Ambient air pollution remains a major public health concern in Europe despite recent improvements. This systematic review synthesizes evidence (2020-2025) on short- and long-term effects of PM10, PM2.5, NO₂ and O₃ on cause-specific mortality, integrating Italian BEEP and BIGEPI projects with European studies for the first time. Searches of PubMed, Web of Science, and Scopus (to 31 July 2025) identified 31 studies; meta-analyses were conducted when ≥ 5 studies were available (18 studies included for PM2.5). Risk of bias was assessed using ROBINS-E (v1, June 2023) by two independent reviewers. PM2.5 was significantly associated with mortality: all-cause RR ≈ 1.10 per 10 µg/m³ (I²=97.9%), cardiovascular RR = 1.026 (95%CI 1.014-1.039; I²=91.7%), and respiratory RR = 1.032 (95%CI 1.013-1.050; I²=88.3%), with stronger effects for long-term exposure. Long-term PM2.5 and NO₂ exposures were consistently linked to increased all-cause, cardiovascular, and respiratory mortality; PM10 showed weaker associations. Short-term increases in PM and NO₂ were associated with acute mortality rises, while O₃ evidence was heterogeneous. Limitations include substantial heterogeneity (I² 78-98%), evidence of small-study effects (Egger p < 0.05), and risk of bias rated "Some concerns" in most studies (16/18). Overall, air pollution continues to impose a measurable mortality burden in Europe, supporting stricter standards aligned with WHO guidelines. Funding: PNC PREV- A-2022-12376981.

Background and Objective:Fractional exhaled nitric oxide (FeNO) is a biomarker of type-2 lung inflammation. Standardized measurement is essential for accurate diagnosis and monitoring. We assess seasonality and environmental determinants of FeNO in individuals with and without chronic respiratory diseases in the general population. Methods:This is a cross-sectional study on 412 individuals with chronic respiratory diseases (asthma, chronic bronchitis/chronic obstructive pulmonary disease, rhinitis) and 605 individuals without these conditions. Participants, aged 20-65 years, were recruited in the Gene-Environment Interactions in Respiratory Diseases study in Verona, Italy (2008-2014). Geocoded residential addresses were linked to daily PM10 and air temperature at the time of the clinical examination using previously developed spatiotemporal models. Associations with log-FeNO were analyzed using adjusted linear regression, accounting for seasonality and disease status. Results:FeNO levels were higher in subjects with respiratory diseases during the warm season, even after adjusting for pollen exposures; a milder seasonal pattern was observed in subjects without chronic respiratory diseases (P for interaction = 0.001). A 10 μg/m3 increase in mean PM10 concentration at lag 0-1 (day of FeNO measurement and day before) was associated with a 3% higher FeNO concentration (Ratio of Geometric Means, RGM: 1.03, 95% confidence interval: 1.00, 1.06) after adjusting for seasonality. Conclusion:FeNO is a sensitive biomarker of environmental exposures. Overlooking seasonality and environmental factors might impact clinical decision-making in chronic respiratory diseases.

Sites of National Interest for Remediation (SNIs) are characterised by contamination of soil and groundwater by numerous hazardous substances with concentrations that exceed environmental risk thresholds for human health; furthermore, air pollution is a non-negligible risk factor. The aim of this study is to perform an Integrated Environmental and Health Impact Assessment (IEHIA) tool to estimate the air pollution impacts on human health in the areas hosting the four Tuscan SNIs (period 2013–2022). For each pollutant considered (PM2.5, PM10, NO2) Population-Weighted Exposure (PWE) and Attributable Deaths (ADs) were calculated considering the difference between the PWE and the latest air quality guidelines suggested by the World Health Organization (2021-AQG). The PWE values for all the SNIs were 10.5 μg/m3, 19.1 μg/m3, and 18.3 μg/m3 for PM2.5, PM10, and NO2, respectively. The ADs from natural causes attributable to annual exposure to PM2.5, PM10, and NO2 were 229, 92, and 90, respectively. The results highlighted higher levels of PWE than the 2021-AQG with ADs accounting approximately 5

