Although pneumococcal colonization is uncommon in adults, it may increase during respiratory viral infections. We investigated the frequency of pneumococcal colonization, associated factors, and serotype distribution in adults with confirmed respiratory viral infection.

We prospectively included adults presenting to the Emergency Department of Bellvitge University Hospital with influenza A virus (IAV), SARS-CoV-2, or respiratory syncytial virus (RSV) infection, as well as 33 virus-negative controls (December 2023-January 2024). Nasopharyngeal swabs were tested for Streptococcus pneumoniae using a RT-PCR assay (lytA and piaB genes). Clinical data were analysed using Cox proportional hazards regression models.

A total of 616 episodes were studied (IAV, n=391; SARS-CoV-2, n=162; RSV, n=28; >1 virus, n=35). Pneumococcal colonization was detected in 85 individuals, with the highest prevalence among IAV-infected patients (14.8%), followed by RSV (10.7%) and SARS-CoV-2 (9.3%). Individuals with viral infection showed higher pneumococcal loads (median lytA C_T 23.1 [18.7-27.4]) compared to those without infection (C_T 31.8 [31.5-33.3]). IAV (OR 3.52; 95%CI 1.30-9.17) and RSV (OR 4.04; 95%CI 1.11-13.50) were independently associated with pneumococcal colonization. Among adults <65 years, female sex (OR for male sex 0.43; 95% CI 0.19-0.90) was associated with colonization, whereas in those ≥65 years, RSV infection (OR 5.56; 95% CI 1.03-27.31) was the main association. Detected serotypes were diverse, predominantly non-PCV serotypes.

Pneumococcal colonization was more frequent during IAV or RSV than SARS-CoV-2 infection. In older adults, RSV infection showed a particularly strong association, highlighting potential implications for pneumococcal and RSV vaccination strategies.

Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder characterized by a predominant bleeding phenotype. However, patients are also at risk of thrombotic events and may require antithrombotic therapy (AT), for which safety data remain limited.

To prospectively evaluate the safety of AT in patients with HHT using standardized longitudinal assessment of bleeding outcomes.

We conducted a prospective observational study at a tertiary HHT referral center. Patients with a definite diagnosis of HHT and a new indication for antiplatelet or anticoagulant therapy were enrolled. The primary outcome was the incidence of hemorrhagic events, classified according to the International Society on Thrombosis and Haemostasis criteria. Secondary outcomes included worsening of epistaxis assessed by the Epistaxis Severity Score, changes in hemoglobin levels, and transfusion requirements.

A total of 33 patients (mean age 65.8 ± 12.9 years; 69.7% male) were included, for a total of 41 AT courses. During a mean follow-up of 21.1 ± 19.2 months, 2 major bleeding events (4.9%) occurred, both during anticoagulant therapy. Three clinically relevant nonmajor bleeds and one minor bleed were recorded. Worsening of epistaxis occurred in 24.4% of treatment courses, but mean Epistaxis Severity Score values did not differ from baseline. Hemoglobin levels and transfusion requirements were not significantly affected.

In this prospective cohort, AT was associated with an acceptable safety profile in selected patients with HHT managed in a multidisciplinary setting. These findings strengthen the currently limited prospective evidence supporting individualized antithrombotic management in HHT, although larger multicenter prospective studies remain warranted.

Asthma-like episodes with cough, wheeze and/or breathlessness are frequent in young children and often triggered by respiratory tract infections. We aimed to examine whether specific microbial triggers of asthma-like episodes were associated with episode duration and severity.

We analyzed 453 nasopharyngeal aspirates collected during acute asthma-like episodes from 268 children aged 0-3 years from the COPSAC-2010 cohort. Samples were tested for common pathogenic respiratory viruses by PCR and for bacteria by culture. Asthma-like episodes were prospectively recorded in diaries. Associations between microbial triggers and episode duration and severity were analyzed by generalized estimating equations. Interactions between microbial triggers and selected asthma risk loci and polygenic risk scores (PRSs) were explored in relation to episode duration.

Rhinovirus was associated with 27% longer episode duration compared to episodes without rhinovirus, predominantly driven by rhinovirus C (50% longer). Rhinovirus was also associated with a more than twofold increased risk of a severe asthma exacerbation (i.e., need for oral prednisolone, high-dose inhaled corticosteroids, and/or hospitalization) (OR 2.26; 95% CI 1.10-4.64; p = .027), with rhinovirus C exhibiting an even higher risk (OR 4.38; 95% CI 1.71-11.25; p = .002). Episodes with Streptococcus pneumoniae, Haemophilus influenzae, and/or Moraxella catarrhalis were associated with 61% longer duration than episodes without these bacteria, which was particularly pronounced for M. catarrhalis (47% longer). In contrast, RSV; parainfluenza and influenza viruses were associated with shorter duration. Younger age correlated with longer episode duration and risk of a severe asthma exacerbation. Exploratory analyses suggested pathogen-specific interactions with selected asthma risk loci and asthma exacerbartion PRS in relation to episode duration.

