Asbestos exposure and asbestosis mortality in Italian cement-asbestos cohorts: Dose-response relationship and the role of competing death causes.

OBJECTIVES: In Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose-response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks. METHODS: Cohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause-specific (CS) Cox-regression models were used to evaluate the dose-exposure relationship between asbestosis mortality and the time-dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death. RESULTS: The cohort included 12,963 asbestos cement workers. During the follow-up period (1960-2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose-response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL-years. Lung cancer and circulatory diseases were the main competing causes of death. CONCLUSIONS: Asbestos exposure among Italian asbestos-cement workers has led to a very high number of deaths from asbestosis and asbestos-related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

[Is the epidemiological surveillance of malignant mesothelioma implemented in Italy still valid and necessary?] / La sorveglianza epidemiologica del mesotelioma maligno attuata in Italia è ancora valida e necessaria?

The register of malignant mesotheliomas can still play an informative role in the context of both remediation activities and the health surveillance of former asbestos-exposed persons, and become an epidemiological surveillance system on the harmful effects of exposure to asbestos. It must, however, maintain and improve the level of quality achieved, resolve the problems that have emerged in the interaction between the local level (where cases and their exposure histories are identified, registered, assessed, and medical insurance procedures activated) and the central insurance body that also manages the national register, and become an active participant in research, including clinical research. All this is important to meet the social and welfare justice needs of individual cases.

Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.

INTRODUCTION: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy. METHOD: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE). RESULT: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE. CONCLUSION: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.

Mesothelioma Risk Among Maritime Workers According to Job Title: Data From the Italian Mesothelioma Register (ReNaM).

The study describes the 466 cases of malignant mesotheliomas (MM) collected by the National Mesothelioma Register (ReNaM) in Italy in the period 1993-2018 relating to subjects with exclusive asbestos exposure in merchant or military navy. The cases among maritime workers represent 1.8% of the total cases with defined exposure registred in the ReNaM, of which 212 cases (45.4%) among merchant maritime workers and 254 cases (54.5%) among navy. The distribution by site of mesothelioma showed 453 (97.2%) MM cases of the pleura, 11 (2.3%) of the peritoneum and 2 (0.4%) of the tunica vaginalis of the testis. With regard to occupational exposure, it was classified as certain in 318 (68.2%) cases, probable in 69 (14.8%) cases and possible in 79 (16.9%) cases. Among the 23 classified jobs, the highest percentages of certain exposures are among naval engineers, motor mechanics, machine captains and sailors. Machine crew accounted for 49.3% of the cases, deck crew for 27.6%. All cases began exposure on board between 1926 and 1988. Seamen were exposed to asbestos while at sea by virtue of living onboard ships and from continual release of asbestos fibers due to the motion of a vessel. Epidemiological surveillance through the ReNaM has allowed us to verify among cases in the maritime, navy and merchant marine sectors, that in the past, subjects were exposed regardless of the ship's department where have provided service therefore all these cases must be considered as occupational diseases.

Mesothelioma Risk among Construction Workers According to Job Title: Data from the Italian Mesothelioma Register.

BACKGROUND: An increased risk of mesothelioma has been reported in various countries for construction workers. The Italian National Mesothelioma Registry, from 1993 to 2018, reported exposure exclusively in the construction sector in 2310 cases. We describe the characteristics of these cases according to job title. METHODS: We converted into 18 groups the original jobs (N=338) as reported by ISTAT codes ('ATECO 91'). The exposure level was attributed at certain, probable and possible in accordance with the qualitative classification of exposure as reported in the Registry guidelines. Descriptive analysis by jobs highlights the total number of subjects for each single job and certain exposure, in descending order, insulator, plumbing, carpenter, mechanic, bricklayer, electrician, machine operator, plasterer, building contractor, painter and labourer. RESULTS: The cases grow for plumbing in the incidence periods 1993-2018, while, as expected, it decreases for insulator. Within each period considered the most numerous cases are always among bricklayers and labourers, these data confirm the prevalence of non-specialised "interchangeable" jobs in Italian construction sector in the past. CONCLUSIONS: Despite the 1992 ban, the construction sector still presents an occupational health prevention challenge, circumstances of exposure to asbestos may still occur due to incomplete compliance with prevention and protection measures.

