Cognitive impairment is a common but underrecognized comorbidity in chronic obstructive pulmonary disease (COPD). Lower arterial oxygenation may be associated with altered spontaneous brain activity, but the regional functional correlates linking oxygenation and cognition remain incompletely understood. This study examined amplitude of low-frequency fluctuation (ALFF) abnormalities in COPD patients with cognitive impairment and explored their associations with arterial oxygenation and cognitive performance.

This cross-sectional study included 90 participants: 30 healthy controls, 30 COPD patients without cognitive impairment, and 30 COPD patients with cognitive impairment. Cognitive status was assessed using the Montreal Cognitive Assessment (MoCA); one point was added for participants with ≤12 years of education, with the adjusted score capped at 30, and an education-adjusted score <26 was used to define cognitive impairment. All participants underwent arterial blood gas analysis and resting-state functional MRI. Whole-brain voxel-wise ALFF differences were evaluated using analysis of covariance, with an uncorrected voxel-wise cluster-forming threshold of p < 0.001; clusters were considered significant at a cluster-level FDR-corrected threshold of p < 0.05. Adjusted regression, restricted cubic spline, and exploratory cross-sectional mediation analyses were performed in patients with COPD.

COPD patients with cognitive impairment showed lower ALFF in the left precuneus, left putamen, and bilateral parahippocampal gyri, with all clusters surviving cluster-level FDR correction (P_FDR = 0.004-0.021). Higher PaO₂ was associated with higher MoCA total score and higher ALFF in the left precuneus and left putamen after adjustment for multiple comparisons. Higher regional ALFF was also associated with better cognitive performance, with the strongest association observed in the left precuneus. In an exploratory cross-sectional mediation model, left precuneus ALFF statistically accounted for part of the association between PaO₂ and MoCA total score.

Reduced left precuneus ALFF may represent a candidate neuroimaging correlate of lower arterial oxygenation and poorer cognitive performance in COPD. Because of the cross-sectional design, the exploratory mediation findings do not establish temporal or causal relationships and require confirmation in larger longitudinal cohorts.

Bronchiolitis is the leading cause of hospital presentation and admission for infants in Australasia. We aimed to synthesise current evidence on the effect of discharge criteria for infants (aged < 12 months) who are presenting to or are admitted to hospital with bronchiolitis, to inform a binational guideline recommendation update. Systematic searches were conducted on MEDLINE, EMBASE, PubMed, Cochrane Library and CINAHL (last search 19 February 2025) for non-randomised studies evaluating hospital discharge criteria in bronchiolitis. The primary outcomes were length of stay (LOS) and readmission rates. The risk of bias (ROBINS-I) and certainty of the evidence (GRADE) were appraised, and findings were narratively synthesised. GRADE evidence-to-decision methodology, expert consensus voting and interest-holder consultation were used to finalise the recommendation update. Two retrospective observational studies were included (N = 2697) (low to very low quality), reporting on unique discharge criteria. In both studies, use of the discharge criteria was associated with a significant reduction in LOS relative to alternative protocols. There was no significant difference in readmission rates observed in either study. There was low to very low certainty evidence across outcomes due to risk of bias, indirectness and imprecision. The review findings informed a recommendation update for safe discharge criteria in the 2025 Australasian Bronchiolitis Guideline update. Updated, prescriptive discharge criteria and flow chart were developed, covering clinical stability, oxygen saturation/support, feeding difficulties, caregiver confidence and education on deterioration, social factors and follow-up. The revised criteria provide clinicians with increased certainty in decision-making in bronchiolitis, albeit with further research needed.

