This study aimed to compare the clinical efficacy of high-dose versus conventional-dose methylprednisolone therapy and the prevalence of chronic lung disease (CLD) at the 6-month follow-up in Chinese children with severe Mycoplasma pneumoniae pneumonia (SMPP).

A retrospective cohort study was performed on 82 children with SMPP admitted from January 2018 to January 2024. Patients were categorized into high-dose and conventional-dose groups based on initial glucocorticoid dosage. Clinical data, laboratory tests, chest imaging, and bronchoscopy findings were reviewed to compare pulmonary conditions and therapeutic efficacy. The prevalence of CLD, oxygen saturation levels, and pulmonary function were assessed at the 6-month follow-up.

The main clinical features of SMPP included persistent high fever, cough, excessive inflammation (C-reactive protein, erythrocyte sedimentation rate, procalcitonin, interleukin-6, lactate dehydrogenase, serum ferritin, and D-Dimer), as well as severe pulmonary involvement, including consolidation, pleural effusion, and lung necrosis on computed tomography, and mucus plugging on bronchoscopy. Disease severity was comparable between groups, but the high-dose group exhibited a shorter fever duration (9.8 vs. 16.1 days), faster defervescence after corticosteroid treatment (1.0 vs. 7.0 days), and reduced hospitalization (13.4 vs. 18.4 days) (all p < 0.001). At the 6-month follow-up, the high-dose group had a significantly lower prevalence of CLD (28.2% vs. 85.4%) (p < 0.001), higher oxygen saturation levels (p = 0.033) and better pulmonary function (p < 0.001).

High-dose methylprednisolone therapy was more effective than conventional-dose treatment for SMPP patients. It was also associated with a lower prevalence of CLD, higher oxygen saturation levels, and better pulmonary function outcomes.

The respiratory epithelium is a dynamic immunopharmacological interface that transcends its traditional role as a passive barrier to become a central coordinator of pulmonary immunity. This review introduces and elaborates on the paradigm of the "Epithelial Immunopharmacological Rheostat," a conceptual framework that posits the epithelium as a dynamic, multidimensional signal processor that continuously calibrates the threshold of immune activation. Distinct from static models of barrier dysfunction or isolated alarmin biology, this rheostat operates through four hierarchically interacting axes: barrier integrity, alarmin/type 2, senescence/repair, and tolerogenic programming. We critically dissect how dysregulation of specific axes-alone or in combination-initiates and perpetuates the pathology of chronic respiratory diseases, including asthma, COPD, and idiopathic pulmonary fibrosis. A rigorous, pharmacology-centric analysis deconstructs the molecular circuitry of epithelial-immune crosstalk, evaluating the druggability of targets from tight junction complexes and pattern recognition receptors to the alarmin (TSLP, IL-33, IL-25) signaling cascades and their downstream JAK-STAT, NF-κB, and MAPK effectors. Beyond cataloguing mechanisms, this review provides a comparative and critical appraisal of emerging therapeutic strategies, including alarmin-targeted biologics, barrier-restorative agents (e.g., postbiotics, short-chain fatty acids), kinase inhibitors, senotherapeutics, and frontier cell-based therapies. A dedicated synthesis addresses pivotal pharmacokinetic hurdles, biomarker-driven stratification, and the imperative of precision endotyping. Finally, we forecast how advanced human organoid models are catalyzing the shift toward personalized interventions designed to reset the defective rheostat. This comprehensive synthesis maps the intricate landscape of epithelial immunopharmacology and identifies critical barriers that must be overcome to translate these insights into transformative clinical outcomes.

The acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is characterized by systemic inflammatory response and neuroimmune dysregulation. The dynamic changes of certain key neuroimmune biomarkers during the course of AECOPD and their impact on long-term patient outcomes have not been thoroughly studied.

This study aims to develop a bedside clinical decision tree based on neuroimmune biomarker dynamics to stratify post-AECOPD patient risk and guide personalized discharge planning.

This prospective observational study included 273 patients hospitalized due to AECOPD. Serum levels of brain-derived neurotrophic factor (BDNF), programmed cell death protein 1 (PD-1), matrix metalloproteinase-9 (MMP-9), and inflammatory cytokines (IL-1β, IL-6, IL-10, and TNF-α) were measured within 24 h of admission (T1) and within 48 h after clinical stability at discharge (T2). Unsupervised clustering analysis was performed based on the dynamic changes in biomarkers, and multivariable logistic regression was used to assess their association with 90-day clinical outcomes (acute exacerbation, readmission). Additionally, a biomarker-based decision tree model was developed, and its performance was compared with traditional clinical assessment methods.

Three distinct biomarker response patterns were identified: "Coordinated Improvement " (60.0%), "Inflammatory Rebound" (27.8%), and "Poor Neuro-repair" (12.1%). Among them, the "Poor Neuro-repair" phenotype was the strongest independent predictor of acute exacerbation events at 90 days (adjusted OR 3.42, 95% CI 1.78-6.57, p < 0.001). The dynamic change in BDNF (ΔBDNF) showed predictive value for acute exacerbation events (AUC 0.84). The biomarker-based decision tree model classified patients into four risk levels, with significant differences in the 30-day event incidence (ranging from 3.6% to 68.4%). Its predictive accuracy (AUC 0.87) was markedly superior to that of clinical judgment (AUC 0.74) and the GOLD standard (AUC 0.68).

The biomarker response patterns after acute exacerbation, particularly the "Poor Neuro-repair" phenotype and its dynamic changes in BDNF, are closely associated with short-term clinical outcomes. The decision tree model developed based on this information provides a preliminary approach for risk stratification and discharge planning in AECOPD patients, demonstrating superior efficacy compared to traditional clinical assessment methods.

Stapled bullectomy is a safe procedure for primary spontaneous pneumothorax (PSP). Early infection-driven staple-line failure with metalloptysis after bullectomy for PSP is rare. A 21-year-old man underwent video-assisted thoracoscopic bullectomy for persistent right PSP. The staple lines were reinforced with polyglycolic acid sheets. The early postoperative course was uneventful, but the patient developed fever, cough, and purulent sputum on postoperative day 21. Computed tomography demonstrated fluid-filled cavitary lesions along the staple lines in the right upper and lower lobes, with partial staple-line disruption. Sputum cultures yielded oral commensals, and an acute lung abscess associated with staple-line failure was diagnosed. Antibiotic therapy was initiated, and he expectorated several surgical staples. The abscess resolved with conservative treatment. This case suggests that acute infection along pulmonary staple lines can lead to staple-line failure and metalloptysis even after routine bullectomy. Persistent postoperative fever or purulent sputum should prompt careful evaluation for staple-line-associated infection.

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.