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Objectives: Due to the inflammatory nature of multiple sclerosis (MS), the most widely used therapeutic approach targets the immune response but can comprise side effects (e.g. secondary immunosuppression). For these reasons, among non-pharmaceutical interventions without known side effects, physical activity (PA) gained importance because it is feasible, safe and a supportive complementary treatment strategy to alleviate symptoms in MS subjects. Consequently, the main aim of this systematic review is to analyze the effect of PA protocols, as a complementary therapy, on inflammatory status in MS patients. Methods: Four electronic databases (PubMed, Embase, CINAHL, and Cochrane CENTRAL) were systematically searched up to 01 June 2023 (Prospero Protocol ID=CRD42021244418). The refined search strategy was based on three concepts: “MULTIPLE SCLEROSIS” AND “PHYSICAL ACTIVITY” AND “INFLAMMATION”. Results: three main findings emerged: 1) untrained subjects showed a negative modulation of inflammatory biomarkers concentrations when compared to trained people (−0.74, 95 %C.I.–1.16, −0.32); 2) training modulated positively inflammatory biomarkers (+0.47, 95 %C.I. 0.24,0.71); 3) Aerobic PA protocol enhance higher positive influence on inflammation. Conclusions: Persistent, low-grade inflammation in MS could be upregulated by non-pharmacological complementary therapies, in particular by regular aerobic PA that could reduce and positively modulate inflammation.

Abstract An association between climatic conditions and asthma incidence has been widely assumed. However, it is unclear whether climatic variations have a fingerprint on asthma dynamics over long time intervals. The aim of this study is to detect a possible correlation of the Summer North Atlantic Oscillation (S-NAO) index and the self-calibrated palmer drought severity index (scPDSI) with asthma incidence over the period from 1957 to 2006 in Italy. To this aim, an analysis of non-stationary and non-linear signals was performed on the time series of the Italian databases on respiratory health (ISAYA and GEIRD) including 36,255 individuals overall, S-NAO, and scPDSI indices to search for characteristic periodicities. The ISAYA (Italian Study on Asthma in Young Adults) and GEIRD (Gene Environment Interactions in Respiratory Diseases) studies collected information on respiratory health in general population samples, born between 1925 and 1989 and aged 20–84 years at the time of the interview, from 13 Italian centres. We found that annual asthma total incidence shared the same periodicity throughout the 1957–2006 time interval. Asthma incidence turned out to be correlated with the dynamics of the scPDSI, modulated by the S-NAO, sharing the same averaged 6 year-periodicity. Since climate patterns appear to influence asthma incidence, future studies aimed at elucidating the complex relationships between climate and asthma incidence are warranted.

Background: The health issues experienced by older people can often be severe and complex, and an increasing number are using residential aged care services to meet their care needs. High-quality nursing care is fundamental to the health and safety of aged care residents and is contingent on nurses' accurate assessment, informed decision-making, and delivery of timely interventions. However, the role of the aged care nurse is often challenging, impeded by factors such as understaffing, high workloads, and a lack of access to clinical infrastructure and resources. When these challenges mount, residents are put at greater risk of adverse outcomes, such as avoidable clinical deterioration and hospital transfers. This study describes the adaptation and implementation of the emergency nursing framework, HIRAID® (History including Infection risk, Red Flags, Assessment, Interventions, Diagnostics, reassessment, communication and plan)-a tool to assist nurses' assessment, decision-making and care in residential aged care., Methods: The HIRAID® framework will be adapted for residential aged care using a real-time Delphi and panel of aged care and nursing experts. The co-designed HIRAID® Aged Care framework will be trialled in 23 residential aged care homes in Sydney, Australia, in a modified stepped-wedge cluster randomised controlled trial design. All homes will be randomised into one of four clusters. Outcomes of interest include the rate of clinical deterioration events resulting from nurses' actions, the rate of hospital transfers determined to be inappropriate, performance against the national mandatory aged care quality indicators, resident satisfaction with care, nurse and medical staff satisfaction with communication, and the quality of nursing documentation. These outcomes will be evaluated using a combination of qualitative and quantitative analysis of routinely collected resident data, expert assessments of facility documentation events against validated criteria, and pre- and post-intervention surveys of residents, family carers, nurses, and medical staff., Discussion: This protocol describes a pragmatic trial that aims to translate an evidence-based framework from the emergency care context into residential aged care. The adapted HIRAID® Aged Care framework will be the first of its kind to standardise and guide holistic nursing assessment, decision-making, and documentation in residential aged care in Australia., Ethics and Dissemination: This research has been approved by the Western Sydney Local Health District Human Research Ethics Committee: 2023/ETH00523. A waiver of consent has been approved to access resident health data and nursing documentation at each participating site., Trial Registration: Australian and New Zealand Clinical Trial Registry, ACTRN12623000481673. Registered 12 May 2023., Protocol Version: Version 1.0 6 February 2024., (© 2024. The Author(s).)

Background: Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have raised concerns about potential consequences on human health and safety, beyond the environmental burden. Given that inhalation is the main exposure route, workers exposed to nanomaterials might be at risk of occurrence of respiratory morbidity and/or reduced pulmonary function. However, epidemiological evidence regarding the association between cumulative exposure to nanomaterials and respiratory health is still scarce. This study focused on the association between cumulative exposure to nanomaterials and pulmonary function among 136 workers enrolled in the framework of the European multicentric NanoExplore project., Results: Our findings suggest that, independently of lifelong tobacco smoking, ethnicity, age, sex, body mass index and physical activity habits, 10-year cumulative exposure to nanomaterials is associated to worse FEV 1 and FEF 25 - 75% , which might be consistent with the involvement of both large and small airway components and early signs of airflow obstruction. We further explored the hypothesis of a mediating effect via airway inflammation, assessed by interleukin (IL-)10, IL-1β and Tumor Necrosis Factor alpha (TNF-α), all quantified in the Exhaled Breath Condensate of workers. The mediation analysis results suggest that IL-10, TNF-α and their ratio (i.e., anti-pro inflammatory ratio) may fully mediate the negative association between cumulative exposure to nanomaterials and the FEV 1 /FVC ratio. This pattern was not observed for other pulmonary function parameters., Conclusions: Safeguarding the respiratory health of workers exposed to nanomaterials should be of primary importance. The observed association between cumulative exposure to nanomaterials and worse pulmonary function parameters underscores the importance of implementing adequate protective measures in the nanocomposite sector. The mitigation of harmful exposures may ensure that workers can continue to contribute productively to their workplaces while preserving their respiratory health over time., (© 2024. The Author(s).)

