Objective To synthesize existing evidence on the risk factors, preventive measures, and long-term outcomes of lower respiratory tract infections (LRTIs) in early childhood, and to identify key gaps in research and policy. Methods A systematic search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2000 and August 2025, supplemented by reports from WHO, UNICEF, and the Global Burden of Disease (GBD) database. Eligible studies included randomized controlled trials, cohort, case–control, and cross-sectional studies, as well as systematic reviews involving children aged 0–5 years. Studies focused solely on acute treatment or adult populations were excluded. Results Early-life LRTIs arise from interacting determinants, including prematurity, malnutrition, indoor air pollution, inadequate immunization, and socioeconomic inequities. Preventive strategies such as vaccination, maternal immunization, exclusive breastfeeding, micronutrient supplementation, and the use of clean fuels—significantly reduce childhood morbidity and mortality. Evidence also indicates long-term health consequences, including asthma, impaired lung function, neurodevelopmental delay, and increased cardiometabolic risk. Conclusions Early-life LRTIs represent both an acute health burden and a determinant of lifelong respiratory and systemic outcomes. Expanding equitable vaccination coverage, improving maternal and child nutrition, reducing environmental exposures, and strengthening health-system capacity are essential to mitigate both short- and long-term global impacts.

ABSTRACT Introduction Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome, is an anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis that can manifest with a wide spectrum of clinical presentations. Indeed, EGPA is characterized by eosinophil-rich inflammation and systemic necrotizing vasculitis affecting small-to-medium-size vessels of different organs. Cardiac involvement is associated with a poor prognosis, and it is mainly described in the form of myocardial eosinophilic infiltration. Aortic valve involvement of EGPA is exceedingly rare. Case study A 51-years-old man with eosinophilic severe asthma and chronic rhinosinusitis with nasal polyps presented to the Emergency Department with worsening dyspnea after a two months history of low-grade fever and malaise; home therapy included anti-IL-5 monoclonal antibody (100 mg every four weeks). At the Emergency Department, the patient developed cardiac arrest and, after advanced life support maneuvers, he underwent surgery for acute torrential aortic regurgitation. Results Pathological examination of native aortic valve showed widespread vasculitis with eosinophilic inflammatory infiltrate and ANCA antibodies (anti-MPO), previously negative, tested positive. A diagnosis of EGPA was therefore made, despite low blood eosinophils probably due to mepolizumab therapy. Mycophenolate mofetil and high dose mepolizumab (300 mg every 4 weeks) were started and the patient was discharged with full resolution of his clinical picture even at the three months follow-up visit. Conclusion To our knowledge, this is the first reported case demonstrating angioplasia and vasculitis on the aortic valve. Our case report shows the importance of appropriate mepolizumab dose to improve EGPA clinical outcomes; moreover, severe disease activity despite low dose mepolizumab could underline the role of alternative pathogenic mechanisms beyond IL-5 pathway, at least in some patients.

Objective The objective of this study is to describe and compare the clinical characteristics, treatment approaches, and associated comorbidities of patients with severe asthma across Greece, Southern Europe, and the global population. This comparative approach aims to enhance the understanding of region-specific differences and similarities among patients living with severe asthma. Methods Data from the International Severe Asthma Registry (ISAR) were analyzed across three cohorts: Greek, Southern European, and Global. Variables included demographics, baseline characteristics, age at asthma onset, medication use, lung function, exacerbation history, biomarkers, and comorbidities. Results A total of 16,063 patients from the global ISAR dataset, 3406 from Southern Europe, and 206 from Greece were included. Greek patients had a lower mean annual exacerbation rate (1.24 ± 1.67) compared with the global cohort (1.84 ± 2.58, p = 0.001) and Southern Europe (1.73 ± 2.56, p = 0.052). Uncontrolled asthma was most prevalent in Greece (60.32%) versus Southern Europe (35.58%, p < 0.001) and the global cohort (57.07%, p = 0.034). Long-term oral corticosteroid use was less frequent in Greece (24.73%) and in global cohort (21.50%, p = 0.287) than in Southern Europe (52.04%, p < 0.001). The prevalence of eosinophilic phenotype was high in all cohorts. However, in Greece, it was lower compared to Southern Europe (73.55% vs. 89.89% p < 0.001) and globally (73.55% vs. 83.34%, p = 0.011). Greek patients also demonstrated lower fractional exhaled nitric oxide (FeNO) levels and lower eosinophil counts than Southern Europe, along with reduced biologic therapy initiation (56.31%) compared to Southern Europe (74.02%, p < 0.001) but higher than global rates (48.40%, p = 0.024). Conclusions Regional differences in severe asthma underline the importance of tailored treatment approaches, and multidisciplinary management of comorbid conditions.

