Transplantation for work-related lung disease in the USA.

OBJECTIVES: Work-related lung diseases (WRLDs) are entirely preventable. To assess the impact of WRLDs on the US transplant system, we identified adult lung transplant recipients with a WRLD diagnosis specified at the time of transplant to describe demographic, payer and clinical characteristics of these patients and to assess post-transplant survival. METHODS: Using US registry data from 1991 to 2018, we identified lung transplant recipients with WRLDs including coal workers' pneumoconiosis, silicosis, asbestosis, metal pneumoconiosis and berylliosis. RESULTS: The frequency of WRLD-associated transplants has increased over time. Among 230 lung transplants for WRLD, a majority were performed since 2009; 79 were for coal workers' pneumoconiosis and 78 were for silicosis. Patients with coal workers' pneumoconiosis were predominantly from West Virginia (n=31), Kentucky (n=23) or Virginia (n=10). States with the highest number of patients with silicosis transplant were Pennsylvania (n=12) and West Virginia (n=8). Patients with metal pneumoconiosis and asbestosis had the lowest and highest mean age at transplant (48.8 and 62.1 years). Median post-transplant survival was 8.2 years for patients with asbestosis, 6.6 years for coal workers' pneumoconiosis and 7.8 years for silicosis. Risk of death among patients with silicosis, coal workers' pneumoconiosis and asbestosis did not differ when compared with patients with idiopathic pulmonary fibrosis. CONCLUSIONS: Lung transplants for WRLDs are increasingly common, indicating a need for primary prevention and surveillance in high-risk occupations. Collection of patient occupational history by the registry could enhance case identification and inform prevention strategies.

A mortality study of beryllium workers.

We aimed at investigating mortality among beryllium-exposed workers, according to solubility of beryllium and beryllium compounds. We conducted an historical cohort study of 16,115 workers employed during 1925-2008 in 15 facilities, including eight entailing exposure to insoluble beryllium and seven entailing exposure to soluble/mixed beryllium compounds, who were followed up for mortality until 2011. Data were analyzed using indirect standardization and Cox regression modeling. Lung cancer standardized mortality ratio (SMR, national reference rates) was 1.02 (95% confidence interval [CI]: 0.94-1.10) in the whole cohort, 0.88 (95% CI: 0.75-1.03) in the insoluble beryllium subcohort, and 1.09 (95% CI: 0.99-1.09) in the soluble/mixed beryllium subcohort. For lung cancer, there was an association with period of hire in soluble/mixed beryllium plants but not in insoluble plants, and, conversely, employment in soluble/mixed plants was associated with increased mortality only among workers hired before 1955. There was no trend with duration of employment. Mortality from chronic beryllium disease increased, in particular, among workers hired before 1955 in soluble/mixed beryllium facilities. There was no increase in lung cancer mortality in the entire cohort and lung cancer mortality was not increased among beryllium workers hired in 1955 or later in soluble/mixed beryllium facilities, or at any time among those employed in insoluble beryllium facilities.

A mortality study of workers exposed to insoluble forms of beryllium.

This study investigated lung cancer and other diseases related to insoluble beryllium compounds. A cohort of 4950 workers from four US insoluble beryllium manufacturing facilities were followed through 2009. Expected deaths were calculated using local and national rates. On the basis of local rates, all-cause mortality was significantly reduced. Mortality from lung cancer (standardized mortality ratio 96.0; 95% confidence interval 80.0, 114.3) and from nonmalignant respiratory diseases was also reduced. There were no significant trends for either cause of death according to duration of employment or time since first employment. Uterine cancer among women was the only cause of death with a significantly increased standardized mortality ratio. Five of the seven women worked in office jobs. This study confirmed the lack of an increase in mortality from lung cancer and nonmalignant respiratory diseases related to insoluble beryllium compounds.

Cohort mortality study of workers at seven beryllium processing plants: update and associations with cumulative and maximum exposure.

