Development Of Progressive Massive Fibrosis Research Articles

Genetic susceptibility to progressive massive fibrosis in coal miners

Progressive massive fibrosis (PMF) is a chronic interstitial lung disease with a complex aetiology that can occur after cumulative dust exposure. A case-control study was conducted to test the hypothesis that single nucleotide polymorphisms (SNPs) within genes involved in inflammatory and fibrotic processes modulate the risk of PMF development. The study population consisted of 648 underground coal miners participating in the National Coal Workers Autopsy Study, of which 304 were diagnosed with PMF. SNPs that influence the regulation of interleukin (IL)-1, IL-6, tumour necrosis factor-alpha, transforming growth factor-beta1, vascular endothelial growth factor (VEGF), epidermal growth factor intercellular cell adhesion molecule (ICAM)-1 and matrix metalloproteinase-2 genes were determined using a 5'-nuclease real-time PCR assay. There were no significant differences in the distribution of any individual SNP or haplotype between the PMF and control groups. However, the polygenotype of VEGF +405/ICAM-1 +241/IL-6 -174 (C-A-G) conferred an increased risk for PMF (odds ratio 3.4, 95% confidence interval 1.3-8.8). The present study suggests that the examined genetic variations that help regulate inflammatory and fibrotic processes are unlikely to strongly influence susceptibility to this interstitial lung disease, although the role of vascular endothelial growth factor, intercellular cell adhesion molecule-1 and interleukin-6 polymorphisms in the development of progressive massive fibrosis may require further investigation.

Fibrose maciça progressiva em trabalhadores expostos à sílica: achados na tomografia computadorizada de alta resolução

To evaluate the radiological characteristics of conglomerate masses using high-resolution computed tomography of the chest. 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. 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. 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.

Emphysema in Silicosis: A Comparison of Smokers with Nonsmokers Using Pulmonary Function Testing and Computed Tomography

The presence of emphysema in silicosis is believed to be secondary to the development of progressive massive fibrosis (PMF). However, it is difficult to separate out other causative factors, particularly cigarette smoking. In order to attempt to distinguish these factors, we examined 30 patients with silicosis by means of pulmonary function testing and computed tomography (CT) scans of the chest. Eighteen of these patients were either exsmokers or current smokers, and 12 of them were nonsmokers. The CT scans were read independently by two observers on two separate occasions. Silicosis was graded on a 5-point scale from 0 to 4; emphysema was graded as a percentage of lung involved. Percent emphysema was associated with level of pulmonary function (FEV1, FVC, and DLCO) independent of its association with either cigarette smoking or silicosis grade (p less than 0.01). Silicosis grade was associated with DLCO (p less than 0.05) independent of its association with either cigarette smoking or percent emphysema, but was not associated with level of FEV1 or FVC. In the group without PMF (silicosis Grade 0, 1, or 2), smokers had worse emphysema than nonsmokers (p less than 0.01); there was no such difference among the patients with PMF (silicosis Grade 3 or 4). Only one of the nonsmoking subjects with silicosis but without PMF had any emphysema detected on CT. Our data suggest that silicosis, in the absence of PMF, does not cause significant emphysema, and that it is primarily the degree of emphysema rather than the degree of silicosis that determines the level of pulmonary function.

Influence of rheumatoid factor in coalminers' pneumoconiosis in the Fujian Shaowu colliery, south China.

Coalminers' pneumoconiosis may be complicated by the development of progressive massive fibrosis (PMF) or by rheumatoid pneumoconiosis (Caplan's syndrome).12 The arthritis in Caplan's syndrome may precede, coincide with, or follow the develop ment of pulmonary radiological shadows. These conditions are common in miners and may be seen in workmen exposed to dusts other than coal.35 The Fujian Shaowu colliery was built in 1958. With improvements in mining technique the density of coalmine dust in the air at the workface decreased. The silicon component of coalmine dust was found to be 6-72%. After the improvements the average density of coalmine dust in the air was 10 mg/m3, which is low. Patients with pneumoconiosis were still found and the cases deteriorated. We think the presence of the rheumatoid factor may have been a promoting factor. We have studied these patients.

Factors associated with the development of progressive massive fibrosis in British coalminers: a case-control study.

