Introduction

Human health and well-being are strongly linked to the state of the environment. Good quality environments can provide multiple benefits to physical, mental, and social well-being (WHO 2013; EEA 2015). By contrast, environmental pollution can have negative effects on health, especially on vulnerable categories of people, such as children and the elderly (Simoni et al. 2015; Cao et al. 2016; Flores-Pajot et al. 2016; Veras et al. 2017; García-Esquinas and Rodríguez-Artalejo 2017). Air pollution (as outdoor particulate matter) is a leading contributor to mortality, with 289,000 deaths only in high-income European regions (IARC 2015; WHO 2016), as well as water and soil pollution, that strongly could affect human health (Villanueva et al. 2014; Swartjes 2015).

The Po Valley, located in Northern Italy, is one of the most anthropized and polluted areas in Europe (Ricciardelli et al. 2017; Carnevale et al. 2015), where systematic exceeding of limit values of PM and ozone occurs (Regione Lombardia 2012; EEA 2016). High industrial pressure along the territory (Istituto Nazionale di Statistica 2015; Provincia di Brescia, Geoportale 2018) and geographical conformation caused environmental concern in this region.

Brescia and its surrounding province (one of the largest in Italy with a territory of 4800 km2) represent an important economic center of the Po valley, with a great economic development started in the early twentieth century, with a variety of industries and sectors (steel industries, mechanical activities, and chemical implants) (Corsini and Zane 2014). In this area live over 1.2 million inhabitants with a demographic density (expressed as number of inhabitants per km2) of 2177 and 264, respectively, for the municipality of Brescia and its province (UrbiStat 2018http://ugeo.urbistat.com/AdminStat/en/it/classifiche/densita-demografica/comuni/brescia/17/3).

The Province of Brescia currently is an area with a very high concentration of industrial companies (almost 120,000 manufacturing companies with more than 162,000 workers) (Camera di Commercio di Brescia 2017).

As discussed by Corvalán et al., beyond the huge benefits, the modern industrial development could generate many hazards for the environment and human health (Corvalán et al. 1999). Indeed, in the Province of Brescia, all the environmental matrices were (or still are) polluted by different industrial activities. Tap water was polluted by heavy metals (Sorlini et al. 2014a), in particular hexavalent chromium (Osservatorio Acqua Bene Comune 2015) and arsenic (Sorlini et al. 2014b). Metals were also present in home gardens soil, with a contamination of some kind of vegetables (Borgese et al. 2013; Ferri et al. 2015). High amounts of organic and inorganic mutagens/carcinogens were detected in fine air particulate (Monarca et al. 1997; Turrio-Baldassarri et al. 2008; Hou et al. 2011; Ceretti et al. 2015). The quality of lake waters was impaired by the presence of cyanobacteria that produced harmful cyanotoxins (Sorlini et al. 2013). Moreover, from 2003, Brescia is included in the National Land Reclamation list (Ministero dell’Ambiente e della Tutela del Territorio 2003) due to the consistent concentration of PCBs, classified as persistent organic pollutants. In the city, there is the Site of National Interest (SIN) Caffaro, a organochlorine compound-producing factory that is the major one responsible for the presence of high concentrations of PCBs in soil, surface water, vegetables, chicken eggs, and cow milk (Turrio-Baldassarri et al. 2009) (Fig. 1).

Fig. 1
figure 1

Geographical position and configuration of Brescia and its Province (modified from Regione Lombardia 2012)

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The aim of this narrative review is to analyze the extant literature to identify the studies that measured and associated the exposure to environmental pollutants to the presence of health effects in the population living in Brescia and its province.

Methods

The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Moher et al. 2010).

Information sources

The literature search covered the period up to October 2018. The search was performed using the PubMed database (PubMed, https://www.ncbi.nlm.nih.gov/pubmed/) and the Google search engine tool (Google Scholar).

Search strategies

The search was conducted in English and Italian using the Medical Subject Headings (MeSH) thesaurus when possible. The detailed searching strategy is summarized in Table 1.

Table 1 Search queries used in the systematic review
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The reference list was scanned for relevant articles up to the second level, and “related articles” of relevant ones were considered in the PubMed database or in Google Scholar. We considered the first 200 items returned by Google Scholar search.

