Lung cancer in relation to exposure to silica dust, silicosis and uranium production in South African gold miners

BACKGROUND: A nested case-control study for lung cancer was performed on a cohort of 2260 South African gold miners in whom an association between exposure to silica dust and risk of lung cancer was previously reported. The objective was to investigate an expanded set of risk factors and also cancer cell type. METHODS: The 78 cases of lung cancer found during the follow up period from 1970 to 1986 were matched with 386 controls. Risk of lung cancer was related to smoking, exposure to silica dust, incidence of silicosis, and uranium production and the uranium content of the mine ore. RESULTS: The risk of lung cancer was associated with tobacco smoking, cumulative dust exposure, duration of underground mining, and with silicosis. The best predictive model included pack years of cigarette consumption (adjusted relative risk (RR) = 1.0 for < 6.5 pack years, 3.5 (95% confidence interval (CI) 0.7 to 16.8) for 6.5-20 pack years, 5.7 (95% CI 1.3 to 25.8) for 21-30 pack years, and 13.2 (95% CI 3.1 to 56.2) for more than 30 pack years) and silicosis (RR = 2.45 (95% CI 1.2 to 5.2)). No association was found with uranium production. The lung tumour cell type distribution was 40.3% small cell carcinoma, 38.8% squamous cell, 16.4% adenocarcinoma, and 4.5% large cell carcinoma. Small and large cell cancer combined were associated with exposure to dust. CONCLUSIONS: The results cannot be interpreted definitively in terms of causal association. Possible interpretations are: (1) subjects with high dust exposure who develop silicosis are at increased risk of lung cancer; (2) high levels of exposure to silica dust on its own is important in the pathogenesis of lung cancer and silicosis is coincidental; and (3) high levels of silica dust exposure may be a surrogate for the exposure to radon daughters.


     

Retroperitoneal silicosis mimicking pancreatic carcinoma in an Alpine miner with chronic lung silicosis.

A miner, known to have had lung silicosis for 30 years, was investigated for abdominal pain. A retroperitoneal mass was found, in which histological examination showed an inflammatory reaction to silica.     

Crystalline silica exposure, radiological silicosis, and lung cancer mortality in diatomaceous earth industry workers.

BACKGROUND: The role of silicosis as either a necessary or incidental condition in silica associated lung cancer remains unresolved. To address this issue a cohort analysis of dose-response relations for crystalline silica and lung cancer mortality was conducted among diatomaceous earth workers classified according to the presence or absence of radiological silicosis. METHODS: Radiological silicosis was determined by median 1980 International Labour Organisation system readings of a panel of three "B" readers for 1809 of 2342 white male workers in a diatomaceous earth facility in California. Standardised mortality ratios (SMR) for lung cancer, based on United States rates for 1942-94, were calculated separately for workers with and without radiological silicosis according to cumulative exposures to respirable crystalline silica (milligrams per cubic meter x years; mg/m3-years) lagged 15 years. RESULTS: Eighty one cases of silicosis were identified, including 77 with small opacities of > or = 1/0 and four with large opacities. A slightly larger excess of lung cancer was found among the subjects with silicosis (SMR 1.57, 95% confidence interval (CI) 0.43 to 4.03) than in workers without silicosis (SMR 1.19, 95% CI 0.87 to 1.57). An association between silica exposure and lung cancer risk was detected among those without silicosis; a statistically significant (p = 0.02) increasing trend of lung cancer risk was seen with cumulative exposure, with SMR reaching 2.40 (95% CI 1.24 to 4.20) at the highest exposure level (> or = 5.0 mg/m3-years). A similar statistically significant (p = 0.02) dose-response gradient was observed among non-silicotic subjects when follow up was truncated at 15 years after the final negative radiograph (SMR 2.96, 95% CI 1.19 to 6.08 at > or = 5.0 mg/m3-years), indicating that the association among non-silicotic subjects was unlikely to be accounted for by undetected radiological silicosis. CONCLUSIONS: The dose-response relation observed between cumulative exposure to respirable crystalline silica and lung cancer mortality among workers without radiological silicosis suggests that silicosis is not a necessary co-condition for silica related lung carcinogenesis. However, the relatively small number of silicosis cases in the cohort and the absence of radiographic data after employment limit interpretations.     

New pathological findings in emphysema of childhood: 3. Unilateral congenital emphysema with hypoplasia—and compensatory emphysema of contralateral lung

A quantitative study is here reported on the lungs of a child of 9 months with unilateral emphysema associated with hypoplasia, and with compensatory emphysema in the contralateral lung. The left lung was judged to show congenital hypoplasia because of the reduced number of bronchi and arteries, its small volume, and a total alveolar number less than that normally found at birth. This last was due mainly to reduction in the number of acini, the intra-acinar number seeming little affected. As the alveoli were eight times the normal volume, the case was considered to be one of congenital hypoplastic emphysema.     

