Respiratory Research最新文献

Background: Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder marked by pathological vascular remodeling, predominantly driven by the hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Although bone morphogenetic protein 7 (BMP7) has been implicated in PASMCs dysregulation, the precise upstream mechanisms governing its expression in PH remain elusive.

Methods: In vitro and in vivo models of hypoxia-induced PH were employed. The mRNA and protein levels of the different molecules were quantified using qRT-PCR and Western blot. The role of BMP7 in PASMCs proliferation, cell cycle progression and apoptosis were assessed using Cell Counting Kit-8 (CCK-8) assays, Western blotting, immunofluorescence, and flow cytometry. Moreover, the epigenetic regulatory mechanisms of BMP7 were elucidated using Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and quantitative methylation-specific PCR (qMSP). In vivo functional roles of BMP7 were validated using recombinant protein administration and AAV5-mediated gene knockdown in hypoxic mice, with evaluations of hemodynamics, echocardiography, and vascular remodeling.

Results: Hypoxia significantly upregulated BMP7 expression in PASMCs and lung tissues of PH models. Exogenous BMP7 enhanced PASMCs proliferation, accelerated cell cycle progression and suppressed apoptosis. Conversely, BMP7 knockdown attenuated these pro-proliferative and anti-apoptotic responses. Mechanistically, DNMT1 was downregulated under hypoxia, and its genetic or pharmacological inhibition elevated BMP7 expression, whereas DNMT1 overexpression suppressed BMP7. ChIP-qPCR verified DNMT1 binding to the BMP7 promoter CpG island, and qMSP confirmed that DNMT1 loss reduced BMP7 promoter methylation. Consistent with a pathogenic role, BMP7 knockdown alleviated hypoxia-induced right ventricular hypertrophy and vascular remodeling, while BMP7 supplementation exacerbated these phenotypes.

Conclusions: Our study unveils the DNMT1-BMP7 axis as a critical epigenetic pathway in PH. Hypoxia-induced DNMT1 downregulation derepresses BMP7 via promoter hypomethylation, driving PASMCs proliferation and pathological vascular remodeling. Targeting this axis may offer novel therapeutic strategies for PH.

Background: Flexible bronchoscopy (FB) is recommended for pediatric Mycoplasma pneumoniae pneumonia (MPP) with persistent consolidation or atelectasis, though substantial heterogeneity in treatment effects exists. This study aimed to develop a causal forest-based predictive model to identify pediatric MPP patients most likely to benefit from FB.

Methods: This retrospective two-center study enrolled pediatric MPP patients in derivation (n = 753) and validation (n = 139) cohorts. Clinical, laboratory, and AI-quantified computed tomography (CT) data were analyzed. Individual treatment effects (ITEs) were estimated using causal forest algorithms. FB-beneficial subgroups were defined using receiver operating characteristic (ROC) analysis of ITEs, with the varying treatment effect across the subgroups validated via multivariable linear regression. Subgroup characteristics, feature importance, and heatmap-based feature interactions were also analyzed.

Results: FB treatment significantly reduced total fever duration in identified FB-beneficial subgroups in both derivation (β = - 1.16, p < 0.001) and validation (β = - 0.68, p = 0.04) cohorts. These beneficial subgroups exhibited significantly higher consolidation/atelectasis volume (CAV), pneumonia attenuation (PA), and consolidation-to-pneumonia ratio (CAR) compared to non-beneficial groups (all p < 0.001). Heatmap analyses confirmed that increased CAV combined with elevated PA or lymphocyte counts could improve FB efficacy.

Conclusions: This study developed and validated an individualized prediction model to identify pediatric MPP patients most likely to benefit from FB treatment. Our model may serve as a tool to support clinicians in optimizing FB utilization, potentially reducing unnecessary interventions and associated risks. An accessible online tool of this model facilitates practical clinical implementation.

Background: Respiratory diseases are a major global health burden, and inhalation therapy offers efficient pulmonary targeting and therapeutic effectiveness. Dihydromyricetin (DMY), a natural flavonoid with anti-inflammatory and antiviral activities, shows limited clinical application due to poor solubility, instability, and low oral bioavailability caused by extensive first-pass metabolism.

Methods: A nebulized inhalation formulation of DMY was developed to enhance solubility, stability, and bioavailability. Pharmacokinetics were evaluated in rats following inhalation and oral administration. Safety was assessed through pulmonary function testing and histological examination of major organs.

Results: Inhalation delivery significantly improved DMY bioavailability in both lung and systemic circulation compared with oral dosing. No differences in pulmonary function or tissue morphology were observed between the inhalation and saline groups after short-term administration, suggesting preliminary safety, which warrants further investigation.

Conclusion: The nebulized DMY formulation demonstrates enhanced bioavailability, effective pulmonary targeting, and favorable safety, providing a promising therapeutic strategy for respiratory diseases.

