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.

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma.