Asbestos is an environmental carcinogen, and asbestos-related diseases are a global-scale public health issue. We report three cases (one male and two females) of pleural malignant mesothelioma (PMM) caused by environmental asbestos exposure reported by the Apulia Regional Operating Centre (COR) to the National Mesothelioma Registry (ReNaM). The patients revealed no history of asbestos exposure even after detailed assessment. The environmental (neighborhood) asbestos exposure for each of the three cases was due to both the residential history of the subjects and their workplace, close to a military barracks, at a distance of between 45 and 100 m. Moreover, in addition to this new source of pollution, an asbestos cement factory was located in the urban area of Bari municipality, in the Apulia region, southern Italy. Environmental-residential/neighborhood asbestos exposure in the city of Bari, a contaminated area classified as a site of national concern for land reclamation, is discussed also with reference to the military barracks. . . . . Keywords Asbestos Environmental-residential-neighborhood exposure Mesothelioma Contaminated town Military . . . barracks Bari, Apulia. Italy Mesothelioma registry Public health Introduction asbestos exposure threshold to delineate an absence of risk (Hillerdal 1999; Goldberg and Luce 2009). Malignant mesothelioma (MM) is a rare, lethal malignancy Not all people exposed to asbestos develop mesothelioma; caused primarily by occupational or environmental asbes- thus, an underlying susceptibility to asbestos-related carcinogene- tos exposure (Bourdès et al. 2000; Delgermaa et al. 2011; sis may exist (Dogan et al. 2006). Cytogenetic studies have shown Lacourtetal. 2014; Røe and Stella 2015). MM generally that MM has highly complex and variable chromosomal aberra- has a poor prognosis, and cases are typically diagnosed at tions and asbestos exposure has been reported to cause genetic an advanced stage of the disease. Recently, with therapeu- alterations at the chromosomal level in MM (Borczuk et al. 2016). tic advancements, the survival has improved (Reid et al. Recent studies have confirmed a significant MM risk due 2014;Faigetal. 2015). There is no evidence of a minimum to asbestos environmental exposure (EE) (Baumann and Carbone 2016; Liu et al. 2017). Many studies have demon- strated an increased risk in the general population associated with a low environmental-type asbestos exposure (Magnani Responsible editor: Philippe Garrigues et al. 1995; Bourdès et al. 2000; Boffetta and Stayner 2006; Kurumatani and Kumagai 2008;Reidet al. 2008;Goldberg * Luigi Vimercati and Luce 2009; Marsh et al. 2017). EE can originate from firstname.lastname@example.org pollution by industrial sites or mines, from the presence of asbestos in buildings (asbestos in a place), and from natural Interdisciplinary Department of Medicine (DIM), Unit of contamination of the soil, allowing for exposure that can begin Occupational Medicine, University Aldo Moro of Bari Medical at birth (Pasetto et al. 2005). School, 11 G. Cesare Square, 70124 Bari, Italy 2 In Italy, Casale Monferrato, where an asbestos cement fac- Department of Emergency and Organ Transplantation (DETO), tory (Eternit) was located, is a dramatic example of asbestos Pathology Division, University Aldo Moro of Bari Medical School, 11 G. Cesare Square, 70124 Bari, Italy pollution risk for people living in a contaminated area. Environ Sci Pollut Res (2018) 25:15692–15701 15693 A recent study (Ferrante et al. 2016) provides strong evidence of an association between pleural mesothelioma and non-occupational exposures to asbestos. An approxi- mately twofold increase in risk was observed for having livedwithafamilymember whoworkedintheEternit asbestos cement plant (OR = 2.4, 95% CI 1.3 to 4.4), or having been exposed from domestic or environmental sources (OR = 2.0, 95% CI 1.2 to 3.2). The area of Bari municipality, Apulia region of southern Italy, has been defined as a contaminated site (CS) of na- tional priority for remediation because of diffuse environ- Fig. 1 The military barracks BRossani.^ The houses built along the mental contamination caused by an asbestos cement facto- perimeter are visible ry (Fibronit). Bari municipality was included in the Italian national priority list of contaminated sites in 2000 (law 388/2000). The former asbestos cement plant (Fibronit) 1940s, urban expansion progressively reduced the distance operated from 1933 until 1985 and employed approximate- from the closest residential areas to less than 5 m in a high- ly 417 workers. (Coviello et al. 2002;Musti etal. 2009). density demographic area. Between 1998 and 2000, dis- Chrysotile (80%), crocidolite (15%), and amosite (5%) mantling of the barracks began. were used in the plant. The contaminated site, as defined In 2001, reclamation of the asbestos in the area began. 