Long-term mortality in miners with coal workers' pneumoconiosis in The Netherlands: a pilot study

In order to investigate whether the prolonged exposure to coal mine dust increases the cancer risk for coal miners, a pilot study in a selected cohort of 334 Dutch miners with coal workers' pneumoconiosis (CWP), followed from 1956 until 1983, was conducted. In total, 165 miners had died (49.4%); for 162 (98.2%) the cause of death was traced. In comparison to the general Dutch male population, total mortality in the cohort was statistically significantly increased (SMR: 153). This was in general due to the significantly higher than expected cancer mortality (SMR: 163), cancer of stomach and small intestine (SMR: 401) and nonmalignant respiratory disease (SMR: 426). The lung cancer mortality was within the expected range.     

Continued increase in lung transplantation for coal workers’ pneumoconiosis in the United States

Background

Severe coal workers’ pneumoconiosis (CWP) is increasingly common, and sometimes requires lung transplantation.

Methods

Using Organ Procurement and Transplantation Network data, we updated the trend for CWP‐related lung transplants, described CWP patients who have been waitlisted but not transplanted, and characterized the primary payer of medical costs for CWP‐related and other occupational lung disease transplants.

Results

There have been at least 62 CWP‐related lung transplants; 49 (79%) occurred in the last decade. The rate of these procedures has also increased. Twenty‐seven patients were waitlisted but did not receive a transplant. Compared to other occupational lung diseases, transplants for CWP were more likely to be paid for by public insurance.

Conclusions

The increase in the frequency and rate of lung transplantation for CWP is consistent with the rising prevalence of severe CWP among U.S. coal miners. Effective exposure controls and identification of early stage CWP remain essential for protecting these workers.

     

Pathological findings in mine workers: I. Description of the PATHAUT database

A computerized system for recording the results of structured, numerically coded autopsy reports on various types of mine workers has been in operation at the National Centre for Occupational Health in Johannesburg since 1975. Historical developments, particularly those associated with compensation for occupational disease, have resulted in very high autopsy rates, especially among whites. Since its inception, the pathology automation (PATHAUT) system has accumulated the results of more than 33,000 autopsies. The data set is described in the hope of stimulating interest in the possible uses of the data and encouraging collaborative research. Some characteristics of the database with potential research implications are discussed. These include differing age and work patterns for blacks and whites and geographic factors with potential influence on whether a body or only the cardiorespiratory organs are sent for examination.     

Pathological findings in mine workers: II. Quality of the PATHAUT data

To assess the feasibility of using the pathology automation system (PATHAUT) for research, the quality of the data was explored by examining who comes to autopsy, the quality of the autopsy material, interobserver variability, and repeatability of diagnoses. The data indicated that autopsy rates in the gold mining industry, especially for whites, are high and that even among blacks, gold miners are represented in proportions exceeding the relative size of the working population. Because of the perception of the autopsy service as a means of obtaining compensation, miners with occupational diseases fully compensated in life are probably underrepresented. The autopsy material submitted for full autopsy is generally better preserved than cardiorespiratory organs that are sent for examination. The gold mining industry has a high proportion of full autopsies as does the Iron and Steel Corporation of South Africa. Full autopsies are more commonly performed on older deceased miners. This was true for both blacks and whites. The allocation of material to pathologists for full autopsies and examinations of the cardiorespiratory organs were clearly not random, and this may affect comparisons among pathologists. Active tuberculosis, silicosis, and emphysema prevalences appeared fairly comparable across pathologists; however, there was wide variability in the prevalence of bronchiolitis as determined by the pathologists. Agreement between the diagnoses on PATHAUT and reclassifications by single pathologists was very good for the severity of emphysema and the histological type of bronchogenic carcinoma.     

