Severe asthma is a heterogeneous condition encompassing multiple phenotypes. Understanding lung-specific mechanisms in children with severe asthma may enable the development of more precise therapeutic strategies. We previously reported that immune components in bronchoalveolar lavages (BALs) differentiate children with severe asthma from non-asthmatic disease-controls and, frequent from non-frequent exacerbators, among children with severe asthma.

To identify a local signature of severe asthma using complementary multi-omics analyses of BALs. A secondary objective was to evaluate whether bacterial taxa and metabolites discriminate severe asthma subtypes associated with distinct phenotypes or endotypes.

BAL microbiome and metabolome were investigated in 20 children with severe asthma and 10 non-asthmatic children using 16S rRNA gene amplicon sequencing and liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), respectively. Data were analysed separately and through integrative multi-omics approaches.

Compared with controls, BALs from children with severe asthma showed increased alpha-diversity, higher relative abundances of Actinobacteriota, Streptococcus, Moraxella, Corynebacterium, Tropheryma, and Treponema, and an altered polyamine pathway characterized by reduced arginine and increased spermine and spermidine levels. Integrated analyses revealed significant associations between Streptococcus and both spermine and spermidine. Independently, each dataset discriminated severe asthma phenotypes, notably exacerbation frequency and co-occurring atopic dermatitis. Unsupervised clustering of microbiome profiles identified four distinct clusters that may reflect severe asthma endotypes.

This study identifies a distinct airway microbiome-metabolome signature associated with pediatric severe asthma. Enrichment of specific bacterial taxa, particularly Streptococcus, together with altered polyamine metabolic pathway, highlights microbial-metabolic interactions potentially involved in disease pathophysiology. The ability of microbiome and metabolome profiles to independently and jointly discriminate clinical phenotypes underscores the relevance of multi-omics approaches for diagnosis and follow-up of severe asthma. Our findings support the importance of airway-level profiling to improve mechanistic understanding of severe asthma and inform on future targeted therapeutic strategies.

Bronchiectasis is increasingly recognised in patients with alpha-1 antitrypsin deficiency (AATD), yet prognostic tools validated in general bronchiectasis populations have not been specifically evaluated in this group. The Bronchiectasis Severity Index (BSI) is a widely used multidimensional score predicting mortality, hospitalisation, and exacerbations in all-cause bronchiectasis. This study aimed to validate the BSI in a cohort of patients with AATD-bronchiectasis. Clinical data were obtained from the Birmingham AATD registry. Patients with severe AATD genotypes and CT-confirmed bronchiectasis were included, while those with non-severe genotypes or alternative causes of bronchiectasis were excluded. BSI scores were calculated using available registry data with minor adjustments reflecting the limitations of cross-sectional data collection. Associations between BSI and mortality were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models adjusted for COPD, smoking status, and sex. Secondary analyses evaluated associations between BSI and lung function decline (FEV1 and KCO) and health-related quality of life (SGRQ). A total of 198 patients were included (mean age 54.3 ± 9.7 years; 53.5% male), the majority with the ZZ genotype (97.5%) and coexisting COPD (87.4%). Median BSI score was 5 (range 0-14). Mortality differed significantly across BSI severity groups (p < 0.001): estimated 1-year mortality was 1.1%, 7.4%, and 20.0% for mild, moderate, and severe disease respectively, while 4-year mortality was 5.7%, 23.7%, and 31.8%. In Cox regression analysis adjusted for COPD, smoking, and sex, BSI remained significantly associated with mortality (hazard ratio 1.13 per point increase; 95% CI 1.05-1.23; p = 0.002). BSI score was also associated with greater decline in gas transfer (KCO) (β = -0.22% per point per year; p < 0.001), but showed no significant association with FEV1 decline or SGRQ score. The Bronchiectasis Severity Index is associated with mortality risk in patients with AATD-associated bronchiectasis, supporting its use as a prognostic tool in this population. These findings provide evidence that a severity score derived from all-cause bronchiectasis cohorts can be applied to AATD, although prospective validation in larger multicentre datasets is warranted.

Respiratory failure is the leading cause of death in amyotrophic lateral sclerosis (ALS). Early detection of CO2 retention is crucial for assessing respiratory failure severity and guiding noninvasive positive pressure ventilation (NPPV) management. However, arterial blood gas analysis is invasive and uncomfortable for routine monitoring.

We investigated whether the serum sodium-chloride difference (Na-Cl value), calculated from routine blood tests, could serve as a screening marker for CO2 retention in ALS patients.

