Congenital central hypoventilation syndrome (CCHS) is characterized by a markedly impaired ventilatory response to CO₂ due to central chemoreceptor dysfunction. Although inadequate ventilation and hypercapnia during exercise have been reported, ventilatory response during exercise has not been quantitatively evaluated in CCHS. This study aimed to quantify ventilatory response during exercise and compare it with that at rest.

Ten patients with genetically confirmed CCHS underwent cardiopulmonary exercise test (CPET) using a stepwise incremental treadmill protocol with breath-by-breath respiratory gas analysis. CPET was terminated when end-tidal CO₂ (EtCO₂) increased by at least 2% (15.2 mmHg) from baseline. Ventilatory response to CO₂ (VRCO₂) was calculated as Δminute volume (MV)/ΔEtCO₂/body weight (mL/min/mmHg/kg). VRCO₂ at rest was measured using the CO₂ rebreathing method. Data are presented as median (interquartile range [IQR]).

Age was 13.5 (12.3-15.5) years, and exercise duration was 5 min 53 s (4 min 47 s-6 min 56 s). Although MV increased during exercise, SpO₂ decreased and EtCO₂ increased, indicating hypoventilation. VRCO₂ during exercise was 2.27 (1.61-3.16), not significantly different from VRCO₂ at rest, 1.56 (1.07-2.83) (p = 0.85). VRCO₂ was markedly lower than values in healthy children (34.6 (29.3-42.8)). No patients reported dyspnea, and no serious adverse events occurred.

VRCO₂ during exercise remains profoundly low in CCHS. No significant difference from VRCO₂ at rest was detected, suggesting persistent impairment of CO₂-driven ventilatory control despite increased metabolic demand. These findings provide insight into exercise-related hypoventilation in CCHS and underscore the importance of objective physiological assessment to support cautious and individualized clinical judgment rather than subjective symptoms.

Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa poses a major therapeutic challenge for critically ill infants and young children.

In this study, we assessed the antimicrobial susceptibility profiles of 42 P. aeruginosa isolates recovered from neonatal and paediatric intensive care unit (NICUs and PICU) patients with VAP between March and September 2021. Five isolates (11.9%) exhibited an extensively drug-resistant (XDR) phenotype and were resistant to both ceftazidime-avibactam and ceftolozane-tazobactam. These five isolates were subjected to whole-genome sequencing (WGS) and comparative genomic analyses.

All five isolates belonged to serogroup O11 and sequence type ST773. Nevertheless, WGS-based phylogenetic analyses, such as core genome MLST and SNP-based phylogeny, showed that the isolates were non-clonal and had a closer genetic relationship to previously identified ST773 strains from Egypt and Germany. Several multidrug efflux systems and a broad range of acquired antimicrobial resistance genes, such as blaNDM-1, rmtB4, tet(G), and flor2, carried on a conserved integrative conjugative element previously reported in ST773, were found by genomic analysis. Furthermore, on a genomic island inserted downstream of the glmS gene, a class 1 integron containing qnrVC1, aadA11, qacEΔ1, and sul1 was found. All strains possessed the same quinolone resistance-determining region alterations (gyrA T83I and parC S87L) and the same array of virulence-associated genes linked to motility, secretion systems, iron acquisition, quorum sensing, and toxin production.

This study reports the identification of non-clonal, XDR P. aeruginosa ST773 isolates associated with VAP in critically ill infants and young children. Despite their non-clonal nature, the isolates shared key features, including mobile genetic elements carrying important resistance genes and a consistent virulence gene profile. These findings highlight the clinical significance of this sequence type and raise concerns about its potential impact in the NICU and PICU settings. Continuous genomic surveillance, along with improved antimicrobial stewardship and stricter infection control practices, remains essential to limit its spread.

Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is a type-2 inflammatory endotype characterised by tissue eosinophilia and mucosal remodelling. γδ T cells are tissue-resident lymphocytes involved in barrier immunity, yet their subset composition and relationship to inflammatory remodelling in eCRSwNP remain incompletely defined.

