidas no âmbito da enfermagem do trabalho.

Objetivo: investigar la difusión del conocimiento sobre la silicosis e identificar las acciones del enfermero trabajo para su prevención. Método: Se trata de una revisión integradora de la literatura realizada en las bases de dados LILACS, SciELO, BDENF y PubMed utilizando las palabras clave “silicosis”, “enfermería de trabajo” y “neumoconiosis”, en Portugués, Inglés y Español. Fueron seleccionados de los años 2004 a 2014 ocho artículos que cumplieron con los criterios de inclusión y respondieron a las preguntas de orientación. Resultados: Los artículos seleccionados cubren silicosis, valorar su prevalencia, definir el perfil de los pacientes, describir los síntomas principales, identificar los factores de riesgo asociados y evaluar la calidad de vida de los afectados. Conclusión: La silicosis es un problema de salud pública con una alta prevalencia, que requiere estrategias específicas para su control y prevención, especialmente las desarrolladas en la enfermería de trabajo.

Erasmus syndrome: silicosis and systemic sclerosis.

The silicosis is the pneumoconiosis more frequent, resulting from the inhalation of silica or silicates containing mineral dust, mainly characterized by irreversible lung fibrosis. It is associated with the development of other diseases, including pulmonary tuberculosis, lung cancer and autoimmune diseases. The connective tissue disease after exposure to silica occurs usually after 15 years of initial exposure.The Erasmus syndrome describes the association of systemic sclerosis following exposure to silica with or without silicosis. The authors report two cases of patients with diagnosis of silicosis who developed systemic sclerosis.

Síndrome de Erasmus: silicose e esclerose sistêmica / Erasmus syndrome: silicosis and systemic sclerosis

A silicose é a pneumoconiose mais frequente, decorrente da inalação de sílica ou de poeiras minerais contendo silicatos, caracterizada principalmente pela fibrose pulmonar de caráter irreversível. Está associada com o desenvolvimento de outras doenças, incluindo tuberculose pulmonar, câncer pulmonar e doenças autoimunes. A doença do tecido conjuntivo posterior à exposição à sílica ocorre geralmente após 15 anos do início da exposição. A síndrome de Erasmus refere-se ao desenvolvimento de esclerose sistêmica em indivíduos previamente expostos à sílica e que apresentavam ou não silicose. Os autores relatam dois casos de pacientes com diagnóstico de silicose que desenvolveram esclerose sistêmica.

The silicosis is the pneumoconiosis more frequent, resulting from the inhalation of silica or silicates containing mineral dust, mainly characterized by irreversible lung fi brosis. It is associated with the development of other diseases, including pulmonary tuberculosis, lung cancer and autoimmune diseases. The connective tissue disease after exposure to silica occurs usually after 15 years of initial exposure.The Erasmus syndrome describes the association of systemic sclerosis following exposure to silica with or without silicosis. The authors report two cases of patients with diagnosis of silicosis who developed systemic sclerosis.

Silicose e Esclerose Sistêmica – Síndrome de Erasmus: relato de um caso / Silicosis and systemic sclerosis – Erasmus' syndrome: case report

A silicoesclerodermia, descrita inicialmente por Erasmus em 1957, é o resultado da interferência na imunidade celular relacionada à citotoxicidade da sílica, responsável pelas reações auto-imunes e pela formação de imunocomplexos circulantes. Neste relato, os autores descrevem o caso de um homem de 61 anos com antecedentes de exposição à sílica e que desenvolveu Síndrome de Erasmus.

Silicoscleroderma, described by Erasmus in 1957, is the result of cellular immunity interference related to the cytotoxicity of silica, and it is responsible for autoimmune reactions and formation of circulating immunecomplexes. In this text, the authors describe a 61-years-old man with previous exposure to silica, and who developed Erasmus’ syndrome.

