Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.

OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis. METHODS: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time. RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer. CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.

Cancer mortality and exposure to nickel and chromium compounds in a cohort of Italian electroplaters.

BACKGROUND: Nickel and chromium-VI compounds are carcinogens for lung cancer, although it is still debated if there is an increased risk at low levels of exposure and for other cancers. METHODS: In a cohort of 2991 Italian electroplaters, a proportion of whom were exposed to low levels of nickel and/or chromium, cumulative exposure to their compounds was obtained by multiplying average concentrations of the metals in each electroplating tank by duration of employment in the company. The association of exposure to compounds with mortality was assessed by multivariable Cox models. RESULTS: No cancer site was associated with chromium exposure controlling for nickel, whereas exposure to nickel significantly increased mortality from lung, rectal, and kidney cancers, even after adjusting for exposure to chromium. CONCLUSIONS: Study results suggest that exposure to nickel compounds may increase the risk of lung cancer even below its occupational exposure limit and indicate possible associations with other cancer sites.

Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure.

OBJECTIVE: Asbestos is a known human carcinogen, with evidence for malignant mesothelioma (MM), cancers of lung, ovary, larynx and possibly other organs. MM rates are predicted to increase with a power of time since first exposure (TSFE), but the possible long-term attenuation of the trend is debated. The asbestos ban enforced in Italy in 1992 gives an opportunity to measure long-term cancer risk in formerly exposed workers. METHODS: Pool of 43 previously studied Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding), with mortality follow-up updated to 2010. SMRs were computed for the 1970â€"2010 period, for the major causes, with consideration of duration and TSFE, using reference rates by age, sex, region and calendar period. RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Mortality was significantly increased for all deaths (SMR: men: 1.05, 95% CI 1.03 to 1.06; women: 1.17, 95% CI to 1.12 to 1.22), all malignancies combined (SMR: men: 1.17, 95% CI to 1.14 to 1.20; women: 1.33, 95% CI 1.24 to 1.43), pleural and peritoneal malignancies (SMR: men: 13.28 and 4.77, 95% CI 12.24 to 14.37 and 4.00 to 5.64; women: 28.44 and 6.75, 95% CI 23.83 to 33.69 and 4.70 to 9.39), lung (SMR: men: 1.26, 95% CI 1.21 to 1.31; women: 1.43, 95% CI 1.13 to 1.78) and ovarian cancer (SMR=1.38, 95% CI 1.00 to 1.87) and asbestosis (SMR: men: 300.7, 95% CI 270.7 to 333.2; women: 389.6, 95% CI 290.1 to 512.3). Pleural cancer rate increased during the first 40 years of TSFE and reached a plateau after. DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. Pleural cancer mortality reached a plateau at long TSFE, coherently with recent reports.

[Mortality study in a cohort of workers employed in the hot working processing of plastics and rubber]. / Studio di mortalità in una coorte di esposti nella lavorazione a caldo di materie plastiche e gomma.

OBJECTIVES: to study mortality rates among workers in companies manufacturing thermoplastic and rubber articles (excluding tyres). DESIGN: cohort study. SETTING AND PARTICIPANTS: the cohort includes 4,543 workers employed up to 2000 in 131 companies in the Province of Bologna (Emilia-Romagna Region, Northern Italy) exposed to emissions from hot processing of plastics (3,937) and rubber (606). MAIN OUTCOME MEASURES: general- and cause-specific Standardized Mortality Rates (SMR), with 95% confidence intervals; entire reference population resides in the Emilia-Romagna Region. RESULTS: excess mortality for all causes (116 Obs; SMR: 1.20; 95%CI 1.00-1.44) and for lung cancer (18 Obs; SMR: 1.67; 95%CI 1.05-2.65) in men of the rubber factories. Increased mortality rates for oesophageal cancers in women (3 Obs; SMR: 5.41; 95%CI 1.74-16.8) and in men (6 Obs; SMR: 2.16; 95%CI 0.97-4.81), for malignant tumours of pancreas (16 Obs; SMR: 1.65; 95%CI 1.01- 2.70), rectum (11 Obs; SMR: 2.17; 95%CI 1.20-3.92) and kidney (11 Obs; SMR: 1.98; 95%CI 1.10-3.58) in men occupied in plastic processing. CONCLUSION: in this study, we observed an excess of mortality rates for lung cancer in men of rubber factories and for malignant tumours of the digestive tract, pancreas, and kidney in workers employed in the production of plastic articles. Nevertheless, these results must be interpreted with caution, because exposures to non-occupational risk factors, like tobacco smoke or other occupational exposures outside the companies concerned, are not known. The results suggest to continue epidemiological surveillance.

[Mortality study update of workers exposed to vinyl chloride in plants located in Ferrara and Ravenna (Emilia-Romagna Region, Northern Italy)]. / Aggiornamento dello studio di mortalità nelle coorti di lavoratori ex esposti a cloruro di vinile monomero a Ferrara e Ravenna.