Single lung transplantation for end stage emphysema.

BACKGROUND-- The first successful single lung transplantation was carried out in 1983 for pulmonary fibrosis. Because of the inherent advantages of single lung transplantation, a transplantation programme has been started for patients with end stage lung disease due to emphysema. METHODS-- Between October 1990 and August 1993 25 patients with severe emphysema (15 men, mean age 51 years) received a single lung transplant at our institution. All patients were severely disabled with a mean (SD) 12 minute walking distance of 281 (165) metres. There were five deaths in the series, four in the first 20 days and one on day 503. Two patients suffered graft compression by air trapping in the native lung. Bronchial narrowing requiring insertion of endobronchial stenting occurred in four patients. RESULTS-- Mean (SD) FEV1 improved from a preoperative value of 17.8(13%) predicted to a six month value of 53.6(13)%, and FEV1/FVC from 23.8(12)% to 68.6(15)%. After the transplant 12 patients are in New York Heart Association (NYHA) class I and the rest of the survivors are in NYHA II. Actuarial survival was 82% at one year and 74% at three years. CONCLUSIONS-- Single lung transplantation is an effective treatment for end stage lung disease due to emphysema and carries an acceptable mortality and morbidity.     

Morbidity, mortality, and early results of single versus bilateral lung transplantation for emphysema.

Both single lung transplantation and bilateral lung transplantation have been successful in patients with chronic obstructive pulmonary disease. Limited availability of donor lungs dictates wider use of single lung transplantation as long as this procedure provides a comparable functional result at less risk. Early morbidity, mortality rates, and functional results were compared in 32 consecutive patients undergoing either single or bilateral lung transplantation for end-stage chronic obstructive pulmonary disease. When pretransplantation and posttransplantation values of forced expiratory volume in 1 second, single breath diffusing capacity, total lung capacity, arterial oxygen tension, and 6-minute walking distance were compared, statistically significant improvement (p less than 0.01) was seen in both groups. However, significantly higher values (p less than 0.01) were attained for forced expiratory volume in 1 second, single breath diffusing capacity, and arterial oxygen tension in the bilateral transplantation group than in the single lung transplantation group. Patients receiving bilateral lung transplants were at greater risk for postoperative complications, especially cardiac arrhythmias and bronchial anastomotic defects. Actuarial survival for the single lung transplantation group was 93% at 1 year, versus 87% at 6 months and 71% at 1 year for the bilateral lung transplantation group. The optimal transplantation procedure for patients with chronic obstructive pulmonary disease has not been determined. Longer follow-up periods are needed to define better the roles of bilateral and single lung transplantation in this group of patients.     

Morbidity and mortality related to the native lung in single lung transplantation for emphysema.

It has been advocated that a major drawback of single lung transplantation (SLT) is the risk of serious complications arising from the native lung. The morbidity and mortality related to the native lung in 46 patients who underwent SLT for pulmonary emphysema in Clichy from 1988 to 1997 were reviewed retrospectively. In particular, infectious complications and native lung hyperinflation were searched. Complications arising from the native lung are not unusual after SLT for subjects with emphysema, and it was concluded they are not responsible for a substantial mortality.     

Metabolic syndrome,endothelial dysfunction,and erectile dysfunction: Association and management

The metabolic syndrome, the criteria for which include glucose intolerance, obesity, hypertension, and dyslipidemia, has rapidly become understood to have a major association with erectile dysfunction (ED). On a mechanistic level, their common grounds may involve endothelial dysfunction, although the conditions of oxidative stress understood to be a pathologic element of the syndrome also may affect various components of the vascular biology of the penis. The foremost importance of recognizing the association between ED and the metabolic syndrome is that addressing ED presentations may afford opportunities to identify and improve a major adverse health profile and thereby promote health maintenance objectives for patients.     

Association of cadmium exposure with rapidly progressive emphysema in a smoker.

Rapidly progressive emphysema developed in a 59 year old smoker after exposure to cadmium fumes in a factory. Very high levels of cadmium in air sampled at the workplace and in the patient's blood, urine, and lung tissue confirmed massive exposure. These data strongly suggest an association between the patient's cadmium exposure and the development of emphysema.     