Pneumoconiose: relato de caso / Case report: pneumoconiosis

VDVB, 38 anos, masculino, há 5 anos trabalha com jatos de areia. Em julho/2007 paciente referiu dispnéiade instalação súbita, associada à tosse seca, sudorese noturna e astenia. Há 4 meses teve perda ponderal de 10 quilos. Foi internado em franca insuficiência respiratória. Não apresenta comorbidades nem faz uso de medicações. Ao exame físico apresentou taquidispnéia (freqüência respiratória: 40mpm), taquicardia (freqüência cardíaca: 135bpm), tiragens intercostais, estertoração crepitanteem bases pulmonares, diminuição de murmúrios vesiculares à direita e saturação de oxigênio de 86%.Ao RX de tórax havia condensações alveolares difusas bilaterais e de aspecto confluente peri-hilar e basal direito. BAAR negativo. PPD não-reator. Ecocardiograma mostrou tronco da artéria pulmonar e calibre mantidos,fração de ejeção de 59% e prolapso de válvula mitral. À tomografia computadorizada, firmou-se o diagnóstico de pneumoconiose, devido à presença de micronódulosconfluentes formando massas parenquimatosas e subpleurais, com presença de adenomegalia para-hilar;cavitações ausentes. Medicações em uso no momento da internação: atrovent, berotec, meticorten, talofilina.Após compensação da insuficiência respiratória e paciente teve alta hospitalar e foi orientado quanto à irreversibilidade caso e a possibilidade de transplante pulmonar.

Silicose: exposição ocupacional e medidas preventivas / Silicosis: occupational exposure and preventive measures

A silicose é uma doença crônica e incapacitante com altas taxas de mortalidade e morbidade tornando-se uma preocupação não só no território nacional mas a n´vel internacional. A silicose é a pneumoconiose mais antiga e mesmo assim, medidas preventivas e tecnologia disponível nas indústrias não são suficientes para diminuir sua incidência. Mesmo com desenvolvimento de sistemas legislativos mais eficientes e conscientes, surtos de silicose aguda continuam a ocorrer em indústrias mesmo nos países mais desenvolvidos. Uma vez estabelecida a doença é irreversível tendo como única alternativa evitar a progressão da doença e o surgimento de complicações . Este trabalho foi realizado através de uma extensa revisão da literatura nacional e internacional, utilizando livros texto e artigos publicados nas principais revistas médicas com o objetivo de conhecer melhor a doença e sua epidemiologia, diferentes apresentações e possíveis formas de manejo terapêutico.

Tuberculosis and silicosis: epidemiology, diagnosis and chemoprophylaxis.

Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis) than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction to about one half of that obtained with placebo. Long-term regimens have potential side effects (particularly hepatotoxicity). In addition, the use of such regimens can jeopardize adherence to treatment. The current guidelines recommend that tuberculin skin tests be performed, and, if positive, that chemoprophylaxis be instituted. There are several possible regimens, varying in terms of the drugs prescribed, as well as in terms of treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10 mg/kg/day) for six months for patients with silicosis, as well as for healthy patients with periods of exposure to silica longer than 10 years and strongly positive tuberculin skin test results (induration > or = 10 mm). Nevertheless, further studies are necessary so that indications, drugs, doses and duration of chemoprophylaxis regimens can be more properly defined.

Tuberculose e silicose: epidemiologia, diagnóstico e quimioprofilaxia / Tuberculosis and silicosis: epidemiology, diagnosis and chemoprophylaxis