Preliminary validation of a questionnaire assessing psychological distress in caregivers of patients with malignant mesothelioma: Mesothelioma Psychological Distress Tool-Caregivers.

OBJECTIVE: To develop a short, flexible, and comprehensive tool to measure psychological distress in caregivers of malignant mesothelioma (MM) patients: the Mesothelioma Psychological Distress Tool-Caregivers version (MPDT-C). METHODS: Based on a systematic review of the relevant literature, aspects associated with caregiver distress were derived. Expert researchers/clinicians developed a pool of items for each identified aspect. Content validity was assessed through a multiple mixed-methods approach. A multicenter study was conducted to explore the factorial structure of the 47-item MPDT-C through Bayesian factor analysis. RESULTS: The Bayesian exploratory factor analysis revealed an underlying three-factor structure. Factors were labeled Secondary Traumatic Stress, Engagement in Caring, and Meaningful Cognitive Restructuring. All scales showed sufficient reliability and corrected item-total correlations. Females scored higher than males for Engagement in Caring. CONCLUSIONS: Taking care of malignant mesothelioma patients is a stressful process that influences the caregiver's physical, emotional, and social wellbeing. Our study offers preliminary evidence in support of the adequate psychometric properties of the MPDT-C, and these should now be replicated. Results suggest that the MPDT-C is a reliable tool with which to detect the psychological distress of this traumatized population.

Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM).

BACKGROUND: The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases' exposures but cannot provide relative risk estimates. OBJECTIVES: i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure-response relationship. METHODS: A population-based mesothelioma case-control study was conducted in 2012-2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16-1.42). CONCLUSIONS: Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure-response relationship.

[Mortality study in a cohort of entertainment workers]. / Studio di mortalità su una coorte di addetti al settore dello spettacolo.

SUMMARY: Introduction. Malignant mesotheliomas have been observed in entertainment workers in the last decades. They have been evaluated as occupationally exposed to asbestos contained in tools used for fireproof and sound-absorbing purposes. Aim of the study. To evaluate the mortality of workers engaged in a Florentine theatre where a large quantity of asbestos was found in the '80s, put in place 20 years earlier. Methods. It is a cohort study on entertainment workers with follow-up period ranged from 1-1-1970 till 31-12-2018. Standardized Mortality Ratios (SMRs) and their 95% Confidence Intervals (95% IC) were calculated by gender and job ("manual workers" and "all other jobs"), using age and sex specific mortality rates of Tuscan population. Results. The cohort includes 826 workers (389 manual workers and 437 engaged in other jobs) engaged by the Florentine theatre between 01/01/1937 and 31/12/1990. Excesses of mortality for all causes are observed in manual workers, either males (301 cases; SMR 304,0; 95% IC 271,5-340,3) or females (86 cases; SMR 429,8; 95% IC 348,0-531,0). The group of the other workers presents deficits of mortality by all causes, cancers and cardiovascular diseases in both genders. One death for pleural cancer is observed in a manual worker. Discussion. The results are in line with previous observations in similar occupations. In the examined Florentine theatre the asbestos exposures were important only for the manual workers who worked in the technical rooms characterized by the presence of friable asbestos sprinkled and in a bad state of maintenance.

[Inventory of occupational exposure to asbestos with particular reference to Tuscan workers]. / Repertorio delle esposizioni occupazionali ad amianto con particolare riferimento ai lavoratori toscani.