This retrospective study included 88 ALS patients with 116 paired samples of arterial blood gas and serum electrolyte data. We analyzed correlations between Na-Cl value and blood gas parameters (HCO3-, PCO2), performed receiver operating characteristic (ROC) analysis for detecting CO2 retention (PCO2 ≥ 45 mmHg), and examined relationships with respiratory function (%FVC).

Na-Cl value showed strong correlation with HCO3- (r = 0.78, p < 0.001) and PCO2 (r = 0.71, p < 0.001). Na-Cl ≥ 37 mEq/L demonstrated sensitivity of 85.11% and specificity of 69.57% for detecting PCO2 ≥ 45 mmHg, with negative predictive value of 87.27% (AUC = 0.842). Na-Cl ≥ 39 mEq/L achieved specificity of 92.75%. Patients with %FVC < 50% had significantly higher Na-Cl, PCO2, and HCO3- values.

Serum Na-Cl value serves as a simple, noninvasive screening marker for CO2 retention in ALS. Na-Cl ≥ 37 mEq/L warrants blood gas analysis, while Na-Cl ≥ 39 mEq/L provides specificity >90%. This marker can be calculated from routine blood tests without additional cost, making it suitable for frequent monitoring and reducing the risk of missing intervention timing.

Assess associations between COVID-19 vaccine availability and differences in COVID-19 mortality risk across subgroups among 122,527 people with HIV (PWH) in Florida.

Analyzed HIV surveillance data, Social Vulnerability Index (SVI), and Rural-Urban Commuting Area Codes using a competing risks model to compare COVID-19 mortality among PWH before (3/1/2020-4/30/2021) and during (5/1/2021-12/31/2021) vaccine availability.

Overall COVID-19 mortality rates increased from before to during the vaccine availability period (22.3 vs. 27.5 per 100,000 person-months), driven in part by the Delta variant surge in mid-to-late 2021. Compared to Non-Hispanic White (NHW) PWH, adjusted COVID-19 mortality hazards remained elevated for Non-Hispanic Black (NHB) PWH both before (HR 2.06, 95% CI 1.45-2.91) and during (HR 1.60, 95% CI 1.13-2.27) vaccine availability. For Hispanic PWH, the relative hazard compared to NHW was elevated before (HR 2.24, 95% CI 1.55-3.23) and attenuated during vaccine availability (HR 1.03, 95% CI 0.68-1.57). In the final model, living in ZIP Code-level areas of high social vulnerability (overall SVI high vs. low) was associated with elevated hazard during vaccine availability (HR 1.75, 95% CI 1.04-2.97).

Overall COVID-19 mortality rates were higher during the vaccine availability period (27.5 vs. 22.3 per 100,000 person-months); however, subgroup patterns varied substantially. Inequities persisted in key subgroups and were most pronounced among PWH living in more socially vulnerable areas. These observational comparisons do not estimate the causal effect of vaccination uptake.

Tailored vaccination strategies and structural interventions remain essential to advancing equity in pandemic response among PWH.

Debates about public trust in science often contrast deficit-based models, which emphasize the role of scientific knowledge, with constructivist perspectives that highlight the coexistence of multiple epistemologies. However, both approaches tend to overlook the mechanisms that link scientific knowledge, alternative epistemic orientations, and mistrust in science. To address this gap, the study applies a multilevel structural equation model within a multidimensional framework to examine conspiratorial reasoning as a key mechanism through which scientific knowledge influences science mistrust. Using cross-national survey data from Europe during the COVID-19 pandemic, the analysis also considers how this pathway is moderated by individual cognitive, motivational, and ideological traits, as well as macro-level political, cultural and economic factors. The findings reveal that conspiratorial reasoning significantly mediates the relationship between scientific knowledge and mistrust at both individual and regional levels. Moreover, the strength of these associations is conditioned by factors like informational engagement, regional value climates, and religiosity. Overall, the results suggest that scientific knowledge serves as a conditional epistemic resource, rather than a consistent buffer against mistrust in science.