Objectives: Due to the inflammatory nature of multiple sclerosis (MS), the most widely used therapeutic approach targets the immune response but can comprise side effects (e.g. secondary immunosuppression). For these reasons, among non-pharmaceutical interventions without known side effects, physical activity (PA) gained importance because it is feasible, safe and a supportive complementary treatment strategy to alleviate symptoms in MS subjects. Consequently, the main aim of this systematic review is to analyze the effect of PA protocols, as a complementary therapy, on inflammatory status in MS patients., Methods: Four electronic databases (PubMed, Embase, CINAHL, and Cochrane CENTRAL) were systematically searched up to 01 June 2023 (Prospero Protocol ID=CRD42021244418). The refined search strategy was based on three concepts: "MULTIPLE SCLEROSIS" AND "PHYSICAL ACTIVITY" AND "INFLAMMATION"., Results: three main findings emerged: 1) untrained subjects showed a negative modulation of inflammatory biomarkers concentrations when compared to trained people (-0.74, 95 %C.I.-1.16, -0.32); 2) training modulated positively inflammatory biomarkers (+0.47, 95 %C.I. 0.24,0.71); 3) Aerobic PA protocol enhance higher positive influence on inflammation., Conclusions: Persistent, low-grade inflammation in MS could be upregulated by non-pharmacological complementary therapies, in particular by regular aerobic PA that could reduce and positively modulate inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Nanomaterials (NMs) are in high demand for a wide range of practical applications; however, comprehensively understanding the toxicity of these materials is a complex challenge, due to the limited availability of epidemiological evidence on the human health effects arising from workplace exposures. The aim of this work is to assess whether and how urinary metal concentrations could be reliable and useful in NM biomonitoring. In the framework of "NanoExplore Project" [EU LIFE17 Grant ENV/GR/000285], 43 not-exposed subjects and 40 exposed workers were recruited to measure exposure to NMs (PCN and LDSA) in the proximity of the workstations and biological biomarkers (urinary metal concentrations-Aluminum (Al), Silica (Si), Titanium (Ti), and Chromium (Cr); urinary OS biomarkers-TAP, Isop, and MDA). The results showed that Si and Ti were directly associated with NM exposure (both PCN and LDSA), as well as with OS biomarkers, especially in exposed workers. Moreover, the mediation analyses showed that Si could account for about 2.8% in the relationship between LDSA and OS biomarkers, possibly by decreasing OS antioxidant defenses in exposed people. In conclusion, our study provides evidence that occupational exposure to mixtures containing NMs can represent an underestimated hazard for exposed people, increasing the body burden and the oxidative balance.

The existing evidence on the association between greenness and respiratory outcomes remains inconclusive. We aimed at systematically summarizing existing literature on greenness exposure and respiratory outcomes in European children and adolescents, with a preliminary attempt to qualify the distribution of dominant tree species across different geographical areas and bioclimatic regions. Overall, 4049 studies were firstly identified by searching PubMed/MEDLINE, EMBASE, Scopus, Web of Science, GreenFile and CAB direct, up to 29 August 2023. Eighteen primary studies were included in the systematic review and six were meta-analyzed. No overall significant association was observed between the Normalized Difference Vegetation Index, assessed within 500-m buffers (i.e. NDVI-500), and the odds of asthma for 0.3-increase in the exposure (OR: 0.97, 95% CI from 0.53 to 1.78). Similarly, an overall exposure to the NDVI-300 highest tertile, as compared to the lowest tertile, was not significantly associated with asthma (OR: 0.65, 95% CI from 0.22 to 1.91): heterogeneity among studies was significant (p = 0.021). We delineated some key elements that might have mostly contributed to the lack of scientific consensus on this topic, starting from the urgent need of harmonized approaches for the operational definition of greenness. Additionally, the complex interplay between greenness and respiratory health may vary across different geographical regions and climatic conditions. At last, the inconsistent findings may reflect the heterogeneity and complexity of this relationship, rather than a lack of scientific consensus itself. Future research should compare geographical areas with similar bioclimatic parameters and dominant or potentially present vegetation species, in order to achieve a higher inter-study comparability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Air pollution is a leading risk factor for global mortality and morbidity. Oxidative stress is a key mechanism underlying air-pollution-mediated health effects, especially in the pathogenesis/exacerbation of airway impairments. However, evidence lacks on subgroups at higher risk of developing more severe outcomes in response to air pollution. This multi-centre study aims to evaluate the association between air pollution and oxidative stress in healthy adults and in patients affected by airway diseases from the Italian GEIRD (Gene Environment Interactions in Respiratory Diseases) multi-case control study. Overall, 1841 adults (49 % females, 20-83 years) were included from four Italian centres: Pavia, Sassari, Turin, and Verona. Following a 2-stage screening process, we identified 1273 cases of asthma, chronic bronchitis, rhinitis, or COPD and 568 controls. Systemic oxidative stress was quantified by urinary 8-isoprostane and 8-OH-dG. Individual residential exposures to NO 2 , PM 10 , PM 2.5 , and O 3 were derived using an innovative five-stage machine-learning-based approach. Linear mixed regression models tested the association between oxidative stress biomarkers and air pollution tertiles, adjusting by age, sex, BMI, smoking, education and season, with recruiting centres as random intercept. Only cases exhibited higher levels of log-transformed 8-isoprostane and 8-OH-dG in association with NO 2 (β: 0.30 95 % CI: 0.08-0.52 and 0.20 95 % CI: 0.03-0.37), PM 10 (0.34 95 % CI: 0.12-0.55 and 0.21 95 % CI: 0.05-0.37) and PM 2.5 (0.27 95 % CI: 0.09-0.49 and 0.18 95 % CI: 0.02-0.34) as compared to the first tertile of exposure. No significant associations were observed for summer O 3 . Our findings suggest that exposure to air pollution may increase systemic oxidative stress levels in people suffering from airway diseases. This introduces a potential novel approach available for future epidemiological studies and Public Health for effective prevention strategies oriented at the quantification of early biological effects in susceptible people, whose additional risk level might be currently underrated. Air-pollution-mediated exacerbations, driven by oxidative stress, still deserve our attention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset)., Methods: We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later (ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV 1 /FVC≥LLN and FVC<10th percentile, obstructive if FEV 1 /FVC

Objective: Office workers spend typically more than two-thirds of their working time sitting and this negative behaviour could have been increased during the pandemic. Low levels of Physical Activity (PA) can have detrimental effects on health, well-being, and Quality of Life (QoL), as well as on the oxidative stress burden. Our aim was to evaluate the role of moderate PA remotely administered in modulating the bio-molecular profile and the QoL of a group of workers during the COVID-19 pandemic., Methods: The 26 subjects recruited were sampled at the beginning of the study (T0), after 3 months of remotely administered training (T1), and 3 months after the suspension of the online workouts (T2). Each of the three times, subjects filled out a questionnaire and provided a spot urine sample for the quantification of oxidative stress (15-F2t-Isoprostane, Thiobarbituric Acid Reactive Substances (TBARS), and Total Antioxidant Power (TAP)) and inflammatory biomarkers (Interleukin (IL)-6 and IL-10)., Results: The PA administration resulted in a significant decrease in 15-F2t-Isoprostane ( p  = 0.02) and TAP ( p  = 0.019). A significant increase in TAP was observed between T1 and T2 ( p  = 0.044)., Conclusion: A PA-based health promotion strategy could be a valuable intervention in the working environment to promote the well-being of an ageing workforce, especially for white collars., (© The Author(s) 2023.)

The increased awareness about possible health effects arising from micro- and nanoplastics (MNPs) pollution is driving a huge amount of studies. Many international efforts are in place to better understand and characterize the hazard of MNPs present in the environment. The literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology in two different databases (PubMed and Embase). The selection of articles was carried out blind, screening titles and abstracts according to inclusion and exclusion criteria. In general, these studies rely on the methodology already in use for assessing hazard from nanomaterials and particles of concern. However, only a limited number of studies have so far directly measured human exposure to MNPs and examined the relationship between such exposure and its impact on human health. This review aims to provide an overview of the current state of research on biomarkers of oxidative stress, inflammation, and genotoxicity that have been explored in relation to MNPs exposure, using human, cellular, animal, and plant models. Both in-vitro and in-vivo models suggest an increased level of oxidative stress and inflammation as the main mechanism of action (MOA) leading to adverse effects such as chronic inflammation, immunotoxicity and genotoxicity. With the identification of such biological endpoints, representing critical key initiating events (KIEs) towards adaptive or adverse outcomes, it is possible to identify a panel of surrogate biomarkers to be applied and validated especially in occupational settings, where higher levels of exposure may occur., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

An association between climatic conditions and asthma incidence has been widely assumed. However, it is unclear whether climatic variations have a fingerprint on asthma dynamics over long time intervals. The aim of this study is to detect a possible correlation of the Summer North Atlantic Oscillation (S-NAO) index and the self-calibrated palmer drought severity index (scPDSI) with asthma incidence over the period from 1957 to 2006 in Italy. To this aim, an analysis of non-stationary and non-linear signals was performed on the time series of the Italian databases on respiratory health (ISAYA and GEIRD) including 36,255 individuals overall, S-NAO, and scPDSI indices to search for characteristic periodicities. The ISAYA (Italian Study on Asthma in Young Adults) and GEIRD (Gene Environment Interactions in Respiratory Diseases) studies collected information on respiratory health in general population samples, born between 1925 and 1989 and aged 20-84 years at the time of the interview, from 13 Italian centres. We found that annual asthma total incidence shared the same periodicity throughout the 1957-2006 time interval. Asthma incidence turned out to be correlated with the dynamics of the scPDSI, modulated by the S-NAO, sharing the same averaged 6 year-periodicity. Since climate patterns appear to influence asthma incidence, future studies aimed at elucidating the complex relationships between climate and asthma incidence are warranted., (© 2023. The Author(s).)