BackgroundPulmonary arterial hypertension (PAH) is a progressive disease that affects the central nervous system. The cardiopulmonary-brain axis hypothesis links right ventricular dysfunction to cerebral hypoperfusion, yet the association between regional cerebral blood flow (CBF) alterations, right heart dysfunction, and the clinical utility of CBF for risk stratification remains poorly understood.ObjectivesTo investigate the association between CBF and right heart dysfunction in patients with PAH, and to evaluate the potential of CBF as a non-invasive biomarker for risk stratification.DesignCross-sectional, retrospective study.MethodsThirty PAH patients and 51 age- and sex-matched healthy controls (HCs) were retrospectively identified. Brain MRI data, including 3D arterial spin labeling (ASL) at 3.0 T for CBF quantification were analyzed. For the PAH cohort, clinical assessment included right heart catheterization (RHC) and transthoracic echocardiography (TTE) to evaluate the structure of the right ventricle (RV) and hemodynamics. Patients were stratified into low and intermediate/high-risk groups according to the 2022 ESC/ERS guidelines. Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory value of CBF for risk stratification. Generalized Linear Models were applied to analyze associations between CBF, cardiac and hemodynamic parameters, and neuropsychological metrics.ResultsCompared with HCs, PAH patients exhibited significant regional hypoperfusion, predominantly in the right hippocampus, frontal gyri, and insula. Regional CBF values correlated inversely with RV area (systolic RV area and right caudate: r = -0.569, P = 0.006, systolic RV area and right thalamus: r = -0.587, P = 0.004, diastolic RV area and right caudate: r = -0.513, P = 0.012, diastolic RV area and right thalamus: r = -0.545, P = 0.007) and septal thickness (right superior frontal gyrus: r = -0.528, P = 0.015, left anterior cingulate: r = -0.495, P = 0.024). Notably, intermediate/high-risk patients demonstrated significantly lower CBF compared to low-risk patients, particularly in the parietal and frontal cortices. ROC analysis indicated that regional CBF, in addition to patient sex and age, could distinguish intermediate/high-risk patients from low-risk patients (right superior frontal region: AUC = 0.793, Sensitivity = 71%). Additionally, reduced CBF in the insula was associated with lower Mini-Mental State Examination (MMSE) scores.ConclusionThis study demonstrates that cerebral hypoperfusion in PAH is closely associated with right ventricular dysfunction and disease severity. ASL-derived CBF holds promise as a non-invasive biomarker to refine risk stratification, offering novel insights into the cardiopulmonary-brain interaction.

Bronchiectasis causes breathlessness and fatigue, reducing quality of life. Many affected individuals are less active than healthy peers, increasing their risk of exacerbations and hospitalizations. Correlates of physical activity (PA) and functional exercise capacity remain inconsistent, and most evidence comes from Western populations. Sex-specific differences in disease presentation and functional outcomes are recognised yet remain underexplored in South Asian cohorts. The aim of the study was to examine the relationship between PA and demographic, clinical, and functional variables; to compare these characteristics between sexes; and to identify predictors of functional exercise capacity in individuals with bronchiectasis. Fifty-five adults with stable bronchiectasis were assessed using the International Physical Activity Questionnaire for PA, the modified Medical Research Council scale (mMRC) for dyspnoea, the six-minute walk distance (6MWD) for functional exercise capacity and the bronchiectasis health questionnaire (BHQ) for health status. Bronchiectasis-related clinical characteristics, including disease severity, exacerbation frequency, microbiological status, radiological severity, and disease duration were also recorded. Associations and predictors were examined using correlation analyses and multivariate regression. Lower PA was associated with greater dyspnoea severity (rs = -0.344) and shorter disease duration (rs = 0.275). Females had shorter absolute walking distance (≈57 metres shorter 6MWD) but no significant difference in % predicted 6MWD compared with males. Females also reported higher PA (+1350 MET-minutes/week) than males. Reduced 6MWD correlated with older age, lower BHQ score, female sex, increased exacerbation frequency, greater dyspnoea severity and higher radiological severity. Dyspnoea severity and radiological severity independently predicted functional exercise capacity. Lower PA was weakly associated with greater dyspnoea severity and shorter disease duration. Females reported higher self-reported PA levels despite shorter absolute walking distances than males. Dyspnoea severity emerged as the strongest predictor of functional exercise capacity, while radiological severity was also associated with reduced 6MWD.

Severe pneumonia caused by respiratory virus infection is one of the main threats to the lifespan of the aged population and physiological aging fundamentally drives poor disease outcomes in respiratory viral infections, necessitating investigation of the underlying mechanisms and the development of effective countermeasures. Pulmonary transcriptomic profiling reveals that diffuse cell death, inadequate antiviral responses, myeloid-driven excessive inflammation and immune-thrombosis dictate the pulmonary microenvironment are typical molecular pathology characteristics of the SARS-CoV-2-infected aged hamsters rather than the adult controls. The elevated pathological baseline and dysregulated immune responses are demonstrated as the key host factors of lethal viral pneumonia in the aged hamsters. Meanwhile, SARS-CoV-2 infection in the adult hamsters usually resulted in an aged-like pulmonary transcriptomic signature, suggesting a potential link among aging, dysregulated immune responses and severe illness. To reverse the progression of lethal severe pneumonia in the aged hamsters, we initiated a multidimensional combination therapy of dexamethasone, heparin and the broad-spectrum viral decoy CoVR-MV at three days after infection. Although single- and dual-drug therapies were insufficient to achieve functional cure, the three-drug combination therapy resulted in a potent reduction of high mortality, body weight loss, viral load, lung pathology and cytokine storm through the synergism of immunoregulatory, anticoagulant and antiviral effects, effectively intercepting the multifaceted pathogenic network. This study highlights physiological aging as a core driver of critical COVID-19 pathogenesis and provides valuable clues for the rational design of multi-drug and multi-target therapies against respiratory viral infections and lethal severe pneumonia in the elderly population.

