Residential exposure to air pollution and incidence of leukaemia in the industrial area of Viadana, Northern Italy.

BACKGROUND: Exposure to air pollution has been proposed as one of the potential risk factors for leukaemia. Work-related formaldehyde exposure is suspected to cause leukaemia. METHODS: We conducted a nested register-based case-control study on leukaemia incidence in the Viadana district, an industrial area for particleboard production in Northern Italy. We recruited 115 cases and 496 controls, frequency-matched by age, between 1999 and 2014. We assigned estimated exposures to particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and formaldehyde at residential addresses, averaged over the susceptibility window 3rd to 10th year prior to the index date. We considered potential confounding by sex, age, nationality, socio-economic status, occupational exposures to benzene and formaldehyde, and prior cancer diagnoses. RESULTS: There was no association of exposures to PM10, PM2.5, and NO2 with leukaemia incidence. However, an indication of increased risk emerged for formaldehyde, despite wide statistical uncertainty (OR 1.46, 95%CI 0.65-3.25 per IQR-difference of 1.2 µg/m3). Estimated associations for formaldehyde were higher for acute (OR 2.07, 95%CI 0.70-6.12) and myeloid subtypes (OR 1.79, 95%CI 0.64-5.01), and in the 4-km buffer around the industrial facilities (OR 2.78, 95%CI 0.48-16.13), although they remained uncertain. CONCLUSIONS: This was the first study investigating the link between ambient formaldehyde exposure and leukaemia incidence in the general population. The evidence presented suggests an association, although it remains inconclusive, and a potential significance of emissions related to industrial activities in the district. Further research is warranted in larger populations incorporating data on other potential risk factors.

Cancer and Pregnancy: Estimates in Italy from Record-Linkage Procedures between Cancer Registries and the Hospital Discharge Database.

The aim of this study is to describe the frequency and trend of pregnancy-associated cancer (PAC) in Italy, an increasingly relevant phenomenon due to postponing age at childbirth. To this purpose, a population-based retrospective longitudinal study design based on cohorts of women aged 15-49 diagnosed with cancer and concomitant pregnancy is proposed. The study uses 19 population-based Cancer Registries, covering about 22% of Italy, and linked at an individual level with Hospital Discharge Records. A total of 2,861,437 pregnancies and 3559 PAC are identified from 74,165 women of the cohort with a rate of 1.24 PAC per 1000 pregnancies. The most frequent cancer site is breast (24.3%), followed by thyroid (23.9%) and melanoma (14.3%). The most frequent outcome is delivery (53.1%), followed by voluntary termination of pregnancy and spontaneous abortion (both 12.0%). The trend of PAC increased from 2003 to 2015, especially when the outcome is delivery, thus confirming a new attitude of clinicians to manage cancer throughout pregnancy. This represents the first attempt in Italy to describe PAC from Cancer Registries data; the methodology is applicable to other areas with the same data availability. Evidence from this study is addressed to clinicians for improving clinical management of women with PAC.

Residential exposure to air pollution and adverse respiratory and allergic outcomes in children and adolescents living in a chipboard industrial area of Northern Italy.