Objectives: occupational exposure to vapours, gases, dusts and fumes (VGDF) plays an important role in the development and exacerbation of respiratory diseases. The aim of this study is to evaluate the possible association of occupational exposure to airborne pollutants and chronic respiratory diseases., Design: multicase-control study., Setting and Participants: cases of chronic respiratory diseases and controls from the Italian multicentric study Gene Environment Interaction in Respiratory Diseases (GEIRD)., Main Outcome Measures: the occurrence of rhinitis, asthma, chronic bronchitis/chronic obstructive pulmonary disease (COPD), asthma severity, spirometry data, exhaled nitric oxide (FeNO) were examined in relation to chronic and acute occupational exposures to airborne pollutants using multiple regression models., Results: 2,943 subjects were enrolled in the study. Regularm exposure to VGDF was associated with a higher prevalence of chronic bronchitis/COPD (OR 1.40, 95%CI 0.98-1.99), especially in those also having asthma (OR 1.80, 95%CI 1.14-2.85), a lower prevalence of remittent asthma (OR 0.53, 95%CI 0.29-0.96) and, in those with asthma, an increased activity of the disease (severity score) (OR 1.77, 95%CI 1.20-2.60). No associations were observed between occupational exposure and prevalence of rhinitis, spirometry and FeNO data. Finally, an association was found between acute exposure to airborne pollutants (occupational and non-occupational) and the respiratory diseases investigated, in particular active asthma and asthma associated chronic bronchitis/BPCO., Conclusions: these data confirm a significant role of occupational exposure to airborne pollutants on respiratory health, underlying the importance of workplace exposure prevention, in particular for more susceptible subjects, as those with respiratory diseases.

The current evidence on nanomaterial toxicity is mostly derived from experimental studies making it challenging to translate it into human health risks. We established an international cohort (N = 141 workers) within the EU-LIFE project "NanoExplore" to address possible health effects from occupational exposures to nanomaterials. We used a handheld direct-reading optical particle counter to measure airborne nanoparticle number concentrations (PNC) and lung-deposited surface areas (LDSAs). Airborne particles were characterized by TEM and SEM-EDAX. We assessed oxidative/nitrosative stress with a panel of biomarkers in exhaled breath condensate (EBC) (8-isoprostane, malondialdehyde, nitrotyrosine), inflammation (high-sensitivity C reactive protein (hs-CRP), IL-1β, TNF-α, IL-10) and KL-6 (considered as biomarker of interstitial lung fibrosis) and urine (total antioxidant power (TAP), 8-isoprostane, and malondialdehyde). Exhaled breath sampled in gas-sampling bags were assessed for oxidative potential. These biomarkers were quantified pre-shift at the beginning of the workweek and post-shift the 4th day. Relationships between airborne nanoparticle concentration and biomarkers were assessed by multiple linear regression with log-transformed exposure and biomarker concentrations adjusted for potential confounders. We found a positive dose-response relationship for three inflammation biomarkers (IL-10, IL-1β and TNF-α) in EBC with both PNC and LDSA. A negative dose-response relationship was observed between PNC and TAP. This study suggests that occupational exposures to nanoparticles can affect the oxidative balance and the innate immunity in occupationally exposed workers. However, owing to the intrinsic variability of biomarkers, the observed changes along with their health significance should be assessed in a long-term perspective study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

During pregnancy, reactive oxygen species (ROS) may physiologically increase due to changes and growth of mother and fetal tissues. Consequently, oxidative stress (OS) may occur and be involved in the onset of pregnancy and newborn complications. Among exogenous antioxidant sources, diet is a cost-effective prevention strategy supporting the health of mothers and newborns; however, there is still a lack of nutritional education during pregnancy interviews. This review aims to systematically summarize the knowledge on the association between OS and diet during pregnancy. Four electronic databases (PubMed Central, EMBASE, Web of Science, and Food Science and Technology Abstracts) were searched on 22 December 2022. Among 4162 records, 13 original articles were finally included. Overall, 80% of the studies considered dietary patterns as exposure and 60% of them assessed the association with malondialdehyde levels in blood and urine. Three studies analyzed the influence of daily intakes of fruit and vegetables on different OS biomarkers (malondialdehyde, nitric oxide and 8-hydroxy-2'-deoxyguanosine). Among studies exploring dietary fat intakes (39%), 80% focused on polyunsaturated fatty acids, finding a positive association with glutathione peroxidase, biopirryn and isoprostane levels, respectively. Four studies analyzed vitamin intakes and 50% of them in association with 8-hydroxy-2'-deoxyguanosine.

Background: air pollution is a complex mixture; novel multipollutant approaches could help understanding the health effects of multiple concomitant exposures to air pollutants., Aim: to assess the relationship of long-term air pollution exposure with the prevalence of respiratory/allergic symptoms and diseases in an Italian multicenter study using single and multipollutant approaches., Methods: 14420 adults living in 6 Italian cities (Ancona, Pavia, Pisa, Sassari, Turin, Verona) were investigated in 2005-2011 within 11 different study cohorts. Questionnaire information about risk factors and health outcomes was collected. Machine learning derived mean annual concentrations of PM 10 , PM 2.5 , NO 2 and mean summer concentrations of O 3 (μg/m 3 ) at residential level (1-km resolution) were used for the period 2013-2015. The associations between the four pollutants and respiratory/allergic symptoms/diseases were assessed using two approaches: a) logistic regression models (single-pollutant models), b) principal component logistic regression models (multipollutant models). All the models were adjusted for age, sex, education level, smoking habits, season of interview, climatic index and included a random intercept for cohorts., Results: the three-year average (± standard deviation) pollutants concentrations at residential level were: 20.3 ± 6.8 μg/m 3 for PM 2.5 , 29.2 ± 7.0 μg/m 3 for PM 10 , 28.0 ± 11.2 μg/m 3 for NO 2 , and 70.9 ± 4.3 μg/m 3 for summer O 3. Through the multipollutant models the following associations emerged: PM 10 and PM 2.5 were related to 14-25% increased odds of rhinitis, 23-34% of asthma and 30-33% of night awakening; NO 2 was related to 6-9% increased odds of rhinitis, 7-8% of asthma and 12% of night awakening; O 3 was associated with 37% increased odds of asthma attacks. Overall, the Odds Ratios estimated through the multipollutant models were attenuated when compared to those of the single-pollutant models., Conclusions: this study enabled to obtain new information about the health effects of air pollution on respiratory/allergic outcomes in adults, applying innovative methods for exposure assessment and multipollutant analyses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maria Beatrice Bilò had speaking and lecture fees supported by Astra Zeneca, GSK, Novartis, Sanofi. The other authors have no competing financial interests or personal relationships to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Nanotechnology applications are fast-growing in many industrial fields. Consequently, health effects of engineered nanomaterials (ENMs) should be investigated. Within the EU-Life project NanoExplore, we developed a harmonized protocol of an international multicenter prospective cohort study of workers in ENM-producing companies. This article describes the development of the protocol, sample size calculation, data collection and management procedures and discusses its relevance with respect to research needs. Within this protocol, workers' ENM exposure will be assessed over four consecutive working days during the initial recruitment campaign and the subsequent follow-up campaigns. Biomonitoring using noninvasive sampling of exhaled breath condensate (EBC), exhaled air, and urine will be collected before and after 4-day exposure monitoring. Both exposure and effect biomarkers, will be quantified along with pulmonary function tests and diagnosed diseases reported using a standardized epidemiological questionnaire available in four languages. Until now, this protocol was implemented at seven companies in Switzerland, Spain and Italy. The protocol is well standardized, though sufficiently flexible to include company-specific conditions and occupational hygiene measures. The recruitment, to date, of 140 participants and collection of all data and samples, enabled us launching the first international cohort of nanotechnology workers. All companies dealing with ENMs could join the NanoExplore Consortium, apply this harmonized protocol and enter in the cohort, concieved as an open cohort. Its protocol meets all requirements of a hypotheses-driven prospective study, which will assess and reassess effects of ENM exposure on workers' health by updating the follow-up of the cohort. New hypothesis could be also considered.