Study selection and eligibility criteria

All the articles relevant to the search topics written in English or in Italian, with abstract and full text available, were included. Search results were merged and duplicates removed. Citations were assessed by two reviewers (CA and LB) independently and disagreement was solved by discussion and consensus or by a third reviewer (UG). We considered the following eligibility criteria: report of original data, explicit measurement of the considered environmental pollutant (the exposure must be described using specific analytic values and not with generic statements), and description of unambiguous human health impact (in terms of biomarkers of DNA damage, physiopathological parameters, pathologies, number of patients hospitalized, mortality). The methodological quality of each study was assessed independently by two authors (CA and LB) using the Kmet tool (Kmet et al. 2004). A score between 0 and 1 was assigned to each paper. Eventual disagreement was solved by consensus or by a third reviewer (UG).

Results

General findings

According to the PRISMA statement reported in Fig. 2, the search strategy returned 13 papers matching the inclusion criteria.

Fig. 2
figure 2

Flow diagram describing the study selection according to PRISMA methodology (Moher et al. 2010)

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All the required information to perform the review were extracted and summarized in Table 2.

Table 2 Studies with a link between environmental pollution and health impacts on people living in the Province of Brescia
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In 5 out of 12 papers, the authors focused their attention on air matrix (Baccarelli et al. 2009; Bertoldi et al. 2012; Ceretti et al. 2014; Rosa et al. 2016; Vaduganathan et al. 2016); in 7 out of 12, instead, the environmental pollution was studied in both air and soil matrices (Donato et al. 2008; Iannili et al. 2016; Lucchini et al. 2012a, b, 2007; Squitti et al. 2009); only one paper considered the pollution present in soil (Maifredi et al. 2011). None of the selected papers reported studies on the water matrix. The assigned quality scores ranged from 0.7 to 0.9 (mean Kmet score 0.88 ± 0.08).

The length of observation time presented in the selected articles is variable (Fig. 3) ranging from 6 months (Ceretti et al. 2014) to 168 months (Maifredi et al. 2011).

Fig. 3
figure 3

Length of the period of observation in the selected studies. Five studies were not included in the graph because periods of observation were not clearly declared

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The number of subjects living in the Province of Brescia included in the selected papers is also variable (Fig. 4), ranging from 14 subjects (Iannili et al. 2016) to 6000 (Vaduganathan et al. 2016).

Fig. 4
figure 4

Number of subjects included in the selected studies. § = the paper did not describe explicitly data on the Province of Brescia, but presented elaboration of regional datasets in which Brescia was assimilated to homogeneous areas

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Table 3 summarizes the age grouping of population in the selected studies. The frequency of micronuclei was studied in young children (3–6 years old) (Ceretti et al. 2014), while risk of asthma (Rosa et al. 2016) and neurobehavioral and cognitive functions (Lucchini et al. 2012a, b; Iannili et al. 2016) were investigated in adolescents (11–14 years old). Parkinsonian disorders (Lucchini et al. 2007), thyroid hormones modifications (Donato et al. 2008), and presence of cutaneous malignant melanoma (Magoni et al. 2018) were evaluated in adults and the elderly (more than 18 years old). Non-Hodgkin lymphoma cases (Maifredi et al. 2011) were investigated in the elderly from 65 to 75 years old. All age categories were correlated with cardiovascular and respiratory diseases (Bertoldi et al. 2012).

Table 3 Age grouping of health parameters measured in individuals exposed to various environmental pollutants
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Association between environmental pollution and acute/chronic health effects

Health impacts could be also divided in two categories: acute and chronic impacts. Figure 5 describe the selected studies according to this. Few papers used as end-point the acute impact of hospitalization in the analysis of the association between PM10 and NOX and CVD and RD (Bertoldi et al. 2012; Vaduganathan et al. 2016) and in the association between PCBs and CMM (Magoni et al. 2018). Instead, the majority of authors chose various parameters of chronic impact, such as biomarkers of damage (Ceretti et al. 2014) and physiological alterations to analyze the impact of air pollution (Baccarelli et al. 2009), heavy metals (Lucchini et al. 2007, 2012a, b; Squitti et al. 2009; Iannili et al. 2016; Rosa et al. 2016), or PCBs (Donato et al. 2008; Maifredi et al. 2011).