Specific microbial triggers and younger age were associated with the duration and severity of asthma-like episodes in young children. These findings may improve prognostic assessment and support more individualized management.

Lung ultrasound (LUS) is an established diagnostic tool for pediatric pneumonia, yet its utility as radiation-free alternative to computed tomography (CT) for monitoring disease progression and differentiating complicated phenotypes, specifically necrotizing pneumonia (NP) and parapneumonic effusion (PPE), has not been prospectively validated in a single comparative cohort. This study aimed to evaluate the diagnostic and longitudinal performance of LUS, including a quantitative LUS score, in children with community-acquired pneumonia (CAP), CT-confirmed NP, and PPE, and to evaluate the diagnostic accuracy and longitudinal performance of LUS for identifying and monitoring complicated pediatric pneumonia, including its potential as a radiation-free follow-up tool.

This prospective single-center diagnostic accuracy study enrolled 257 children diagnosed with CAP (n = 116), NP (n = 54), and PPE (n = 87). NP was confirmed by CT in all 54 cases; LUS was performed by trained operators at admission and on day five as a paired assessment against CT and chest radiograph findings. LUS qualitative features and quantitative scores were compared between groups and over time. Multivariable regression and ROC analysis were performed to assess diagnostic accuracy and identify predictors of clinical outcome.

At admission, NP and PPE showed significantly higher LUS scores and more frequent absent lung sliding and heterogeneous hypoechoic consolidation than CAP (p < 0.001). A LUS score cutoff of > 8 demonstrated strong diagnostic performance at both time points (admission AUC: 0.881, sensitivity 79.02%; Day 5 AUC: 0.861, specificity 93.86%), supporting its potential role as an early screening marker and as a radiation-free bedside monitoring tool during follow-up. Longitudinal LUS assessment demonstrated significant re-aeration by Day 5 (p < 0.001), evidenced by an increased proportion of separated B-lines (35.0% to 54.9%) and a reduction in lung consolidation. On multivariable analysis, higher LUS scores independently predicted longer hospitalization on both admission (β = 0.221, p < 0.001) and Day 5 (β = 0.215, p < 0.001), and elevated D-dimer on admission (β = 0.334, p < 0.001) and Day 5 (β = 0.386, p < 0.001).

A LUS score > 8 showed promising diagnostic performance for identifying complicated pediatric pneumonia at admission and during Day 5 follow-up. Although internal bootstrap validation supported the stability of its performance, prospective validation in independent cohorts is required before implementation as a CT-sparing follow-up strategy.

Management of severe bronchopulmonary dysplasia (sBPD) remains challenging and poorly standardized. In 2021, France established multidisciplinary team meetings (MDT) dedicated to sBPD patients. This study described discussed patients, their outcomes and physicians' satisfaction. This multicenter retrospective observational and uncontrolled study included patients presented between June 2021 and September 2024 at the MDT. Data were collected from medical records and the RespiFil database. Questionnaires evaluated physicians' satisfaction and patient outcomes. The data of 38 patients, median gestational age 26 weeks and median age at presentation 46 weeks' postmenstrual age, were analyzed. Systemic steroids were administered before 36 weeks in 31/36 (86%) of the patients. Ventilatory weaning was recommended in 23/37 patients (62%). Recommendations were fully followed in 30/36 patients (83%). Satisfaction was rated between 8 and 10/10 on a 10-point scale by 28/30 physicians (93%). Physicians rated the benefit they perceived for their patients between 8 and 10 on a 10-point scale in 27/36 patients (75%). The frequency of the meetings needed to be increased over time to meet the demand of physicians. At a median follow-up of 11 months, 32/38 patients (84%) were reported as clinically improved and 24/34 lived patients (71%) were weaned from ventilatory support and oxygen.

This descriptive study shows that sBPD MDT is feasible, well accepted by referring physicians, with high adherence to recommendations. By supporting coordinated and individualized care, they may help harmonize practices across centers. Comparative studies are now needed to evaluate their impact on patient outcomes.

• Management of severe bronchopulmonary dysplasia (sBPD) remains challenging owing to its multifactorial origin and the lack of standardized treatment. • Multidisciplinary team meetings (MDT) are well-established, effective tools in oncology and rare diseases.

• This study is the first multicenter report describing the implementation, feasibility and sustainability of an sBPD-dedicated MDT. • 93% of responding physicians reported high satisfaction, and recommendations were fully followed in 83% of cases supporting the feasibility and acceptability of this model, whose impact on clinical outcomes remains to be prospectively evaluated.