γδ T cell subsets were analysed in nasal mucosa and polyp tissue from patients with eCRSwNP (n=21) and control subjects (n=10). Mononuclear cells isolated from nasal polyps and middle turbinate mucosa were examined by flow cytometry to quantify Vδ1⁺Vδ2^-, Vδ1^-Vδ2⁺ and Vδ1^-Vδ2^- subsets. Targeted transcriptional analyses using RT-qPCR assessed expression of TRDV1, TRDV2 and type-2 inflammatory markers. Clinical indices included symptom scores, radiologic disease severity and histological eosinophilia.

eCRSwNP was associated with marked numerical and compositional remodelling of mucosal γδ T cells. Diseased tissue showed expansion of Vδ1^-Vδ2⁺ and Vδ1^-Vδ2^- subsets, whereas Vδ1⁺Vδ2^- cell numbers remained stable but declined proportionally within the expanding γδ compartment. These shifts followed a gradient from healthy mucosa to non-lesional tissue and nasal polyps and correlated with increasing disease severity, tissue eosinophilia and tissue-level type-2 inflammatory signatures.

Progressive γδ T cell remodeling across the sinonasal mucosa in eCRSwNP is associated with type-2 inflammatory activity, tissue eosinophilia and disease severity.

Chronic rhinosinusitis (CRS) is a highly prevalent and debilitating inflammatory condition of the upper airway, affecting 5-28% of the global population and imposing a substantial socioeconomic burden. Despite major advances in endoscopic sinus surgery, pharmacological management, and targeted biologic therapies, long-term disease recurrence following treatment remains an unresolved clinical challenge. Current pathophysiological frameworks centered on adaptive type 2 immunity, eosinophilic inflammation, and pathogen persistence fail to fully account for the chronification and therapy resistance of CRS. Emerging evidence positions trained immunity (the epigenetic and metabolic reprogramming of innate immune cells enabling non-antigen-specific functional memory) as a fundamental and previously underappreciated mechanism driving CRS recurrence. Persistent sinonasal microbial colonizers, including Staphylococcus aureus biofilms and fungal components, along with viral pathogens and dysbiotic microbiome communities, function as potent epigenetic training stimuli that reprogram sinonasal macrophages, group 2 innate lymphoid cells (ILC2s), and epithelial progenitor cells. The recent identification of a TLR4+ trained ILC2 subset in nasal polyp tissue, sustained by AP-1-driven chromatin remodeling at the Tlr4 locus, exemplifies the cellular specificity of this phenomenon. Concurrently, nasal basal stem cells acquire heritable pro-inflammatory chromatin states following type 2 cytokine exposure, encoding an epithelial inflammatory memory that perpetuates mucosal dysfunction independent of ongoing stimulation. This review systematically examines the microbial triggers, epigenetic mechanisms, key cellular mediators, and therapeutic implications of trained immunity in CRS, proposing a new framework for disease-modifying strategies targeting the sinonasal epigenetic inflammatory landscape.

Positive end-expiratory pressure (PEEP) can improve oxygenation and reduce the work of breathing in patients with acute respiratory distress. In the prehospital setting, systems providing continuous positive airway pressure (CPAP), bi-level positive airway pressure (BiPAP) and adjustable pressure-limiting (APL) valves are used inconsistently, and the evidence base is heterogeneous across their use in patients with chronic obstructive pulmonary disease, asthma, pneumonia and cardiogenic pulmonary oedema.

This scoping review aims to map the existing evidence on prehospital use of PEEP-based ventilation in adults with acute respiratory distress, including reported clinical outcomes and safety.