2 2 by the law, includes an area of approximately 150,000 m From an initial estimate, 5000 m of roofs and tiles made of (Ministerial Decree 468/01). Currently, definitive environ- Eternit are needed to be removed. The first efforts intended to mental remediation action is in progress and definitive remove hazardous materials. In 2004, an inspection by Arpa work to increase safety started in October 2016. The envi- Puglia, the Apulia environmental protection agency, certified ronmental risk of the Fibronit company was confirmed in that the work was not in accordance with the security regula- 2009. A spatial case-control study of the environmental tions. The residues of the removed materials remained on the impact of asbestos fibers spread by the Fibronit plant, an- ground, and on windy days, the fibers were dispersed in the alyzing data from the database of the Apulia Regional air. After the Arpa Puglia inspection, the job was stopped. In Operating Centre (COR) of the National Mesothelioma 2005, the work resumed despite strong protests by the citizens Registry (ReNaM), showed an MM odds ratio of 5.29 who were probably aware of the severity of this environmental (95% CI 1.18–23.74) for people living close to the factory emergency. During the wave of the BFibronit problem,^ few and residents within a range of up to 500 m from the fac- security measures and precautions were implemented at the tory. A low risk was found with increasing distance from work site. Specifically, the temporary deposition of hazardous the factory, which was the major urban source of asbestos waste, rather than transporting it immediately to a specialized pollution (Musti et al. 2009). landfill, was criticized. Following a new inspection by Arpa The military barracks, BRossani,^ were built between Puglia, the job was stopped because the most basic security 1907 and 1912 (Figs. 1, 2,and 3). The use of materials standards were not adhered to. The public prosecutor such as asbestos, which was a cutting-edge material at that suspended the activity of the firm that had won the contract. time, was huge, including all the roofs and the chimneys of the buildings. The barracks are located on a total area of 2 2 80,000 m , with 14,000 m of covered space. In 1920, a transfer to the artillery barracks area BS. Lorenzo^ oc- curred. In 1927, it was named BRossani^ barracks. In 1933, the Ministry of War decided to expand and set up the barracks BDuca delle Puglie,^ which included the ex- tension and elevation of the former carriageway, the con- struction of new stables for horses, replacement work on the old Eternit shells of the barracks, various improvement work, completion of the sewerage drainage network, and courtyard accommodation. The handrails at the barracks have Eternit covering the wooden beams and the Eternit coverings required continuous maintenance due to deteri- oration. During the earliest years, from 1920, the barracks Fig. 2 The military barracks BRossani.^ The houses built along the were located outside the urban area. Later, in the 1930s and perimeter are visible 15694 Environ Sci Pollut Res (2018) 25:15692–15701 military, and residential histories. The complete residential history, corresponding to the residence addresses throughout the life of an individual, includes the date of taking up and leaving the residence at each address. Information on the res- idential locations includes the house type, the address, and a description of each dwelling and its neighborhood environ- ment, including the presence of close industries (asbestos ce- ment, petro-chemical, railroad, shipbuilding industries, etc.). The questionnaire enables the collection of information on Fig. 3 The military barracks BRossani.