OBJECTIVES: To extend follow-up of cause-specific mortality in workers at seven beryllium processing plants and to estimate associations between mortality risk and beryllium exposure. METHODS: 9199 workers were followed for mortality from 1940 through 2005. Standardised mortality ratios (SMRs) were estimated based on US population comparisons for lung, nervous system and urinary tract cancers, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and categories containing chronic beryllium disease (CBD) and cor pulmonale. Associations with maximum and cumulative exposure were calculated for a subset of the workers. RESULTS: Overall mortality in the cohort compared with the US population was elevated for lung cancer (SMR 1.17; 95% CI 1.08 to 1.28), COPD (SMR 1.23; 95% CI 1.13 to 1.32), and the categories containing CBD (SMR 7.80; 95% CI 6.26 to 9.60) and cor pulmonale (SMR 1.17; 95% CI 1.08 to 1.26). Mortality rates for most diseases of interest increased with time-since-hire. For the category including CBD, rates were substantially elevated compared to the US population across all exposure groups. Workers whose maximum beryllium exposure was ≥ 10 µg/m(3) had higher rates of lung cancer, urinary tract cancer, COPD and the category containing cor pulmonale than workers with lower exposure. Significant positive trends with cumulative exposure were observed for nervous system cancers (p = 0.0006) and, when short-term workers were excluded, lung cancer (p = 0.01), urinary tract cancer (p = 0.003) and COPD (p < 0.0001). CONCLUSION: These findings reaffirm that lung cancer and CBD, and suggest that COPD and nervous system and urinary tract cancers, are related to beryllium exposure. Cigarette smoking and exposure to other lung carcinogens are unlikely to explain these elevations.

Long-term complications and prognosis of chronic beryllium disease.

BACKGROUND: Chronic beryllium disease (CBD) is a rare disease, and there are no previous reports that have followed CBD patients over several decades. Thus, the long-term complications and prognosis of this illness still remain unclear. OBJECTIVE: The aim of this study was to investigate long-term complications and prognosis of CBD patients. STUDY DESIGN AND METHODS: This was a retrospective study based on the medical records of all CBD patients diagnosed at Kyoto University Hospital between the period 1973 to the present day. Ultimately, ten patients whose diagnoses had been made during the period 1973 to 1977 were included. Long-term physiological and radiological change, complications and prognosis of these patients were investigated. RESULTS: Three patients completely remitted, and one died of cor-pulmonale. Among the remaining six patients, four have been followed up for more than thirty years in our institute. The majority developed mixed patterns of lung function impairment, cavity lesions of the lung, pneumothorax, and respiratory infections. CONCLUSIONS: Long-term prognosis of CBD was poor with several complications due to chronic parenchymal and airway lesions.

Current treatment of chronic beryllium disease.

The current mainstay of management of chronic beryllium disease involves cessation of beryllium exposure and use of systemic corticosteroids. However, there are no randomized controlled trials to assess the effect of these interventions on the natural history of this disease. Despite this limitation, it is prudent to remove patients with chronic beryllium disease from further exposure and consider treating progressive disease early with long-term corticosteroids. The effect of treatment should be monitored using pulmonary function tests and high-resolution computed tomography of the chest. However, once pulmonary fibrosis has developed, corticosteroid therapy cannot reverse the damage.

United Kingdom Beryllium Registry: mortality and autopsy study.

This report is based on 30 deaths from chronic beryllium disease (CBD) in the United Kingdom with details of 19 autopsies. The majority were fluorescent lamp workers and machinists who died from respiratory failure. There were no cases of lung cancer. The survival times ranged from less than 1 to 29 years and was longest in machinists. All of the workers showed interstitial pulmonary fibrosis with varying degrees of cystic change. The majority showed hyalinized, and a few active sarcoid-type, granulomas. Extrathoracic granulomas, as in a U.K. sarcoid autopsy series, were rare. A notable difference was the absence of myocardial involvement in CBD compared to an incidence of 20% in the sarcoid autopsies. The detection of beryllium in the criteria for diagnosis is emphasized and the cases classified as definite include 12 of 19 positive analysis, 6 of 19, negative or unavailable analysis. The remaining case was classified as dubious because, despite a positive analysis, granulomas were absent. The main differential diagnosis is sarcoidosis.

The epidemiological evidence on the carcinogenicity of beryllium in humans.