This Catalogue is a collection of information on the use of raw asbestos and asbestos-containing materials used in several industries and occupational activities, with particular attention to the situation of Tuscany, a region of Central Italy. The work was developed at the Institute for Cancer Research, Prevention and Clinical Network (ISPRO) of Florence, where epidemiologic research and surveillance activities have been developing since 1988 and where the coordination and evaluation of the regional health surveillance programme provided to past asbestos workers started in 2016 and is still ongoing. The Catalogue aims at being a working tool for all health professionals engaged in examining and classifying the occupational asbestos exposures of subjects both affected by diseases that could be associated to this carcinogen and examined within the regional health surveillance programme. It is necessary for the health personnel engaged in the above-mentioned activities to know or to have the possibility to find exact and detailed data on asbestos exposure by occupational sector. These data are briefly described in the 29 factsheets this Catalogue consists of. In each factsheet, the presence and every use of asbestos are described, with reference to a precise occupational sector. Several occupational sectors can be considered together because of analogies on asbestos exposure. Occupations are considered on the basis of existing evidence on the use of raw asbestos or asbestos-containing materials (as semi-finished or finished products or as auxiliary materials in production processes). Besides the presence and use of asbestos, a description of the possible exposures of workers is reported. Sources of information were scientific and grey literature as well as the 7,187 occupational histories of mesothelioma registered by the specific Tuscan registry. Some factsheets have been revised and enhanced by Italian experts on the asbestos exposure with a specific competence in the examined sectors. Each factsheet includes also questions to be addressed to workers in order to examine in depth their possible asbestos exposure. For those who would like to expand their knowledge on this topic, references are reported both at the end of each factsheet and at the end of the volume. In all industrialized countries, also in those which have not already banned asbestos use, a decrease in the use of this material and in the relative exposure have been observing since the end of the Seventies, few years after the general consensus within the scientific community on asbestos carcinogenicity. This decreasing trend has been becoming greater and greater since the end of the Eighties, when more restrictive regulations have been approved and applied, especially in occupational settings. Nevertheless, nowadays asbestos-related diseases are still diagnosed due to past exposures, although during next decade a decreasing incidence of malignant mesothelioma - the cancer most specifically related to this carcinogen and characterized by a very bad prognosis and the longest latency - could be observed. Particular attention will be paid to jobs regarding renovation of old buildings containing asbestos and to decontamination activities. In conclusion, this Catalogue is a working tool - although it is not exhaustive and could be upgraded with new information - for all professionals engaged in asbestos risk prevention activities as health personnel, personnel of insurance companies, employers, and employee representatives.

[The Tuscan experience on the asbestos discharge process 28 years after the ban: critical issues and future perspectives]. / L'esperienza toscana sul processo di dismissione dell'amianto a 28 anni dal bando: criticità e prospettive future.

OBJECTIVES: to examine the progress of the remediation and disposal of asbestos containing materials (ACMs) in Tuscany Region (Central Italy), the relative workforce employed, and how these activities are framed and reflected in the Italian panorama. DESIGN: descriptive study on the asbestos removal process in Tuscany. SETTING AND PARTICIPANTS: Reports drawn up according to article No. 9 of Law No. 257/92 received by the Tuscany Region from 1993 to 2019. The on-line submission of the reports has been available since 2011. MAIN OUTCOME MEASURES: quantities and characteristics of used or removed ACMs by compact and friable matrix, the ones transferred to temporary storage and/or landfill plants during 1995-2019; number of employees engaged in activities with asbestos presence, by type and duration of activity during 2015-2019. RESULTS: from 1993 to 2019, the Tuscany Region received a total of 5,284 reports. From 1995 to 2019, a total of 423,487 tons of ACMs were removed in Tuscany, 402,897 in a compact matrix and 20,590 in a friable matrix. Over the past five years, the workers employed in these activities were on average 1,500, with around 182,000 hours per year in contact with ACMs. CONCLUSIONS: Reports article No. 9 are an essential tool to monitor and evaluate the impact of political choices to incentivize the process of ACM removal, which is still proceeding too slowly: still 3/4 of installed ACMs remain in place 28 years after the ban. Furthermore, Reports article No. 9 are a source to identify workers who are potentially exposed to lower doses than in the past; they can be included in epidemiological cohort studies as well as in health surveillance programmes of past asbestos workers, an essential assistance level of collective prevention.

[BRIC-59 study: first results and considerations on the pathway on the access to health care for malignant pleural mesotheliomas]. / Studio BRIC-59: primi risultati e riflessioni sul percorso sanitario dell'accesso alle cure per mesotelioma maligno pleurico.