^ The houses built along the other circumstances of exposure to asbestos, such as the pres- perimeter are visible ence of asbestos-containing materials at home, asbestos ce- ment tiles or water tanks, and the occupations of the persons with whom the patients lived with. In particular, the patient is asked to provide information on the longest occupation of Non-compliance was related to fragments containing asbestos each cohabitant (industry, job), how many years the patient that were poorly guarded, a lack of decontamination units, and lived with the cohabitant, whether the cohabitant used to bring higher pollutant emissions than expected in the operational dirty work clothes home, and whether the patient used to program. In 2006, the reclamation works were resumed and brush or wash them. Furthermore, exposure during hobby/ completed at the end of the year. leisure activities, starting from childhood, and school activities We report three peculiar cases of PMM that were caused by is investigated. Domestic activities that involve potential as- environmental (neighborhood) asbestos exposure close to the bestos exposure are also investigated, including ironing on military barracks located in the urban area of Bari municipal- asbestos-coated ironing boards, do-it-yourself (DIY) projects ity. Additionally, we analyze the environmental exposure in in home maintenance and renovations such as small repair the city, a contaminated town that is already classified as a site work (such as a masonry, plumbing, motor mechanics, or of national interest for land reclamation. electrical work), thermal insulation work, the use of asbestos gloves, talcum powder use for personal hygiene, and the use of any asbestos-containing objects. Material and methods The patients were enrolled in the Apulia Regional Mesothelioma Register by the local occupational medicine The Apulia mesothelioma registry unit. According to the standardized register procedures, we administered a questionnaire to investigate his lifestyle habits The National Mesothelioma Register (ReNaM) is active in and work history, including any possible asbestos exposure Italy, and the notification of new cases is compulsory by law during military service (Nesti et al. 2003). (DPCM n. 308/2002). It is organized in regional operational units that are responsible for data collection and exposure reconstruction and are coordinated by ReNaM, home of the Results national database. The records of the three MM cases described here were The histological, clinical, and genetic features listed in the Apulia regional mesothelioma register, the region- and exposure of the cases al operational unit of the national registry. The register ensures complete, quality information on exposure and diagnosis due Case 1 to the adoption of operative guidelines that have been agreed upon at the national level (Nesti et al. 2003). All cases in the In August 2015, a 74-year-old man suffering from familial register are from subjects with histologically confirmed meso- Becker-type muscular dystrophy was admitted to the chest thelioma. Histories of any occupational, i.e., certain, probable, surgery division of BOspedale San Paolo^ in Bari, Apulia or possible occupational exposure, or non-occupational, i.e., region, southern Italy, for dyspnoea and pleural effusion. household, neighborhood, or environmental, exposure to as- Thoracentesis and intrapleuric coalescence were per- bestos are assessed and classified through face-to-face inter- formed. His past medical history was unremarkable. He views conducted by trained interviewers with the subjects had been a smoker (7 cigarettes per day) since he was affected by mesothelioma or their relatives using a standard- 20 years old. On the CT scan, extensive irregular thicken- ized questionnaire following ReNaM guidelines. The ques- ing of the parietal and visceral pleura in the left tionnaire is designed to determine demographic characteris- hemithorax and mediastinal adenopathies were observed. tics, lifestyle habits and, among others, lifelong occupational, Routine laboratory tests were unremarkable. A pleural Environ Sci Pollut Res (2018) 25:15692–15701 15695 biopsy was performed. Histology showed MM with a pre- and her residential history, she had lived near the same source dominant solid epithelial pattern. The immunohistochem- of asbestos pollution, asbestos in situ (in buildings), at a dis- ical analysis showed the positive expression of tance between 50 and 500 m for 30 years from the age of cytokeratins, calretinin, WT-1, and vimentin. TTF-1 was 26 years, from 1979 to 2009. negative. The patient opted for chemotherapy (Alimta + cisplatin) with external hyperthermia. In January 2016, he Case 3 underwent a seventh cycle of chemotherapy. In February 2016, he started radiotherapy. A total body PET scan In February 2013, a 54-year-old woman was admitted to the showed increased pleural thickening and pleural effusion chest surgery division of Hospital La Madonnina Bari for located in the left side. In September 2016, he underwent recurrent pleural effusion. Her past medical history was unre- repeated chemotherapy cycles (Alimta + cisplatin) with markable. She had been a smoker (10 cigarettes per day) since