BACKGROUND: Chipboard production is a source of wood dust, formaldehyde, and combustion-related pollutants such as nitrogen dioxide (NO2) and particulate matter (PM). In this cohort study, we assessed whether exposures to NO2, formaldehyde, PM10, PM2.5, and black carbon were associated with adverse respiratory and allergic outcomes among all 7525 people aged 0-21 years residing in the Viadana district, an area in Northern Italy including the largest chipboard industrial park in the country. METHODS: Data on hospitalizations, emergency room (ER) admissions, and specialist visits in pneumology, allergology, ophthalmology, and otorhinolaryngology were obtained from the Local Health Unit. Residential air pollution concentrations in 2013 (baseline) were derived using local (Viadana II), national (EPISAT), and continental (ELAPSE) exposure models. Associations were estimated using negative binomial regression models for counts of events occurred during 2013-2017, with follow-up time as an offset term and adjustment for sex, age, nationality, and a census-block socio-economic indicator. RESULTS: Median annual exposures to NO2, PM10, and PM2.5 were below the European Union annual air quality standards (40, 40, and 25 µg/m3) but above the World Health Organization 2021 air quality guideline levels (10, 15, and 5 µg/m3). Exposures to NO2 and PM2.5 were significantly associated with higher rates of ER pneumology admissions (13 to 30 % higher rates per interquartile range exposure differences, all p < 0.01). Higher rates of allergology and ophthalmology visits were found for participants exposed to higher pollutants' concentrations. When considering the 4-km buffer around the industries, associations with respiratory hospitalizations became significant, and associations with ER pneumology admissions, allergology and ophthalmology visits became stronger. Formaldehyde was not associated with the outcomes considered. CONCLUSION: Using administrative indicators of health effects a priori attributable to air pollution, we documented the adverse impact of long-term air pollution exposure in residential areas close to the largest chipboard industries in Italy. These findings, combined with evidence from previous studies, call for an action to improve air quality through preventive measures especially targeting emissions related to the industrial activities.

Risk of thyroid as a first or second primary cancer. A population-based study in Italy, 1998-2012.

BACKGROUND: The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC. METHODS: We analyzed two population-based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population-based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer. RESULTS: A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12-1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42-1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon-rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers. CONCLUSIONS: The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow-up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies.

Spatial variability of nitrogen dioxide and formaldehyde and residential exposure of children in the industrial area of Viadana, Northern Italy.

Chipboard production is a source of ambient air pollution. We assessed the spatial variability of outdoor pollutants and residential exposure of children living in proximity to the largest chipboard industry in Italy and evaluated the reliability of exposure estimates obtained from a number of available models. We obtained passive sampling data on NO2 and formaldehyde collected by the Environmental Protection Agency of Lombardy region at 25 sites in the municipality of Viadana during 10 weeks (2017-2018) and compared NO2 measurements with average weekly concentrations from continuous monitors. We compared interpolated NO2 and formaldehyde surfaces with previous maps for 2010. We assessed the relationship between residential proximity to the industry and pollutant exposures assigned using these maps, as well as other available countrywide/continental models based on routine data on NO2, PM10, and PM2.5. The correlation between NO2 concentrations from continuous and passive sampling was high (Pearson's r = 0.89), although passive sampling underestimated NO2 especially during winter. For both 2010 and 2017-2018, we observed higher NO2 and formaldehyde concentrations in the south of Viadana, with hot-spots in proximity to the industry. PM10 and PM2.5 exposures were higher for children at < 1 km compared to the children living at > 3.5 km to the industry, whereas NO2 exposure was higher at 1-1.7 km to the industry. Road and population densities were also higher close to the industry. Findings from a variety of exposure models suggest that children living in proximity to the chipboard industry in Viadana are more exposed to air pollution and that exposure gradients are relatively stable over time.

Residential proximity to an industrial incinerator and risk of soft-tissue sarcoma, 1999-2014.