OBJECTIVES: to update the mortality study of subjects exposed to vinyl chloride in the phases of synthesis of the monomer and polymerization in the plants of Ferrara and Ravenna (Emilia-Romagna Region, Northern Italy). DESIGN: both for the whole cohort and for the two plants, standardized mortality ratios (SMRs), with 95% confidence intervals (95%CI), were calculated for different death causes, then stratified by duration and latency, periods of the beginning of work and cumulative exposure (ppm-years). SETTING AND PARTICIPANTS: the cohort includes 1,540 subjects (469 in Ferrara hired from 1953 to 1999; 1,071 in Ravenna hired from 1959 to 2000), with at least six months of work. RESULTS: by the end of the follow-up (31.12.2013), 348 deaths occurred. Overall observed mortality, contrasted to that expected based on Emilia-Romagna Region mortality rates, appeared to be lower than expected in the whole cohort (348 cases, SMR: 0.85; 95%CI 0.77-0.95) and in Ravenna (173 cases, SMR: 0.71; 95%CI 0.61-0.83). Mortality for all neoplasms was in excess in Ferrara (79 cases, SMR: 1.27; 95%CI 1.02-1.58), but lower than expected in Ravenna (83 cases, SMR: 0.80; 95%CI 0.64-0.99). An excess in mortality was observed in the whole cohort (16 cases, SMR: 1.74; 95%CI 1.07-2.85) and in Ferrara for liver cancer (7 cases, SMR: 2.12; 95%CI 1.02-4.46), and only in Ferrara for respiratory tract cancer (30 cases, SMR: 1.45; 95%CI 1.02-2.07) and larynx cancer (4 cases, SMR: 3.35; 95%CI 1.26-8.92). In the whole cohort, SMR for liver cancer was in excess since a cumulative exposure of 5,000 ppm-year and 12 cases belong to the job title of autoclave workers (12 cases, SMR 4.6; 95%CI 2.6-8.0), duration of work higher than 20 years (8 cases, SMR 2.4; 95%CI 1.2-4.9), and latency higher than 40 years (7 cases, SMR 2.5; 95%CI 1.2-5.2). The excess in mortality for lung cancer is statistically significant for and with cumulative exposure higher than 7,330 ppm-years (6 cases, SMR 3.2 95%CI 1.4-7.0). There are not excesses among subjects hired after 1971. CONCLUSIONS: the study findings confirm and expand the ones of previous studies. It was not possible to apply a best evidence approach to the study of liver cancer, and consequently it is not possible to distinguish between hepatic angiosarcoma and hepatocellular carcinoma. The evidence of a causal link between vinyl chloride exposure and liver cancer is anyhow confirmed. The causal link between vinyl chloride exposure and lung cancer must be further investigated.

[Time trend in mesothelioma and lung cancer risk in asbestos workers in Italy]. / Valutazione della variazione temporale del rischio di mesotelioma e di tumore del polmone nelle coorti di esposti ad amianto per lavoro in Italia.

This study aims at investigating, in asbestos exposed workers, the time trend of their risk of mesothelioma and of other neoplasm after very long latency and after the cessation of asbestos exposure. We pooled a large number of Italian cohorts of asbestos workers and updated mortality follow-up. The pool of data for statistical analyses includes 51,988 workers, of which 6,058 women: 54.2% was alive at follow-up, 42.6% was dead, and 2.8%was lost. Cause of death is known for 94.3%: 2,548 deaths from lung cancer, 748 frompleural cancer, 173 fromperitoneal cancer, and 434 from asbestosis. An exposure index is being developed to compare the different cohorts. Data analysis is in progress. This study will have the size for analysing not only time trends in mesothelioma, but also the occurrence of rarer diseases and cancer specific mortality in women.

Air pollution and multiple acute respiratory outcomes.

Short-term effects of air pollutants on respiratory mortality and morbidity have been consistently reported but usually studied separately. To more completely assess air pollution effects, we studied hospitalisations for respiratory diseases together with out-of-hospital respiratory deaths. A time-stratified case-crossover study was carried out in six Italian cities from 2001 to 2005. Daily particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10)) and nitrogen dioxide (NO2) associations with hospitalisations for respiratory diseases (n = 100 690), chronic obstructive pulmonary disease (COPD) (n = 38 577), lower respiratory tract infections (LRTI) among COPD patients (n = 9886) and out-of-hospital respiratory deaths (n = 5490) were estimated for residents aged ≥35 years. For an increase of 10 µg·m(-3) in PM10, we found an immediate 0.59% (lag 0-1 days) increase in hospitalisations for respiratory diseases and a 0.67% increase for COPD; the 1.91% increase in LRTI hospitalisations lasted longer (lag 0-3 days) and the 3.95% increase in respiratory mortality lasted 6 days. Effects of NO2 were stronger and lasted longer (lag 0-5 days). Age, sex and previous ischaemic heart disease acted as effect modifiers for different outcomes. Analysing multiple rather than single respiratory events shows stronger air pollution effects. The temporal relationship between the pollutant increases and hospitalisations or mortality for respiratory diseases differs.

[Mortality study in metal electroplating workers in Bologna (Northern Italy)]. / Studio di mortalità in una coorte di esposti a metalli nel comparto galvanotecnica del territorio di Bologna.