Background: Preterm birth and respiratory diseases disproportionately affect low-and middle-income countries. Although preterm birth is a major contributor to the burden of respiratory morbimortality in early childhood, most evidence comes from high-income settings. To address this gap, we examined respiratory-related hospitalisations and deaths among preterm children in Brazil.

Methods: We conducted a population-based cohort study using the CIDACS Birth Cohort, which included all live births in Brazil from January 1, 2011, to November 30, 2018. Preterm infants were defined as infants born before 37 weeks of gestation. We examined respiratory-related hospital admissions and deaths in children under five. Mean ratios (MR) and 95% confidence intervals (CI) were estimated using the Ghosh-Lin model; hazard ratios (HR) were estimated using Cox models. Maternal characteristics were adjusted through inverse probability weighting, with treatment probabilities estimated via entropy balancing.

Results: The study included 3,239,563 live births, with 288,466 (8.9%) classified as preterm. The MR for under-five respiratory hospitalisation, comparing preterm to term births, was 1.40 (95%CI:1.38-1.42), peaking at 1.68 (1.63-1.72) between 28 and 90 days, declining to approximately 1.18 (1.10-1.28) at the fourth year. For respiratory disease deaths, the under-five HR was 3.94 (3.62-4.30). Respiratory-related mortality was highest between 28-90 days of age, with an HR of 4.66 (4.00-5.43), decreasing to 1.25 (0.62-2.51) by three years of age.

Conclusion: Preterm newborns have a higher risk of respiratory illness than full-term children, particularly in their first year. This understanding can guide health strategies to address premature birth issues by identifying important periods of vulnerability.

Rationale: Idiopathic Pulmonary Fibrosis (IPF) is a progressive scarring disease marked by the accumulation of aberrant basal cells that are thought to promote disease progression. The cellular origin and disease-relevant cues that lead to aberrant basal cells remain poorly understood.

Objectives: We sought to identify the signals regulating formation and maintenance of aberrant basal cells from human alveolar type II (ATII) cells using 3D spheroids, and test whether inhibition of select pathways could reduce aberrant basal signatures in human precision-cut lung slices (PCLS) from diseased lungs.

Methods: We characterized aberrant basal cell signatures in human ATII spheroids in response to TGFβ1 and hypoxia mimic dimethyloxalylglycine (DMOG) treatment alone or in combination. We tested whether a Notch inhibitor (LY-411575) could inhibit/reverse these signatures in human ATII spheroids and IPF PCLS. Readouts included immunofluorescence analysis, western blotting, and quantitative PCR of aberrant basal signature genes.

Main results: We found that human ATII spheroids acquire aberrant basal cell signatures upon TGFβ1 and DMOG treatment, with the combination most effectively programming cells to an aberrant basal state. LY-411575 was able to significantly inhibit or reverse a subset of the aberrant basal cell signatures in 3D spheroids and IPF PCLS.

Conclusions: TGFβ1 and hypoxia are disease relevant signals capable of driving ATII cells to acquire aberrant basal cell signatures found in IPF. Notch inhibition may provide a tractable approach to normalize these programs in the fibrotic human lung.

Background: Acute respiratory distress syndrome (ARDS) is a common complication after type A aortic dissection surgery and often leads to worsened clinical outcomes for patients. The early prediction of postoperative ARDS is a crucial challenge in clinical practice; however, there have been few reports on related studies based on the 2023 global new definition.

Methods: A retrospective analysis was conducted on the clinical data of 423 patients who were diagnosed with type A aortic dissection and who underwent surgery at Northern Jiangsu People's Hospital in Jiangsu Province from November 2019 to April 2025. A 7:3 random division was applied to the patients, resulting in a training set n = 296 and a validation set n = 127. Risk factors were identified via LASSO analysis, and a comprehensive risk prediction model was subsequently constructed by integrating five machine learning algorithms. The receiver operating characteristic (ROC) curve was utilised, and the model with the best predictive performance was selected based on the area under the curve (AUC).

Results: Among the 423 included patients, 192 developed ARDS, with an incidence rate of 45.39%. LASSO analysis revealed 13 risk factors. Among the five machine learning models constructed based on these factors, the random forest model demonstrated the highest prediction efficiency for ARDS (AUC = 0.978), followed by the logistic regression (AUC = 0.965), decision tree (AUC = 0.881), support vector machine (AUC = 0.835), and K-nearest neighbour (AUC = 0.807) models.

Conclusion: The development of a nomogram model using machine learning algorithms for predicting ARDS risk in patients with type A aortic dissection after surgery could identifying high-risk patients at an early stage and enable timely implementations of preventive strategies.

Trial registration: The medical research ethics committee of the Northern Jiangsu People's Hospital provided approval for this study (ethics number: 2024ky314). This study is registered in the Chinese Clinical Trial Registry under registration number ChiCTR2500099730.The registration date was March 27,2025.