Interleukin 1α and 1ß gene variations are associated with tuberculosis in silica exposed subjects.

INTRODUCTION: Silicosis is a fibrotic lung disease resulting from the inhalation of crystalline silica and can be classified as simple or complicated according to the International Labour Organization criteria. Furthermore, individuals exposed to crystalline silica also have a higher risk for the development of tuberculosis (Tb). The contribution of inflammatory cytokines to the risk of silicosis and Tb in different populations has previously been reported. Since genetic background might be related to susceptibility to silicosis and Tb, the study of polymorphisms within IL-1α, IL-1ß, and tumor necrosis factor protein-coding genes may contribute to elucidating the genetic basis of these diseases. METHODS: Single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction using restriction fragment length polymorphism or by Taqman methodology, in a sample of 102 silica-exposed patients from Brazil. RESULTS: No significant associations were observed between the SNPs studied and the severity of silicosis. However, significant associations were found between Tb and the C allele (odds ratio [OR] = 1.93, 95% confidence interval [CI], 1.01-3.73) and the CC genotype (OR = 2.34, 95% CI, 1.04-5.31) of IL1A -899C>T. The IL1B +3954C>T polymorphism also showed an association with Tb (T allele dominant model OR = 2.38, 95% CI, 1.04-5.41). CONCLUSION: These preliminary results demonstrate that the IL1A and IL1B gene variations may contribute to some extent to susceptibility to Tb, but not silicosis. However, additional studies are still needed to confirm these results.

Interferon gamma response to combinations 38 kDa/CFP-10, 38 kDa/MPT-64, ESAT-6/MPT-64 and ESAT-6/CFP-10, each related to a single recombinant protein of Mycobacterium tuberculosis in individuals from tuberculosis endemic areas.

Several antigens of Mycobacterium tuberculosis have been identified and specificity to one or multiple antigens could determine the distinction between protective and pathogenic host reaction. Therefore T cell immune response to combinations 38 kDa/CFP-10, 38 kDa/MPT-64, ESAT-6/MPT-64 and ESAT-6/CFP-10 (each related to a single protein of Mycobacterium tuberculosis) in individuals from tuberculosis endemic areas have been examined. ELISA was used to detect IFN-gamma production in PBMC priming with single proteins and combinations in a panel of 105 individuals: 38 tuberculosis patients (6 untreated and 32 treated) and 67 healthy controls with tuberculin skin test positive or negative (TST). Brazilian TB patients highly recognized ESAT-6 (66%), but combinations improved response in the following order: ESAT-6/MPT-64 (89%) > ESAT-6/CFP-10 (73%) > 38 kDa/CFP-10 (70%), the last combination showing the highest specificity (TST(/) = 42% and TST(-) = 83%). Average IFN-gamma production in TB patients was signifi-cantly higher for 38 kDa/CFP-10 (P = 0.012) and 38 kDa/MPT-64 (P <0.035), when compared to single antigens. None of the combinations was able to discriminate TB patients from TST(+) controls; however, 38 kDa/CFP-10 displayed a borderline significance (P = 0.053). Similar to the ESAT-6/CFP-10 combination, IFN-gamma response to 38 kDa/CFP-10 showed an increased tendency in treated patients, although not signifi-cant (P = 0.16). We demonstrated for the first time that 38 kDa/CFP-10 had prediction sensitivity for TB patients similar to the ESAT-6/CFP-10 combination and also significant response improvement related to the single proteins with more selective reactivity among TST-positive individuals, which could be of potential interest for diagnostic evaluation for tuberculosis infection.

Cell proliferation and interferon-gamma response to recombinant MBP-3, NarL, MT-10.3, and 16kDa Mycobacterium tuberculosis antigens in Brazilian tuberculosis patients

Human pulmonary tuberculosis (TB) is a worldwide public health problem. In resistant individuals, control of the infection mainly requires development of a Th1 cell immune response with production of cytokines, of which interferon-gamma (IFN-gamma)plays an important role. Several antigens from Mycobacterium tuberculosis complex has been described for use in vaccine development or for diagnostic purposes, however little evaluation has been done in endemic area for TB. The proliferative and IFN-gamma human T cell immune responses, to four recombinant proteins (MBP-3, NarL, MT-10.3, 16 kDa) and PPD, of 38 Brazilian TB patients (6 untreated and 32 treated) and 67 controls (38 positive and 29 negative tuberculin skin test - TST) were compared. The highest reactivity mean rate was obtained with PPD followed by 16 kDa in TB patients. While most of the patients (87 percent) and controls (> 64 percent) respond to the PPD, 16kDa was more specifically recognized (> 21 percent) although less sensitive (54 percent). When TB patients were divided according to treatment status, opposite to PPD, higher average level of IFN-gamma was induced by 16kDa in untreated (505 pg/ml) compared to treated TB patients and TST+ (269.8 pg/ml x 221.6pg/ml, respectively), although the difference was not significant. These data show that in contrast with the other recombinant proteins, the stimulatory potency of 16kDa to induce proliferative and INF-gamma response was more effective and is more recognized by active TB untreated patients, eliciting in control individuals a more selective immune response than PPD.