Delivery by cesarean section (CS) is a risk factor for childhood asthma and a strong determinant of the early-life gut microbiome. It has been reported that a CS-perturbed gut microbiome plays a mediating role in the association between CS and asthma risk. However, the underlying mechanisms remain unclear. Here, using deeply phenotyped participants in the Canadian birth cohort (CHILD), we characterized the CS microbial composition at 3 months and 1 year of age using machine learning models and described the perturbation using CS scores. The association between CS and the gut microbiota composition was more pronounced at 3 months (area under the curve (AUC) = 0.78) and attenuated at age 1 year (AUC = 0.60). An increased asthma risk at age 5 years was associated only with 1-year CS microbial scores (Odds ratio 1.41, P = 0.004; adjusted odds ratio 1.30, P = 0.034), consistent with our previous work. Extending this, we identified metabolic imbalances associated with 1-year CS microbial scores, marked by elevated tryptophan metabolites in the stool metabolome. These results replicate our previous findings about the mediating role of the 1-year CS microbial signature in the association between CS and asthma risk from the Danish COPSAC₂₀₁₀ cohort, and provide new insight into the underlying mechanism of host-microbe interaction following cesarean section.

Sjögren's disease (SD) is a chronic systemic autoimmune disorder that can affect multiple organ systems. Interstitial lung disease (ILD) is a clinically significant pulmonary manifestation of SD and is associated with impaired quality of life and increased mortality. Interferon-γ (IFN-γ), a major effector cytokine of Th1 immunity, has been implicated in immune dysregulation and chronic inflammation; however, its contribution to SD-associated ILD (SD-ILD) and its relationship with fibrotic remodeling remain incompletely understood.

This pathway-oriented narrative review synthesized evidence identified through a structured and iterative search of PubMed, Embase, and Web of Science, updated through August 2026. Priority was given to direct evidence from SD-ILD. When disease-specific evidence was limited, mechanistic findings from SD without characterized ILD, related connective tissue disease-associated ILDs, fibrotic lung diseases, and experimental models were considered and interpreted as indirect or extrapolated evidence.

Available evidence supports a conceptual network in which IFN-γ may function as a potential signaling node interacting with JAK/STAT, PI3K/AKT, NF-κB, MAPK, WNT/β-catenin, and IDO-kynurenine-AhR pathways. These pathways may contribute at different levels to immune-cell activation, inflammatory amplification, immunometabolic regulation, epithelial injury, fibroblast activation, and fibrotic remodeling. Evidence is strongest for the biological relevance of IFN-γ-JAK/STAT signaling, whereas support for PI3K/AKT, NF-κB, and MAPK is more indirect, and the relevance of WNT/β-catenin and particularly IDO-Kyn-AhR to SD-ILD remains less well established.

The proposed IFN-γ-associated network should be regarded as a conceptual mechanistic framework rather than a fully validated signaling hierarchy in SD-ILD. Distinguishing direct disease-specific evidence from mechanistic extrapolation highlights important knowledge gaps and provides a rationale for future investigation of pathway-informed biomarkers and stage-specific therapeutic strategies. Prospective SD-ILD studies integrating longitudinal clinical data with spatial and single-cell approaches are needed to validate these relationships and clarify their translational relevance.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently accompanied by epithelial barrier disruption and tissue remodeling. This study aimed to investigate whether epithelial-mesenchymal transition (EMT), fibroblast activation, collagen deposition, and TGF-β/Smad signaling are coordinated during CRSwNP nasal mucosal remodeling.

Publicly available single-cell RNA sequencing datasets from two independent human cohorts were integrated to characterize epithelial, fibroblast, and myeloid heterogeneity, disease-associated transcriptional changes, pseudotime dynamics, and cell-cell communication, with CellChat applied to the COLLAGEN and TGF-β signaling modules. Immunofluorescence, Masson's trichrome, and periodic acid-Schiff (PAS) staining were performed on nasal polyps from CRSwNP patients and control nasal mucosa. An ovalbumin (OVA)/Staphylococcus aureus enterotoxin B (SEB)-induced CRSwNP-like mouse model, including a dexamethasone intervention arm, was used for histopathological, immunofluorescence, and Western blot validation.

In CRSwNP, fibroblasts shifted toward activated, matrix-remodeling states, and epithelial cells displayed enhanced injury-repair and EMT-related features, while TGFB1 was preferentially detected in a GPNMB-expressing macrophage subset expanded in polyps. Potential epithelial-fibroblast communication was enriched within COLLAGEN and TGF-β modules, with TGFB1-TGFBR1/TGFBR2 and COL1A1-SDC4/CD44 emerging as candidate ligand-receptor pairs. Human polyps showed collagen deposition, α-SMA-high fibroblast enrichment, EMT-like epithelial changes, and nuclear p-Smad3 accumulation. The mouse model recapitulated this pattern, and dexamethasone partially reversed it at the protein level.