BACKGROUND Common variable immunodeficiency (CVID) is an inborn error of immunity characterized by impaired antibody production, poor vaccine responses, and reduced serum immunoglobulin levels, resulting in respiratory manifestations that can progress to pulmonary complications. Although vitamin D has been associated with pulmonary outcomes in other populations, the association between serum 25-hydroxyvitamin D [25(OH)D] status and pulmonary manifestations, particularly atelectasis, in CVID remains unclear. MATERIAL AND METHODS We conducted a retrospective cross-sectional study of 48 adult patients with CVID stratified by serum 25(OH)D concentration (<30 ng/mL [insufficient] vs ≥30 ng/mL [sufficient]). Pulmonary outcomes (atelectasis, bronchiectasis, recurrent pneumonia, and chronic obstructive pulmonary disease [COPD]) were obtained from medical records. Associations were assessed via Fisher's exact test. Exploratory analyses included a longitudinal imaging review and descriptive Kaplan-Meier curves illustrating atelectasis-free disease duration by baseline 25(OH)D status. RESULTS Among 48 patients, 35 (73%) had 25(OH)D concentrations below 30 ng/mL. Atelectasis was more frequent in the insufficient group (15/35; 43%) (odds ratio=0.12; 95% confidence interval, 0.01-0.97; P=0.02). No significant associations were observed for bronchiectasis (63% vs 46%; P=0.53), recurrent pneumonia (91% vs 84%; P=0.49), or COPD (3% vs 8%; P=0.46). Kaplan-Meier curves did not show an apparent separation between groups. CONCLUSIONS Serum 25(OH)D sufficiency was associated with lower atelectasis prevalence in patients with CVID. This finding reflects a cross-sectional association and does not establish causality; it supports a potential link between 25(OH)D status and atelectasis. Prospective studies are needed to further evaluate this relationship.

Dyspnea is a symptom that can cause significant burden on activities of daily living. Overall, dyspnea has associations with increasing age, high body mass index (BMI), female sex and cardiorespiratory diseases. Aside from pharmacological treatments for underlying cardiorespiratory conditions that cause dyspnea, menthol has been discussed as a potential non-pharmacological intervention. However, its role remains contentious with uncertainty regarding efficacy and potential harm. Thus, this systematic review aims to explore the impact of menthol on dyspnea.

A comprehensive search of databases (MEDLINE, Embase, Cochrane Library) was performed from inception of each database to June 2026. Appropriate randomized controlled trials (RCTs) investigating the effects of menthol on dyspnea outcomes were identified based on strict inclusion criteria. The RCTs included patients with dyspnea from underlying respiratory conditions and lab-based studies that simulated dyspnea in people with no underlying lung pathology through exercise. Studies with patients with respiratory conditions also induced dyspnea through exercise and inspiratory loaded breathing. The primary outcome was dyspnea which was measured through scores like Borg and Multidimensional Dyspnea Profile (MDP). Secondary outcomes included adverse events identified and impact on physiological parameters. Subsequently a descriptive analysis of data was carried out.

All eight studies selected showed improvement in dyspnea scores. Four studies positively impacted the immediate perception and sensory qualities domains of the MDP, while one study using a visual analogue scale score decreased dyspnea scores by 42% in one subgroup (flow-resistive loading) and 19% in another (elastic loading). Four studies used the modified Borg score to report dyspnea. Amongst these, Kanezaki et al [12] demonstrated a reduction in score by - 2 at maximal time and - 1 with maximal inspiratory resistive load showing a minimal clinical important difference in dyspnea (MCID). Prieur et al. [16]; Schaeffer et al. [14] and Vanden Bossche et al. [21] reduced Borg scores by 0.3, 0.7, 0.67 respectively but did not reach the MCID. However, all three studies did have participants that showed MCID. One study used the 11-point feeling scale to measure breathing comfort and showcased 1.5-point increase in bre̲athing comfort with menthol ingestion and 1 point increase in comfort with menthol rinse. There were no significant documented negative implications of menthol. Menthol had no impact on forced expiratory volume in one second and airway resistance measures.

Menthol is an effective and safe treatment option for the short-term and symptomatic relief of dyspnea both at rest and during exercise.

ObjectivesTo investigate the prognostic value of the systemic immune-inflammation index (SII), lactate-to-albumin ratio (LAR), and D-dimer for in-hospital adverse outcomes in patients with acute pulmonary embolism (APE).MethodsThis single-center retrospective cohort study screened 248 patients with computed tomography pulmonary angiography-confirmed APE between June 2022 and February 2026; 151 patients were included after 97 exclusions. Predictors were defined using the first measurements obtained within 24 hours after admission and before anticoagulation, thrombolysis, vasopressor therapy, or any related adverse event. The primary outcome was an in-hospital composite of intensive care unit transfer, shock or vasopressor use, cardiopulmonary resuscitation, catheter-based therapy or thrombolysis, and fatal outcome (in-hospital death or withdrawal of life-sustaining treatment after irreversible deterioration). Multiple imputation and logistic regression were used to construct and compare an sPESI model, a biomarker model, and a combined model. Performance was assessed using receiver operating characteristic curves, calibration analysis, bootstrap internal validation, and decision curve analysis.ResultsAmong 151 patients, 37 (24.5%) experienced the composite outcome and 114 did not. SII, LAR, and D-dimer remained associated with the outcome after adjustment for sPESI. Model 2 had an AUC of 0.891, compared with 0.637 for model 1 and 0.661 for ESC risk classification. Adding sPESI or ESC classification to model 2 increased the AUC to 0.912 and 0.900, respectively, without a significant further improvement in discrimination (P=.221 and P=.409). The bootstrap-corrected AUC for model 2 was 0.885, the Brier score was 0.091, and internal decision-curve analysis showed potential net benefit.ConclusionsAdmission SII, LAR, and D-dimer were associated with in-hospital adverse outcomes and remained associated after adjustment for sPESI. The exploratory three-biomarker model may complement sPESI and ESC risk classification, but multicenter external validation is required before clinical application.