Fig. 5
figure 5

Health impacts of different environmental pollutants reported in the included studies

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Three papers considered the association between the hospitalization and pollutants present in the Brescia area: two papers described acute health impacts of PM10 and NOX in terms of hospitalizations due to acute CV and respiratory diseases. CV diseases are associated with the increase of PM10 concentration, even below the current limit set by the European Union (50 μg/m3 averaged over a 24-h period) (Vaduganathan et al. 2016). Another evaluation of air pollution and health effects was done by Bertoldi and co-workers, with a case-control study on acute effects of air emission of a cement plant on children and adults. They found an association between NOX concentrations and the risk of hospitalization for cardiovascular or respiratory disease, especially in children. In particular, it was estimated that 38% of children hospitalization could be avoided if the NOx concentration was below 110 μg/m3, in the considered areas (Bertoldi et al. 2012). Magoni et al., instead, examined the acute health impacts in terms of hospitalization due to CMM diagnosis and its association with PCB serum levels and specific PCB congeners, considering also the main risk factors for the melanoma. They found association between CMM and some phenotypic, constitutional characteristics and UV exposure but that the hypothesis of the investigated association was not supported by the case-control study and no relation was found between risk of CMM and total PCB plasma levels. Considering the 33 PCB congeners, they found that most of them were not observed in cases (n = 205) and in controls (n = 205).

Eight papers described chronic traits of impacts of pollution through the analysis of biomarkers of early effect or pathologies. Only one group used the frequency of MN as a biomarker of air pollution exposure. They analyzed the DNA damage in exfoliated buccal mucosa cells of healthy 3–6-year-old children living in the urban area of Brescia. Children exposed to high levels of air pollutants (PM10, PM2.5, and NO2) in winter have a high frequency of MN in buccal mucosa cells (mean ± SD = 0.29 ± 0.13), higher than usually found in children living in areas with medium/high levels of air pollution (Ceretti et al. 2014). The air pollution, measured as concentration of PM10, was also associated with an increased risk of deep vein thrombosis development, correlated with the distance from major traffic roads (OR = 1.74, living 3 m from a major road). Despite the overall result, the risk for the population of Brescia had an OR = 0.32, probably due to the restricted number of subjects involved (Baccarelli et al. 2009). Another category of pollutants in the Province of Brescia is represented by heavy metals, especially Mn, Pb, Ni, and Cr, present in air and soil. Mn is a well-known neurotoxic agent and the prolonged environmental exposure is considered a supposed accelerator of the onset of IPD. Lucchini et al. established an association between environmental exposure to Mn and prevalence of Parkinsonian disorders in population resident in municipalities near ferromanganese plants (with a standardized prevalence of 492/100000) (Lucchini et al. 2007). Lifetime exposure to neurotoxicant metals (in particular Mn) was also correlated to an increased risk of neurodegenerative disorders when accompanied by alteration of metal metabolism due to a subclinical dysfunction of the liver (Squitti et al. 2009). Specific attention was given by many authors to the adolescents’ exposure to metals, a particularly susceptible population subgroup. Parental report of asthma in 11–14-year-old adolescents was associated with Mn (RR = 1.09), Ni (RR = 1.11), and Cr (RR = 1.08) levels in sampled air. Significant associations were also found between increased risk of asthma medication use and concentrations of Mn (RR = 1.13) and Ni (RR = 1.13) (Rosa et al. 2016). A positive association between Mn in air and soil with motor coordination, hand dexterity, and odor identification and between Mn found in blood and hair with tremor was established in adolescents residing in areas with previous heavy metal emissions from ferroalloy plants (Lucchini et al. 2012a). Furthermore, a negative association between blood Pb levels and IQ was demonstrated in the same cohort of adolescents (Lucchini et al. 2012b). More recently, a pilot fMRI experiment suggested a reduction of bold signal, odor sensitivity, and olfactory bulb volume in subjects exposed to Mn (Iannili et al. 2016).

Two reports investigated the relation between serum levels of PCBs and some health aspects. Donato et al. established that the environmental exposure to relatively high PCBs levels did not alter thyroid functions, measured as hormone serum levels (Donato et al. 2008). On the other hand, some evidence for an association between PCBs exposure and an increased risk of non-Hodgkin’s lymphoma was recognized (Maifredi et al. 2011).