Introduction: Adolescence is a critical period of life, and the level of wellbeing acquired during this stage might have an influence on health status in adulthood. The wellbeing of adolescents is associated with both biological and environmental determinants. To date, few studies have evaluated the effect of exposure to urban green spaces (i.e., greenness) on adolescents' wellbeing. Therefore, the aim of this study is to assess the association between exposure to greenness and the wellbeing of adolescents, accounting for the level of urbanization surrounding schools., Methods: In the frame of the 2018 Italian Health Behaviour in School-aged Children (HBSC), we analyzed cross-sectional data from the Piedmont Region. Exposure to greenness was quantified by the Normalized Difference Vegetation Index (NDVI). Schools were geocoded, and a fixed buffer (radius 1,500 m) centered on each school was then built to enable average NDVI calculations. Adolescents' wellbeing was assessed by self-reported psychological, somatic, and psychosomatic health complaints as follows. Respondents were asked how often, in the last 6 months, they had experienced: (a) headache, (b) stomachache, (c) backache, (d) dizziness, (e) feeling low, (f) irritability or bad temper, (g) feeling nervous, and (h) difficulties getting to sleep using the HBSC Symptom Checklist (HBSC-SCL), an eight-item tool. Multivariable, multilevel logistic regression models tested the association between exposure to NDVI and psychosomatic, somatic, and psychological health complaints, one at a time, using schools as a random intercept., Results: In total, 2065 subjects (47.6% girls) aged 11 (48.4%) and 13 (51.6%) years were involved. Greenness was found to be inversely associated with reported psychosomatic (OR 0.72, 95% CI: 0.53-0.98) and psychological health complaints (OR 0.67, 95% CI: 0.49-0.92) in boys only, adjusting for age, urbanization level, and socioeconomic status, and stratifying by gender., Discussion: Our results support the implementation of future policies for urban environmental design supporting the increase of green spaces, as suggested by the United Nations Sustainable Development Goals. Further studies are needed to confirm our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Scaioli, Squillacioti, Bersia, Bellisario, Borraccino, Bono, Dalmasso and Lemma.)

Inflammation is a comprehensive set of physiological processes that an organism undertakes in response to a wide variety of foreign stimuli, such as viruses, bacteria, and inorganic particles. A key role is played by cytokines, protein-based chemical mediators produced by a broad range of cells, including the immune cells recruited in the inflammation site. The aim of this systematic review is to compare baseline values of pro/anti-inflammatory biomarkers measured in Exhaled Breath Condensate (EBC) in healthy, non-smoking adults to provide a summary of the concentrations reported in the literature. We focused on: interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-α), and C reactive protein (CRP). Eligible articles were identified in PubMed, Embase, and Cochrane CENTRAL. Due to the wide differences in methodologies employed in the included articles concerning EBC sampling, storage, and analyses, research protocols were assessed specifically to test their adherence to the ATS/ERS Task Force guidelines on EBC. The development of reference intervals for these biomarkers can result in their introduction and use in both research and clinical settings, not only for monitoring purposes but also, in the perspective of future longitudinal studies, as predictive parameters for the onset and development of chronic diseases with inflammatory aetiology.

Residential greenness exposure has been reported to positively impact health mainly by reducing overweight/obesity risk, improving mental health and physical activity. Less is known on biological pathways involved in these health benefits. We aimed to investigate the association between multisite greenness exposure and oxidative stress in children and explore the potential mediating role of physical activity in this association. This cross-sectional study involved 323 healthy subjects (8-11 y) from five schools in Asti (Italy). Children's parents filled a questionnaire providing the residential address, parental education, and physical activity frequency. Oxidative stress was quantified in spot urine by isoprostane (15-F 2t -IsoP) using ELISA technique. Residential and scholastic greenness were defined by the Normalized Difference Vegetation Index (NDVI) in buffers with 100, 250, 300, 500 and 1000 m radii, and vegetated portion was also estimated. Multisite exposures were derived accounting for NDVI around home and school, weighted for time spent in each location. Linear mixed models, age-adjusted, with schools as random intercept, tested the association between 500 m-radius buffer multisite grenness variables and log (15-F 2t -IsoP), reporting decreased oxidative stress per interquartile range (IQR) increase in multisite NDVI (β: 012, 95%CI -0.240 to 0.004) and multisite vegetated portion (β: 0.14, 95%CI -0.270 to -0.006). The mediation analysis did not support the hypothesis that physical activity frequency could mediate these associations. Multisite greenness exposure is associated with decreased oxidative stress in children and our data did not support the mediating role of physical activity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Recent studies have examined how the environment can influence obesity in young people. The research findings are conflicting: in some studies, green spaces have shown a protective association with obesity and urbanization has turned out to worsen this condition, while other studies contradicted these results. The aim of the study was to examine the relationships between greenness, urbanization, and weight status among Italian adolescents. Student data (11-13 years old) on weight and height, physical activity (PA), and demographic characteristics were extracted from the 2018 Health Behaviour in School-aged Children (HBSC) survey in Piedmont, Northwest of Italy. Data on Normalized Difference Vegetation Index (NDVI) and urbanization were obtained from satellite images and the National Institute of Statistics (ISTAT). A multilevel regression model was used to assess the association between NDVI, urbanization, and obesity, controlling for PA. Students living in greener areas reported a lower likelihood of being obese [OR = 0.11, 95% CI 0.02-0.56, p = 0.007], while students living in areas with a higher level of urbanization showed a significantly increased risk of obesity [OR = 2.3, 95% CI:1.14-4.6, p = 0.02]. Living surrounded by higher amounts of greenness and lower levels of urbanization may positively influence health status through lower risk of obesity among youth.

Formaldehyde (FA) is a ubiquitous toxic chemical employed worldwide due to its disinfectant and preservative properties. Despite being classified as a human carcinogen, FA is still employed as formalin in pathology wards as standard fixative. We evaluated its relationship with the formation of sister-chromatid exchanges (SCEs) in cultured peripheral blood lymphocytes on 57 pathologists and 48 controls and the risk/protective role played by several genetic polymorphisms. All subjects were assessed for SCEs and genotyped for the most common cancer-associated gene polymorphisms: CYP1A1 exon 7 (A > G), CYP1A1*2A (T > C), CYP2C19*2 (G > A), GSTT1 (presence/absence), GSTM1 (presence/absence), GSTP1 (A > G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα - 308 G > A), IL10 - 1082 (G > A), and IL6 - 174 (G > C). Air-FA concentration was assessed through passive personal samplers. Pathologists, exposed to 55.2 μg/m 3 of air-FA, showed a significantly higher SCEs frequency than controls, exposed, respectively, to 18.4 μg/m 3 . Air-FA was directly correlated with SCEs frequency and inversely with the replication index (RI). Regression models showed FA exposure as a significant predictor in developing SCEs, while did not highlight any role of the selected polymorphisms. Our study confirms the role of low air-FA levels as genotoxicity inductor, highlighting the importance to define exposure limits that could be safer for exposed workers., (© 2022. The Author(s).)