Parsimonious analysis of time-dependent effects in the Cox model

Cox's proportional hazards model can be extended to accommodate time-dependent effects of prognostic factors. We briefly review these extensions along with their varying degrees of freedom. Spending more degrees of freedom with conventional procedures (a priori defined interactions with simple functions of time, restricted natural splines, piecewise estimation for partitions of the time axis) allows the fitting of almost any shape of time dependence but at an increased risk of over-fit. This results in increased width of confidence intervals of time-dependent hazard ratios and in reduced power to confirm any time-dependent effect or even any effect of a prognostic factor. By means of comparative empirical studies the consequences of over-fitting time-dependent effects have been explored. We conclude that fractional polynomials, and similarly penalized likelihood approaches, today are the methods of choice, avoiding over-fit by parsimonious use of degrees of freedom but also permitting flexible modelling if time dependence of a usually a priori unknown shape is present in a data set. The paradigm of a parsimonious analysis of time-dependent effects is exemplified by means of a gastric cancer study.     

The incidence and progression of pneumoconiosis over nine years in U.S. coal miners: I. Principal findings

Chest radiographs, taken at a 9-year interval for 1,261 U.S. coal miners, were read for pneumoconiosis side-by-side by six readers in a controlled trial. Incidence and progression of small, rounded opacities were consistent with levels predicted from dose-response curves developed by the British Pneumoconiosis Field Research interpolated at a concentration derived from U.S. compliance levels mandated over the last 9 years. The results imply that the level of pneumoconiosis in U.S. miners is being reduced through application of the current 2 mg/m3 standard. The long developmental period for pneumoconiosis necessitates that further study be undertaken to verify this finding and to determine whether 2 mg/m3 is an appropriate regulatory dust level for the prevention of category 2 or greater simple pneumoconiosis over a 35-year period.     

Exposure-response relationships for coal mine dust and obstructive lung disease following enactment of the Federal Coal Mine Health and Safety Act of 1969.

Underground U.S. coal miners were studied cross-sectionally for the association of respirable coal mine dust exposure with pulmonary function and symptoms of airways obstruction. The study group included 1,185 miners participating in Round 4 of the National Study of Coal Workers' Pneumoconiosis who had started mining in or after 1970 when comprehensive exposure regulations first came into effect. Quantitative estimates of cumulative exposure, derived using respirable dust measurements taken by the Mine Safety and Health Administration over the entire study period, were used in linear and logistic regression models on indicators of pulmonary function and chest symptoms while controlling for smoking status, pack-years, and other potential confounders. Statistically significant associations between log cumulative exposure and decrements in FVC, FEV1, and FEV1/FVC were observed. In logistic models, statistically significant associations of cumulative exposure with increasing prevalence of FEV1 and FEV1/FVC less than 80% predicted and symptoms including chronic phlegm, chronic bronchitis, breathlessness, wheeze, and wheeze with shortness of breath were found. It is concluded that exposures to respirable coal mine dust present in U.S. mines since 1970 continue to affect respiratory health in underground miners.     

Exposures to silica mixed dust and cohort mortality study in tin mines: exposure-response analysis and risk assessment of lung cancer

BACKGROUND: Mineral dusts that contain crystalline silica have been associated directly or indirectly with the development of pneumoconiosis or silicosis, non-malignant respiratory diseases, lung cancer, and other diseases. The health impacts on workers with silica mixed dust exposure in tin mines and dose-response relationships between cumulative dust exposure and the mortality from lung cancer are investigated. METHODS: A cohort of 7,837 workers registered in the employment records in 4 Chinese tin mines between 1972 and 1974 was identified for this study and the mortality follow-up was traced through 1994. Of the cohort, the cause of death was ascertained for 1,061 (97%) of the 1,094 deceased workers. Standardized mortality ratios (SMRs) were calculated for all workers, non-exposed workers, and dust-exposed workers with different exposure levels, silicotics, and non-silicotics based on Chinese national rates. RESULTS: The mortality from all causes in four tin mines was nearly the same as the national mortality. Malignant neoplasm, cerebrovascular disease, and cardiovascular disease accounted for 68.6% of all deaths. Mortality excess from lung cancer, liver cancer, all malignant diseases, and non-malignant respiratory diseases was observed among dust-exposed workers; a 50-fold excess of pneumoconiosis was observed. There was an upward trend for SMRs of lung cancer was noted from no exposure to low, medium, and high exposure levels (SMRs=1.29, 2.65, 2.66, 3.33). The shape of the exposure-response curve for risk of lung cancer at high exposure levels was inconsistent in these four mines. CONCLUSIONS: The findings indicated a positive dose-response relation between exposure to cumulative dust and the mortality of lung cancer. High arsenic content in dust particles, together with crystalline silica, may play an important role in causing increased mortality from lung cancer.     