Integrating human single-cell transcriptomics with tissue- and protein-level validation, this study characterizes a coordinated, TGF-β/Smad3-associated epithelial-fibroblast remodeling program underlying collagen deposition in CRSwNP. These candidate axes, together with a macrophage source of TGFB1, offer mechanistic clues to epithelial-fibroblast-immune crosstalk; their partial reversibility by dexamethasone supports pathway-targeted anti-remodeling strategies, while causal roles await spatial and functional validation.

Observational studies have linked the gut microbiota (GM) to infectious diseases, but confounding, reverse causation, and disease-related microbiome changes limit causal interpretation. We combined Mendelian randomization (MR) with focused experimental analyses to investigate microbiota-infection relationships.

Two-sample MR evaluated genetically predicted microbial taxa across 75 infectious outcomes. Inverse-variance weighted (IVW) estimates were used as the primary analysis, with weighted-median and MR-Egger estimates as complementary methods. Benjamini-Hochberg false discovery rate (FDR) and Bonferroni corrections were applied across all IVW tests. Instrument strength, Cochran's Q, MR-Egger intercepts, leave-one-out analysis, MR-PRESSO, and Steiger directionality testing were used to assess robustness. Exploratory association patterns were used to prioritize a Coriobacteriia-related respiratory signal for experimental investigation using Collinsella aerofaciens cell-free supernatant and A549 epithelial cells.

Among 15,728 IVW tests, 659 associations had nominal P < 0.05. After global correction, three taxonomically related associations with urinary tract infection (UTI) remained significant. Higher genetically predicted abundance of genus Bifidobacterium was associated with lower UTI risk (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.17-0.49; FDR-adjusted P = 0.029), while order Bifidobacteriales and family Bifidobacteriaceae showed similar estimates (both OR 0.25, 95% CI 0.14-0.45) and met the Bonferroni threshold. Sensitivity analyses showed no significant heterogeneity or MR-PRESSO-detected outliers, and leave-one-out and Steiger analyses were supportive, although MR-Egger intercepts suggested possible directional pleiotropy. Exploratory analyses identified clustering between Coriobacteriia-lineage taxa and respiratory outcomes. C. aerofaciens cell-free supernatant altered 993 genes and enriched inflammatory pathways in A549 cells. qPCR supported increased CSF2, CXCL8, and CCL20 expression, while ELISA detected IL-8 and MIP-3α but not quantifiable GM-CSF. Untargeted metabolomics identified 201 differential metabolites between bacterial supernatant samples and matched BHI controls.

The corrected Bifidobacterium-related UTI association was the principal MR finding, while the broader analysis identified exploratory microbiota-infection patterns. The C. aerofaciens model linked extracellular metabolic remodeling during bacterial growth with epithelial transcriptional and inflammatory responses, providing focused directions for further investigation.

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by persistent airway inflammation, oxidative stress, and structural remodeling, leading to progressive impairment of lung function. Melatonin has anti-inflammatory and antioxidant properties and may represent a promising therapeutic strategy for chronic airway diseases.

To evaluate the therapeutic effects of melatonin on airway hyperresponsiveness, inflammation, oxidative stress, and remodeling in experimental models of asthma and COPD.

Forty male BALB/c mice were allocated into five groups (n = 8/group): SAL, OVA, OVA+MEL, ELA, and ELA+MEL. Asthma and emphysema were induced by ovalbumin and elastase, respectively. Melatonin (15 mg/kg, intraperitoneally) was administered from days 22 to 27. Respiratory mechanics, bronchoalveolar lavage fluid, immunohistochemistry, and gene expression analyses were performed to evaluate inflammatory cytokines, remodeling markers, and oxidative stress-related proteins.

Melatonin significantly attenuated airway hyperresponsiveness in the asthma model, reducing respiratory mechanical parameters, inflammatory cell infiltration, and eosinophilia. In both asthma and emphysema models, melatonin markedly decreased the expression of pro-inflammatory cytokines, remodeling markers (MMP-9, MMP-12, TIMP-1, and TGF-β), and oxidative stress-related mediators (NF-κB and iNOS). These findings were further supported by gene expression analyses, demonstrating broad suppression of inflammatory cytokines following treatment.

Melatonin attenuated inflammation, oxidative stress, and airway remodeling while improving lung function, particularly in experimental asthma. These findings highlight melatonin as a promising adjunctive therapeutic strategy for chronic inflammatory lung diseases by simultaneously targeting multiple pathogenic pathways.