Among particulate matter composing paints, titanium dioxide (TiO2) forms about 20% of the final suspension. Although TiO2 is broadly used in many applications, TiO2 powders represent an established respiratory hazard for workers with long-term exposure. In 35 workers of a paints production plant (15 exposed and 20 not exposed), we assessed pro-inflammatory cytokines (IL-1β, TNF-α, IL-10, IL-17), surfactant protein D (SP-D) and Krebs von den Lungen-6 glycoprotein (KL-6) in exhaled breath condensate (EBC). In urine samples, we measured 8-isoprostane (Isop) and Malondialdehyde (MDA) as biomarkers of oxidative stress, and Titanium (Ti-U) as a biomarker of exposure. Health status, habits and occupational history were recorded. Airborne respirable dusts and Ti were quantified. Particle number concentration and average diameter (nm) were detected by a NanoTracer™ monitoring device. Ti was measurable in filters collected at the respiratory breathing zone (0.11−0.44 µg/m3 8-h TWA). IL-1β and IL-10 values were significantly higher in exposed workers, whereas SP-D was significantly lower (p < 0.001). KL-6 was significantly higher in workers than in controls (p < 0.01). MDA levels were significantly increased in exposed workers and were positively correlated with Ti-U. Exposure to TiO2 in paint production is associated with the subtle alterations of lung pathobiology. These findings suggest the need for an integrated approach relying on both personal exposure and biomarker assessment to improve the hazard characterisation in occupational settings.

Background: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant., Objective: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study., Methods: A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made., Results: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without., Conclusions & Clinical Relevance: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis., (© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Physical activity may benefit health by modulating oxidative stress and inflammation. However, the selection of suitable exercise-induced oxidative stress biomarkers is still challenging. This study aimed at systematically summarizing the available evidence on exercise-induced oxidative stress measured in urine and/or saliva. Two meta-analyses including the most frequently quantified biomarkers of oxidative stress, namely, urinary isoprostane and DNA oxidation products, were performed. Three electronic databases (PubMed, EMBASE and Cochrane CENTRAL) were interrogated. Among 4479 records, 43 original articles were included in the systematic review and 11 articles were included in meta-analysis I and II, respectively. We observed a pooled trend of increase of urinary isoprostanes in response to physical activity (+0.95, 95% CI: -0.18; 2.09). In comparison with aerobic exercise, anaerobic training determined a greater induction of isoprostanes (+5.21, 95% CI: 2.76; 7.66, p < 0.0001), which were markedly increased after vigorous physical activity (+6.01, 95% CI: 1.18; 10.84, p < 0.001) and slightly decreased in response to exercise interventions protracted over time (e.g., months) (-1.19, 95% CI: -2.25; -0.12, p < 0.001). We recommend the most integrative approach of oxidative stress multi-marker panels in response to physical activity instead of selecting one preferential biomarker to quantify physical activity-induced oxidative stress in humans.

Despite the toxicity and health risk characteristics of formaldehyde (FA), it is currently used as a cytological fixative and the definition of safe exposure levels is still a matter of debate. Our aim was to investigate the alterations in both oxidative and inflammatory status in a hospital working population. The 68 workers recruited wore a personal air-FA passive sampler, provided a urine sample to measure 15-F 2t -Isoprostane (15-F 2t -IsoP) and malondialdehyde (MDA) and a blood specimen to measure tumour necrosis factor α (TNFα). Subjects were also genotyped for GSTT1 (Presence/Absence), GSTM1 (Presence/Absence), CYP1A1 exon 7 (A > G), and IL6 (-174, G > C). Workers were ex post split into formalin-employers (57.3 μg/m 3 ) and non-employers (13.5 μg/m 3 ). In the formalin-employers group we assessed significantly higher levels of 15-F 2t -IsoP, MDA and TNFα (<0.001) in comparison to the non-employers group. The air-FA levels turned out to be positively correlated with 15-F 2t -IsoP ( p = 0.027) and MDA ( p < 0.001). In the formalin-employers group the MDA level was significantly higher in GSTT1 Null ( p = 0.038), GSTM1 Null ( p = 0.031), and CYP1A1 exon 7 mutation carrier ( p = 0.008) workers, compared to the wild type subjects. This study confirms the role of FA in biomolecular profiles alterations, highlighting how low occupational exposure can also result in measurable biological outcomes.

Green spaces may benefit human health mainly by mitigating noise and air pollution, promoting physical or social activities and improving mental health. Based on the influence that green space exposure seems to exert on Public Health and using a multidisciplinary approach, we investigated, the association between oxidative stress (OS) and green exposure in children. Overall, 207 subjects (10-13 yrs) living in Torino (NW- Italy) were involved in this study. Each participant provided a urinary sample, used to quantify a reliable OS biomarker (15-F2t-IsoP), and their residence addresses, used for geocoding. Green exposure was characterised by calculating i) the Soil Adjusted Vegetation Index (SAVI) within fixed buffers around each participant's home, using remotely-sensed data; ii) Tree Map accounting for evergreen/broadleaf species; iii) The percentage of green cover (PGC). Significant negative correlation (Pearson's r = -0.758, p < 0.001) between PGC and 15-F2t-IsoP was found. Greater SAVI was associated with lower OS (Pearson's r = -0.717, p < 0.001). Noticeably, evergreens seemed to determine a significant OS reduction compared to broadleaves (slope = -0.12 and -0.02, respectively; Warton-test F = 12.48, p = 0.0011). Finally, a spatial distribution of 15-F2t-IsoP estimates map, overlying with 2011 Census Data on same-aged dwellers of Torino, was generated. Predictive models accounting for green spaces influence on OS can be useful tool derived from geomatic employ in the Public Health field. Future developments of such a multidisciplinary approach should be considered in urban planning and policy-makers decisions to better define priority zones to requalify in urban settings., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Formaldehyde (FA) is a human carcinogen used as formalin in hospital laboratories. We evaluated its association with human chromosomal aberrations (CAs) and the risk/protective role played by several genetic polymorphisms in this relationship, on a cohort of 57 exposed pathologists vs 48 controls. All subjects were assessed for CAs on peripheral blood lymphocytes and genotyped for the most common cancer-associated gene polymorphisms which could be related with the genotoxic outcome: CYP1A1 exon 7 (A>G), CYP1A1*2A (T>C), CYP2C19*2 (G>A), GSTT1 (Positive/Null), GSTM1 (Positive/null), GSTP1 (A>G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPD (A751C), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα - 308 (G>A), IL10 - 1082 (G>A), IL10 - 819 (C>T) and IL6 - 174 (G>C). Air-FA concentration was assessed through personal samplers. The comparison between pathologists and controls showed a significantly higher CAs frequency in pathologists. Significant positive correlations were found between CAs frequency and air-FA concentration while significant associations were found between variation in CAs frequency and the mutated allele for CYP1A1 exon 7 (A>G), CYP2C19*2 (G>A), GSTT1-positive, GSTM1-positive and XRCC1 (G399A). Our study confirms the role of FA as genotoxicity inductor, even in workers chronically exposed to low air-FA levels and reveals the role played by some genetic polymorphisms in this association, highlighting the importance of individual susceptibility biomarkers assessment in occupational health studies.

