Exposure to cigarette smoke, allergens, viruses, and other environmental contaminants, as well as a detrimental lifestyle, are the main factors supporting elevated levels of airway oxidative stress. Elevated oxidative stress results from an imbalance in reactive oxygen species (ROS) production and efficiency in antioxidant defense systems. Uncontrolled increased oxidative stress amplifies inflammatory processes and tissue damage and alters innate and adaptive immunity, thus compromising airway homeostasis. Oxidative stress events reduce responsiveness to corticosteroids. These events can increase risk of asthma into adolescence and prompt evolution of asthma toward its most severe forms. Development of new therapies aimed to restore oxidant/antioxidant balance and active interventions aimed to improve physical activity and quality/quantity of food are all necessary strategies to prevent asthma onset and avoid in asthmatics evolution toward severe forms of the disease.

Mothers’ knowledge about childhood asthma influences management practices and disease control, but validating knowledge/practice questionnaires is difficult due to the lack of a gold standard. We hypothesized that Latent Class Analysis (LCA) could help identify underlying mother profiles with similar knowledge/practices. A total of 438 mothers of asthmatic children answered a knowledge/practice questionnaire. Using answers to the knowledge/practice questionnaire as manifest variables, LCA identified two classes: Class 1, “poor knowledge” (33%); Class 2, “good knowledge” (67%). Classification accuracy was 0.96. Mothers in Class 2 were more likely to be aware of asthma-worsening factors and indicators of attacks. Mothers in Class 1 were more likely to prevent exposure to tobacco smoke (91.1% vs. 78.8%, p = 0.005). For attacks, mothers in Class 2 were more likely to go to the emergency department and follow the asthma action plan. Mothers in Class 2 more frequently had a high education level (79.5% vs. 65.2%, p = 0.004). Children in Class 2 more frequently had fully controlled asthma (36.7% vs. 25.9%, p = 0.015) and hospitalizations for attacks in the previous 12 months (24.2% vs. 10.7%, p = 0.003). LCA can help discover underlying mother profiles and plan targeted educational interventions.

Identifying asthma comorbidities in children is fundamental for improving disease management. We aimed to investigate the frequency of allergy-related comorbidities in children and adolescents with asthma, and to identify associated risk factors and disease burden. Between September 2015 and December 2018, 508 asthmatic patients (5–17 years) were consecutively enrolled. Parents answered a standardized questionnaire on the history of disease and risk factors. Comorbidities were classified based on the involvement of respiratory and/or extra-respiratory districts: asthma only (A, 13%), asthma with respiratory comorbidities (AR, 37%), asthma with extra-respiratory comorbidities (AER, 10%), and asthma with both respiratory and extra-respiratory comorbidities (ARER, 40%). Multinomial logistic regression showed that membership in the AR group was significantly associated with a maternal history of asthma (OR = 3.08, 95% CI: 1.23–7.72), breastfeeding ≥ three months (OR = 1.92, 1.06–3.46), early mold exposure (OR = 2.39, 1.12–5.11), and current environmental tobacco smoke exposure (OR = 2.06, 1.11–3.83). Membership in the AER group was significantly associated with the female gender (OR = 3.43, 1.54–7.68), breastfeeding ≥ three months (OR = 2.77, 1.23–6.22). ARER was significantly associated with all the aforementioned exposures. Patients with AR reported exacerbations in the last 12 months more frequently (p = 0.009). Several personal and environmental risk factors are associated with comorbidities in asthmatic children and adolescents, possibly worsening the disease burden.

Personalized medicine, an approach to care in which individual characteristics are used for targeting interventions and maximizing health outcomes, is rapidly becoming a reality for many diseases. Childhood asthma is a heterogeneous disease and many children have uncontrolled symptoms. Therefore, an individualized approach is needed for improving asthma outcomes in children. The rapidly evolving fields of genomics and pharmacogenomics may provide a way to achieve asthma control and reduce future risks in children with asthma. In particular, pharmacogenomics can provide tools for identifying novel molecular mechanisms and biomarkers to guide treatment. Emergent high-throughput technologies, along with patient pheno-endotypization, will increase our knowledge of several molecular mechanisms involved in asthma pathophysiology and contribute to selecting and stratifying appropriate treatment for each patient.

Macrophage polarization is a dynamic process through which macrophages acquire specific features whose extremes are represented by M1 and M2 polarization. Interleukin (IL)-6, IL-1β, IL-12 and IL-8 belong to M1 macrophages while transforming growth factor-beta (TGF-β belongs to M2 cytokines. M2 polarization prevalence is observed in allergic diseases. Tyndallization is a thermal process able to inactivate microorganisms and to allow their use for chronic respiratory disease treatment via immune response modulation. The present study explores the effects of a blend of tyndallized bacteria (TB) on macrophage polarization. THP-1-derived macrophages were exposed to different concentrations of TB (10⁶, 5 × 10⁶, 10⁷, 5 × 10⁷, 10⁸ CFU/mL) and then cell viability and TB phagocytosis, and IL-8, IL-1β, IL-6, IL-12 and TGF-β1 gene expression and release were assessed. TB were tolerated, phagocyted and able to increase IL-8, IL-1β and IL-6 gene expression and release IL-12 gene expression, as well as decrease TGF-β1 gene expression and release. The effects on IL-8, IL-6 and TGF-β1 release were confirmed in human monocyte-derived macrophages (hMDMs) exposed to TB. In conclusion, TB promote M1 polarization, and this mechanism might have valuable potential in controlling allergic diseases and infections, possibly preventing disease exacerbations.

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.