BACKGROUND:The long-term evolution of COVID-19 in patients hospitalized during the pandemic's first wave remains largely unexplored. This study aimed to identify COVID-19 pulmonary phenotypes and their longitudinal patterns over a 12-month follow-up. METHODS:COVID-19 patients discharged from Pisa University Hospital (Italy) between March-September 2020, were evaluated at T3, T12, and T24 months post-discharge. Assessments included spirometry, lung volumes, DLCO, and chest CT for those with persistent pneumonia signs (PS). Latent transition analysis (LTA) identified COVID-19 phenotypes and longitudinal patterns based on PS and lung function (PFTs). Risk factors for these patterns were evaluated using multinomial logistic regression. RESULTS:Of 307 discharged patients, 175, 136, and 33 were followed-up at T3, T12, and T24, respectively. At T12, 21.6 % had impaired DLCO, 4.4 % a restrictive ventilatory pattern, and 31,6 % still had PS, persisting until T24. LTA identified three cross-sectional phenotypes at both T3 and T12 (no PS with normal PFTs; PS with normal PFTs; PS with impaired PFTs), and four longitudinal patterns from T3 to T12: persistence of no PS with normal PFTs (47.9 %); resolution of both PS and PFTs (15.4 %); persistent PS (36.7 %), either with (11 %) or without (25.7 %) impaired PFTs. The last two patterns correlated significantly with longer hospitalization, more comorbidities, and severe COVID-19. CONCLUSIONS:In our cohort of COVID-19 patients hospitalized during the pandemic's first wave, we observed distinct pulmonary phenotypes and longitudinal recovery patterns. More comorbidities and severe acute disease correlated with worse progression up to 24 months, suggesting long-term monitoring for such patients.

BACKGROUND:Evidence on the association between endotoxin exposure and respiratory health in children remains inconsistent, with limited research addressing school environments-key settings for daily exposure. This study investigates the relationship between classroom endotoxin levels and respiratory health among European schoolchildren. METHODS:Within the EU-funded SINPHONIE project, endotoxin concentrations were measured in 285 classrooms across 102 schools in 22 European countries. A total of 5,140 children completed a standardized health questionnaire; 4,633 had endotoxin data, 4,170 performed spirometry, and 746 underwent fractioned exhaled nitric oxide (FeNO) testing. FINDINGS:Endotoxin levels varied geographically, with the highest averages in Italy and the lowest in Finland. After adjusting for confounders, exposure to endotoxin levels at or above the median was associated with higher odds of upper and lower respiratory symptoms-runny nose, nasal obstruction, cough, dry throat, breathing difficulty, and feverishness-as well as reduced lung function (p < 0.05). Meta-analysis by WHO European clusters confirmed these associations, though region-specific analyses indicated a possible protective effect of endotoxin exposure in Northern Europe. INTERPRETATION:Findings from SINPHONIE highlight classroom endotoxin as a potential environmental determinant of respiratory health. Reducing exposure in schools-currently an overlooked setting-may support respiratory well-being in children and inform future public health policies.

Background Emphysema Severity Index (ESI) is a recently developed parameter describing the curvilinear shape of the expiratory flow/volume curve to evaluate the emphysema contribution to airflow obstruction (AO), as observed in COPD patients and geriatric populations. Aim to assess ESI usefulness in respiratory epidemiology studies where spirometry is typically the only available objective tool. Methods an adult population sample of Pisa (Central Italy) (n= 685, 47.3% males, mean age 53.3 years) participated in an epidemiological survey through standardized questionnaire and spirometry (2009–11); information on hospital admissions was available up to 2017. The input variables for the ESI computing algorithm are Peak Expiratory Flow, Forced Vital Capacity (FVC) and the Forced Expiratory Flows at 25%, 50%, and 75% of FVC. ESI is a numerical value ranging from 0 (no emphysema) to 10 (very severe emphysema). Statistics included descriptive analyses, Kruskas-Wallis nonparametric test and logistic regression models. Results ESI value was: 1.16±0.78 (mean± sd ), 0.98–0.39 (median- interquartile range IQR). ESI had significantly higher values in males, ex-smokers, elderly, subjects with asthma/COPD, and in those with limited daily activities, higher numbers of doctor visits, and hospital admission for respiratory disease. For each increment of an ESI IQR, higher odds of respiratory outcomes, daily activity limitations, and use of health services emerged in the total sample, but also in subjects without AO. Conclusions ESI represents a potentially valuable indicator in epidemiological surveys on the general population and allows to identify early changes in lung function also in subjects without AO, valuable for secondary prevention.