Introducción. Los pacientes pediátricos suelen presentar COVID‑19 menos grave que los adultos; sin embargo, los resultados clínicos finales en niños inmunosuprimidos siguen siendo heterogéneos y controversiales. Algunos estudios plantean un mayor riesgo de complicaciones, mientras que otros sugieren que la inmunosupresión podría modular la respuesta inflamatoria asociada con la enfermedad grave.

Comparar los resultados clínicos finales de los pacientes pediátricos inmunosuprimidos e inmunocompetentes hospitalizados con COVID-19 en un centro de alta complejidad de Colombia durante la pandemia. Materiales y métodos. Se llevó a cabo un estudio retrospectivo de cohortes que incluyó pacientes menores de 18 años hospitalizados entre el 2020 y el 2023 con COVID-19 confirmado. Se compararon las características clínicas y los resultados finales entre ambos grupos. Se usó estadística descriptiva y la prueba de ji al cuadrado o la exacta de Fisher para las variables categóricas, y la prueba t de Student o la U de MannWhitney para las variables continuas, con significancia de p < 0,05.

Se analizaron 705 pacientes: 124 (17,6 %) inmunosuprimidos y 581 (82,4 %) inmunocompetentes. Los inmunosuprimidos tuvieron mayor mediana de edad (10 frente a 2 años) y mayor mortalidad (4,03 % frente a 2,1 %; p < 0,001). Por otro lado, los inmunocompetentes requirieron con mayor frecuencia intubación al ingreso (4,6 % frente a 0,8 %; p = 0,02) y presentaron una estancia hospitalaria más prolongada (6 frente a 5 días; p = 0,04). La falla renal fue más frecuente en los inmunosuprimidos (2,4 % frente a 0,3 %; p = 0,04).

Los pacientes pediátricos inmunosuprimidos no presentaron mayor gravedad clínica aguda medida por la necesidad de soporte crítico; sin embargo, hubo mayor mortalidad. Estos resultados evidencian la variabilidad de la evolución clínica según el estado inmunológico y subrayan la necesidad de estudios adicionales para identificar los factores de riesgo y los posibles mecanismos protectores en esta población.

The relationship between vertebral vascular canal dilation and raised intra-abdominal and intrathoracic pressures has been observed in humans. Vertebral vascular canal dysplasia (VVCD) has recently been reported as a vertebral anomaly in brachycephalic dogs. This retrospective, single-institutional study aimed to estimate the prevalence of VVCD number and type in thoracic vertebrae of three brachycephalic breeds and a non-brachycephalic control group, and to correlate the findings with the brachycephalic obstructive airway syndrome (BOAS) functional grading. Thoracic CT studies of French Bulldogs, English Bulldogs, and Pugs that had previously undergone BOAS assessment were retrospectively reviewed. Non-brachycephalic dogs that underwent a thoracic CT scan were matched by weight with the BOAS group and randomly selected to be part of the control group. The prevalence of VVCD involving ≥1 thoracic vertebra was 20% (6/30) in the control group, 56.9% (136/239) in French Bulldogs, 95.3% (41/43) in English Bulldogs, and 87.3% (55/63) in Pugs. French Bulldogs had significantly fewer vertebrae affected than the other brachycephalic breeds (p < 0.001). BOAS grade III dogs had more affected vertebrae; however, this was not statistically significant on multivariable analysis. The difference between the VVCD type and BOAS grades was not significant (p = 0.33). As BOAS severity was not correlated with either the presence or type of VVCD, no evidence was found to support a causative link between BOAS grading and the degree of vertebral vascular canal dilation. The potential role of raised intrathoracic or intra-abdominal pressures in the development of VVCD therefore remains hypothetical.