This scoping review will be conducted in accordance with the JBI methodology for scoping reviews and reported in line with the PRISMA extension for Scoping Reviews (PRISMA-ScR). We will systematically search MEDLINE, Embase, CINAHL, Cochrane CENTRAL and the Cochrane Database of Systematic Reviews (CDSR) with support from a research librarian. Empirical studies of adults (≥ 18 years) receiving PEEP-based ventilation in the prehospital setting will be eligible, including randomised controlled trials, observational studies, case series and well-described case reports. Two independent reviewers will screen, extract and map the data on study characteristics, interventions, comparators and outcomes, with disagreements resolved by a third reviewer. Methodological quality will be appraised at study level using the Jadad Scale for randomised trials and the Newcastle-Ottawa Scale for cohort and case-control studies.

We expect to identify a limited but clinically relevant body of evidence reporting effects on oxygenation, dyspnoea severity, escalation to advanced airway management, adverse events and feasibility. The findings will be synthesised narratively and presented in descriptive and tabular form. We specifically anticipate sparse evidence for the prehospital use of APL systems.

This scoping review will provide a comprehensive mapping of prehospital PEEP use in adults with acute respiratory distress, summarising its clinical effects, safety signals and feasibility, and identifying gaps to inform future studies.

Pulmonary fibrosis (PF) is a chronic and progressive respiratory disorder marked by aberrant activation of pulmonary fibroblasts and the occurrence of epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AECs). This disease process is primarily driven by inflammation and oxidative stress (OS), leading to excessive deposition of the extracellular matrix (ECM). Current treatments provide limited efficacy and are associated with significant side effects. Leonurine and its sulfate derivative SCM198, derived from Herba Leonuri, exhibit anti-inflammatory and antioxidant properties. However, their therapeutic effects and mechanisms of action in PF remain poorly understood.

Bleomycin (BLM) was delivered intratracheally to mice to establish a model of PF. Human Fetal Lung fibroblast-1 (HFL-1) fibroblasts and A549 AECs were subjected to transforming growth factor-beta 1 (TGF-β1) exposure for in vitro assays. This study comprehensively evaluated the effects of SCM198 on PF and explored its underlying molecular mechanisms through metabolomics analysis, western blotting, and additional biological techniques.

SCM198 significantly ameliorated lung pathology and micro-Computed Tomography (CT) findings and reduced collagen deposition in BLM-treated mice. Furthermore, the levels of inflammatory markers and cytokines were decreased in lung tissue and Bronchoalveolar Lavage Fluid (BALF). In vitro, SCM198 inhibited fibroblast activation, EMT, and OS. It also down-regulated the TGF-β1/Smad2/3 pathway and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway.

The ameliorative action of SCM198 on BLM-induced pulmonary fibrosis is associated with suppression of the TGF-β1/Smad2/3 signaling axis and activation of Nrf2-mediated antioxidant defenses during the EMT process. However, further studies are needed to confirm the direct involvement of these pathways.

Cystic fibrosis (CF) airway disease is characterized by exaggerated inflammatory responses and progressive respiratory failure. Although interleukin-8 (IL-8) is a central mediator of neutrophilic inflammation in the CF airway, the upstream epithelial pathways that regulate cytokine production remain incompletely understood. Interleukin-17C (IL-17C) is an epithelial-derived IL-17 family cytokine that can promote inflammatory signaling in an autocrine/paracrine manner, but its regulation in CF-derived airway epithelial cells remains poorly defined. Here, we examined Toll-like receptor (TLR) ligand-induced IL-17C regulation in primary human airway epithelial cells derived from bronchial and small airway compartments, including normal human bronchial epithelial cells, CF-derived human bronchial epithelial cells, small airway epithelial cells (SAEC), and CF-derived SAEC (D-SAEC-CF). Among the ligands tested, polyinosinic-polycytidylic acid [poly(I:C)], a synthetic TLR3 ligand, consistently revealed differences in IL-17C and IL-8 induction between non-CF and CF-derived cells in both epithelial cell systems. Time-course analyses showed that poly(I:C)-induced IL-17C expression increased gradually and exhibited relatively delayed kinetics compared with the rapid interferon-β response, resembling IL-8 induction. Pharmacological inhibition indicated that c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and nuclear factor-κB, but not extracellular signal-regulated kinase, were involved in poly(I:C)-induced IL-17C expression. Basal TLR3 and IL-17RE mRNA levels were elevated most clearly in D-SAEC-CF cells; however, IL-17RE knockdown did not significantly reduce poly(I:C)-induced IL-8 production in bronchial epithelial cells. Together, these findings suggest that poly(I:C)-induced IL-17C production may represent a TLR3-dependent epithelial inflammatory response in CF-derived primary airway epithelial cells.