Background: Overweight and obesity frequently occur as comorbid conditions in people with asthma, particularly among those with poor disease control or more severe clinical profiles. However, the extent to which exposure to grey spaces may influence the link between overweight/obesity and asthma remains insufficiently explored. Aim: To assess the association between overweight/obesity and asthma in an Italian general population sample and the influence of residential grey space on such relationship. Methods: A total of 2841 individuals (54.7% women; age range 8–97 years) residing in Pisa, Italy, were surveyed in 1991–1993 using a standardised questionnaire on health conditions and relevant risk factors. The proportion of grey space within a 1000 m buffer around each participant’s home was quantified using the CORINE Land Cover database. Multinomial logistic regression models were applied to assess the association between asthma status (1. asthma symptoms without doctor diagnosis, 2. diagnosis ± symptoms, 3. no diagnosis/symptoms − reference category) and overweight/obesity, adjusting for sex, age, educational level, smoking, physical activity and grey space exposure. Analyses were further stratified according to high vs. low grey space exposure (above vs. below 63%, corresponding to the second tertile). Mediation and interaction analyses were also performed. Results: The prevalence of asthma diagnosis ± symptoms, overweight and obesity was 18.7%, 35.8% and 12.8%, respectively. In the full sample, asthma symptoms without medical diagnosis were positively associated with overweight (Odds Ratio—OR 1.43; 95% Confidence Interval—CI 1.08–1.88), obesity (OR 1.99; 95% CI 1.38–2.88) and residential grey space (OR 1.06; 95% CI 1.01–1.13). Stratified models showed that, among participants with high exposure to grey areas, asthma symptoms were linked to both overweight (OR 2.03; 95% CI 1.29–3.19) and obesity (OR 2.57; 95% CI 1.36–4.86). In individuals with low grey space exposure, an association was observed only with obesity (OR 1.80; 95% CI 1.15–2.82). Mediation analysis did not reveal any weight-related effect modification. Measures of additive interaction indicated that 32% of asthma symptoms were attributable to the interaction between excess body weight and high grey space exposure. Conclusions: This study showed that overweight/obesity and grey space exposure are factors associated with asthma symptoms. These findings advocate for an early identification of overweight/obese-asthma symptom phenotype since it may help prevent the onset or worsening of asthma, particularly in urban environments. These insights highlight the need for integrated public health and urban planning strategies to promote more sustainable, health-supportive environments.

BACKGROUND:Recent evidence showed that 50% of chronic obstructive pulmonary disease (COPD) may be attributable to air pollution. We aimed to investigate the association between long-term air pollution exposure and COPD symptoms/diagnosis in an Italian epidemiological study. METHODS:A total of 14 420 adults living in Ancona, Pavia, Pisa, Sassari, Turin and Verona were investigated in 2005-2011. Data on risk factors and health outcomes were collected by questionnaires; mean annual concentrations of particulate matters (PM) like PM10 and PM2.5 as well as NO2 and mean summer concentrations of O3 (µg/m3) at residential level with a 1 km resolution (period 2013-2015) were obtained by machine learning techniques. The relationship of pollutant exposure and COPD prevalence was assessed by logistic regression models (single pollutant) and principal component logistic regression models (multipollutant) adjusting for sex, age, education level, smoking habits, season of interview, and city-specific climatic index and including a random intercept for cohorts. RESULTS:A 10 µg/m3 increase of PM10, PM2.5 and NO2 exposure was related to COPD diagnosis and symptoms (OR 1.31, 95% CI 1.03 to 1.65 for PM2.5; OR 1.26, 95% CI 1.03 to 1.54 for PM10 and OR 1.07, 95% CI 1.00 to 1.15 for NO2) using a multipollutant approach. Similar results emerged for dyspnoea (OR 1.24, 95% CI 1.05 to 1.47 for PM2.5; OR 1.21, 95% CI 1.05 to 1.39 for PM10 and OR 1.06, 95% CI 1.01 to 1.11 for NO2). Associations between COPD symptoms and summer O3 were less clear. By multipollutant models, OR estimates were lower than those by single pollutant models. CONCLUSIONS:Further evidence about the relationship between air pollution and respiratory effects in Italian adults was provided indicating PM as the main driver.

