Introduction: Exposure to environmental pollutants such as diesel exhaust particles (DEP) increases the risk of respiratory disease exacerbation. However, the possible effects of these particles on the general population remain poorly understood. The present study aimed to assess the immunomodulatory and inflammatory effects of the inhalation of DEP in a model of healthy mice undergoing short-, mid- and long-term exposure. Materials and Methods: BALB/c ByJ mice were randomly divided into five experimental groups. The control group received three intranasal instillations of saline over 8 days while the other four groups received intranasal instillations of 150 µg of DEP 3 days per week for 8, 17, 26, and 53 days. Lung function assessment and flow cytometry were performed. Results: In lung tissue, intranasal exposure to DEP decreased total monocytes (p < 0.015 in all groups). At 26 days, a reduction in inflammatory monocytes and an increase in resident monocytes were observed, p = 0.001 and 0.0001, respectively. Eosinophils and neutrophils decreased at 26 days (p = 0.017 and p = 0.041, respectively). The intranasal challenges of DEP increased the total population of dendritic cells (DC) at 26 and 53 days (p = 0.017 and p = 0.022, respectively) and decreased the total and alveolar populations of macrophages (p < 0.003 for all groups compared to control), while interstitial macrophage populations increased over the time period (p = 0.0001 for all groups compared to control). Conclusions: Continuous DEP exposure triggers immune mechanisms that predispose healthy individuals to a pro-inflammatory and hyper-reactive microenvironment. This mouse model provides evidence of the capacity of DEP to increase DC, interstitial macrophages, and resident monocytes.

The lockdown imposed to combat the COVID-19 pandemic produced a historic fall in air pollution in cities like Barcelona. This exceptional situation offered a unique context in which to examine the effects of air pollutants on human health. The present study aims to determine and compare the oxidative stress biomarkers Th1/Th2 and inflammatory-related cytokines in healthy individuals first during lockdown and then six months after the easing of the restrictions on mobility. A prospective study of a representative sample of 58 healthy, non-smoking adults was carried out. During lockdown and six months post-easing of restrictions, blood samples were drawn to measure the percentage of eosinophils, levels of Th1/Th2 and inflammatory-related cytokines assessed by a multiplex assay (BioRad Laboratories S.A., Marnes-la-Coquette, France), and levels of 8-isoprostane, glutathione peroxidase activity, and myeloperoxidase (Cayman Chemical Co., Ann Arbor, MI, USA), to assess their value as biomarkers of oxidative stress. Six months after easing mobility restrictions, increases in the levels of 8-isoprostane (p < 0.0001), IL-1β (p = 0.0013), IL-1ra (p = 0.0110), IL-4 (p < 0.0001), IL-13 (p < 0.0001), G-CSF (p = 0.0007), and CCL3 (p < 0.0001) were recorded, along with reductions in glutathione peroxidase (p < 0.0001), IFN-γ (p = 0.0145), TNFα (p < 0.0001), IP-10 (p < 0.0001), IL-2 (p < 0.0001), IL-7 (p < 0.0001), basic FGF (p < 0.0001), CCL4 (p < 0.0001), and CCL5 (p < 0.0001). No significant differences were observed in the rest of the biomarkers analyzed. The reduction in environmental pollution during the COVID-19 lockdown significantly lowered the levels of oxidative stress, systemic inflammation, and Th2-related cytokines in healthy people.

Introduction: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) affecting genetically predisposed individuals following recurrent inhalation of environmental antigens. The aim of the study is to evaluate YKL-40 and KL-6 as markers of exposure and progression in patients with HP caused by the inhalation of bird or fungal antigens. Materials and methods: Patients were classified into progressive (n=18) and non-progressive HP (n=73) using ATS 2022 criteria in relation to patients with ILD. A population of park workers (n=74) was used as control group. Serum levels of KL6 and YKL-40 were determined as well as IgG antibodies specific to: pigeon, parrot, Aspergillus sp. and Penicillium sp. Results: Serum KL6 levels were higher in the progressive HP group than in the non-progressive HP and control groups (p=0.0401 and p<0.0001, respectively). In patients with non-progressive HP, KL6 was also increased than the control group (p<0.0001). Serum YKL-40 levels were higher in HP patients with and without progression than in the control group (p<0.0001). Significant higher levels of specific IgGs to Penicillium sp and parrot were observed in both HP patient groups (progressive and non-progressive) than in the control group (p=0.0010 and 0.0017 for Penicilium sp and p=0.0347 and p<0.0001 for parrot). Conclusion: KL-6 and YKL-40 can be used as a biomarkers of diagnosis in patients with HP besides KL-6 can be used as a biomarker of progression. In all groups a high exposure to pigeon, parrot, Aspergillus sp. and Penicilium sp. was observed. Funded by: European Union's Horizon 2020 research and innovation programme under grant agreement No 874707.

Introduction: Exposure to road traffic air pollutants (TRAP) has been associated with worsening asthma symptoms and increased inflammatory responses. MicroRNAs (miRNAs) regulate gene expression and participate in the pathophysiology of asthma by modulating immune responses. This study aims to compare miRNA expression profiles in asthmatic patients and healthy controls exposed to polluted and unpolluted environments and to identify miRNAs related to TRAP exposure. Methods: 20 asthmatic patients and 15 healthy were exposed for two hours to an urban area with a high TRAP concentration and, in a separate session, to an unpolluted area. Levels of PMX, NOx, CO were measured and lung function was assessed in each exposure. Blood samples were collected for miRNA sequencing, differentially expressed miRNAs were validated by qPCR and pathway enrichment studies were performed. Results: Pollutants concentrations were significantly higher in the pollutend area (p<0.05). Short-term exposure to TRAP induced distinct changes in miRNA profiles in both healthy individuals and asthmatic patients. In healthy controls, miR-30c-5p, miR-4286, and miR-365a-3p increased significantly after exposure to TRAP. In contrast, asthmatic patients had lower expression of miR-15a-5p, miR-101-3p, and miR-365a-3p compared to healthy individuals after exposure to TRAP. Conclusions: TRAP exposure induces different miRNA expression profiles in healthy individuals and asthmatic patients. This exposure was associated with the activation of adaptive immune mechanisms, which could contribute to asthma exacerbation and biological changes even in people without respiratory disease. Funded by FUCAP, Carlos III Health Institute (PI21/01346), European Regional Development Fund (FEDER) and SEPAR.