BACKGROUND: exposure to dioxins has been associated with an increased risk of soft-tissue sarcoma (STS). In a study relating to 1989-1998, a significant excess of STS was found in the population living within a 2-kilometre radius of an industrial incinerator located inside a Mantua industrial site. In the years 1974-1991, the incinerator burned hazardous chlorine-containing waste that resulted in the emission of dioxins. After 1991, it was exclusively fed with organic synthetic products not containing chlorine. OBJECTIVES: the aim of this case-control study was to estimate the STS risk, for 1999-2014, in the population living in four Mantua districts located in the proximity of the industrial incinerator, compared to subjects resident in the remaining parts of Mantua province, regarded as non-exposed. METHODS: the cases analysed were subjects with a first-incident diagnosis of STS between 1999 and 2014 resident at diagnosis in Mantua Province. Cases were selected using the 2013 criteria from the WHO classification. Cases of Kaposi sarcoma, PEComas and STS occurring in a previously irradiated field were excluded. For each case of soft-tissue sarcoma, four controls were randomly selected from all individuals resident in Mantua Province included in the Regional Health Service database in the years of incidence of each case (calendar year), and individually matched for gender and year of birth. Residential and occupational history (for employment in an oil refinery, and petrochemical and chemical plants) was reconstructed for all study subjects (cases and controls) since 1961. Subjects were considered exposed if they had lived in the four Mantua districts most affected by the incinerator emissions, on the basis of an atmospheric dispersion model and a dioxins biomonitoring survey. Four analyses were performed according to variously defined residential time windows. Odds ratios and corresponding 95% confidence intervals (95%CI) were calculated using conditional regression models adjusted for occupational history. RESULTS: 391 cases (203 males and 188 females) and 1,564 controls were included. The number of exposed cases and controls in the four analyses were 8 and 55, 8 and 60, 15 and 68, and 15 and 73, respectively. An increased STS risk was not observed in any of the analyses. CONCLUSIONS: in this study, no increased risk of STS was observed in subjects who had lived, in the study's time window, in the Mantua districts most affected by the incinerator emissions. The most likely interpretation of the present finding is a real STS risk reduction for subjects resident in the most recent decades in the Mantua districts most affected by the incinerator emissions, due to the cessation of burning chlorine-containing waste in the incinerator, development of some remediation plans, and implementation of new industrial procedures.

[Excess mortality risk in nursing care homes before and during the COVID-19 outbreak in Mantua and Cremona provinces (Lombardy Region, Northern Italy)]. / L'eccesso di rischio di morte nelle residenze sanitarie assistenziali prima e durante l'epidemia di COVID-19 nelle province di Mantova e Cremona.

OBJECTIVES: 1. to evaluate mortality risk excess in the population residing in nursing care homes (NCHs) compared to non-NCHs before the COVID-19 outbreak; 2. to verify if the outbreak modified risk excess; 3. to estimate the COVID-19 impact; 4. to ascertain incidence-mortality relationship. DESIGN: cohort study. SETTING AND POPULATION: Mantua and Cremona provinces (Lombardy Region, Northern Italy) - included in ATS Val Padana - with COVID-19 incidence rate 7.5‰ and 16.9‰, respectively. Inhabitants aged >= 75 years as of 1st January 2018, 2019, and 2020 (three cohorts), stratified in NCH or not. The indicators calculated were: 1. rate ratio (RR) for NCH vs non-NCH, adjusted by gender, age, chronic diseases number, at least 1 hospitalisation, at least 1 Emergency room access in the previous year, for 2018, 2019, and 2020; 2. adjusted RR, 2019 and 2020 vs 2018, both sub-cohorts (i.e., NCH and non-NCH). MAIN OUTCOME MEASURES: first four-month period mortality of the considered years. RESULTS: aproximately 100,000 inhabitants by year, 7% in NCH. In the 2020 first four-month period, 4,343 deaths occurred of which 45% in NCH. RR in NCH population vs non-NCH for the year 2018 was 2.13 (95%CI 1.94-2.34); for the year 2019 was 2.70 (95%CI 2.43-3.00); for the year 2020 was 6.98 (95%CI 6,49-7,50). Adjusted RR for NCH population in 2020 vs 2018 was 2.22 (95%CI 2.05-2.42) in the whole ATS Val Padana; 1.58 (95%CI 1.40-1.77) in Mantua Province; 2.93 (2.62-3.27) in Cremona Province. Adjusted RR in non-NCH population in the year 2020 vs 2018 was 1.59 (95%CI 1.48-1.70) in the whole ATS; 1.34 (95%CI 1.23-1.46) in Mantua Province; 1.89 (95%CI 1.73-2.07) in Cremona Province. CONCLUSIONS: the NCH population experienced an excess risk mortality compared to non-NCH before the COVID-19; this excess increased during the outbreak. In 2020, in NCHs the risk was more than double compared to the 2018 risk, while in non-NCHs it rose approximately by 60%. The gap between NCHs/non-NCHs COVID-19 impact was higher in Cremona than in Mantua.

