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.

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 NO₂, PM₁₀, PM_2.5, and O₃ 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 NO₂ (β: 0.30 95 % CI: 0.08-0.52 and 0.20 95 % CI: 0.03-0.37), PM₁₀ (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 O₃. 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.

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.

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/m³) and non-employers (13.5 μg/m³). 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.

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.

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.