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 FEV 1 and FEV 1 /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 FEV 1 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 FEV 1 and FeNO levels in non-smokers and women, regardless of asthma status., Conclusions: We found a relationship between elevated FeNO and larger FEV 1 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., Competing Interests: DF reports grants from Asthma Foundation of Victoria, grants from Allen and Hanbury’s, grants from National Health & Medical Research Council, during the conduct of the study. VS reports grants from The Wood Dust Foundation (Project No. 444508795), during the conduct of the study. RJ reports grants from Estonian Research Council Personal Research Grant no 562, during the conduct of the study; personal fees from Consultancy, grants from Grants/grants pending, personal fees from Payment for lectures, personal fees from Travel/accommodations/meeting expenses, outside the submitted work. PD reports grants from ALK, Stallergenes Greer, grants from AstraZeneca, ThermoFisherScientific, Ménarini, grants from Bausch & Lomb, personal fees from Sanofi, Regeneron, outside the submitted work. RN reports grants and personal fees from AstraZeneca, grants from Novartis, grants from Boehringer Ingelheim, grants and personal fees from GlaxoSmithKline, outside the submitted work. IP reports other from NOVARTIS, other from ASTRA ZENECA, personal fees from AGIRadom, outside the submitted work. All other authors declare no conflicts of interests. The following grants contributed to funding ECRHS I. Australia: Asthma Foundation of Victoria, Allen and Hanbury’s. Belgium: Belgian Science Policy Office, National Fund for Scientific Research. Denmark: The Danish Lung Association. Estonia: Estonian Science Foundation, grant no 1088. France: Ministère de la Santé, Glaxo France, Institut Pneumologique d'Aquitaine, Contrat de Plan Etat-Région Languedoc-Rousillon, CNMATS, CNMRT (90MR/10, 91AF/6), Ministre delegué de la santé, RNSP, France; GSF. Germany: Bundesminister für Forschung und Technologie. Greece: The Greek Secretary General of Research and Technology, Fisons, Astra and Boehringer-Ingelheim. India: Bombay Hospital Trust. Italy: Ministero dell'Università e della Ricerca Scientifica e Tecnologica, CNR, Regione Veneto grant RSF n. 381/05.93. New Zealand: Asthma Foundation of New Zealand, Lotteries Grant Board, Health Research Council of New Zealand. Norway: Norwegian Research Council project no. 101422/310. Portugal: Glaxo Farmacêutica Lda, Sandoz Portugesa. Spain: Fondo de Investigación Sanitaria (#91/0016-060-05/E, 92/0319 and #93/0393), Hospital General de Albacete, Hospital General Juan Ramón Jiménez, Dirección Regional de Salud Pública (Consejería de Sanidad del Principado de Asturias), CIRIT (1997 SGR 00079), and Servicio Andaluz de Salud. Sweden: The Swedish Medical Research Council, the Swedish Heart Lung Foundation, and the Swedish Association against Asthma and Allergy. Switzerland: Swiss National Science Foundation grant 4026-28099. UK: National Asthma Campaign, British Lung Foundation, Department of Health, South Thames Regional Health Authority. USA: United States Department of Health, Education and Welfare Public Health Service (grant #2 S07 RR05521-28). The coordination of this work was supported by the European Commission. The following grants contributed to funding ECRHS III. Australia: National Health & Medical Research Council. Belgium: Antwerp South, Antwerp City – Research Foundation Flanders (FWO), grant code G.0.410.08.N.10 (both sites). Estonia: Tartu – SF0180060s09 from the Estonian Ministry of Education. France: (All) Ministère de la Santé, Programme Hospitalier de Recherche Clinique (PHRC) national 2010. Bordeaux: INSERM U897 Université Bordeaux Segalen. Grenoble: Comite Scientifique AGIRadom 2011. Paris: Agence Nationale de la Santé, Région Ile de France, domaine d’intérêt majeur (DIM). Germany: Erfurt: German Research Foundation HE 3294/10-1. Hamburg: German Research Foundation MA 711/6-1, NO 262/7-1. Iceland: Reykjavik, The Landspítali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation, California, USA, Orkuveita Reykjavíkur (Geothermal plant), Vegagerðin (The Icelandic Road Administration (ICERA). Italy: All Italian centres were funded by the Italian Ministry of Health, Chiesi Farmaceutici SpA. Verona received additional funding from the Cariverona foundation, Education Ministry (MIUR). Norway: Norwegian Research Council grant no 214123, Western Norway Regional Health Authorities grant no 911631, Bergen Medical Research Foundation. Spain: Fondo de Investigación Sanitaria (PS09/02457, PS09/00716 09/01511) PS09/02185 PS09/03190), Servicio Andaluz de Salud, Sociedad Española de Neumología y Cirurgía Torácica (SEPAR 1001/2010), Fondo de Investigación Sanitaria (PS09/02457). Barcelona: Fondo de Investigación Sanitaria (FIS PS09/00716). Galdakao:Fondo de Investigación Sanitaria (FIS 09/01511). Huelva: Fondo de Investigación Sanitaria (FIS PS09/02185) and Servicio Andaluz de Salud. Oviedo: Fondo de Investigación Sanitaria(FIS PS09/03190). Sweden: All centres were funded by the Swedish Heart and Lung Foundation, the Swedish Asthma and Allergy Association, the Swedish Association against Lung and Heart Disease, and the Swedish Research Council for Health, Working Life and Welfare (FORTE). Göteborg also received further funding from the Swedish Council for Working Life and Social Research. Umeå also received funding from a Västerbotten County Council ALF grant. Switzerland: The Swiss National Science Foundation (grants no 33CSCO-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099), The Federal office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, the canton’s government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League, the canton’s Lung League of Basel Stadt/ Basel, Landschaft, Geneva, Ticino, Valais, and Zurich, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, UK: Medical Research Council (Grant Number 92091). Support was also provided by the National Institute for Health Research through the Primary Care Research Network., (© 2021 The Author(s).)

The aim of the present study was to assess the effects of bisphenol (BP) exposure on pregnancy and neonatal life. We have (a) determined BP (BPA and BPS) concentration levels in a group of newborns and their mothers; (b) identified factors, habits, and devices possibly responsible for BP uptake; and (c) determined the effect of BP exposure. No significant correlations were detected between maternal and neonatal BP concentration levels. In newborns, positive correlations between pacifier use and BPS total ( p = 0.04) and free BPS ( p = 0.03) concentrations were detected. A significant correlation was also found between oral glucose administration and concentration levels of free BPA ( p < 0.05). Our study points to a central role of lifestyle, hospital procedures, and neonatal devices in inducing BP exposure, especially during the perinatal period. This is the first report of BP contamination in newborns due to widely non-alimentary products designed for newborn care, such as glucose-solution containers for BPA and pacifiers for BPS. Further studies are advocated in order to clarify both the impact of other BP forms on human health and development, as well as potential BPA exposure sources during neonatal and childhood life.

Although there are many health benefits from being active, there was no benefit observed in this study from vigorous physical activity in reducing the risk of asthma onset in middle-aged adults https://bit.ly/3bEtHDn., Competing Interests: Conflict of interest: M.A. Russell has nothing to disclose. Conflict of interest: S. Dharmage has nothing to disclose. Conflict of interest: E. Fuertes has nothing to disclose. Conflict of interest: A. Marcon has nothing to disclose. Conflict of interest: A-E. Carsin has nothing to disclose. Conflict of interest: S. Pascual Erquicia has nothing to disclose. Conflict of interest: J. Heinrich has nothing to disclose. Conflict of interest: A. Johannessen has nothing to disclose. Conflict of interest: M.J. Abramson has nothing to disclose. Conflict of interest: A.F.S. Amaral has nothing to disclose. Conflict of interest: I. Cerveri has nothing to disclose. Conflict of interest: P. Demoly reports board fees from Chiesi, IQVIA, Ménarini and Sanofi; board and speaker bureau fees from AstraZeneca, Bausch & Lomb and ThermoFisher Scientific; and speaker fees from Mylan and Novartis, all outside the submitted work. Conflict of interest: V. Garcia-Larsen has nothing to disclose. Conflict of interest: D. Jarvis has nothing to disclose. Conflict of interest: J. Martinez-Moratalla has nothing to disclose. Conflict of interest: D. Nowak has nothing to disclose. Conflict of interest: L. Palacios-Gómez has nothing to disclose. Conflict of interest: G. Squillacioti has nothing to disclose. Conflict of interest: W. Raza has nothing to disclose. Conflict of interest: M. Emtner has nothing to disclose. Conflict of interest: J. Garcia-Aymerich has nothing to disclose., (Copyright ©The authors 2021.)