A silicose, a mais prevalente das pneumoconioses, é provocada pela inalação de partículas de sílica cristalina. Indivíduos expostos à sílica, com ou sem silicose, apresentam risco aumentado de tuberculose e de micobacterioses não-tuberculosas. O risco de silicóticos desenvolverem tuberculose em relação a controles sadios varia de 2,8 a 39 vezes, em conformidade com a gravidade da doença de base. Têm sido estudados diferentes esquemas de quimioprofilaxia para tuberculose em silicóticos, todos com eficácia semelhante e com redução final de risco para cerca da metade em relação ao uso de placebo. São, no entanto, esquemas de longa duração, o que, acrescido dos possíveis efeitos colaterais (particularmente hepatotoxicidade), podem prejudicar a aderência. As diretrizes atuais recomendam a realização de prova tuberculínica e, se positiva, a instituição de quimioprofilaxia. São vários os esquemas possíveis, tanto em termos de drogas quanto de duração. Nossa recomendação é de que se use isoniazida na dose de 300 mg/dia (ou 10 mg/kg/dia) por seis meses para os indivíduos com silicose ou sadios com exposição superior a 10 anos, se forem reatores fortes à prova tuberculínica (induração > 10 mm). São necessários, no entanto, novos estudos para que indicações, drogas, doses e duração da profilaxia sejam definidas mais apropriadamente.

Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis) than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction to about one half of that obtained with placebo. Long-term regimens have potential side effects (particularly hepatotoxicity). In addition, the use of such regimens can jeopardize adherence to treatment. The current guidelines recommend that tuberculin skin tests be performed, and, if positive, that chemoprophylaxis be instituted. There are several possible regimens, varying in terms of the drugs prescribed, as well as in terms of treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10 mg/kg/day) for six months for patients with silicosis, as well as for healthy patients with periods of exposure to silica longer than 10 years and strongly positive tuberculin skin test results (induration > 10 mm). Nevertheless, further studies are necessary so that indications, drugs, doses and duration of chemoprophylaxis regimens can be more properly defined.

Fibrose maciça progressiva em trabalhadores expostos à sílica: achados na tomografia computadorizada de alta resolução / Progressive massive fibrosis in silica-exposed workers: high-resolution computed tomography findings

OBJETIVO: Avaliar as características radiológicas das massas conglomeradas pela tomografia computadorizada de alta resolução de tórax. MÉTODOS: Foram selecionados 75 pacientes silicóticos, a maioria jateadores de areia, portadores de fibrose maciça progressiva, atendidos no Hospital Universitário Antônio Pedro entre 1986 e 2004. Os pacientes foram submetidos a avaliação clínica, radiografia simples de tórax e tomografia computadorizada de alta resolução. RESULTADOS: Mais da metade dos pacientes com silicose complicada mostrou na radiografia de tórax grandes opacidades dos tipos B e C, denotando a gravidade da doença nesses pacientes. Dos 75 casos, apenas um apresentou massa unilateral simulando câncer de pulmão. Quarenta e quatro pacientes realizaram tomografia computadorizada de alta resolução do tórax. As massas predominaram nos terços superiores e posteriores (88,6 por cento). Broncograma aéreo e calcificações no interior das massas foram observados em 70,4 por cento e 63,8 por cento dos casos, respectivamente. História de tuberculose foi relatada em 52 por cento dos pacientes estudados. CONCLUSÃO: Na grande maioria dos casos as massas eram bilaterais, predominando nas regiões póstero-superiores dos pulmões, com broncogramas aéreos e calcificações de permeio. Associação com calcificações linfonodais foi um achado freqüente. A exposição a elevadas concentrações de poeira e a tuberculose foram consideradas fatores de risco para o desenvolvimento da fibrose maciça progressiva.

OBJECTIVE: To evaluate the radiological characteristics of conglomerate masses using high-resolution computed tomography of the chest. METHODS: From among the patients treated between 1986 and 2004 at the Antonio Pedro University Hospital, 75 patients with silicosis and massive fibrosis, most working in the field of sandblasting, were selected for study. These patients were submitted to a clinical evaluation, chest X-ray and high-resolution computed tomography of the chest. RESULTS: In more than half of the patients with accelerated silicosis, the chest X-ray revealed large type B and C opacities, denoting the severity of the disease in those patients. In 1 case, a unilateral mass simulating lung cancer was observed. High-resolution computed tomography scans of the chest were acquired for 44 patients. In most cases (88.6 percent), the masses were located in the superior and posterior thirds of the lung. Common findings within the masses included air bronchograms (in 70.4 percent) and calcifications (in 63.6 percent). A history of tuberculosis was reported by 52 percent of the patients. CONCLUSION: In the vast majority of cases, the masses were bilateral, predominantly located in the superior and posterior regions of the lung, featuring air bronchograms and interposed calcifications. Concomitant calcification of the mediastinal and hilar lymph nodes was another common finding. Exposure to high concentrations of dust and having a history of tuberculosis were considered significant risk factors for the development of progressive massive fibrosis.