The mechanistic target of rapamycin complex 1 (mTORC1) has been implicated in coronavirus pathogenesis, yet its precise role in shaping antiviral defenses in pneumocytes remains unresolved. This study combines ex vivo human lung tissue assays with a literature-curated, logic-based (Boolean) signaling model to study how mTORC1 influences SARS-CoV-2 replication and type-I interferon (IFN) responses. Our in-vitro data showed that pharmacologic inhibition of mTORC1 with sirolimus was associated with reduced viral replication and increased IFN- β expression across donor samples. To interpret these data, we constructed a network integrating inflammation, stress, apoptosis, and RIG-I-IFN signaling, and evaluated four mechanistic hypotheses for explaining our experiments in which mTORC1 either promotes replication, inhibits IFN, both, or neither. The model was constructed according to the best evidence in the literature and evaluated against 56 independent protein/phosphoprotein readouts from 26 studies not used for model construction; the model achieved high qualitative accuracy overall (F1 ≳ 0.75 ) and on live-virus experiments (F1 ≳ 0.9 ). We found that the hypotheses where mTORC1 promotes viral replication, inhibits IFN, or both were able to qualitatively reproduce the empirical data, i.e., mTORC1 inhibition by sirolimus leads to lower viral replication and higher IFN expression. We queried the robustness of those predictions through a systematic edge knock-in/knockout screen generating 6,328 network variants per scenario (25,312 total). We found that the scenario where mTORC1 enhances viral replication is the more plausible, due to parsimony (this mechanism is also observed in other viral infections), higher robustness (more variants still reproduce the result), and stronger inhibition that is more likely to be observed in biological experiments with low statistical power. This scenario supports the idea that the mTORC1 effects on IFN expression are indirectly mediated by viral replication itself.

Home spirometry has been widely adopted in the delivery of cystic fibrosis (CF) care. While existing literature largely supports its feasibility and positive outcomes, behavior around home disease monitoring remains poorly understood. Inaccurate assumptions about home spirometry behavior may affect resource prioritization and influence clinical decisions and follow-up.

This study aimed to evaluate health care professionals' (HCPs') ability to estimate home spirometry use among people with CF and compare these estimates with actual recorded data.

Home spirometry data from 48 people with CF attending a large adult CF center in the United Kingdom were obtained from the NuvoAir platform for the period from January to December 2024. The home spirometry data were sampled to represent 3 predefined use categories: infrequent, expected, and highly frequent users. A paper-based survey was distributed to HCPs with experience using home spirometry within the CF service, including physicians, CF specialist nurses, and physiotherapists, with survey dissemination and data collection completed in January 2025. Participants rated their familiarity with each person with CF and estimated their spirometry use both categorically (infrequent, expected, or highly frequent user) and numerically as an open-ended response. CF experience was defined as the number of years worked within the CF service. Estimation accuracy was evaluated using mean bias and mean absolute error (MAE).

Of the 29 HCPs invited to participate, 28 (96.6%) responded to the survey, including 10 (35.7%) physicians, 6 (21.4%) nurses, and 12 (42.9%) physiotherapists. There were 790 completed categorical estimates and 794 numerical estimates. The mean CF experience was 15.7 (SD 8.2) years. Across all roles, HCPs systematically underestimated home spirometry use (mean bias -4.9, SD 8.9; MAE 6.32, SD 8.1). No substantial differences in estimation accuracy were observed based on professional role, reported familiarity, or CF experience. Estimation accuracy declined with increasing actual spirometry use, with a strong negative Spearman rank correlation (ρ=-0.88; P<.001). HCPs tended to cluster their estimates within a narrow range, with a median of 4 (IQR 1-5) spirometry sessions per year.

This study suggests that clinical perception by HCPs alone may not accurately reflect real-world engagement with home spirometry in people with CF. As CF care increasingly incorporates remote monitoring and virtual consultations, understanding actual patient engagement becomes increasingly important. Further qualitative and mixed methods research is needed to better understand the factors influencing home spirometry use and how different patterns of engagement can be effectively identified and supported.