Polymorphisms in the promoter of the tumor necrosis factor-α gene in coal miners

Tumor necrosis factor-α (TNF) is recognized as a central mediator of mineral dust-induced lung fibrosis, and genetic polymorphisms of the TNF promoter have been reported to influence levels of TNF production. To assess whether polymorphisms within the TNF promoter gene are associated with susceptibility to coal workers' pneumoconiosis (CWP), the DNA of 78 coal miners was typed for G-to-A transitions at positions −238 and −308. Our results show that frequency of A⁻³⁰⁸ genotype (T2) is significantly overpresented in coal miners with CWP (50%), as compared with miners without CWP (25%) and controls (29%). After correction for cumulative dust exposure and smoking, the A⁻³⁰⁸ transition genotype is still associated with the presence of CWP (OR = 3.0, 95%CI = 1.0–9.0). Both A⁻²³⁸ and A⁻³⁰⁸ transition genotypes were related to TNF release from endotoxin-stimulated blood monocytes; only the A⁻²³⁸ transition and not the A⁻³⁰⁸ transition was associated to coal dust-induced TNF release. In summary, this study shows that the A⁻³⁰⁸ transition is related to CWP, but this relation is not paralleled by a different TNF release in this genotype. A larger number of patients coupled to frequent TNF release are required to evaluate genotype screening to estimate individual health risks for effects of coal mine dust exposure. Am. J. Ind. Med. 34:318–324, 1998. © 1998 Wiley-Liss, Inc.     

限制平均生存时间回归模型在生存分析中的应用

目的 探讨限制平均生存时间(restricted mean survival time,RMST)回归模型在生存数据分析中的应用。 方法 运用伪值估计方法对医学数据进行限制平均生存时间回归模型实例分析,并与常见生存分析模型进行比较。 结果 RMST回归模型无特定模型假设,适用于不满足比例风险假定的生存数据;实例分析显示,RMST模型构建灵活,可通过设定多个τ值在多个时间段内进行估计;犯第一类错误的概率低于Cox比例风险模型,模型估算结果容易解释,能够提供在临床实践中更为实用的结论。 结论 在不满足比例风险假定且生存曲线有较大交叉的情形下,限制性平均生存时间模型能够提供稳定有效且易于解释的效应估计,在生存分析领域具有优良的适用性,可以作为Cox比例风险模型分析结果的补充。     

Occupation and lung cancer risk among women in Northern China

Lifetime occupational histories were obtained in a case-control study of 965 female lung cancer patients and 959 controls selected from the general population in Shenyang and Harbin, People's Republic of China, where most women have worked outside the home. After adjusting for smoking, we found a significantly increased risk of lung cancer associated with employment involving the manufacture of transportation equipment (OR = 1.6, 95% CI = 1.0, 2.6), in particular the manufacturing of automobiles (OR = 3.0, 95% CI = 1.4, 6.4). Metal smelting and treatment workers were at an increased risk of lung cancer (OR = 1.5, 95% CI = 1.0, 2.1); the highest risks were observed among metal surfacers (OR = 3.1, 95% CI = 1.1, 9.0) and currently employed foundry workers (OR = 13.0, 95% CI = 1.7, 99.4). On the other hand, about a 50% decreased risk of lung cancer was observed among those employed in textile industries or as leaders of state and party organizations. Based on self-reports, exposures to coal dust and smoke from burning fuel at the workplace were also significant risk factors. The findings were similar when the analyses were confined to nonsmokers and were comparable across the major cell types of lung cancer. © 1993 Wiley-Liss, Inc.     