Possible associations between the incidence of progressive massive fibrosis (PMF) over periods of average length 11 years during 1963-80 and a range of explanatory variables, both environmental and medical, were examined in a study group of 4772 miners and ex-miners using case-control methods. Cases were members of the study group who developed PMF during the study period; controls were men who remained free of the disease. Cases and controls were matched on cumulative dust exposure to the start of the study period, colliery of employment, and whether or not employment before and during the study period had been at a single colliery only. Of 257 cases of PMF, 142 were matched to four controls each, 39 to three controls, 33 to two controls, and 31 to a single control only. Twelve cases could not be matched. Age and category of simple pneumoconiosis were each found to be associated with the incidence of PMF, confirming the results of many previous studies. Quetelet's index of body mass (a measure of weight, normalised for height) was found to differ considerably between cases and controls, cases tending to be lighter for their height. The difference did not vary significantly between three groups of collieries, defined by coal rank. Regression analysis confirmed the high level of statistical significance of the difference (p less than 0.001), allowing for the effects of age and prior category of simple pneumoconiosis. Of the environmental factors considered, an index of residence time of dust in the lungs was found to have the most statistically significant association with the incidence of PMF. The crudeness of the measure used, however, together with unreliability in estimates of early exposure to dust for some of the men studied, means that further work is necessary to investigate the magnitude and significance of this apparent association. In low and medium rank collieries there were large differences between the proportion of cases and controls showing a range of respiratory symptoms, cases consistently displaying a higher prevalence. In the high rank collieries of south Wales, however, symptoms occurred with equal frequency in cases and controls, the prevalence at these collieries being the same as among cases generally. Regression analysis (low and medium rank collieries only) showed that the presence of breathlessness was the symptom most strongly associated with the risk of attack of PMF, allowing for the effects of age and Quetelet's index.

Progression of Silicosis in Relation to Silica Dust Exposure

Abstract The progression of silicosis was measured for 631 South African gold miners to determine the effect of silica dust exposure on the rate of progression of simple silicosis and the development of progressive massive fibrosis (PMF). Silicosis was found to be a progressive disease regardless of whether exposure was continued after onset (94.6% progressed) or not (88.3% progressed). Cumulative dust exposure was significantly associated with the rate of progression ( p = 0.0014). When dust exposure before and after onset was considered, it was found that exposure after onset was significantly associated with progression ( p = 0.0001) whereas dust exposure before onset was not ( p = 0.95). Silicotics developing PMF had more exposure after onset of simple silicosis than silicotics who did not develop PMF. Progression appears to slow as the category of profusion increases; however, this cannot be stated with assurance given the study design used. The data suggest that the removal of silicotics from continued dust exposure will reduce the rate of progression of silicosis as well as the risk of developing PMF. It is also speculated that individual susceptibility to develop silicosis may not be related to the susceptibility to progress.

Autoantibodies in coalminers: their relationship to the development of progressive massive fibrosis.

Sera from 2421 coalminers, representing all the radiological categories of pneumoconiosis, and from 260 healthy blood donors, as controls, were examined for antinuclear factor and rheumatoid factor. Antinuclear factors were present in 21.5% of sera from the controls and in 23.1% from the coalminers' group. Rheumatoid factor was present in 5.3% of coalminers and as expected occurred particularly in the few men with progressive massive fibrosis who also had rheumatoid disease. The combined prevalence of both factors showed an increase with age at all disease levels and a significant association with pneumoconiosis category only in men older than 60 years. This study provides no evidence that autoantibodies are likely to be of value in detecting men predisposed to the development of massive fibrosis other than those with rheumatoid disease.

Factors predisposing to the development of progressive massive fibrosis in coal miners.

Altogether 238 759 miners employed by the National Coal Board were examined in the third of the Board's radiological surveys from 1969 to 1973 inclusive. Excluding those diagnosed as having progressive massive fibrosis (PMF) on that occasion, 210 847 were in collieries still operating at the time of the fourth survey four to five years later 132 728 attended for radiography at the same colliery on the second occasion, and were used to study the attack rate of PMF. In all groups in the age range 35-54 and having category 2 simple pneumoconiosis (SPN) or less, 80% or more had a second radiograph. It was found that the probability of developing PMF increased sharply with rising category of SPN; however, half the cases occurred in men having SPN categories 0 or 1, who were in the majority. Current coalface work had no significant effect on the attack rate. Age increased the attack rate of PMF within each major SPN category (0, 1, 2, and 3), especially the higher categories. All or part of this effect may have been due to the fact that SPN in younger men with categories 1 and 2 tends to lie in the lower range within these categories. Similarly, a lower distribution of SPN within each category associated with a low overall local prevalence may account wholly or in part for the great difference between the attack rates of PMF supervening on each category of SPN in Scotland and South Wales. The rank (quality) of coal mined had no effect on the attack rate.

Massive fibrosis in gold miners—A radiological evaluation

Serial roentgenographs of histologically confirmed massive fibrotic lesions in 14 deceased gold miners were retrospectively studied. Planimetric measurements to assess progress was made. The study revealed progression after exposure to “dust” was discontinued. The patients revealed a surprising longevity. Apart from tuberculosis as a possible etiological factor, suggestive evidence indicates that inflammation or fibrosis of lung parenchyma may play a role in the development of progressive massive fibrosis. The advent of large opacities was not primarily associated with respiratory disability in the group studied.