Avaliação das características resistivas do sistema respiratório de indivíduos portadores de silicose pela técnica de oscilações forçadas / Using the forced oscillation technique to evaluate respiratory resistance in individuals with silicosis

OBJETIVO: Avaliar o comportamento dos parâmetros resistivos obtidos por meio da técnica de oscilações forçadas em pacientes portadores de diferentes graus de obstrução respiratória em decorrência da silicose. MÉTODOS: Foram analisados 40 indivíduos não tabagistas, sendo 10 sadios, sem história de doença pulmonar e exposição à sílica, e 30 portadores de silicose. Os voluntários foram examinados por meio da técnica de oscilações forçadas e da espirometria, técnica utilizada como referência para se classificar os diferentes níveis de obstrução. Desta classificação resultou a separação dos indivíduos em cinco grupos: controle (n = 10); normal ao exame, composto por indivíduos com laudo clínico e radiológico de silicose, porém normais ao exame espirométrico (n = 7); com obstrução leve (n = 10); com obstrução moderada (n = 8); e com obstrução acentuada (n = 5). RESULTADOS: A redução dos parâmetros espirométricos correspondeu a um significativo aumento na resistência total do sistema respiratório (p < 0,001), assim como na resistência associada às vias aéreas (p < 0,003). Foi também observada uma significativa redução na homogeneidade do sistema respiratório (p < 0,004). CONCLUSÃO: As informações adicionais referentes às propriedades resistivas do sistema respiratório, obtidas por meio da técnica de oscilações forçadas, podem contribuir para a complementação dos dados obtidos a partir de exames espirométricos em indivíduos portadores de silicose, o que ressalta o elevado potencial desta técnica na análise desses pacientes.

OBJECTIVE: To evaluate the resistance values obtained through the use of the forced oscillation technique in patients with varying degrees of airway obstruction resulting from silicosis. METHODS: A total of 40 never-smoking volunteers were analyzed: 10 were healthy subjects with no history of pulmonary disease or silica exposure, and 30 had silicosis. The forced oscillation technique was used to examine the subjects, and spirometry was used as a reference in order to classify the obstruction by degree. This classification resulted in five groups: control (n = 10); normal exam, composed of individuals diagnosed clinically and radiologically with silicosis but presenting normal spirometry results (n = 7); mild obstruction (n = 10); moderate obstruction (n = 8); and severe obstruction (n = 5). RESULTS: The reduction observed in the spirometric values corresponded to a significant increase in the total respiratory resistance (p < 0.001), as well as in airway resistance (p < 0.003). A significant reduction in ventilation homogeneity was also observed (p < 0.004). CONCLUSION: In individuals with silicosis, the additional respiratory resistance-related data obtained through the use of the forced oscillation technique can complement spirometric data. Therefore, the forced oscillation technique presents great potential for the analysis of such patients.

Using the forced oscillation technique to evaluate respiratory resistance in individuals with silicosis.