The detection of interval colorectal cancers following screening by fecal immunochemical test may predict worse outcomes and prompt ethical concerns: a 6-year population-based cohort study in a full district.

The rates of colorectal cancer (CRC) interval surveyed in screen-detected patients using a fecal immunochemical test (FIT) are not negligible. The aim of this study was to assess the effect of interval cancer on outcomes compared with a population with cancer diagnosed after a positive test result. All patients between 50 and 71 years of age, who were residents of the Mantua district, affected by CRC and operated on from 2005 to 2010 were reviewed. Other than patient-related, disease-related, and treatment-related factors and tumor location, this population was differentiated as either participating or not to screening and then into populations developing interval cancer after a negative FIT result. Mortality was investigated by univariate analysis and by overall survival rates. The mean age of the 975 patients enrolled was 62 years (61.7% males). Most patients (n=575, 59%) were not screen detected, and 400 (41%) were screen detected. Fifty-six (5.7%) patients in the latter group, representing 14% of the participants, developed interval cancer after a negative FIT result. Their cancer was mostly localized in the right colon (41.1%) instead of the left colon and rectum (P=0.02). They also showed higher stages (P=0.001), a moderate degree of differentiation (P=0.001), and overall higher mortality rates than patients with cancer diagnosed after a positive test result (P=0.001). The effect of interval CRC after screening with FIT resulted in worse outcomes compared with the FIT-positive group. With such findings, patients who had negative results for FIT should be informed of the risk of developing cancer within the rounds of screening to independently gain educational skills in the area of health prevention.

Outdoor formaldehyde and NO2 exposures and markers of genotoxicity in children living near chipboard industries.

BACKGROUND: Industrial air pollution is a public health hazard. Previous evidence documented increased respiratory symptoms and hospitalizations in children who live near the factories in the largest chipboard manufacturing district in Italy (Viadana). OBJECTIVES: We evaluated the association of outdoor exposure to formaldehyde and nitrogen dioxide (NO2) with markers of early genotoxic damage in oral mucosa cells of randomly selected children (6-12 years of age) living in Viadana. METHODS: In 2010-2011, DNA strand breaks and nuclear abnormalities were evaluated in exfoliated buccal cells by the comet and micronucleus assays, respectively, and formaldehyde and NO2 were monitored by passive sampling. Annual exposure estimates to pollutants were assigned to children's houses by spatial interpolation. RESULTS: Of 656 children, 413 (63%) participated. Children living near (< 2 km) the chipboard industries had the highest average exposure to formaldehyde and NO2 (p < 0.001). A 1-SD increase in formaldehyde (0.20 µg/m(3)) was associated with a 0.13% (95% CI: 0.03, 0.22%) higher comet tail intensity, a 0.007 (95% CI: 0.001, 0.012) higher tail moment, and a 12% relative increase [relative risk (RR) = 1.12; 95% CI: 1.02, 1.23] in nuclear buds. A 1-SD NO2 increase (2.13 µg/m(3)) was associated with a 0.13% (95% CI: 0.07, 0.19%) increase in binucleated cells and a 16% relative increase (RR = 1.16; 95% CI: 1.06, 1.26) in nuclear buds. CONCLUSIONS: Exposure to pollutants was associated with markers of genotoxicity in exfoliated buccal cells of children living in a region with chipboard industries. These findings, combined with previously reported associations between chipboard industrial activities and respiratory outcomes in children, add to concerns about potential adverse effects of industry-related exposures in the Viadana district.

