Background: miRNAs are master regulators of signaling pathways critically involved in asthma and are transferred between cells in extracellular vesicles (EV). We aimed to investigate whether the miRNA content of EV secreted by primary normal human bronchial epithelial cells (NHBE) is altered upon asthma development.Methods: NHBE cells were cultured at air‐liquid interface and treated with interleukin (IL)‐13 to induce an asthma‐like phenotype. EV isolations by precipitation from basal culture medium or apical surface wash were characterized by nanoparticle tracking analysis, transmission electron microscopy, and Western blot, and EV‐associated miRNAs were identified by a RT‐qPCR‐based profiling. Significant candidates were confirmed in EVs isolated by size‐exclusion chromatography from nasal lavages of children with mild‐to‐moderate (n = 8) or severe asthma (n = 9), and healthy controls (n = 9).Results: NHBE cells secrete EVs to the apical and basal side. 47 miRNAs were expressed in EVs and 16 thereof were significantly altered in basal EV upon IL‐13 treatment. Expression of miRNAs could be confirmed in EVs from human nasal lavages. Of note, levels of miR‐92b, miR‐210, and miR‐34a significantly correlated with lung function parameters in children (FEV₁FVC_%pred and FEF_25‐75%pred), thus lower sEV‐miRNA levels in nasal lavages associated with airway obstruction. Subsequent ingenuity pathway analysis predicted the miRNAs to regulate Th2 polarization and dendritic cell maturation.Conclusion: Our data indicate that secretion of miRNAs in EVs from the airway epithelium, in particular miR‐34a, miR‐92b, and miR‐210, might be involved in the early development of a Th2 response in the airways and asthma.

Due to the complex interplay among different urban-related exposures, a comprehensive approach is advisable to estimate the health effects. We simultaneously assessed the effect of “green”, “grey” and air pollution exposure on respiratory/allergic conditions and general symptoms in schoolchildren. This study involved 219 schoolchildren (8–10 years) of the Municipality of Palermo, Italy. Data were collected through questionnaires self-administered by parents and children. Exposures to greenness and greyness at the home addresses were measured using the normalized difference vegetation index (NDVI), residential surrounding greyness (RSG) and the CORINE land-cover classes (CLC). RSG was defined as the percentage of buffer covered by either industrial, commercial and transport units, or dump and construction sites, or urban fabric related features. Two specific categories of CLC, namely “discontinuous urban fabric - DUF” - and “continuous urban fabric - CUF” - areas were found. Exposure to traffic-related nitrogen dioxide (NO2) was assessed using a Land-Use Regression model. A symptom score ranging from 0 to 22 was built by summing affirmative answers to twenty-two questions on symptoms. To avoid multicollinearity, multiple Logistic and Poisson ridge regression models were applied to assess the relationships between environmental factors and self-reported symptoms. A very low exposure to NDVI ≤0.15 (1st quartile) had a higher odds of nasal symptoms (OR = 1.47, 95% CI [1.07–2.03]). Children living in CUF areas had higher odds of ocular symptoms (OR = 1.49, 95% CI [1.10–2.03]) and general symptoms (OR = 1.18, 95% CI [1.00–1.48]) than children living in DUF areas. Children living in proximity (≤200 m) to High Traffic Roads (HTRs) had increased odds of ocular (OR = 1.68, 95% CI [1.31–2.17]) and nasal symptoms (OR = 1.49, 95% CI [1.12–1.98]). A very high exposure to NO2 ≥ 60 μg/m3 (4th quartile) was associated with a higher odds of general symptoms (OR = 1.28, 95% CI [1.10–1.48]). No associations were found with RGS. A Poisson ridge regression model on the symptom score showed that children living in proximity to HTRs (≤200 m) had a higher symptoms score (RR = 1.09, 95% CI [1.02–1.17]) than children living > 200 m from HTRs. Children living in CUF areas had a higher symptoms score (RR = 1.11, 95% CI [1.03–1.19]) than children living in DUF areas. Multiple exposures related to greenness, greyness (measured by CORINE) and air pollution within the urban environment are associated with respiratory/allergic and general symptoms in schoolchildren. No associations were found when considering the individual exposure to greyness measured using the RSG indicator.

