The objective of this study was to characterize the association between personal measures of Mn, Ni, Cr, Zn and Fe and respiratory outcomes in a cross-section of children living in an industrial province in Italy. In this study we found that increasing personal concentrations of Mn, Ni and Cr were associated with increased risk of adverse respiratory outcomes in Italian adolescents. Furthermore, these associations were independent of PM₁₀ concentrations and the observed associations remained significant after adjustment for a number of important confounders. These findings add to the growing literature on the effects of PM composition on respiratory health.

Recent studies in Europe have reported on the effects of metals on children’s respiratory health. In a birth cohort in the Netherlands, metal fractions of PM_2.5 and PM₁₀ were measured in filters by x-ray fluorescence and used for development of LUR models for these metals [25]. Concentration of K and S in PM_2.5 and K and Zn in PM₁₀ at the children’s residence were associated with higher risk of incident asthma and these associations appeared to be independent from PM mass [25]. This same study reported associations between annual PM_2.5 abs, Cu and Fe in PM_2.5 at children’s current addresses and small but significant decreases in FEV₁ ranging between 0.9 and 1.1 % [25]. Elemental fractions of PM₁₀ and PM_2.5 were also examined as predictors of lung function measures at ages 6–8 in a meta-analysis of European birth cohorts [26]. In meta- analysis results, there were small reductions in FEV₁ associated with Ni concentrations in PM₁₀ and the associations were independent of PM mass [26]. These studies are in line with a recent review of literature on the respiratory effects of metals in which the epidemiological studies reviewed reported positive associations between increasing metal concentrations, particularly Fe, Ni and Zn, and increased risk of respiratory morbidity [14].

Even though several studies have documented the long-term [27] and acute effects [28, 29] of Mn and Cr from welding fumes on respiratory health, few have focused on the effect of these metals on children’s health. One study in China found that children in an e-waste province in China exposed to Mn, Ni and Cr fumes from an e-waste facility had decreased lung function measures when compared to a reference area, although the effect was only limited to boys in the 8–9 year age group [9]. The authors also reported a significant association between increased blood Mn and serum Ni and decreased forced vital capacity [9]. Another study in South Korea found associations between central site measures of Mn in PM and decreased peak flow measures in school children [30].

One of the mechanisms through which inhaled metals may lead to airway disease is through oxidative stress. A study in Germany reported increased secretion of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α and elevated levels of oxidant radicals in bronchoalveolar lavage fluid (BAL) after in vivo instillation of ambient particles rich in Ni, Zn, Cd and Cu [31]. The e-waste study in China also found significant associations between increased blood Mn and serum Ni and increased malondialdehyde, a marker of lipid peroxidation [9]. Another potential mechanism by which these metals may affect the respiratory system involves the dysregulation of Fe homeostasis in the lungs. Inhaled Ni may compete with the uptake of endogenous Fe, leading to elevated levels of available Fe and release of reactive oxygen species (ROS) [32, 33]. Recent exposure to ambient metals has also been associated with increases in airway inflammation in inner-city children living in NYC [34]. Ni concentrations in particular were associated with increases in distal airway inflammation and such inflammation has been be associated airway hyper-responsiveness and symptom exacerbation [35, 36].

We did not see any associations between Fe and Zn and any respiratory outcome. A potential explanation for the lack of effect is the distribution of these metals on different-sized particles. In a study of airborne pollutants in Greece, Ni and Mn were found in fine, intermediate and coarse airborne particles, with Ni being predominant in the alveolar fraction of PM (<0.8 μm), while Fe was mainly found in particles with a diameter >2.7 μm [37]. These findings suggest that Fe might not travel as deep into the airways as Mn and Ni. Another potential explanation is that we did not see significant differences in Zn concentrations across the 3 study sites. While Fe and Zn were the most abundant metals in PM₁₀, Mn, Ni and Cr concentrations were much higher than concentrations reported in other epidemiological studies [14]. We also did not see any associations with report of wheeze in the past 12 months; perhaps due to the low prevalence of this outcome in our cohort we did not have sufficient statistical power to detect any associations.

Even though we have focused on the role of ferroalloy emissions as the source for these ambient metals, these metals are also emitted during a variety of other processes. Motor vehicle emissions are important sources of ambient Mn, Fe, Cr and Zn [38, 39]. Other sources of ambient Fe include oil combustion, road dust, and re-suspended soils [38, 40]. Ni is also released during oil combustion and other industrial activities [41]. However in support of ferroalloy emissions as the major source in our study area, we previously reported on fingerprint analyses used to identify exposure sources as potentially related to industrial vs. traffic emission, based on specific interrelations of elements [42]. Principal Component Analysis confirmed the industrial origin of these metal emissions [42].

There are several strengths to our study. We were able to examine the effect of several metals on respiratory health. The associations between metals and respiratory outcomes remained significant after adjustment for PM₁₀ concentrations. Ambient air pollution studies have typically relied on central-site monitoring data or modeling exposure variables. The use of personal monitoring may provide a better representation of actual daily exposure; a study in NYC schoolchildren found the strongest associations to be between personal measures of elemental carbon (EC) and asthma symptoms, when compared to EC exposure measures from stationary school monitors [43].

There are also some limitations to our study. Our sample size was relatively small and personal sampling was only done for 24 h and we were not able to control for long-term exposure to these pollutants. However, children are likely to spend most of their time in their neighborhood (typically at home and school) and they travel less than adults. Moreover, adjusting for season and day of the week did not change our association estimates. We cannot rule out that ambient metals may be surrogates for other components found in PM₁₀ or other pollutants that are known to be correlated with PM (ie NO₂). The effect sizes for these associations were small and our analyses were also cross-sectional in nature, and we cannot prove causality. The study outcomes were not objectively assessed but reported by the parents. Thus, it could be argued that health risk perception in the population may be a source of bias [44]. However, when further adjusting the analyses for an indicator of health risk perception [44] our conclusions were unchanged. Asthma questionnaires have a low sensitivity, however their high specificity ensures that the children who report the outcomes were correctly identified [45]. Our results are also in line with published data from both SIDRIA 1 and 2 (ISAAC Italy) where the prevalence of self/parent reported asthma in the 13–14 year old population was around 10 % [46, 47]. It is also important to highlight that the association estimates of Ni and Mn concentrations were similar when analyzing a lifetime asthma vs current asthma. Finally, our population was Caucasian and the majority were of medium-high SES, limiting the generalizability of our results.