Job-related exposures play a significant, often disregarded, role in respiratory outcome development. Evaluating how this exposure impacts the incidence of respiratory illnesses in the general population is crucial for prevention and occupational health surveillance. A total of 823 workers/ex-workers from ​​Pisa (Italy) participated in 2 surveys over 18 years (PI2 1991-93, PI3 2009-11). Health status, occupational sector, and individual risk factors were assessed through a questionnaire; airway obstruction (AO) by spirometry. Exposure was defined as working for at least 3 months in a sector at risk for respiratory diseases at PI2. Cumulative incidence was calculated as "incident cases/population at risk". The relationship between outcome incidence and occupational exposure was assessed through multiple logistic regressions adjusted for baseline (PI2) risk factors. Analysis of covariance estimated the effect of occupational exposure on changes in FEV1/FVC over time. Associations were found among occupational exposure and outcome incidence: agriculture for usual cough/phlegm (OR 2.16, 90% CI 1.17-3.99) and AO ( 3.06, 1.14-8.24); mining industry/quarries/excavation for attacks of shortness of breath with wheezing (SOBWHZ) (2.41, 1.16-5.02) and AO (2.95, 1.20-7.26); textile industry for asthma (2.61, 1.00-6.79), chronic obstructive pulmonary disease (COPD) (2.56, 1.35-4.85), SOBWHZ (3.09, 1.57-6.06) and wheezing (2.00, 1.00-3.97); wood industry for asthma (3.16, 1.21-8.26); mechanical industry for AO (2.34, 1.06-5.18). Agriculture and mining industry/quarries/excavation were also related to a greater decrease in the FEV1/FVC values. Longitudinal analyses confirm that employment in high-risk sectors, particularly the textile industry, is a significant determinant of respiratory disease incidence and lung function decline.

Introduction:Within the framework of the SINPHONIE study, this study aimed to examine the dose-response relationship between increasing endotoxin concentrations and reduced lung function parameters, seeking potential threshold effects and accounting for regional differences. Methods:Spirometry data from 3870 schoolchildren across 21 European countries were analysed to assess the impact of endotoxin exposure on lung function parameters. A general additive model was applied, adjusting for country, age, height, weight and sex. Additionally, a linear regression model with random effects was employed, treating country as a panel variable. In that latter model, "asthma ever" was also included as a possible moderator of endotoxin effects. Results:For most parameters, a linear decline in lung function was observed with increasing endotoxin levels, with no clear threshold effect. For example, forced expiratory volume in 1 s decreased by 4.8 mL per an increase in endotoxin concentration of 1000 EU·m-2 and peak expiratory flow by 10 mL·s-1 (both p<0.001). However, some parameters showed a plateau at higher endotoxin concentrations. The association remained mostly unchanged and statistically significant across most spirometry values except for forced vital capacity, when adjusting for country as a panel variable. "Asthma ever" was reported for 272 (7.3%) of 3737 children. While these children performed significantly worse in the lung-function test, "asthma ever" did not increase vulnerability to endotoxin. Conclusion:The school environment in general and endotoxin levels in particular, have an impact on children's respiratory health, calling for additional efforts for improvements, including improved cleaning measures and ventilation.