OBJECTIVES: to define the most frequent health pathways of cases affected by malignant pleural mesothelioma according to those suggested and evaluated by the most recent specific guidelines. DESIGN: epidemiological descriptive study. SETTING AND PARTICIPANTS: 100 cases histologically or cytologically well defined during 2015-2017 are extracted from the archive of two Regional Mesothelioma Registries: in Tuscany Region (Central Italy) they are randomly extracted, while in Lombardy Region (Northern Italy) cases treated by a highly-specialized health centre are collected. MAIN OUTCOME MEASURES: frequency of the diagnostic and therapeutic procedures; development and application of the checklist with evaluation of the duration of some phases of the predefined pathway. RESULTS: all hospital medical records were collected only for 34 cases in Tuscany and 20 cases in Lombardy. The health examinations were supplied according to each case's health condition and it was not possible to define one or more structured and standardized pathways. The pre-diagnostic phase has a variable duration according to the initial health condition of the patient, also for his/her comorbidity, and to the hospital where he/she was hospitalized at first. The examinations in outpatient services (medical examinations, blood chemistry tests and radiological examinations) are several, but they are specially requested during the pre-diagnostic phase and during the period of chemotherapy. The checklist applied to a subset of Tuscan cases shows a large variation of the length of the pre-diagnostic phase (6-330 days), of the time interval between diagnosis and reporting to mesothelioma registry (1-200 days), and of the survival time (8 days - alive at 31.12.2019). CONCLUSIONS: to obtain the best health pathways for malignant pleural mesotheliomas, it is necessary a strong network among the health regional services with a clinical multiprofessional coordination located in hospitals characterized by a long experience on these cases, and with an active regional monitoring on all clinical, psychological, epidemiological, and legal aspects of the pathway. The regional mesothelioma registries could give a high contribution thanks to their epidemiological skills which are necessary for the monitoring.

[Epidemiological study on the population resident in the neighbourhood of an incinerator in Tuscany Region (Central Italy)]. / Indagine epidemiologica sulla popolazione residente nell'area circostante un impianto di combustione di rifiuti solidi in Toscana.

OBJECTIVES: to evaluate the health impact of the emissions of two waste incinerators located in the same area in Pietrasanta (Tuscany Region, Central Italy) at the border with the municipality of Camaiore, especially for diseases suggested in previous studies to be related to those emissions. DESIGN: epidemiological geographic study. SETTING AND PARTICIPANTS: the study population was defined on the basis of residence in the two municipalities and in the areas characterized by Particulate Matter with diameter equal or less than 2.5 µm (PM2.5) and poli-chloro-dibenzo-dioxin / poli-chloro-dibenzo-furans (PCDD/F) pollution defined with a dispersion model. From the resident population, for each cancer case it was sampled a control, matched to case by gender and age at case's diagnosis, and for each premature and low-weight newborn a control matched was sampled by year of birth, gender, and mother's residence. MAIN OUTCOME MEASURES: standardized (standard: European population) mortality and hospitalization rates in the residents of the two municipalities were calculated for liver, larynx, lung cancer, soft tissue sarcoma (STM), non-Hodgkin lymphoma (NHL), multiple myeloma, leukaemia, flu-excluded respiratory diseases, and circulatory diseases. The risk related to each PM2.5 and PCDD/F pollution level from the old incinerator for cancer and from the new plant for reproductive outcomes was analysed using logistic conditional regression model adjusted by gender and age. RESULTS: the mortality and hospitalization rates observed in the study area are similar to those calculated for the Versilia area excluded the two municipalities under study. There is a higher case distribution in the higher pollution levels, with significant increases in the highest level: • liver cancer: PM2.5 OR 2.3 (95%CI 1.5-3.6); PCDD/F OR 4.4 (95%CI 2.8-7.0); • larynx cancer: PCDD/F OR 3.2 (95%CI 1.5-6.7); • lung cancer: PCDD/F OR 1.5 (95%CI 1.1-2.0); • NHL: PCDD/F OR 8.5 (95%CI 3.1-23.5); • leukaemia: PCDD/F OR 4.1 (95%CI 1.8-9.3). The risks estimated for STM, although non significant, are consistent with those obtained in previous studies undertaken in areas characterized by dioxin pollution. There is a deficit of premature births in the area under study compared to the regional area, and no differences are observed among the different pollution areas. CONCLUSIONS: it cannot be excluded that the emissions from the old incinerator had a health impact on the population living in the neighbourhood. Nevertheless, it is possible that other risk factors (occupations and life styles) could have had a role on the obtained results. Better estimates could be obtained also taking into consideration the residential histories of the subjects under study.