Antibodies are crucial for providing protection against influenza virus infection; however, protective humoral immunity is limited by antigenic drift and shift. Hence, the discovery of broadly neutralizing antibodies (bnAbs) targeting conserved epitopes on hemagglutinin protein evokes the hope of developing a universal influenza vaccine. Because of such historical reasons, much of the effort in universal vaccine design has focused on B cell epitopes. In contrast, despite the critical role of T follicular helper cells in bnAb induction, T cell epitopes have received far less attention. In this review, we summarize the cellular and molecular factors that impact the bnAb development and discuss key limitation factors that restrict their efficient induction.

Coronary artery disease (CAD) has been epidemiologically linked to idiopathic pulmonary fibrosis (IPF); however, the genetic basis of this association remains unclear. Therefore, this study aims to investigate the potential causal relationships between IPF and CAD using a bidirectional two-sample Mendelian randomization (MR) strategy.

Inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode approaches were applied to summary statistics obtained from CAD and IPF genome-wide association studies. Heterogeneity among instrumental variables was assessed using Cochran's Q test. Pleiotropy was assessed using MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) analyses. Additionally, the robustness and reliability of the findings were validated by applying a leave-one-out analysis.

The forward MR analysis revealed no evidence supporting a genetic causal association between IPF and CAD (odds ratio [OR] = 0.989, 95% confidence interval [CI]: 0.967-1.010, p = 0.305) after excluding an outlier single-nucleotide polymorphism (SNP) (rs7725218). However, reverse MR analysis demonstrated a significant negative genetic causal association between CAD and IPF (OR = 0.832, 95% CI: 0.711-0.975, p = 0.023). Sensitivity analysis revealed heterogeneity in the forward MR analysis, which was resolved after excluding an outlier SNP, with no evidence of horizontal pleiotropy detected.

This study demonstrates a potential negative genetic influence of CAD on the risk of IPF, providing valuable insights that may guide the development of more enhanced preventive and therapeutic strategies. Future research should further assess the interactions between CAD and IPF to improve disease management and patient outcomes.

ObjectiveSuperselective adrenal arterial embolization with ethanol has demonstrated promising efficacy in patients with primary aldosteronism and lateralized aldosterone secretion. However, approximately 40% of patients have nonlateralized disease, defined as bilateral primary aldosteronism based on adrenal venous sampling.MethodsIn this prospective observational cohort study, 30 patients with primary aldosteronism underwent superselective adrenal arterial embolization, including 16 patients with unilateral primary aldosteronism and 14 patients with bilateral primary aldosteronism confirmed by adrenal venous sampling. Patients were stratified into the unilateral primary aldosteronism and bilateral primary aldosteronism groups. Blood pressure and biochemical parameters were assessed at 15-40 h and at 1, 3, and 6 months after the procedure.ResultsPlasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio improved significantly in both groups within 15-40 h after superselective adrenal arterial embolization compared with baseline. At 6 months, the rates of complete or partial clinical and biochemical success were 85.7% and 92.9%, respectively, in the bilateral primary aldosteronism group compared with 81.3% and 87.5%, respectively, in the unilateral primary aldosteronism group. Significant reductions in serum sodium levels and microalbuminuria were observed in patients undergoing bilateral superselective adrenal arterial embolization. Body mass index also decreased significantly at 1, 3, and 6 months in both groups. No procedure-related complications were observed during a median follow-up of 6 months.ConclusionsBilateral superselective adrenal arterial embolization may represent a valuable adjunctive treatment strategy for patients with bilateral primary aldosteronism.