Environmental exposures across the life course may be a contributor to the increased worldwide prevalence of respiratory and allergic diseases occurring in the last decades. Asthma and rhinoconjunctivitis especially contribute to the global burden of disease. Greenness has been suggested to have beneficial effects in terms of reduction of occurrence of allergic respiratory diseases. However, the available evidence of a relationship between urban greenness and childhood health outcomes is not yet conclusive. The current review aimed at investigating the current state of evidence, exploring the relationship between children's exposure to residential urban greenness and development of allergic respiratory diseases, jointly considering health outcomes and study design. The search strategy was designed to identify studies linking urban greenness exposure to asthma, rhinoconjunctivitis, and lung function in children and adolescents. This was a narrative review of literature following PRISMA guidelines performed using electronic search in databases of PubMed and Embase (Ovid) from the date of inception to December 2018. Our search strategy identified 2315 articles; after exclusion of duplicates (n = 701), 1614 articles were screened. Following review of titles and abstracts, 162 articles were identified as potentially eligible. Of these, 148 were excluded following full-text evaluation, and 14 were included in this review. Different methods for assessing greenness exposure were found; the most used was Normalized Difference Vegetation Index. Asthma, wheezing, bronchitis, rhinoconjunctivitis, allergic symptoms, lung function, and allergic sensitization were the outcomes assessed in the identified studies; among them, asthma was the one most frequently investigated. The present review showed inconsistencies in the results mainly due to differences in study design, population, exposure assessment, geographic region, and ascertainment of outcome. Overall, there is a suggestion of an association between urban greenness in early life and the occurrence of allergic respiratory diseases during childhood, although the evidence is still inconsistent. It is therefore hard to draw a conclusive interpretation, so that the understanding of the impact of greenness on allergic respiratory diseases in children and adolescents remains difficult.

Knowledge on multiple interdependences between quality of life (QoL) and behavioural problems in relation to asthma severity and control is undetermined. The aims of the study were: (i) to assess the relationship of QoL and behavioural problems with asthma severity and control (ii) to predict children’s “abnormal/borderline” status with variation in QoL. For these purposes a multicenter case-control study on 47 Severe Asthma (SA) and 94 Moderate Asthma (MA) children was performed. The MIMIC approach was applied to investigate the effect of SA and non-controlled asthma (NC) on QoL and behavioural disorders. Logistic regression was used to estimate probabilities of having an “abnormal/borderline” status with variation in QoL. The MIMIC model showed that the magnitude of the effect of SA and NC was larger on QoL (β = −0.37 and β = −0.30, respectively) than on behavioural problems (β = 0.27). With regards to the probability of having a borderline status, in MA a QoL of 1 returned a probability of 0.81, whereas in SA a QoL of 1 returned a probability of 0.89. In conclusion, SA children are highly affected by impaired QoL and behavioural problems. The MIMIC model allowed us to obtain a comprehensive assessment of QoL and behavioural problems with asthma severity and control.

To summarize the main updated evidence about the health effects of air pollution and to focus on Italian epidemiological experiences on the respiratory effects. the recent literature indicates that there is strong evidence for causal relationships between PM_2.5 air pollution exposure and all-cause mortality as well as mortality from acute lower respiratory infections, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer. A growing body of evidence also suggests causal relationships with type II diabetes and impacts on neonatal mortality from low birth weight and short gestation as well as neurologic effects in both children and adults. Italy, a Southern European country, faces a more threatening air pollution challenge because of the effects of both anthropogenic pollutants and natural dust (particulate matter, PM). The 2020 Report of the European Environment Agency highlighted the number of premature deaths in Italy attributable to main pollutants: 52,300 for PM_2.5, 10,400 for NO₂ and 3,000 for O₃ in 2018. In Italy, original time series and analytical epidemiological studies showed increased cardio-respiratory hospital admissions and mortality and increased risk of respiratory diseases in people living in urban areas. adverse health effects of air pollutants, even at low levels, have been confirmed by recent epidemiological studies. Further studies should focus on the potential link between air pollution exposure and respiratory infections. This topic has become particularly important in the current SARS-COV-2 pandemic. Based on strong scientific evidence, the Italian government, which hosts the Global Alliance against Chronic Respiratory Diseases (GARD)-Italy at the Ministry of Health, the scientific respiratory societies and the patients' associations, as well as others in the health sector and civil society, must increase their engagement in advocacy for clean air policies, especially in light of the new Air Quality Guidelines of the World Health Organization.

Background: Repeatability and reproducibility are essential for clinicians for several purposes. Although discouraged, use of the Coefficient of Variation (CV) for assessing repeatability and reproducibility, rather than the Intraclass Correlation Coefficient (ICC), is still widespread. The aim of the present study was to highlight how using inappropriate indices may lead to misleading results, and this is done by simulation study and using real data on Anterior Active Rhinomanometry (AAR) in both healthy children and ones with rhinitis.Methods: A simulation study was carried out to highlight how using inappropriate indices could be misleading. Then a comparison was made between CV and ICC to assess repeatability and reproducibility of AAR, for which previous studies have given underestimated results. AAR is recommended as the gold standard tool for measuring nasal resistance in clinical practice.Results: A simulation study showed that the ICCs estimated from data generated assuming a true CV yielded results in agreement with estimated CVs; by contrast, if data were generated assuming a true ICC, CVs yielded conflicting results. For AAR, ICCs showed good repeatability, whereas CVs showed unacceptable repeatability. AUC and 95% CI for AAR showed good performance in predicting current symptoms of rhinitis in the overall study population.Conclusions: The present study focused on the importance of the choice of appropriate indices of repeatability and reproducibility, demonstrating the repeatability of AAR in both healthy children and ones with rhinitis.Trial registration: ClinicalTrials.gov(ID:NCT03286049; Registration Date: September 15, 2017; Actual Study Start Date: January 10, 2018).