The decomposition of gain in life expectancy in Tuscany Region (Central Italy) for age-group and cause of death.

BACKGROUND: changing of life expectancy at birth (LE) over time is an important indicator of welfare and healthcare infrastructure of a Country. OBJECTIVES: to evaluate the impact of age and cause-specific mortality on the change in LE in the Tuscany Region (Central Italy). DESIGN: the decomposition of LE gain was realized with Pollard's method, using Epidat software. SETTING AND PARTICIPANTS: mortality data relative to residents that died during the period 1987-2015 were provided by the Tuscan Regional Mortality Registry. The analyzed causes of death were cardiovascular (CVS), respiratory (RESP), infective (INF) diseases and cancer (TUM). MAIN OUTCOME MEASURES: changing of LE expressed in years in relation to cause and age-specific mortality. RESULTS: the overall LE gain was 6.5 years for males and 4.3 years for females, the major gain was observed in the age groups 65-89 years (for females 75-89 years) and <1 year. The highest gain (2.6 years) was attributable to the reduction of mortality for CVS, followed by TUM (males: 1.42 vs females: 0.83) and RESP (males: 0.4 vs females: 0.1). The causes responsible for the loss of LE were INF (females: -0.16 vs males: -0.07) and lung cancer in females (-0.13). CONCLUSIONS: the prompt treatment of acute CVS events and prevention (both primary and secondary) are responsible for the gain in LE. The reduction of mortality for TUM can be attributed to the evolution of diagnostic-therapeutic possibilities, but also to the implementation of the cancer screening programmes. Lung cancer was responsible for the loss of LE in Tuscan females; the targeted anti-smoke campaigns should, therefore, be intensified. The INF comported the loss of LE; explainable by diffusion of multi-drug resistant bacteria. The programmes of Hospital Infection Control and Antimicrobial Stewardship should be potentiated to contain the phenomenon.

[Effects of Asbestos on Human Health. Document of the Italian Epidemiological Association (AIE)]. / Effetti dell'amianto sulla salute. Documento dell'Associazione Italiana di Epiemiologia (AIE).

OBJECTIVES: the Italian Epidemiological Association (AIE) intends to formulate assessments and recommendations on the most relevant and critical aspects in the preparation, conduct, and interpretation of epidemiological investigations on the health effects of exposure to asbestos and asbestos-like fibres. DESIGN, SETTING, AND PARTICIPANTS: the document was prepared by a working group of AIE associates, with a broad curriculum of epidemiological investigations, starting from the evaluation of scientific evidence, and was subsequently evaluated by the AIE governing body. RESULTS: the topics covered included: • consumption and presence of asbestos; • association between asbestos exposure and disease; • epidemiological surveillance of asbestos related diseases in Italy; • risk function for asbestos related diseases; • increased risk and anticipation of the disease; • interaction between asbestos and other carcinogens; • diagnosis in epidemiological studies; • assessment of exposure to asbestos; • epidemiological evidence on asbestos related diseases. CONCLUSIONS: the document ends with a summary of the conclusions of scientific research shared by AIE, with reflection on the methodology to be followed for the application at individual level of the results of epidemiological studies, and the proposal of themes on which to direct research.

The epidemiological surveillance of malignant mesothelioma in Italy (1993-2015): methods, findings, and research perspectives.