Background In addition to the established link between obesity and asthma, the precise role of adiposity, both total and central, as measured by waist-to-height ratio (WHtR), remains underexplored in pediatric asthma. We aimed to investigate the association between WHtR and asthma in United States (U.S.) children and adolescents. Methods This cross-sectional study included 34,957 participants aged 3–17 years from the National Health and Nutrition Examination Survey (NHANES, 1999–2020). Multivariable logistic regression models were used to assess the relationship between WHtR and asthma. Generalized additive models and two-piecewise logistic regression were employed to examine nonlinearity. Results A total of 5,847 (16.7%) children had asthma. Each 0.1-unit increase in WHtR was associated with a 25% higher odds of asthma (OR = 1.25, 95% CI: 1.20–1.30) after full adjustment. A nonlinear relationship was identified with an inflection point at WHtR = 0.467. Below this point, each 0.1-unit increase in WHtR was associated with a 61% increase in asthma odds (OR = 1.61, 95% CI: 1.38–1.88); above it, the increase was 18% (OR = 1.18, 95% CI: 1.11–1.24). Conclusion In U.S. children and adolescents, WHtR was positively associated with asthma prevalence in a nonlinear pattern. An elevated WHtR was associated with an increased risk of asthma.

Objective Asthma is a common chronic respiratory disease affecting people of all ages, but little is known about age-related differences in treatment strategies. The present study aims to explore age-related differences in inhaled corticosteroid (ICS) use and place of asthma management. Methods All Danish adults with a registered secondary care asthma diagnosis or active treatment (>1 redemption of ICS within 365 days) in 2021 were included. Individuals with chronic obstructive pulmonary disease and individuals who migrated or died during the observation period were excluded. Danish national registries provided all treatment data. Results A total of 184,565 patients with asthma (median age 57 [IQR 43–69], 59% female) were included. Overall, 15.7% of the asthma population was treated with high (>800–1600 budesonide-equivalent ug/day) or supratherapeutic (>1600 budesonide-equivalent ug/day) doses of ICS, and the proportion increased with age before reaching a plateau from age 56 onwards (lowest: 18–45 years, 9.7%; highest: 66–75 years, 18.9%; p < .001). Significantly fewer of the patients in the oldest age group were seen in specialist care (highest: 56–65 years, 18.9%; lowest: >86 years, 11.4%; p < .001), and 77.3% of patients exposed to high or supratherapeutic doses of ICS were managed only in primary care. Conclusion The prevalence of high- and supratherapeutic ICS exposure was higher among patients ≥56 years, and when exceeding 76 years of age, a smaller proportion were managed in secondary care. With an increased focus on adverse effects of high-dose ICS treatment and earlier initiation of other treatments, our findings will, hopefully, facilitate less age inequity in asthma management.

Background Cough variant asthma (CVA) is characterized by chronic cough and airway hypersensitivity, in which transient receptor potential vanilloid 1 (TRPV1)-mediated neurogenic inflammation plays a critical role. Objective This study aimed to investigate whether chemical ablation of TRPV1-expressing nociceptor neurons alleviates CVA symptoms and to explore their involvement in airway inflammation via substance P (SP)-dependent macrophage polarization. Methods A murine CVA model was induced by OVA. TRPV1+ nociceptor neurons were ablated intrathecally using resiniferatoxin (RTX). We assessed cough response, lung inflammation (BALF cytometry, ELISA, histology), fibrosis (Masson/Sirius Red), and neurogenic mediators (SP/CGRP). In vitro, a dorsal root ganglion (DRG) neuron-RAW264.7 macrophage co-culture system, combined with TRPV1 knockdown and NK-1R blockade, was used to define the TRPV1-SP-macrophage polarization axis. Results In an OVA-induced CVA mouse model, chemical ablation of TRPV1+ DRG neurons with RTX significantly reduced cough frequency, attenuated pulmonary inflammation and fibrosis, and suppressed neurogenic inflammatory factors including SP and CGRP. In vitro, TRPV1 activation in primary DRG neurons promoted SP release, which via neurokinin-1 receptor drove macrophages toward an M1 phenotype, upregulating pro-inflammatory markers. Inhibition of SP signaling blocked this polarization. Conclusions Our results reveal a novel TRPV1-SP-macrophage M1 axis in CVA pathogenesis, suggesting that targeting this neuroimmune pathway may offer a therapeutic strategy for CVA.