Authoritative reviews of the question of whether occupational exposure to beryllium compounds is associated with increased risk of respiratory cancer were published in 1987 and were critical of the quality of the evidence available up to that time. No clear conclusion could be drawn from it as to the carcinogenicity of beryllium to humans. If studies published since 1987 are to lead to a revision of the regulatory status of beryllium compounds they must clearly be of high quality and scientific validity. These studies, as well as the earlier reports, are reviewed here. I argue that the small and inconsistent excess of lung cancer deaths in employees of one or two plants seen in two post-1987 studies is compatible with a number of explanations other than that they are attributable to occupational exposure to beryllium. Specifically, information on cigarette smoking is poor, and the data do not exist to rule out the possibility that the small number of excess deaths results from residual confounding by cigarette smoking patterns in the populations studied. Indeed, excess deaths from emphysema and ischemia heart disease in the same cohort suggest that confounding by cigarette smoking is a more likely explanation of the lung cancer excess than is occupational exposure to beryllium compounds.

A mortality study of workers at seven beryllium processing plants.

The International Agency for Research on Cancer (IARC) has found that the evidence for the carcinogenicity of beryllium is sufficient based on animal data but "limited" based on human data. This analysis reports on a retrospective cohort mortality study among 9,225 male workers employed at seven beryllium processing facilities for at least 2 days between January 1, 1940, and December 31, 1969. Vital status was ascertained through December 31, 1988. The standardized mortality ratio (SMR) for lung cancer in the total cohort was 1.26 (95% confidence interval [CI] = 1.12-1.42); significant SMRs for lung cancer were observed for two of the oldest plants located in Lorain, Ohio (SMR = 1.69; 95% CI = 1.28-2.19) and Reading, Pennsylvania (SMR = 1.24; 95% CI = 1.03-1.48). For the overall cohort, significantly elevated SMRs were found for "all deaths" (SMR = 1.05; 95% CI = 1.01-1.08), "ischemic heart disease" (SMR = 1.08; 95% CI = 1.01-1.14), "pneumoconiosis and other respiratory diseases" (SMR = 1.48; 95% CI = 1.21-1.80), and "chronic and unspecified nephritis, renal failure, and other renal sclerosis" (SMR = 1.49; 95% CI = 1.00-2.12). Lung cancer SMRs did not increase with longer duration of employment, but did increase with longer latency (time since first exposure). Lung cancer was particularly elevated (SMR = 3.33; 95% CI = 1.66-5.95) among workers at the Lorain plant with a history of (primarily) acute beryllium disease, which is associated with very high beryllium exposure. The lung cancer excess was not restricted to plants operating in the 1940s, when beryllium exposures were known to be extraordinarily high. Elevated lung cancer SMRs were also observed for four of the five plants operating in the 1950s for workers hired during that decade. Neither smoking nor geographic location fully explains the increased lung cancer risk. Occupational exposure to beryllium compounds is the most plausible explanation for the increased risk of lung cancer observed in this study. Continued mortality follow-up of this cohort will provide a more definitive assessment of lung cancer risk at the newer plants and among cohort members hired in the 1950s or later at the older plants. Further clarification of the potential for specific beryllium compounds to induce lung cancer in humans, and the possible contribution of other exposures in specific processes at these plants, would require a nested case-control study. We are currently assessing whether available industrial hygiene data would support such an analysis.

Lung cancer incidence among patients with beryllium disease: a cohort mortality study.

We have conducted a cohort mortality study on 689 patients with beryllium disease who were included in a case registry. An earlier mortality study on 421 of these patients was limited to males and resulted in a determination of a nonsignificant twofold lung cancer excess based on only seven lung cancer deaths. We have extended this earlier study by including females and by adding 13 years of follow-up. Comparison of the 689 beryllium disease patients with the U.S. population resulted in a lung cancer standardized mortality ratio (SMR) of 2.00 (95% confidence interval = 1.33-2.89) based on 28 observed lung cancer deaths. Adjustment for smoking did not change these results. All causes of mortality were also significantly elevated (SMR = 2.19), largely because of the very high rate of deaths due to pneumoconioses (primarily beryllium disease) (SMR = 34.23; 158 deaths). No other causes of death were significantly elevated. The excess of lung cancer was consistent for both sexes and did not appear to increase with duration of exposure to beryllium or with time elapsed since first exposure to this element. The case registry included those with acute beryllium disease, which resembles a chemical pneumonitis, and those with chronic beryllium disease, which resembles other pneumoconioses. The lung cancer excess was more pronounced among those with acute disease (SMR = 2.32) than among those with chronic disease (SMR = 1.57).