The World Health Organization prioritizes pregnant women for influenza vaccination; in China, flu vaccination during pregnancy has not been widely adopted. This gap is due to a lack of targeted policies and limited public health promotion. We aimed to describe knowledge and attitudes toward seasonal influenza vaccination among women of reproductive age (15-49 y old) (WRA), to inform evidence-based policy interventions. A cross-sectional survey assessed WRA's influenza and vaccine awareness, vaccination route preference, and influencing factors, analyzed via chi-square tests and multivariate logistic regression. The knowledge score among WRA in Shanghai Pudong was 3.77 ± 1.23, and the influenza vaccine knowledge score was 3.55 ± 1.66; the pass rates were 60.61% and 56.46%, respectively. Healthcare workers had the highest cognitive levels. Multivariate analysis indicated that education level and being a healthcare professional were predictors of the influenza vaccine pass rate. In particular, the preference for injection decreased sharply from 41.25% among non-pregnant women to 13.31% in the hypothetical pregnancy scenario. In comparison, nasal spray preference rose from 10.60% to 23.17%, and unwillingness increased from 10.19% to 35.58% (P < .05). Pregnant women preferred the nasal spray at 41.67%, a rate significantly higher than that of non-pregnant women (10.60%, P < .05). When receiving influenza vaccine recommendations, 87.63% of participants were more inclined to follow the advice of obstetricians and gynecologists. While WRA in Pudong New Area, Shanghai, demonstrates a relatively high level of attention to influenza and influenza vaccines, key gaps still exist. Strengthening obstetricians' guidance, promoting non-injectable influenza vaccines, and delivering targeted health education are important strategies to improve vaccination uptake in this population.

BackgroundAlthough hospitalization in idiopathic pulmonary fibrosis (IPF) is associated with poor outcomes, it occurs during the disease course and may lead to overestimation of its prognostic impact when analyzed as a fixed exposure.ObjectivesWe aimed to evaluate the association between hospitalization and transplantation-free survival in patients with IPF by modeling hospitalization as a time-dependent exposure and applying a standardized definition of respiratory-related hospitalization.DesignThis was a retrospective cohort study conducted at Asan Medical Center, a tertiary referral center in Seoul, South Korea.MethodsA total of 223 patients with IPF were included. Hospitalization was treated as a time-dependent exposure in Cox regression models. Changes in pulmonary function and exercise capacity before and after hospitalization were assessed using linear mixed-effects models.ResultsSeventy patients (31%) experienced hospitalization during follow-up, whereas 153 (69%) did not. Hospitalized patients had significantly worse lung function and exercise capacity at baseline compared with non-hospitalized patients. When modeled as a time-dependent exposure, hospitalization was strongly associated with increased risk of transplantation or death (adjusted hazard ratio: 8.87, 95% confidence interval [CI]: 5.57-14.11; P<0.001). After excluding patients who died within 10 days of hospitalization, long hospital stay (≥10 days) was associated with poorer transplantation-free survival than short stay (<10 days) (P=0.022). Pulmonary function and exercise capacity declined significantly during hospitalization. Forced vital capacity decreased both before (-7.6%, 95% CI: -11.2 to -4.1; P<0.001) and after hospitalization (-4.8%, 95% CI: -9.4 to -0.2; P=0.04). Minimum oxygen saturation during the six-minute walk test decreased significantly both before (-2.5%, 95% CI: -3.8 to -1.3; P<0.001) and after hospitalization (-2.3%, 95% CI: -4.4 to -0.3; P=0.029).ConclusionHospitalization in IPF was associated with poorer transplantation-free survival and subsequent physiological decline. It may serve as an important time-dependent marker of clinical deterioration and disease progression.

Congenital esophageal atresia (EA), a severe malformation of the digestive tract, has an incidence of approximately 1 in every 2500 to 3000 live births. It is characterized by an interruption in the continuity of the esophagus and is often accompanied by tracheoesophageal fistula (TEF) . The etiology of EA is complex. With continuous advancements in prenatal imaging technology, fetal medicine, and neonatal surgery, the prenatal detection rate, perinatal management, and postoperative outcomes of EA have improved. However, the clinical management of EA still faces significant challenges, including, primarily, the inefficiency of prenatal diagnostic techniques in detecting the most common Type C EA, the lack of quantitative decision-making criteria for individualized timing of surgical intervention, and prognostic evaluations that overemphasize short-term anatomical reconstruction while neglecting long-term quality of life. This article systematically reviews the latest research advances in the etiology, prenatal diagnostic strategies, surgical management, and prognostic evaluation of EA. Given the significant improvement in the overall survival rate of pediatric patients with EA, future clinical research and disease management urgently require a paradigm shift-transitioning from a sole focus on surgical anatomical reconstruction to overcoming technical limitations in prenatal diagnosis, optimizing decision-making for individualized surgical timing, and bridging the gap between short-term anatomical reconstruction and long-term quality of life. Furthermore, it is imperative to further strengthen the multidisciplinary collaborative model and establish standardized, whole-life-cycle follow-up and intervention protocols spanning from the prenatal period through adulthood, with the goal of comprehensively improving the long-term physiological and psychological outcomes of these patients.