AIM: to investigate general and cause-specific mortality of workers exposed to metals and other chemicals in the electroplating industry in Bologna Province. MATERIALS AND METHODS: factory records of workers employed in 90 electroplating companies present in 1995 were used to build a cohort of subjects potentially exposed to carcinogenic and other substances in this industry, defined as "revised cohort", which was followed-up for mortality from 1960, or since first employment in an electroplating company if later, to 2008. Mortality risk was also examined separately in a subset of the cohort, composed of workers with at least one year of employment in electroplating, denominated "final cohort". Death rates of residents in Emilia-Romagna Region (Northern Italy) were used as a reference. RESULTS: follow-up completeness was 99%. During the observation period, 533 deaths out of 2,983 subjects were observed in the revised cohort and 317 out of 1,739 in the final cohort. Significantly increased Standardized Mortality Ratios were estimated for overall mortality and for mortality from AIDS in the revised cohort and for bladder and rectal cancer in both cohorts. CONCLUSIONS: the present study is, to authors' knowledge, the largest mortality investigation conducted in Italy on electroplating workers, for both size and temporal extension. The presence of excess mortality from causes of death not consistently associated in the literature with exposure to agents in this industry suggests that further research is needed to confirm these associations.

Italian pool of asbestos workers cohorts: asbestos related mortality by industrial sector and cumulative exposure.

OBJECTIVE: Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers. METHODS: Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period. RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most also from peritoneal and lung cancer and asbestosis, with exposure related trend. Increased mortality was also observed for ovarian cancer and for bladder cancer. DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. A large increase in mortality from asbestosis was observed.

[Environmental indicators in ten Italian cities (2001-2005): the air quality data for epidemiological surveillance]. / Indicatori ambientali in dieci città italiane (2001-2005): i dati di qualità dell'aria per la sorveglianza epidemiologica.

OBJECTIVE: to produce environmental indicators suitable for an epidemiological surveillance in 10 Italian cities part of the EpiAir Project (2001-2005). METHODS: the environmental parameters that correlate to relevant health effects are the particles with diameters less than or equal to 10 micrometers (PM10), the nitrogen dioxide (NO2) and the ozone (O3). The necessary meteorological data are: temperature, relative humidity, barometric pressure and apparent temperature.We have identified some criteria to select monitoring stations and have taken standard methods of calculation to produce environmental indicators starting from the daily data available after closely evaluating the completeness of the existing data. Furthermore, we have checked the homogeneity of the selected data to ensure that it represents the population's exposure. RESULTS: close examination of descriptive statistics shows a critical situation of the considered pollutants. The analysis of the yearly state underlines for PM10 values higher than 40 microg/m3 in the area of Mestre-Venice and in Milan, Turin, Bologna e Taranto. For NO2, values are consistently above 40 microg/m3 in Milan, Turin, Bologna, Florence, Rome and Palermo. For ozone, the concentrations were stable, with the exception of Summer 2003 when we recorded, on average, an increase of 13% compared to the mean value estimated for the ten cities during the study period, especially in Mestre-Venice, Turin and Palermo. CONCLUSIONS: it is important to ensure the consistency of the methods and instruments in environmental monitoring. To evaluate health effects and perform interventions over the longterm, it is therefore fundamental that the data be homogenous, especially during the periodic reorganizations and rationalizations of air quality management. It is also necessary to include daily meteorological data that influence pollutant dispersion and population health status.

Vulnerability to heat-related mortality: a multicity, population-based, case-crossover analysis.

BACKGROUND: Although studies have documented increased mortality during heat waves, little information is available on the subgroups most susceptible to these effects. We evaluated the effects of summertime high temperature on daily mortality among population subgroups defined by demographic characteristics, socioeconomic status, and episodes of hospitalization for various conditions during the preceding 2 years. METHODS: We studied a total of 205,019 residents of 4 Italian cities (Bologna, Milan, Rome, and Turin) age 35 or older who died during 1997-2003. The case-crossover design was applied to evaluate the association between mean apparent temperature (same and previous day) and all-cause mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) of dying at 30 degrees C (apparent temperature) relative to 20 degrees C were estimated accounting for time, population changes, and air pollution. RESULTS: We found an overall OR of 1.34 (CI = 1.27-1.42) at 30 degrees C relative to 20 degrees C. The odds ratio increased with age and was higher among women (OR = 1.45; 1.37-1.52) and among widows and widowers (1.50; 1.33-1.69). Low area-based income modestly increased the effect. Among the preexisting medical conditions investigated, effect modification was detected for previous psychiatric disorders (1.69; 1.39-2.07), depression (1.72; 1.24-2.39), heart conduction disorders (1.77; 1.38-2.27), and circulatory disorders of the brain (1.47; 1.34-1.62). Temperature-related mortality was higher among people residing in nursing homes, and a large effect was also detected for hospitalized subjects. CONCLUSIONS: Subsets of the population that are particularly vulnerable to high summer temperatures include the elderly, women, widows and widowers, those with selected medical conditions, and those staying in nursing homes and healthcare facilities.