external hyperthermia. she was 29 years old until 2013. On the CT scan, irregular Regarding the patient exposure, he was exempted from thickening of the parietal and visceral pleura in the right military service due to pathology. The work histories of co- hemithorax was observed. Thoracoscopy and histological ex- habiting family members and his family history of cancer amination diagnosed MM with a solid epithelial pattern. The were also evaluated. Exposure during leisure activities, travel, immunohistochemical analysis showed the positive expres- or hobbies and any exposure to ionizing radiation were ex- sion of cytokeratins, calretinin, CEA, WT-1, and vimentin. cluded. The ascertained asbestos exposure was residential: he The patient opted for surgery at a specialist center in had lived near a source of asbestos pollution, asbestos in situ Brescia, Italy, and was subjected to right pleuropneumectomy, (in buildings), at a distance of less than 45 m away for 17 years followed by cycles of chemotherapy (Alimta + CDDP). from the age of 28 years. The subject had lived in an apartment Regarding the patient exposure, the work histories of co- overlooking the military barracks from 1969 to 1986. habiting family members and her family history of cancer At a follow-up in October 2017, more than 2 years after were also evaluated. Exposure during leisure activities, travel, diagnosis and 27 months from the beginning of chemotherapy or hobbies and any exposure to ionizing radiation were ex- treatment, the patient had left shoulder pain and general weak- cluded. The ascertained asbestos exposure was environmental ness but good respiratory expansion. due to both her workplace, she was employed in regional offices from 1980 to 2000 100 to 250 m far from the Case 2 Rossani barracks, and her residential history, she had lived near the Fibronit site at a distance of 200 m for 54 years since In September 2009, a 56-year-old woman was admitted to birth from 1959 to 2013. the chest surgery division of Hospital Bari Consorziale As a follow-up in October 2017, more than 4 years Policlinico for recurrent pleural effusion. Thoracentesis (55 months) after treatment, the patient is alive and disease- and intrapleuric coalescence were performed. Her past free without recurrence. medical history reported hysterectomyin1999andmyo- cardial infarction in 2008. She had been a smoker (20 cig- arettes per day) since she was 20 years old until 2008. On Discussion the CT scan, extensive irregular thickening of the parietal and visceral pleura in the left hemithorax was observed. A Environmental asbestos exposure pleural biopsy was performed. Histology showed MM with a predominant solid epithelial pattern. The immunohisto- Since 1960, in the first epidemiologic study in South chemical analysis showed the positive expression of Africa, a risk of pleural mesothelioma was shown to be cytokeratins, calretinin, WT-1, and vimentin. TTF-1 was associated with asbestos exposure; some of the cases re- negative. Ki67 was 5%. The patient opted for surgery at a ported were attributed to environmental exposure (Wagner specialist center in Brescia, Italy, and was subjected to left et al. 1960) The MM cases presented here are emblematic pleuropneumectomy, followed by cycles of chemotherapy cases of environmental exposure in a large polluted city. In (Alimta + cisplatin). She died after 28 months in 2011. fact, the general population often suffers from exposure to Regarding the patient exposure, the work histories of co- environmental contaminants that cannot be directly con- habiting family members and her family history of cancer trolled by the individual. In a recent review, Liu et al. were also evaluated. Exposure during leisure activities, travel, (2017) summarized the most recent studies of the associa- or hobbies and any exposure to ionizing radiation were ex- tion between MM and environmental asbestos exposure. cluded. The ascertained asbestos exposure was environmental EE is defined as neighborhood exposure based on resi- due to both her workplace, she was a bank employee from dence in close proximity to industrial/mining sources of 1986 to 1996 in an agency 50 m far from Rossani barracks, asbestos or residence in urban or polluted areas. EE is also 15696 Environ Sci Pollut Res (2018) 25:15692–15701 defined as any exposure that occurs during residence in a Studies of neighborhood exposure have reported that in- town where asbestos-processing plants were located. By creased distance from the sources is associated with a the way, IARC 2012, no. 100 reported that BIn studies of decreased MM risk (Maule et al. 2007;Mustietal. asbestos concentrations in outdoor air, chrysotile is the 2009). Moreover, it is known that worn asbestos products predominant fibre detected. Low levels of asbestos have can release asbestos fibers which have the same carcino- been measured in outdoor air in rural locations (typical genic potency as Bstandard^ chrysotile (Spurny 1989). 