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Abstract
Exposure to metal oxides nanomaterials (NMs) might trigger adverse health effects. NMs can generate Oxidative Stress (OS), causing redox effects detectable in urine through suitable biomarkers. We evaluated the cross-sectional association of urinary OS biomarkers with urinary metal concentrations, using data collected in the multicenter international study NanoExplore. One hundred forty-one workers were recruited at three R&D and four industrial facilities employing NMs in different processes (paints/coating[PC];construction chemicals[CC]). Only 129 workers had complete data and, based on the personal work-shift exposure to NMs, they were classified as unexposed workers (n=41), workers with negligible/low exposure (n=37), and with moderate/high exposure (n=51). OS biomarkers (IsoP,MDA,TAP) and metals (27Al,47Ti,52Cr,118Sn) were quantified in urine samples collected before and after exposure monitoring campaign (2-4 work-shifts). Between-group comparisons were performed with non-parametric tests according to the data distribution. Highly exposed workers had significantly higher pro-oxidant (IsoP and MDA,p<0.005) and antioxidant (TAP,p<0.05) biomarkers concentrations. 47Ti,118Sn and 29Si were significantly higher in CC workers (p<0.005). IsoP and TAP were positively associated with 29Si (both p<0.001), 47Ti (p=0.036,p=0.003), 52Cr (p=0.048,p=0.003) and 118Sn (p=0.047,p=0.022). The ongoing analyses will assess the potential mediation role of OS and metal biomarkers. Occupational exposure to NMs can represent an underestimated hazard for people handling NMs products, increasing OS and potentially beginning pathological processes. Although the health significance of such findings needs to be further elucidated, the assessment of metals in urine may represent a useful tool for estimating the body burden of NMs long-term exposure.

Abstract
The production of paints, coatings and construction materials may generate nanoparticles (NP) with potential adverse health effects. We carried out a study aimed at investigating exposure biomarkers reflecting the internal dose of inhaled particles and NP. NTA was used to quantify particle number concentration and size in EBC collected at the end of shift in 81 workers employed in companies producing technological materials. External exposure was characterized in terms of particle number concentration, size and lung deposited surface area (LDSA) in the near operational field by using a set of DiSCmini. Three subgroups were identified: Low-Exposure (LE, n=30), High-Exposure (HE n=35), and non-occupationally exposed (UC, n=16). Comparisons between groups were made using non-parametric analyses. LE and HE workers showed significantly higher number of NP in EBC (p=0.024, p=0.041, respectively) as compared to UC. The HE groups showed higher levels of inflammatory biomarkers, such as IL-1β and IL-10 as compared to LE and UC (p=0.02, p<0.01, respectively). Positive correlations were observed between particle number concentration recorded by DiscMini and NTA data (Rho=0,225, p=0.04) and between the NTA and IL-10 and IL-1β (Rho=0.246, p=0.012; Rho=0.223, p=0.022, respectively). In contrast, LDSA did not correlate with NTA data. These findings provide evidence of the relationship between increasing exposure to NP and the burden of particles in the airways which, in turn, results in sustained inflammation. Given the lack of exposure biomarkers for dusts, these results are promising to investigate the relationship between internal dose of particles and changes in lung pathobiology.

Abstract
Exposure to nanomaterials (NMs) may harm biological systems by altering the redox status and triggering inflammatory processes, which in turn may affect respiratory health. In the NanoExplore cohort of 141 workers, we observed a positive dose-response relationship between the short-term exposure to NMs and biomarkers of inflammation, measured in Exhaled Breath Condensate (EBC), but no relationship with lung function parameters (LFP). This study focuses on the association between cumulative exposure to NMs over the last 10 years and changes in LFP and the potential mediating role of airways inflammation. Individual cumulative exposure was estimated by multiplying the nanoparticle concentration, measured at workers' workstations by DiSCmini, by the duration of worker's employment at the corresponding workstation up to last 10 years. In EBC, we measured High-Sensitivity CRP (Hs-CRP), IL-1β, TNF-α, and IL-10 as biomarkers of inflammation. LFP were assessed according to ATS/ERS standards. Their association with cumulative exposure was examined using logistic regression models adjusted for tobacco consumption (in pack-years), among 136 workers with complete data (19-62 yrs., 70% males). We found that per unit increase in 10-year exposure, the risk of observing FEV1 values below the normal limit increases by 0.3% (95%CI: 1.000-1.005, p=0.049) and by 0.8% (95%CI: 1.000-1.015, p=0.039) with the exposure expressed as number of particles and lung deposited surface area, respectively. The ongoing mediation analysis will investigate the potential mediating role of inflammation in the association between cumulative exposure to NMs and lung function

Abstract
We aimed at analyzing dose-response relationship between occupational exposure to a mixture of nanomaterials (NMs) and effect biomarkers measured according to the NanoExplore protocol in exhaled breath condensate (EBC, local pulmonary level)) and urine (systemic level) of 141 workers. Two exposure metrics: particle number concentration (PNC) and lung deposited surface area (LDSA) were monitored using DiSCMini for 2-4 8h-workshifts. Biological samples were collected twice, before and after exposure monitoring. We assumed that current or short-term exposure to NMs is associated in a linear dose-response manner to the effect biomarker concentration. We analyzed each biomarker separately, using the multilevel mixed-effects interval regression models to properly manage the biomarker concentrations the LOD or in the interval between the LOD and the limit of quantification. We used directed acyclic graphs to identify all potential confounders: age, smoking status, medication status, and study center. Center and the participant's ID were modeled as random effect variables. For IL-10, IL-1β and TNF-α in EBC we observed consistent positive dose-response relationships with both PNC and LDSA. For urinary Total Antioxidant Power the relationship was consistently negative. For MDA, KL-6, hs-CRP or NOTyr in EBC and urinary MDA and 8-Isoprostane, no relationship was found. These results suggest an activation of the innate immune response rather than oxidative stress as the main effect of the mixture of NM investigated. This study offers new insights into the dose-response relationship between exposure to NMs and possible indicators of early and long-term biological alterations in the cohort of recruited workers.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download ; Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. Results: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. Conclusions: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects. Keywords: Bronchodilatation; Epidemiology; FeNO; Lung function. ; UK Research & Innovation (UKRI) Medical Research Council UK (MRC) European Commission Spanish Government Generalitat ...

Publisher's version (útgefin grein) ; Background: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). Methods: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. Results: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV 1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV 1 declines. We found no association between weight change profiles and FEV 1 /FVC decline. Conclusion: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life. ; Funding The present analyses are part of the ageing lungs in european cohorts (alec) study (www.alecstudy.org), which has received funding from the european Union's horizon 2020 research and innovation programme under grant agreement no. 633212. The local investigators and funding agencies for the european community respiratory health survey are reported in the online supplement. isglobal is a member of the cerca Programme, generalitat de catalunya. ; Peer Reviewed