OBJECTIVE: To evaluate the resistance values obtained through the use of the forced oscillation technique in patients with varying degrees of airway obstruction resulting from silicosis. METHODS: A total of 40 never-smoking volunteers were analyzed: 10 were healthy subjects with no history of pulmonary disease or silica exposure, and 30 had silicosis. The forced oscillation technique was used to examine the subjects, and spirometry was used as a reference in order to classify the obstruction by degree. This classification resulted in five groups: control (n = 10); normal exam, composed of individuals diagnosed clinically and radiologically with silicosis but presenting normal spirometry results (n = 7); mild obstruction (n = 10); moderate obstruction (n = 8); and severe obstruction (n = 5). RESULTS: The reduction observed in the spirometric values corresponded to a significant increase in the total respiratory resistance (p < 0.001), as well as in airway resistance (p < 0.003). A significant reduction in ventilation homogeneity was also observed (p < 0.004). CONCLUSION: In individuals with silicosis, the additional respiratory resistance-related data obtained through the use of the forced oscillation technique can complement spirometric data. Therefore, the forced oscillation technique presents great potential for the analysis of such patients.

Progressive massive fibrosis in silica-exposed workers. High-resolution computed tomography findings.

OBJECTIVE: To evaluate the radiological characteristics of conglomerate masses using high-resolution computed tomography of the chest. METHODS: From among the patients treated between 1986 and 2004 at the Antonio Pedro University Hospital, 75 patients with silicosis and massive fibrosis, most working in the field of sandblasting, were selected for study. These patients were submitted to a clinical evaluation, chest X-ray and high-resolution computed tomography of the chest. RESULTS: In more than half of the patients with accelerated silicosis, the chest X-ray revealed large type B and C opacities, denoting the severity of the disease in those patients. In 1 case, a unilateral mass simulating lung cancer was observed. High-resolution computed tomography scans of the chest were acquired for 44 patients. In most cases (88.6%), the masses were located in the superior and posterior thirds of the lung. Common findings within the masses included air bronchograms (in 70.4%) and calcifications (in 63.6%). A history of tuberculosis was reported by 52% of the patients. CONCLUSION: In the vast majority of cases, the masses were bilateral, predominantly located in the superior and posterior regions of the lung, featuring air bronchograms and interposed calcifications. Concomitant calcification of the mediastinal and hilar lymph nodes was another common finding. Exposure to high concentrations of dust and having a history of tuberculosis were considered significant risk factors for the development of progressive massive fibrosis.

Cavitação pulmonar infectada em pacientes com silicoesclerodermia (síndrome de Erasmus) / Infected pulmonary cavity in a patient with silica induced scleroderma (Erasmus' syndrome)

Inicialmente descrita em 1957, a associação entre silicose e esclerose sistêmica (síndrome de Erasmus) ocorre, possivelmente, por alterações humorais e celulares, desencadeadas pela toxicidade da sílica. Neste relato, os autores descrevem o caso de um homem de 41 anos, com síndrome de Erasmus, admitido com uma cavitação pulmonar infectada.

Tracheobronchopathia osteochondroplastica in a patient with silicosis: CT, bronchoscopy, and pathology findings.

A case of tracheobronchopathia osteochondroplastica in a patient with silicosis is reported, showing a rare association of disease. Etiological hypotheses and clinical aspects are discussed. Radiologic, bronchoscopic, and pathologic findings are demonstrated with emphasis on the role of computed tomography (CT) in the diagnosis of this disease.

Silicosis associated with systemic lupus erythematosus

The hypothesis that exposure to silica might be associated with a wide range of autoimmune diseases including SLE (Systemic Lupus Erythematosus) has been discussed over the last decade, but only few cases of silicosis and SLE were described in the literature. We report the case of a male patient in his fifth decade of life, with previous exposure to silica, who worked as a well digger for ten years. The patients's clinical picture started with articular symptoms, sporadic peaks of fever, anemia, positive anti-nuclear factor, peripheral (1/10) and homogeneous (1/500) standard, and productive cough. Computed tomography of the chest showed a diffuse interstitial process, bilateral nodules, para-aortic and para-tracheal hilar calcifications, compatible with pulmonary and ganglial silicosis. He developed acute respiratory distress syndrome (ARDS) and died.