3 3 concentration, 10 fibres/m [f/m ]). Typical concentrations Our patients (Table 1) had lived or worked at distances 45 are about 10-fold higher in urban locations and about 1000 to 100 m from the source of pollution considered, the military times higher in close proximity to industrial sources of barracks. Regarding the Fibronit site, all patients had lived exposure(e.g. asbestos mine or factory, demolition site, or from 200 to 1200 m far. In particular, the case number 3 have improperly protected asbestos-containing waste site).^ had an important exposure because she lived and worked When mesothelioma is due to environmental exposure, closely the two pollution sources. With these features, the the M:F sex ratio is 1:1 and the median age at diagnosis is typical time variable for environmental exposure of the cases 60 years: in the cases mentioned here, it is reported to be here discussed may be considered as continuous for 168 h per 61 years. Asbestos is an environmental carcinogen, and week. By the way, the latest data published by ReNaM, the asbestos-related diseases are a global-scale public health Italian national mesothelioma registry, referred to 21.463 issue. The cumulative exposure to asbestos and duration cases occurred in the period 1993–2012, showed 694 cases of exposure increase the MM risk (Espina et al. 2015;Imai with ascertained environmental exposure, 4.2% of total cases and Hino 2015). The role of non-occupational asbestos ex- reported (Quinto rapporto 2015). posure (para-occupational, domestic, or environmental) in The study of MM due to the environmental risk is often the occurrence of MM has already been demonstrated in hindered because of the long latency period and the small several studies (Bourdès et al. 2000; Magnani et al. 2001; number of cases. Additionally, this type of exposure is invol- Pasetto et al. 2005; Ferrante et al. 2007; Goldberg and Luce untary and is unknown in most cases (Baumann and Carbone 2009;Lacourtetal. 2014). In a recent review and meta- 2016). In Italy, the ReNaM data (Marinaccio et al. 2015)show analysis, Marsh et al. (2017) confirmed an increased risk that people with EE, in 514 cases from 1993 to 2008, were of pleural MM from non-occupational (neighborhood) as- younger at diagnosis (67.2 versus 68.1 years [p = 0.01]), were bestos exposure (RR= 6.9; 95% CI 4.2 to 11.4).The main younger at first exposure (18.5 versus 22.5 years [p = feature of non-professional exposure is the long latency and 0.0001]), and had longer latency times (49 ± 14 versus 46 ± duration of exposure in subjects often very young at the 12 years) with respect to occupationally exposed patients with beginning of exposure. Also in analysis limited to non- MM. Consistent with these data, our patients (Table 1)were occupationally exposed subjects, the risk of MM increases diagnosed at ages from 54 to 74 years and were younger at with cumulative doses of asbestos. first exposure, with latencies from 30 to 54 years. In our cases (Table 1), exposure started at birth or at 26– 28 years of age, with a duration of 17 to 54 years and latency Sources of environmental exposure in the town: between 30 and 54 years. the asbestos cement factory (Fibronit) and military The duration of exposure is the duration of the residence barracks (Rossani) period; it is a proxy of the cumulative dose to which the res- idents are exposed, that is, an estimate of effective exposure This study extends our previous investigations (Bilancia et al. (Magnani et al. 2015). 2003; Musti et al. 2009) and, consistent with the literature, Other studies have detected a significant MM risk confirms the adverse health effects of asbestos environmental caused by residential proximity to asbestos cement plants pollution in the town of Bari. The distance between the two in the absence of occupational exposure (Fazzo et al. contaminated sites described here is 1400 m (Fig. 4). 