BACKGROUND: as a legacy of the large asbestos consumption until the definitive ban in 1992, Italy had to tackle a real epidemic of asbestos related diseases. The Italian National Registry of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with a regional structure. Aims, assignments and territorial network of ReNaM are described, as well as data collection, recording and coding procedures. OBJECTIVES: to describe the Italian epidemiological surveillance system of mesothelioma incidence, to provide updated data about occurrence of malignant mesothelioma in Italy, and to discuss goals, attainments, and expectations of registering occupational cancer. DESIGN: analysis of data by malignant mesothelioma incident cases surveillance system. SETTING AND PARTICIPANTS: Italy, network of regional surveillance system, all Italian regions. MAIN OUTCOME MEASURES: a Regional Operating Centre (COR) is currently established in all the Italian regions, actively searching incident malignant mesothelioma cases from health care institutions. Occupational history, lifestyle habits, and residential history are obtained using a standardized questionnaire, administered to the subject or to the next of kin by a trained interviewer. The extent of dataset, epidemiological parameters, and occupations involved are reported updated at 31.12.2016, and standardized incidence rates are calculated. RESULTS: at December 2016, ReNaM has collected 27,356 malignant mesothelioma cases, referring to the period of incidence between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of defined cases (14,818). CONCLUSIONS: the Italian experience shows that epidemiological systematic surveillance of asbestos related diseases incidence has a key importance for assessing and monitoring the public health impact of occupational and/or environmental hazards, programming preventive interventions, including remediation plans and information campaigns, and supporting the efficiency of insurance and welfare system. Monitoring the incidence of malignant mesothelioma through a specialized cancer registry is essential to follow-up the health effects of changing modalities and extent of occupational exposures over years and of environmental contamination. Such consolidated surveillance system is recommended also for occupational cancers with low aetiological fraction.

Reconstruction of the asbestos exposure in a textile company producing sewing threads through the use of an unusual information source.

BACKGROUND: The Tuscan Regional Operating Center (ROC) of Malignant Mesotheliomas has identified a cluster of 11 cases of malignant mesothelioma occurred in a textile plant manufacturing sewing thread. Using the common research method, the ROC had not previously been able to identify the specific sources of asbestos exposure causing such a large cluster. OBJECTIVES: The ROC's objective was to review all cases of the cluster and to better identify their occupational asbestos exposures. METHODS: The cases' occupational histories of asbestos exposure have been reviewed, using information deriving from the annual reports sent to the Tuscany Region since 1988 by all the asbestos removal companies according to the Law no. 257/1992, article 9, and from interviews to former employees of the plant. RESULTS: The work cycle has been reconstructed and enriched with the new information about the asbestos presence and its uses in the plant. The eleven cases were all reclassified as "certainly occupational exposed" given that the new collected information depicted a widespread asbestos pollution of the workplace during the period of employment of all cases. CONCLUSIONS: Using different sources of information, in addition to those traditionally collected through questionnaires, to reconstruct past asbestos exposuresallowed us to clarify the existence of the cluster of mesothelioma cases and the highest level of occupational asbestos exposure was attributed to all cases with consequent activation of the medico-legal procedure.

[Causes of death of Tuscan centenarians]. / Le cause di morte dei centenari toscani.

INTRODUCTION: in Italy and Tuscany the resident population aged> 99 reached its all-time high in 2015. Respiratory diseases in men and ischemic heart diseases in women were the leading causes of death for Italian centenarians in 2015. The aim of this study is to describe the mortality of Tuscan centenarians by cause. MATERIALS AND METHODS: population-based observational study using current health data, extracted from the Tuscan Regional Mortality Register. Main outcome measures are: proportional mortality and annual mortality trend at age >99, age-specific mortality rates (85-89; 90-94; 95-99, >99). RESULTS: at age >99 ischemic heart diseases, cerebrovascular diseases and respiratory diseases are among the top 5 causes of death as in the less elderly age, the relative frequency of tumors decreases and that of the ill-defined causes increases. If ill-defined and ischemic heart diseases are separated, the first cause of death is cerebrovascular diseases in males and senility in females. In the period 2002-2015 at age >99 all-cause mortality fell on average every year by -0.15% for males and -0.14% for females, mortality due to arteriosclerosis decreases -10% (males) and -12% (females) every year, due to cardiac arrest and other non-specific cardiopathies -5% (males) and -7% (females) and due to cerebrovascular diseases -3% (females). Mortality due to senility increases +6% per year in women. CONCLUSIONS: in Tuscany the first cause of death is different by gender (cerebrovascular diseases in males and senility in females) and differs from what has been observed nationally. In the 2000s, mortality from cardiovascular diseases without diagnostic significance decreased in Tuscan centenarians and that from senility increased.

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.

Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.

BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos. METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution. RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%. CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.