The incidence and progression of pneumoconiosis over nine years in U.S. coal miners: II. Relationship with dust exposure and other potential causative factors

Examination of the incidence and progression of pneumoconiosis over 9 years in 1,261 nationally distributed U.S. coal miners has been undertaken in relationship to potential causative factors. Use has been made of a large body of data on dust levels collected by the Mine Safety and Health Administration principally for compliance purposes. Reported dust levels were low and generally under the current 2 mg/m3 standard. No link between dust level and disease progression could be detected. Some evidence was seen that radiological change was related to dust exposures prior to the study in both coal and noncoal mines, and thus experienced before the current dust standards were mandated. Neither migration of miners nor mining method appeared to be associated with disease incidence or progression. None of these findings can be taken as final, as the period of study is short and the number of cases of pneumoconiosis few. Further study is under way to obtain more reliable information over a longer period of follow-up.     

Association between Birth Region and Time to Tuberculosis Diagnosis among Non–US-Born Persons in the United States

Approximately 90% of tuberculosis (TB) cases among non–US-born persons in the United States are attributable to progression of latent TB infection to TB disease. Using survival analysis, we investigated whether birthplace is associated with time to disease progression among non–US-born persons in whom TB disease developed. We derived a Cox regression model comparing differences in time to TB diagnosis after US entry among 19 birth regions, adjusting for sex, birth year, and age at entry. After adjusting for age at entry and birth year, the median time to TB diagnosis was lowest among persons from Middle Africa, 128 months (95% CI 116–146 months) for male persons and 121 months (95% CI 108–136 months) for female persons. We found time to TB diagnosis among non–US-born persons varied by birth region, which represents a prognostic indicator for progression of latent TB infection to TB disease.     

煤工尘肺肺动脉病变的定量分析

[目的]研究煤工尘肺(CWP)肺细小动脉病变与肺心病的关系.[方法]取48例矿工尸检肺组织和12例非矿工手术标本进行了病理观察.对外径＜200μm的细小动脉在光镜观察的基础上用德国Kontron公司IBAS/Ⅱ图象分析仪进行测试.[结果]尘肺组细小动脉壁增厚与对照组相比EA/TA、WA/TA、WD/TD三项比值,Ⅰ期尘肺差异有显著性(P＜0.05),ⅡⅢ期差异有非常显著性(P＜0.01),ⅡⅢ期与Ⅰ期相比60～200μm小动脉差异有显著性(P＜0.05)说明CWP肺血管病变范围随尘肺病变加重而加重,CWP肺细小动脉壁尘细胞沉积及尘性纤维化是造成肺血管硬化使其顺应性降低的主要原因之一.与年龄因素相比,尘肺细小的动脉病变与粉尘破坏作用有更大关系.吸烟也不足以掩盖粉尘对血管这的损伤作用.[结论]尘性气管炎和尘斑气肿是导致煤工尘肺肺动脉高压的主要原发疾病.     

Regression analysis for current status data using the EM algorithm

We propose new expectation–maximization algorithms to analyze current status data under two popular semiparametric regression models: the proportional hazards (PH) model and the proportional odds (PO) model. Monotone splines are used to model the baseline cumulative hazard function in the PH model and the baseline odds function in the PO model. The proposed algorithms are derived by exploiting a data augmentation based on Poisson latent variables. Unlike previous regression work with current status data, our PH and PO model fitting methods are fast, flexible, easy to implement, and provide variance estimates in closed form. These techniques are evaluated using simulation and are illustrated using uterine fibroid data from a prospective cohort study on early pregnancy. Copyright © 2013 John Wiley & Sons, Ltd.