2014; Mensi et al. 2015). These studies highlight the im- Continuous airborne emissions were due to dispersion portance of assessing the impact of asbestos exposure not from the barracks area and from the asbestos cement factory only among workers but also among their cohabitating area by wind. Data on the environmental asbestos concentra- family members and in the general population. tion inside the barracks area and the Fibronit site were not In Italy, several of these areas have been included among available. The concentration of asbestos fibers in the ambient national priority contaminated sites and environmental reme- air close to asbestos cement factories in Bari has been inade- diation has been prescribed, but in Bari, it has only been par- quately monitored in the past, when the factory was active. tially implemented (Pirastu et al. 2013). Fiber concentration measurements related to Fibronit were Orenstein and Schenker (2000) studied the associations only available with limited data for the latest years. Until between the residential distance from environmental as- 1970, up to 20 fibers/cm of airborne asbestos (length 5 μm bestos, decreased exposure duration, and the MM risk. and diameter 0.3 μm) were measured. Measurements in the Environ Sci Pollut Res (2018) 25:15692–15701 15697 Table 1 The exposure features of Exposure features Case 1 Case 2 Case 3 the cases Sex Male Female Female Anatomical site Pleura Pleura Pleura Year of diagnosis 2015 2009 2013 Age at diagnosis (years) 74 56 54 Year of first exposure 1969 1979 1959 Age at first exposure (years) 28 26 1 Hours/week 168 168 168 Frequency Continuous Continuous Continuous Duration of exposure (years) 17 30 54 Calendar years of exposure 1969–1986 1979–2009 1959–2013 Latency (years) 46 30 54 Distance of the home or workplace from 45 homes 50 workplaces, 100 workplaces the source of pollution: military 500 homes barracks (Rossani) (meters) Distance of the home from: asbestos 1100 1200 200 cement factory (Fibronit) (meters) following years were reported up to 10 fibers/cm in 1972 and current level of background pollution. The reference back- from 4 to 19 fibers/cm in 1974 after reclamation (Coviello ground level exposure index corresponds to a mean lifetime et al. 2002). However, the relevance of the environmental cumulative exposure of Bless than 0.1 fibres/mL-y, an average exposure was not considered until the mid-1970s, when envi- concentration of approximately 0.1 fibres/l^,as reportedby ronmental measurements were taken close to the plant in near- the International Agency for Research on Cancer (IARC) by areas located far from the roads, without much pollution monograph no. 100 (IARC International Agency for from urban traffic. Mean concentration values equal to Research on Cancer (IARC) 2012). Moreover, WHO estimat- −4 16.06 × 10 Bparticles (5 micron in size) per cc. of air^ were ed that Bwith continuous exposure to 0.4–1 fibre/l, the lifetime reported (Napoli 1975) but are certainly not representative of risk of MM would be from (4 to 10) × 100,000. Linear ex- the high pollution level in earlier decades. The amount of trapolation to 0.1 fibre/l (the current background level) would environmental pollution from asbestos present at the time in correspond to lifelong excess in the order of one case (from the city of Bari, corresponding to the years of exposure in the 0.4 to 2.5) of MM in every 100,000 persons^ (World Health cases discussed here, is also given by a comparison with the Organization Regional Office for Europe 2000). Fig. 4 Bari map: Fibronit and Rossani sites BARI CITY (view from the satellite) Area Fibronit AREA ROSSANi 15698 Environ Sci Pollut Res (2018) 25:15692–15701 The diffusion process of the asbestos fibers, both from the Apulia regions who were not occupationally exposed to factory and from the military barracks to the surrounding asbestos showed values ranging from 110,000 to zones, was favored by physical mechanisms and has been 4,300,000 fibers per gram (f/g) of dry lung. Five patients, confirmed by the history of urban expansion in the city of with ages at diagnosis from 36 to 65 years, lived at dis- Bari around the two sites. Also, the deterioration due to time tances ranging from 200 to 2000 m from the Bari Fibronit and weather has contributed to the release of asbestos fibers plant between 1960 and 1997. into the city environment. Basedonthe informationonthe asbestos types,we It is known that the concentration of asbestos fibers in the found, in that study, a detectable amount of mainly amphi- air surrounding the emission point depends on wind direction bole asbestos fibers, and the long persistence of these fi- and velocity (Laamane et al. 1965). Abakay et al. (2016)stud- bers could represent a marker of EE. In particular, in three ied the risk of developing environmental mesothelioma for non-occupationally exposed MM patients, there were inhabitants near naturally occurring asbestos (NOA) source. 