Background Asthma prevalence increases with age, yet assessment in elderly patients is often limited by difficulties in performing reliable spirometry. Alternative, noninvasive methods such as the Forced Oscillation Technique (FOT) and fractional exhaled nitric oxide (FeNO) measurement may improve evaluation of asthma control in this population. Objective To evaluate asthma control and treatment effectiveness in elderly patients using the Asthma Control Test (ACT), GINA classification, spirometry, FOT, and FeNO, and to compare their clinical usefulness. Methods A total of 105 patients aged ≥65 years with diagnosed bronchial asthma were enrolled. All participants completed the ACT and underwent spirometry (FEV1, FVC, FEV1/FVC), FOT (R5, R20, R5–R20, X5, AX), and FeNO measurement according to ATS/ERS recommendations. Treatment intensity was classified by GINA steps (1–5). Nonparametric tests and Spearman’s rank correlation were used for statistical analysis. Results ACT scores correlated significantly with spirometric, oscillometric, and FeNO parameters. Lower ACT scores were associated with reduced FEV1% predicted and increased airway resistance and reactance (R5, AX), as well as higher FeNO levels (all p < 0.001). Patients treated at higher GINA steps (4,5) exhibited poorer asthma control, higher FeNO, and less favorable FOT indices. Reductions in FeNO following treatment intensification were accompanied by improvements in FEV1 and FOT parameters, particularly AX and R5–R20. Conclusions FOT provides a useful, noninvasive assessment of asthma control in elderly patients and complements spirometry. FeNO adds important information on airway inflammation and treatment response. Their combined use may enhance monitoring of asthma control when spirometry is limited.

Objective This study aimed to measure the impact of repeated counseling on asthma control and inhaler technique using pressurized metered-dose inhaler (pMDI) alone and in combination with pMDI PLUS® (cardboard-based spacer) or AeroChamber2go® in adult asthma patients. Methods This is a prospective randomized clinical trial in which a cohort of 300 asthma patients was randomly allocated into three equal groups (n = 100): (1) pMDI alone, (2) pMDI + MDI PLUS®, and (3) pMDI + AeroChamber2go®. The patient groups were interviewed to assess the inhalation technique of the three devices, in parallel, upon three monthly separate visits. At baseline and during two subsequent monthly visits, each group received three standardized training sessions. Before each session, patients performed the inhalation steps with their assigned device, and the number of technical errors was recorded. Lung function (Forced Expiratory Volume in one second (FEV1) % of predicted, Peak Expiratory Flow (PEF) % of predicted) and Asthma Control Test (ACT) scores were also assessed. Results At the first visit, MDI PLUS® and AeroChamber2go® groups made significantly fewer inhalation errors than the pMDI alone group (p = 0.04 and p = 0.041, respectively). Error rates with pMDI alone only decreased significantly by the third visit (p = 0.04). Throughout all visits, MDI PLUS® consistently showed fewer errors than AeroChamber2go®, although this difference did not reach statistical significance (p > 0.05). Regarding clinical outcomes, both spacer groups experienced significant, visit-to-visit improvements in FEV1% of predicted, PEF% of predicted, and ACT scores (all p < 0.05 between visit 1 and 2 and between visit 2 and 3). In contrast, the pMDI alone group showed no significant change between visits 1 and 2, with statistically significant improvement only by visit 3 (FEV1, p = 0.04; PEF, p = 0.03; ACT, p = 0.04). Conclusion Counseling asthmatic patients with either spacer has significantly reduced inhalation errors and provided greater and earlier improvements in terms of lung function and asthma control compared to pMDI alone.

This letter critiques a trial of fermented wheat germ for pediatric asthma. We commend exploring the gut-lung axis but note key limitations: the control (standard bread) precludes isolating fermented wheat germ -specific effects; significant between-group differences were absent; and proposed mechanisms lack analytical support. Results from adolescents with mild asthma are preliminary. We recommend future placebo-controlled trials with mechanistic biomarkers in more severe populations to conclusively determine fermented wheat germ’s role in asthma management.