BACKGROUND AND OBJECTIVE:There are few population-based longitudinal studies on the relationship of the single breath nitrogen (SBN2) test (which functionally explores the small airways) with pulmonary diffusing capacity for carbon monoxide (DLCO). This study aimed to evaluate whether the slope of phase 3 (N2-slope) from the SBN2 test may predict DLCO and DLCO/alveolar volume (KCO) decline, and whether the N2-slope and DLCO are related to COPD incidence. METHODS:Participants from an observational longitudinal population study underwent a SBN2 test at baseline, and DLCO and spirometry at both baseline and follow-up, 8 years apart. Multivariable regressions adjusted for sex, age, height, and smoking status were run: (1) linear regression to assess the association between N2-slope and DLCO or KCO decline; (2) logistic regression to assess the association between patterns of baseline normal/abnormal N2-slope/DLCO and COPD incidence (both GOLD and ATS-ERS criteria). RESULTS:Six hundred and eighty-seven participants (54.6% males, mean age 37.0 years) showed a mean DLCO decline of -0.12 ± 0.76 mL/mmHg/min/year, a mean KCO decline of -0.03 ± 0.12 mL/mmHg/min/L/year, COPD incidence of 9.0% (GOLD) and 3.9% (ATS-ERS). The N2-slope was significantly associated with DLCO and KCO decline (-0.137 mL/mmHg/min/year and -0.014 mL/mmHg/min/L/year, respectively, for a one-unit change in N2-slope). Participants with abnormal N2-slope and DLCO had the highest risk of developing COPD as measured by GOLD and ATS-ERS criteria (RR 4.42, 95% CI 1.20-16.26, and 6.68, 95% CI 1.48-30.23, respectively). CONCLUSION:In this longitudinal population study, the N2-slope is a predictor of DLCO and KCO decline, and abnormal N2-slope combined with abnormal DLCO is related to COPD development.

Background: Pesticides are used to control pests, but they are toxic and may severely harm children's health. We assessed health outcomes in Italian children living close to cultivations sprayed with pesticides. Method: In 2011-2012, 2,367 schoolchildren (6-14 years) living in eight Italian cities participated in the Indoor-School observational study. Parents filled in a standardised questionnaire on children's health and related risk factors. Children were classified as exposed to pesticides if living close to cultivations sprayed with pesticides. The association between the last three months of respiratory, allergic or systemic symptoms and pesticide exposure was assessed by multinomial logistic regression models, accounting for host/environmental risk factors. Result: Overall, 14% of children were exposed to pesticides, with significant differences among geographical areas: 21.2% in Northern Italy, 11.6% in Central Italy, and 9.7% in Southern Italy. Pesticide exposure was significantly associated with having: 1) 'often': eye symptoms (OR 3.81, 95% CI 2.06-7.05), skin symptoms (OR 2.60, 95% CI 1.34-5.03), lower airway symptoms (OR 2.38, 95% CI 1.41-4.01), systemic symptoms (OR 1.56, 95% CI 0.96-2.53, borderline); 2) 'daily': upper airways symptoms (OR 2.25, 95% CI 1.25-4.07) and systemic symptoms (OR 2.76, 95% CI 1.43-5.34). Conclusions: Self-reported pesticide exposure was associated with respiratory, allergic or systemic symptoms in children. Public authorities should be aware of and intervene to mitigate this health risk.

Abstract Due to the increasing importance of exposome in environmental epidemiology, feasibility and usefulness of an Environmental Data Management System (EDMS) using Open Data was evaluated. The EDMS includes data from 10 European cities (Celje (Slovenia), Łódź (Poland), Manchester (UK), Palermo (Italy), Paris (France), Porto (Portugal), Regensburg (Germany), Reus (Spain), Rijeka (Croatia), Thessaloniki (Greece)) about external non-specific and specific exposome factors at the city or country level (2017–2020). Findings showed that the highest values of life expectancy were in Reus females (86 years) and Palermo males (81 years). UK had the highest obesity rate (28%), Croatia the highest prescribed drug consumption (62%), Greece and Portugal the highest smoking rates (37%, 42%) and daily alcohol consumption (21%), respectively. The most polluted cities were Thessaloniki for PM10 (38 µg/m3), Łódź for PM2.5 (25 µg/m3), Porto for NO2 (62 µg/m3) and Rijeka for O3 (92 µg/m3). Thessaloniki had the highest grey space (98%) and Łódź the highest cumulative amount of pollen (39,041 p/m3). The highest daily noise levels ≥ 55 dB was in Reus (81% to traffic) and Regensburg (21% to railway). In drinking water, arsenic had the highest value in Thessaloniki (6.4 µg/L), boron in Celje (24 mg/L) and lead in Paris (46.7 µg/L). Portugal and Greece showed the highest pesticide residues in food (7%). In conclusion, utilizing open-access databases enables the translation of research findings into actionable strategies for public health interventions.