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.

Cell proliferation and interferon-gamma response to recombinant MBP-3, NarL, MT-10.3, and 16 kDa Mycobacterium tuberculosis antigens in Brazilian tuberculosis patients.

Human pulmonary tuberculosis (TB) is a worldwide public health problem. In resistant individuals, control of the infection mainly requires development of a Th1 cell immune response with production of cytokines, of which interferon-gamma (IFN-gamma)plays an important role. Several antigens from Mycobacterium tuberculosis complex has been described for use in vaccine development or for diagnostic purposes, however little evaluation has been done in endemic area for TB. The proliferative and IFN-gamma human T cell immune responses, to four recombinant proteins (MBP-3, NarL, MT-10.3, 16 kDa) and PPD, of 38 Brazilian TB patients (6 untreated and 32 treated) and 67 controls (38 positive and 29 negative tuberculin skin test - TST) were compared. The highest reactivity mean rate was obtained with PPD followed by 16 kDa in TB patients. While most of the patients (87%) and controls (> 64%) respond to the PPD, 16 kDa was more specifically recognized (> 21%) although less sensitive (54%). When TB patients were divided according to treatment status, opposite to PPD, higher average level of IFN-gamma was induced by 16 kDa in untreated (505 pg/ml) compared to treated TB patients and TST+ (269.8 pg/ml x 221.6 pg/ml, respectively), although the difference was not significant. These data show that in contrast with the other recombinant proteins, the stimulatory potency of 16 kDa to induce proliferative and INF-gamma response was more effective and is more recognized by active TB untreated patients, eliciting in control individuals a more selective immune response than PPD.

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.

The role of bronchoalveolar lavage in quantifying inhaled particles in silicosis.

Silicosis is a disease caused by inhalation and deposition of crystalline silica that produces a fibrous tissue reaction. Bronchoalveolar lavage is a noninvasive technique that allows identifying particles, thus characterizing exposure to mineral dust. The aim of this work was to study bronchoalveolar lavage as a mean of estimating the amount of alveolar particles in different forms of silicosis. Bronchoalveolar lavage was carried out in 27 silicotic patients with simple (n = 12), complicated (n = 13), and acute (n = 2) forms of the disease and 7 healthy individuals as a control group. Macrophages were scored enumerating the percentage of cells with particles by polarizing light microscopy. Silicotic patients showed a marked increase in BAL cell particles compared to control population, however, relating simple to complicated silicosis, no significant difference was observed. In acute silicotic patients with massive silica dust exposure, more than 70% of BAL alveolar macrophages contained dust particles. When duration of exposure and retirement from work were evaluated, an inverse correlation between duration of exposure and the amount of alveolar dust, and a tendency to a smaller involvement on macrophages with the greater period of retirement from work were observed. These results suggest that particle analysis in BAL may be important in order to establish the nature and intensity of exposure.

[Comparative study of high resolution computer-assisted tomography with chest radiograph in silicosis]. / Estudo comparativo da tomografia computadorizada de alta resolução com a radiografia de tórax na silicose.

The diagnosis of silicosis is based on the history of exposure to silica dust associated with the radiological alterations compatible with the disease. With the main objective of comparing the alterations found in the chest radiography to those of high resolution computed tomography 49 patients with silicosis were selected. These imaging methods were evaluated separately by three readers and the results summarized through the median of the readings. The following alterations were analysed: nodules, coalescences, large opacities, lynfadenopathy. The patients were male, at an average age of 47.1 years, the majority being sandblasters, with an average exposure time to dust of 15.3 years. When the chest radiography was compared to high resolution computed tomography the following alterations were observed: i) the high resolution computed tomography showed greater profusion of nodules in 19 cases; ii) the high resolution computed tomography detected isolated coalescence and large opacities in 28 cases, seven of them who were classified initially as having simple silicosis were later changed to the complicated form; iii) the high resolution computed tomography was superior in the evaluation of lynfadenopathy in 16 cases. So, from the 49 analysed patients the high resolution computed tomography was more sensitive than the chest radiography in the evaluation of the alterations studied in 38 (77,5%) cases. Other alterations such as cavities, pleural thickening and emphysema were also observed only by this method in 5 cases. In the last 6 (12,2%) cases the high resolution computed tomography did not add any data when compared to chest radiography, four of these showed the initial form of the disease.