Association between environmental pollution and different indicators of health damage

After having analyzed the selected studies from the point of view of the indicators of health damage used (Table 4), we can recognize different classes of indicators. As biological damage indicators, micronuclei were analyzed in relation to air pollutants, such as PM2.5, PM10, CO, NO2, or SO2 (Ceretti et al. 2014). Different biochemical parameters were analyzed: AST/ALT ratio was correlated to heavy metal concentration (Squitti et al. 2009); some thyroid hormones were analyzed to monitor the PCBs exposure (Donato et al. 2008). Several neurobehavioral alterations, such as cognitive function and behavior (Lucchini et al. 2012b), olfactory functions (Iannili et al. 2016), and neurobehavioral functions (Lucchini et al. 2012a), were analyzed to investigate the consequence of the exposure to heavy metals. Many authors focused the attention on pathologies correlated to different pollutants. Acute cardiovascular events (Vaduganathan et al. 2016) and deep vein thrombosis (Baccarelli et al. 2009) were associated to PM10 concentration. Asthma was correlated to both PM10 and heavy metals (Rosa et al. 2016). Cardiovascular and respiratory diseases (Bertoldi et al. 2012) were studied in association with the air concentration of NOX. The onset of non-Hodgkin’s lymphoma was analyzed in people exposed to PCBs (Maifredi et al. 2011) and the arising of parkinsonian disorders were evaluated in a population exposed to heavy metals (Lucchini et al. 2007).

Table 4 Indicators of health damage in relation with different environmental pollutants
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Considered together, despite the wide range of analyzed parameters, almost all of the studies (11/13) highlighted a positive association between the pollutants and the health indicators.

Discussion

We conducted a comprehensive narrative review of published studies that evaluated the association between environmental pollution and health effects in the Province of Brescia. This is the most extended province of the Lombardy Region and represents an important industrial center. Regarding the link between industrial development and the environment in the territory of Brescia, it is noticeable that all the environmental matrices are subjected to the pollution caused by human activities. Brescia is indeed one of the affected zones with exceedance of the annual limit of PM10 for which, in April 2017, the EU Commission urges Italy to take actions against air pollution to safeguard public health (European Commission 2017). In the urban area of Brescia, one of the 39 contaminated SIN is also located, because of the presence of high concentrations of PCBs (Ministero dell’Ambiente e della Tutela del Territorio 2003). The water quality was also impaired by Cr(VI) pollution, solved in 2015 with an abatement system based on the addition of iron sulphate (Osservatorio Acqua Bene Comune 2015; A2A 2017).

The literature concerning the surveillance of pollutants in environmental matrices in the Province of Brescia is certainly extensive, but few works relate the levels of pollutants to a measurable health effect. To the best of our knowledge, this is the first review taking into account this kind of topic. Moreover, the total absence of studies on the water system is an unexpected result, due to the abovementioned water quality impairment caused by the high concentration of Cr(VI) or other metals (Sorlini et al. 2014a) and mixture known to be genotoxic (Ceretti et al. 2016).

The mean quality Kmet score is 0.88, describing an overall high quality of the reported information but the great variability in the studies’ size and especially in the analyzed end-points, made it difficult to draw precise conclusions. Nevertheless, the fact that in almost all the studies (11 out 13), the investigated health effects show to have a positive association with the pollution, allows to hypothesize that the considered population live under a recognizable environmental pressure. The two articles that did not reveal connection between pollutants and health effects investigated both the PCB serum level and specific PCB congeners.

Our narrative review presents some limitations: our findings were limited by the quantity, the heterogeneity of reported data, and the diversified end-points. Moreover, the case study area is not extensively covered by the studies.

These results represent a fundamental element of a comprehensive quantitative approach that could effectively support public health policies (Guariso et al. 2016). The DPSIR scheme adopted by the European Environment Agency (EEA 2012) represents a link between the scientific knowledge and methods and the need of decision makers design effective environmental plans. The DPSIR analytical concept is the causal framework for describing the interactions between society and environment. It includes the assessment of the State of the system, as the result of the Pressures exerted on the environment by human and natural activities or interventions (Drivers). The alteration of environmental conditions, inducing adverse Impacts on human health, vegetation, and ecosystem, requires actions (Responses) aimed at improving the environmental system quality. The actions are related to human activity and needs changes (Drivers), to emission reduction measures (Pressure), on direct concentration reductions (State), or on impact attenuation (Impacts). Turrini et al. (Turrini et al. 2017) is an example of the implementation of such decision framework on a regional domain including the study area of this paper.

In conclusion, more studies should be conducted in order to effectively identify criticisms that negatively affect the population health, even in synergy with an integrated assessment modeling, that combine environmental exposure and health risks and decision models. These could be helpful to the public policy-makers, to improve the protection of citizens and the environment.