Background: Many workers are exposed to wood dust (WD) and formaldehyde (FA), whose carcinogenic activity is supposed to be oxidative stress-mediated. This study aims to assess to what extent the occupational exposure to WD and FA, albeit within regulatory limits, could result in OS induction in a woodworkers' population., Methods: The sample population consisted of 127 woodworkers from 4 factories and 111 unexposed controls. Individual exposure was assessed by personal air-samplers. Each participant enrolled in the study filled out a questionnaire and provided a urinary sample to quantify OS biomarkers, namely 15-F 2t -IsoProstane (15-F 2t -IsoP) and 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dGuo). The main confounding factor for OS, i.e. tobacco smoking exposure, was assessed by measuring cotinine in urine samples., Results: Woodworkers were exposed to significantly higher amounts of WD and FA as compared to controls (p < 0.001). Among OS biomarkers, 15-F 2t -IsoP showed statistically significant higher values in woodworkers compared to controls (p = 0.004). A significant, positive correlation was observed between 15-F 2t -IsoP and 8-oxo-dGuo (p = 0.005), cotinine (p = 0.05), FA (p < 0.001) and WD (p = 0.01); 8-oxo-dGuo was significantly correlated with cotinine (p = 0.001) and WD (p = 0.004). In addition, WD and FA were significantly correlated each other (p < 0.001)., Conclusions: The study confirms that WD and FA may induce OS in woodworkers, and highlights that even the compliance with occupational exposure limits can result in measurable biological outcomes.

Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up. Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking. Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV 1 and the FEV 1 /FVC ratio for exposure to biological dust, mineral dust, and metals (FEV 1  = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV 1 /FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts. Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

We estimated the association between regular physical activity and the incidence of restrictive spirometry pattern. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and physical activity were assessed in 2 population-based European cohorts (European Community Respiratory Health Survey: n = 2,757, aged 39-67 years; and Swiss Study on Air Pollution and Lung and Heart Diseases in Adults: n = 2,610, aged 36-82 years) first in 2000-2002 and again approximately 10 years later (2010-2013). Subjects with restrictive or obstructive spirometry pattern at baseline were excluded. We assessed the association of being active at baseline (defined as being physically active at least 2-3 times/week for ≥1 hour) with restrictive spirometry pattern at follow-up (defined as a postbronchodilation FEV1/FVC ratio of at least the lower limit of normal and FVC of <80% predicted) using modified Poisson regression, adjusting for relevant confounders. After 10 years of follow-up, 3.3% of participants had developed restrictive spirometry pattern. Being physically active was associated with a lower risk of developing this phenotype (relative risk = 0.76, 95% confidence interval: 0.59, 0.98). This association was stronger among those who were overweight and obese than among those of normal weight (P for interaction = 0.06). In 2 large European studies, adults practicing regular physical activity were at lower risk of developing restrictive spirometry pattern over 10 years., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Concerns exist that the positive association of physical activity with better lung function, which has been suggested in previous longitudinal studies in smokers, is due to reverse causation. To investigate this, we applied structural equation modeling (SEM), an exploratory approach, and marginal structural modeling (MSM), an approach from the causal inference framework that corrects for reverse causation and time-dependent confounding and estimates causal effects, on data from participants in the European Community Respiratory Health Survey (ECRHS, a multicentre European cohort study initiated in 1991-1993 with ECRHS I, and with two follow-ups: ECRHS II in 1999-2003, and ECRHS III in 2010-2014). 753 subjects who reported current smoking at ECRHS II, with repeated data on lung function at ECRHS I, II and III, physical activity at ECRHS II and III, and potential confounders at ECRHS I and II, were included in the analyses. SEM showed positive associations between physical activity and lung function in both directions. MSM suggested a protective causal effect of physical activity on lung function (overall difference in mean β (95% CI), comparing active versus non-active individuals: 58 mL (21-95) for forced expiratory volume in one second and 83 mL (36-130) for forced vital capacity). Our results suggest bi-directional causation and support a true protective effect of physical activity on lung function in smokers, after accounting for reverse causation and time-dependent confounding., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: Competing interests: JG-A reports personal fees from Esteve, Chiesi and AstraZeneca, outside the submitted work. MJA reports grants from Pfizer, grants from Boehringer-Ingelheim and personal fees from Sanofi, outside the submitted work. PD reports personal fees from ALK, Stallergenes Greer, IQVIA, Chiesi, AstraZeneca, Thermo Fisher Scientific, Menarini, Bausch & Lomb, Mylan, ASIT Biotech, Novartis, Sanofi and Regeneron, outside the submitted work. RJ reports grants from Estonian Research Council (Personal Research Grant no 562) and personal fees from GSK, Boehringer and Novartis, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Recent research focused on the interaction between land cover and the development of allergic and respiratory disease has provided conflicting results and the underlying mechanisms are not fully understood. In particular, green space, which confers an overall positive impact on general health, may be significantly contributing to adverse respiratory health outcomes. This study evaluates associations between surrounding residential land cover (green, grey, agricultural and blue space), including type of forest cover (deciduous, coniferous and mixed), and childhood allergic and respiratory diseases., Methods: Data from 8063 children, aged 3-14 years, were obtained from nine European population-based studies participating in the HEALS project. Land-cover exposures within a 500 m buffer centred on each child's residential address were computed using data from the Coordination of Information on the Environment (CORINE) program. The associations of allergic and respiratory symptoms (wheeze, asthma, allergic rhinitis and eczema) with land coverage were estimated for each study using logistic regression models, adjusted for sex, age, body mass index, maternal education, parental smoking, and parental history of allergy. Finally, the pooled effects across studies were estimated using meta-analyses., Results: In the pooled analyses, a 10% increase in green space coverage was significantly associated with a 5.9%-13.0% increase in the odds of wheezing, asthma, and allergic rhinitis, but not eczema. A trend of an inverse relationship between agricultural space and respiratory symptoms was observed, but did not reach statistical significance. In secondary analyses, children living in areas with surrounding coniferous forests had significantly greater odds of reporting wheezing, asthma and allergic rhinitis., Conclusion: Our results provide further evidence that exposure to green space is associated with increased respiratory disease in children. Additionally, our findings suggest that coniferous forests might be associated with wheezing, asthma and allergic rhinitis. Additional studies evaluating both the type of green space and its use in relation to respiratory conditions should be conducted in order to clarify the underlying mechanisms behind associated adverse impacts., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Personal air formaldehyde (air-FA) was measured as risk factor of airways inflammation and oxidative stress (SO) induction. Overall, 154 police officers were enrolled from two differently urbanised Italian cities, Turin and Pavia. Urinary F2t-isoprostane (15-F2t-IsoP), a prostaglandin-like compound, was quantified as a biomarker of general OS in vivo and fractional exhaled nitric oxide (FeNO) was measured for monitoring local inflammatory processes. Urinary cotinine was quantified as a biomarker of tobacco smoking exposure. Traffic police officers living in Turin showed an increased level of log air-FA ( p < 0.001), equal to +53.6% ( p < 0.001). Log air-(FA) mean values were 3.38 (C.I. 95% 3.33-3.43) and 2.84 (C.I. 95% 2.77-2.92) in Turin and Pavia, respectively. Log (air-FA) was higher in "outdoor workers" (3.18, C.I. 95% 3.13-3.24, p = 0.035) compared to "indoor workers", showing an increase of +9.3%, even controlling for sex and city. The analyses on 15-F2t-IsoP and FeNO, both adjusted for log air-FA, highlighted that OS and inflammation were higher (+66.8%, p < 0.001 and +75%, p < 0.001, respectively) in Turin traffic police officers compared to those from Pavia. Our findings suggest that even low exposures to traffic-related emissions and urbanisation may influence both general oxidative stress levels and local inflammation., Competing Interests: The authors declare no conflict of interest.