110,000 (resident at a distance of 2000 m) and 1,700,000 They found that the distance of a residence from NOA and the (resident at a distance of 200 m) ff/g of dry lung in two predominant wind direction can influence the MM risk. Also, men and 2,300,000 ff/g of dry lung in a woman (resident at Kurumatani and Kumagai (2008) and Tarrés et al. (2013) a distance of 500 m). These data confirm a direct relation- studied the effect of meteorological conditions on MM. Also ship between the lung fiber burden and the distance be- in their studies, the dominant wind direction influenced the tween the residence and the factory (Barbieri et al. 2012). MM risk. Especially, Kurumatani and Kumagai (2008)sug- Due to these data on asbestos pollution in Bari, we can hy- gest that a parameter that includes meteorological conditions pothesize the past asbestos exposure of the three new cases here can be a better proxy for exposure assessment than residential discussed that lived at a distance from 200 to 1200 from Fibronit. distance alone, in the study of the effects of environmental The second Italian Consensus Conference on Malignant exposure to asbestos in populations living in polluted areas. Mesothelioma of the Pleura has confirmed that the quanti- Fazzo et al. (2016), in a study on the incidence of cancer, tative relationship between MM and asbestos exposure in- reported that the highest values around polluting industries crease with cumulative exposure to asbestos, the lung fiber were consistent with prevailing wind directions and confirmed burden, and the duration of exposure (Pinto et al. 2013). In that the air quality of CS areas is affected by industrial atmo- the study of MM epidemiology, cumulative exposure is a spheric emissions. proxy for relevant exposure and the duration and the inten- In this study, meteorological data from the period of sity of exposure are independent determinants of MM oc- interest, from 1912 for Rossani and from 1933 for currence (Pinto et al. 2013). Thesameconclusion wasre- Fibronit, were not available, so the meteorological data ported in the third Italian Consensus Conference on from more recent years, namely, 1961–1990, were consid- Malignant Mesothelioma of the Pleura (Magnani et al. ered in our previous study (Musti et al. 2009). The direc- 2015; Novello et al. 2016). Furthermore, a recent case- tion of the winds was also evaluated as a possible cause of control study (Ferrante et al. 2016) explored the relation- exposure to verify the predominant direction and the rel- ship between cumulative exposure and pleural MM after ative geographical distribution of MM cases. Data on the non-occupational exposure and investigated the risk asso- frequency of wind by intensity and direction were ac- ciated with asbestos materials in residential areas, with a quired from the BBari Palese Macchie Station^ of the cumulative exposure index to estimate the frequency, du- Military Air Force National Center for Meteorology and ration, and intensity of exposure. The study showed a re- Aeronautical Climatology. The station provided the lationship between the pleural MM risk and cumulative monthly ground frequency distributions for each of the exposure after non-occupational exposure and confirmed synoptic hours (00, 03, 06, 09, 12, 15, 18, 21). The period the quantitative relationship between the MM incidence covered by the climatic processing is from 1961 to 1990, and cumulative exposure to asbestos, even at low levels approximately the same years of exposure in our three of exposure. Consistent with Ferrante et al. (2016), in the cases. The analysis highlighted the distribution of the present study, the assessment of EE was based on the dis- wind (the average over the period 1961–1990) during tance between the home and the pollution source. the various months of the year. Wind diffusion did not The national register of mesothelioma (ReNaM) docu- seem to play an important role given the absence of clear- mented that 10.2% of MM cases are due to non- ly predominant winds. So it corroborates with the hypoth- occupational exposure to asbestos (Marinaccio et al. 2015). esis that the proximity to the source of risk may increase In particular, in our regional register, 10.9% of cases are due to the incidence of disease (Musti et al. 2009). environmental exposure (Quinto rapporto 2015). These data Moreover, our previous study (Barbieri et al. 2012)ofas- confirm the difficulty in recognizing and attributing non- bestos fiber burden in the lungs of eight pleural mesothelioma occupational exposure to asbestos even though this type of patients residing near asbestos cement plants in Piedmont and exposure is becoming increasingly more common among Environ Sci Pollut Res (2018) 25:15692–15701 15699 new cases of mesothelioma. Consistent with Armstrong and urbanization phenomenon of the city of Bari around the Driscoll (2016), this finding can be defined as the Bthird-wave barracks. In the 1930s when the barracks opened, the site exposure.