Children living near chipboard and wood industries are at an increased risk of hospitalization for respiratory diseases: a prospective study.

Pollutants emitted from wood processing factories may be harmful to the health of the population. The aim of this prospective cohort study was to evaluate whether proximity to wood factories was associated with the risk of hospital admissions in children living in the Viadana district (Italy), where two big chipboard industries and other smaller wood factories (sawmills, multi-strata layer manufacturing) are located. In 2006, children (3-14 years) living in the Viadana district were surveyed through a parental questionnaire (n=3854), their home/school addresses were geocoded and the distances to the wood industries were calculated. Hospital discharge records for the years 2007-2009 were obtained. Cox proportional hazard regression models were used to estimate the association between hospitalization rates and distance to the factories, adjusting for sex, age, nationality, parents' education, exposure to passive smoking and reported traffic near home. During the 3-year follow-up, the risk of hospitalization for all diagnoses (Hospitalization Hazard Ratio, HHR=1.55; 95% CI: 1.24-1.95) and for respiratory diseases (HHR=1.80; 95% CI: 1.14-2.86) was greater in the children living close (<2 km) to the chipboard industries, with respect to the children who lived at ≥2 km from any wood factory. The children living close to the smaller wood factories were also at increased risk of hospitalization for respiratory diseases (HHR=1.74; 95% CI: 1.06-2.85). This study highlights a health problem for the children living close to chipboard and wood factories in the Viadana district. Further research should develop accurate exposure models based on objective measurements of air pollution in order to confirm these findings.

[Chronic kidney disease in the province of Mantua and its developments over the last 40 years]. / Evoluzione della malattia renale cronica nella provincia di Mantova in 40 anni.

The incidence and prevalence of end-stage renal disease increased steadily for 35 years in the population of Italy's Mantua province until the end of 2007, when they started to decrease. We describe the results of providing information and raising awareness among residents of the province's capital, Mantua, and of direct teaching and short training courses in hospital wards for general practitioners over a period of 3 years. During this period there was also more consultation activity for all kidney outpatients, from the first to the last stages of chronic kidney disease. Clinical data collected by the local NHS section (ASL) showed an increase in age and comorbidities (mainly type 2 diabetes) in kidney patients. As a result of the preventive measures, there has been an effective reduction of the yearly incidence and prevalence for all kinds of treatment, with the exception of kidney transplants, which have increased progressively during the last years.

[Epidemiology of chronic kidney disease in the population of the Mantua district]. / Epidemiologia della insufficienza renale cronica in una popolazione: i residenti nella provincia di Mantova.

The Epidemiology Unit of NHS Mantua (Italy) used health data from digital archives to study chronic kidney disease (CKD) in the population of the Mantua District. Incidence and prevalence measures were calculated with a focus on dialyzed patients. We estimated the relative risk of CKD as a function of past hospitalizations and evaluated the healthcare consumption of a cohort of incident cases in the 5 years following the diagnosis of CKD. The prevalence of CKD was 2356 cases in 2007, 13% of which treated with dialysis. Dialyzed patients had a mean of 86 treatments per year, amounting to a total of 25,937 treatments. In 2008 we calculated 701 new cases of CKD, 4.5% of which treated with dialysis. Women were older than men at the time of first diagnosis (81 vs 75 years) but the age is increasing in both genders. In the 5 years following diagnosis, outpatient healthcare consumption increased in parallel with a decrease in hospitalizations. A diagnosis of CKD was found to be associated with past hospitalizations for urinary and kidney diseases but also for cardiovascular and metabolic diseases. CKD is a major public health concern in terms of mortality, hospitalizations and health spending. The increasing age at diagnosis indicates better treatment of previous CKD-associated diseases such as cardiovascular and metabolic diseases. Hospitalization for these diseases is strongly associated with a future diagnosis of CKD. The results of this study could be interesting for general clinical practice with a view to preventing complications, among which CKD.