Paediatric Asthma contributes in paediatric global burden of diseases, as the most common chronic disease in children. Children are exposed to many environmental risk-factors, able to determine or worsen respiratory diseases, and contributing to asthma and asthma-like symptoms increases, especially in metropolitan areas. In urban settings, surrounding vegetation (greenness) may provide important benefits to health, including the promotion of physical activity and the mitigation of air and noise pollution. The aim of this study was to investigate the association between greenness and respiratory health. A total of 187 children (10-13 yrs old) were recruited in Turin, the north-western part of Italy. The prevalence of asthma and asthma-like symptoms was calculated from self-reported data collected by SIDRIA questionnaire. Spirometry test was performed to obtain respiratory flow measurements. Greenness was measured at individual level through the Normalised Difference Vegetation Index (NDVI) estimations from remote-sensing images. Higher exposure (3rd tertile vs. 1st tertile) to NDVI was associated to significantly lower ORs for asthma [0.13 CI 95% 0.02-0.7, p = 0.019], bronchitis [0.14 CI 95% 0.05-0.45, p = 0.001], and current wheezing [0.25 CI 95% 0.09-0.70, p = 0.008]. A significative positive association was found between greenness and FEF 25-75 , since children exposed to the 2nd tertile of NDVI reported a significantly decreased FEF 25-75 compared to those in the 3rd tertile [B: -2.40; C.I.95%: -0.48-0.01; p = 0.049]. This cross-sectional study provided additional data on still inconsistent literature referring to respiratory health in children and green spaces, attesting a positive effect of greenness in a specific area of Italy. Further research is still needed.

Background and Objectives: Cardiovascular and respiratory diseases can frequently coexist. Understanding their link may improve disease management. We aimed at assessing the associations of chronic bronchitis (CB), asthma and rhinitis with cardiovascular diseases and risk factors in the general population., Methods: We used data collected in the Gene Environment Interactions in Respiratory Diseases study, an Italian multicentre, multicase-control study. Among 2463 participants (age 21-86, female 50%) who underwent standardized interviews, skin prick and lung function tests, we identified 254 cases of CB without airflow obstruction, 418 cases of asthma without CB, 959 cases of rhinitis alone, and 832 controls. The associations of respiratory diseases with reported cardiovascular risk factors (lifestyles, hypertension, dyslipidaemia), heart disorders (myocardial infarction, coronary thrombosis, angina, aorta or heart surgery) and intermittent claudication were estimated through relative risk ratios (RRR) by multinomial logistic regression models., Results: Compared to controls, CB cases were more likely to be heavy smokers, alcohol consumers, physically inactive, and to suffer from hypertension or dyslipidaemia; rhinitis cases were less obese but more likely to have hypertension. Asthma was significantly associated with current smoking. After adjusting for cardiovascular risk factors, heart disorders were associated with CB (RRR[95%CI]: 1.58[1.12-2.22]) and rhinitis (1.35[0.98-1.85]) and intermittent claudication was associated with CB (3.43[2.52-4.67]), asthma (1.51[1.04-2.21]) and rhinitis (2.03[1.34-3.07])., Conclusions: CB, asthma and rhinitis were associated with cardiovascular risk factors and diseases. In particular, CB shared with cardiovascular diseases almost all risk factors and was strongly associated with a higher risk of heart disorders and intermittent claudication., Competing Interests: The authors have declared that no competing interests exist.

Risk monitoring in childhood is useful to estimate harmful health effects at later stages of life. Thus, here we have assessed the effects of tobacco smoke exposure and environmental pollution on the respiratory health of Italian children and adolescents using spirometry and the forced oscillation technique (FOT). For this purpose, we recruited 188 students aged 6-19 years living in Chivasso, Italy, and collected from them the following data: (1) one filled out questionnaire; (2) two respiratory measurements (i.e., spirometry and FOT); and (3) two urine tests for Cotinine (Cot) and 15-F 2t -Isoprostane (15-F 2t -IsoP) levels. We found a V-shape distribution for both Cotinine and 15-F 2t -IsoP values, according to age groups, as well as a direct correlation ( p = 0.000) between Cotinine and tobacco smoke exposure. These models demonstrate that tobacco smoke exposure, traffic, and the living environment play a fundamental role in the modulation of asthma-like symptoms ( p = 0.020) and respiratory function ( p = 0.007). Furthermore, the results from the 11-15-year group indicate that the growth process is a protective factor against the risk of respiratory disease later in life. Lastly, the FOT findings highlight the detrimental effects of tobacco smoke exposure and urbanization and traffic on respiratory health and asthma-like symptoms, respectively. Overall, monitoring environmental and behavioral factors in childhood can provide valuable information for preventing respiratory diseases in adulthood.

Objectives: The purpose of this study was to investigate bisphenol A (BPA) and its role in the induction of oxidative stress and confirm the same for tobacco smoke., Methods: A total of 223 young, healthy students (7-19 years old) were recruited in Chivasso, Italy. A spot of urine of each subject was analyzed to quantify BPA, cotinine, and 15F2t-isoprostane., Results: BPA showed a slight increase of concentration proportional with increasing age, even though the 11-14 years age group had slightly lower results, inducing a V-shape. The same trend was observed for 15F2t-isoprostane and cotinine. The result of piecewise linear robust regression shows a break point of the effect of BPA on 15F2t-isoprostane at 6 ng/mg CREA ( p < 0.001). At higher levels, 15F2t-isoprostane shows an exponential increase by more than threefold for each one-log unit of BPA. An increase of oxidative stress due to BPA was observed, but only from 6 ng/mg of CREA up. Passive tobacco smoke is also able to induce an increase in oxidative stress., Conclusion: Prevention against BPA and passive tobacco smoke represents an important tool for promoting the highest health standard.

Obesity and exposure to second-hand tobacco smoking (SHS) may influence oxidative stress (OS) levels, especially in children. This study investigated body composition and SHS influence on OS induction in the paediatric population. The first purpose was identifying an appropriate BMI standard for adiposity assessment in OS investigations. Secondly, SHS and obesity were analysed as inductors of OS. The epidemiologic sample involved 330 children. Three BMI (body mass index) references (IOTF, CDC, and WHO) and an impedentiometric scale supplied body-composition measurements. Partecipants filled out a questionnaire and provided urinary samples for biomarker quantifications: isoprostane (15-F2t IsoP) and cotinine as OS and SHS biomarker, respectively. Obesity prevalence changed over different BMI references (14%, 21%, and 34% for IOTF, CDC, and WHO, respectively). Obese children, by IOTF, showed an increase of 56% in 15-F2t IsoP compared to those normal weight ( p = 0.020). Children belonging to the third and the fourth cotinine quartile compared to those of the first quartile had higher 15-F2t IsoP (1.45 ng/mg, 95% CI: 1.06⁻1.97, p = 0.020 and 2.04 ng/mg, 95% CI: 1.55⁻2.69, p < 0.0001, respectively). Obesity assessment in children requires appropriate BMI reference depending on research field. Both SHS exposure and obesity may increase OS in children.