^ Indeed, they defined Bthird-wave exposure as both was outside the urban area. Over the following three to four occupational and non-occupational exposure to asbestos as a decades, the city grew and incorporated the barracks. The consequence of repairs, renovations, demolition of buildings failure to reclaim and safely decontaminate the area inside and environmental exposure to asbestos^. the city has been a serious public health problem. The history of these military barracks shows that the dete- Consistent with the second Governing Conference rioration of asbestos in situ, the removal of asbestos, and the (November 2012) and the National Asbestos Plan (2013), related exposure require accurate monitoring of asbestos fiber the theme of MM cases of environmental origin was iden- concentrations in urban air and in areas proximal to circum- tified as a research priority with aspecificmandatefor stances that are thought to present a particular hazard, such as ReNaM and COR: Bregions will have to, by committing the renovation or demolition of homes and buildings con- the COR Regional or other competent structures, investi- structed with asbestos cement products. The current scientific gate the magnitude of mesothelioma risk connected to non- knowledge was not known in the 1960s and 1970s, when the professional exposure (environmental or para- Rossani barracks were used. In all the cases reported here, we occupational).^ It must also be stressed that the scientific assessed EE via the lifetime residential distance from the support of the case series collected by our regional meso- sources of environmental exposure in the town, the asbestos thelioma register and the continuous documentation of the cement factory (Fibronit) and military barracks (Rossani), the effects of environmental asbestos exposure have increased calendar years of residence, and the duration of residence awareness among the citizens of Bari and have prompted (Table 1) as proxies for the intensity of exposure. Finally, to the authorities to schedule the decontamination of the site better assess EE to asbestos in addition to collecting informa- to safeguard public health. tion via direct, face-to-face interviews, we performed a histor- Author contributions LV, as a principal investigator, planned and de- ical reconstruction of asbestos pollution in the two sources signed the study and drafted and revised the manuscript; DC, as a princi- within the urban perimeter using residential histories and the pal investigator, planned and designed the study and drafted and revised periods 1969–1986, 1979–2009, and 1959–2013, when re- the manuscript; PL and GMF revised the manuscript; LDM and AC spectively the three subjects were exposed. This kind of in- administered questionnaires; and GS performed histological analysis and revised the manuscript. vestigation is consistent with the World Health Organization’s comprehensive approach in the assessment of the health status Compliance with ethical standards of residents in contaminated sites (WHO 2013) and with rec- ommendations for epidemiological surveillance programs Conflict of interest The authors declare that they have no conflict of (Zona et al. 2014). The public health relevance of environ- interest. mental asbestos exposure in Italian national priority contami- nated sites, such as Bari, has also been stressed in the final Ethical approval Written informed consent was obtained from the report of the governmental conference on asbestos and ARDs patients. (Comba et al. 2013). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, Conclusion distribution, and reproduction in any medium, provided you give appro- priate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. It is confirmed, according to Binazzi et al. (2017), that asbestos environmental pollution is a risk for people living in contaminated sites. The past extensive use of asbestos has generated severe public health consequences among References Bari inhabitants and these cases emphasize the association between MM and asbestos environmental pollution in the Abakay A, Tanrikulu AC, Ayhan M, Imamoglu MS, Taylan M, Kaplan city. 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