Postmortem evaluation of the use of diaphragmatic excursus in assessment of pulmonary emphysema in coal miners

In a series of 89 subjects (all coal miners or ex-coal miners) a high order of correlation has been found between diaphragmatic excursus measured within five years of death and the necropsy assessment of emphysema in the lungs. In the absence of other common factors that reduce the range of movement of the diaphragm, measurements of diaphragmatic excursus provide a statistical prediction of the severity of emphysema. The individual variance, however, is such that this assessment should be used only as part of a range of clinicoradiological, physiological, and electrocardiographic indicators of emphysema severity.     

Lung transplantation for aspiration-induced silicosis of the lung

Silicosis, a slowly progressing chronic disease, is rare in lung transplantation patients. Herein, we report a case of single lung transplantation in a 35-year-old man for acute and accelerated silicosis, without a history of inhalation of silicium. A pathology examination of the explanted lung revealed that aspiration of a scouring powder was the cause of lung silicosis. Aspiration-induced lung silicosis is rare.     

Causes of allograft dysfunction after single lung transplantation for emphysema: extrinsic restriction versus intrinsic obstruction. Brigham and Women's Hospital Lung Transplantation Group.

BACKGROUND: A subset of patients with emphysema who have undergone single lung transplantation (SLT) may subsequently present with dyspnea, worsening airways obstruction, hypoxemia, and progressive chronic native lung hyperinflation. The leading cause of late allograft dysfunction is bronchiolitis obliterans syndrome (BOS). However, extrinsic restriction manifests with a similar clinical presentation and is an additional mechanism to consider. We describe the use of the inspiratory lung resistance (RLi) to distinguish a decline in respiratory status due predominantly to either extrinsic restriction or BOS. METHODS: We studied five patients who underwent SLT for emphysema between 1992 and 1995, in whom the diagnoses of BOS and extrinsic restriction were subsequently entertained. Forced expiratory volume in 1 second (FEV1), RLi, static lung compliance, elastic recoil pressure at total lung capacity (TLC), and the slope of the maximum flow static recoil (MFSR) plot were measured. RESULTS: All patients had severe airflow obstruction, with mean FEV1 0.98 +/- 0.24 liter (26 +/- 5% predicted), elevated static lung compliance, reduced elastic recoil pressure at TLC, and reduced slope of the MFSR plot. Three patients had "low" RLi (9.3-12.8 cm H20/L/sec). Obstruction was attributed predominantly to extrinsic restriction. These patients underwent lung volume reduction surgery (LVRS) on the native lung; improvements in pulmonary mechanics were observed at 6 months. In contrast, two patients had markedly elevated RLi (17.3 and 17.4 cm H2O/L/sec). Obstruction was attributed predominantly to intrinsic airway disease from BOS that was subsequently documented at autopsy. CONCLUSIONS: The RLi appears to be a useful adjunct to the clinical history in distinguishing a decline in respiratory status due predominantly to either BOS or extrinsic restriction in patients who have undergone SLT for emphysema. Determination of the mechanism of allograft dysfunction may allow the selection of an appropriate subset of patients who would benefit from LVRS.     

Thirteen-year experience in lung transplantation for emphysema

BACKGROUND: Emphysema is the most common indication for lung transplantation. Recipients include younger patients with genetically determined alpha-1 antitrypsin deficiency (AAD) and, more commonly, patients with chronic obstructive pulmonary disease (COPD). We analyzed the results of our single-institution series of lung transplants for emphysema to identify outcome differences and factors predicting mortality and morbidity in these two groups. METHODS: A retrospective analysis was undertaken of the 306 consecutive lung transplants for emphysema performed at our institution between 1988 and 2000 (220 COPD, 86 AAD). Follow-up was complete and averaged 3.7 years. RESULTS: The mean age of AAD recipients (49 +/- 6 years) was less than those with COPD (55 +/- 6 years; p < 0.001). Hospital mortality was 6.2%, with no difference between COPD and AAD, or between single-lung transplants and bilateral-lung transplants. Hospital mortality during the most recent 6 years was significantly lower (3.9% vs 9.5%, p = 0.044). Five-year survival was 58.6% +/- 3.5%, with no difference between COPD (56.8% +/- 4.4%) and AAD (60.5% +/- 5.8%). Five-year survival was better with bilateral-lung transplants (66.7% +/- 4.0%) than with single-lung transplants (44.9% +/- 6.0%, p < 0.005). Independent predictors of mortality by Cox analysis were single lung transplantation (relative hazard = 1.98, p < 0.001), and need for cardiopulmonary bypass during the transplant (relative hazard = 1.84, p = 0.038). CONCLUSIONS: AAD recipients, despite a younger age, do not achieve significantly superior survival results than those with COPD. Bilateral lung transplantation for emphysema results in better long-term survival. Accumulated experience and modifications in perioperative care over our 13-year series may explain recently improved early and long-term survival.