Canadian respiratory journal最新文献

Objective: This study aimed to elucidate the impact of HO-1 on cognitive function in chronic obstructive pulmonary disease (COPD) exacerbation mice and uncover the bridging role of exosomes in the interorgan transport of HO-1 along the "lung-brain" axis, providing novel insights into COPD-associated cognitive dysfunction.

Methods: HO-1(-/-) and wild-type mice were subjected to COPD exacerbation modeling through cigarette smoke and LPS exposure. Four groups were divided: (A) HO-1(+/+) mice; (B) HO-1(+/+) COPD exacerbation mice; (C) HO-1(-/-) mice; and (D) HO-1(-/-) COPD exacerbation mice. Cognitive function was assessed using the Morris water maze. Lung-derived exosomal HO-1 was quantified by Western blot. Fluorescently labeled exosomes from Groups A/B were injected into HO-1(-/-) mice via tail vein, generating four new cohorts: Group I: HO-1(+/+) mice injected with PBS; Group II: HO-1(-/-) mice injected with PBS; Group III: HO-1(-/-) mice injected with exosome (Exos) from Group A; Group IV: HO-1(-/-) mice injected with Exos from Group B; Exos biodistribution was tracked via in vivo imaging, followed by cognitive reassessment and HO-1 quantification.

Results: Groups B/D showed reduced target quadrant dwell time versus Groups A/C, and Group B exhibited longer target quadrant dwell time than Group D. This shows that COPD exacerbation mice had cognitive decline, which was exacerbated by HO-1 deficiency. Group B exhibited higher HO-1 expression in lung exosomes than Group A. Injected exosomes accumulated preferentially in lungs over brain; Group IV displayed worse cognitive impairment than Group III.

Conclusions: COPD exacerbation mice exhibit cognitive decline regardless of HO-1 expression status, but HO-1 knockout COPD exacerbation mice demonstrate more pronounced cognitive impairment. In COPD exacerbation mice, HO-1 expression is elevated in lung-derived exosomes. Cross-organ transduction experiments confirm that HO-1 can be transported via Exos and mediate cognitive dysfunction in COPD exacerbation mice. Thus, HO-1 exerts a concentration-dependent dual effect on brain function: protective at physiological levels yet detrimental when in excess.

Objective: To investigate the mediating role of body mass index (BMI) in the association between obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD).

Methods: In this cross-sectional study, 445 adult patients diagnosed with OSA at Zigong Fourth People's Hospital (2022-2024) were initially enrolled. After applying inclusion/exclusion criteria, 309 participants were included. Demographic characteristics and clinical parameters were collected. Correlation analysis and structural equation modeling (SEM) were utilized to assess BMI's mediation effect between OSA and NAFLD.

Results: Correlation analyses revealed significant positive associations of BMI with both OSA (r = 0.296, p < 0.001) and NAFLD (r = 0.225, p < 0.001), while OSA and NAFLD were directly correlated (r = 0.199, p < 0.001). Mediation analysis demonstrated a significant indirect effect of OSA on NAFLD through BMI (β = 0.044, 95% CI: 0.004-0.084), accounting for 22.5% of the total effect. These findings remained robust after adjusting for covariates including sex, age, smoking status, hypertension, and diabetes mellitus.

Conclusion: BMI serves as a critical mediator in the OSA-NAFLD relationship, suggesting that integrated weight management strategies should be incorporated into OSA therapy to reduce hepatic risk.

Background: Chest computed tomography (CT) is widely used in the diagnosis and follow-up of diffuse parenchymal lung diseases like sarcoidosis. This study investigated the relationship between the Thoracic CT Severity Score (TCTSS) and parameters from pulmonary function tests (PFTs), diffusing capacity for carbon monoxide (DLCO), and the 6-min walk test (6MWT) in sarcoidosis patients, comparing its utility to the radiograph-based Scadding staging system.

Methods: This retrospective study analyzed data from 60 sarcoidosis patients with concurrent chest radiograph, CT, PFT, DLCO, and 6MWT results. Patient demographics, TCTSS, Scadding stage, PFT parameters (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], FEV1/FVC, PEF, and FEF25-75), DLCO, DLCO/VA, and 6MWT parameters (initial SpO2, final SpO2, desaturation percentage, distance, and predicted distance percentage) were collected. Correlations between these functional parameters and both TCTSS and Scadding stages were analyzed to compare the strengths of the two staging systems.

Results: TCTSS showed moderate negative correlations with FEV1% (r = -0.44, p < 0.001), FVC% (r = -0.477, p < 0.001), DLCO (r = -0.522, p < 0.001), final 6MWT SpO2 (r = -0.417, p=0.001), and 6MWT% (r = -0.511, p < 0.001). Weaker correlations were observed between TCTSS and initial SpO2, desaturation, and 6MWT distance. The Scadding stage also demonstrated negative correlations with these parameters, although generally weaker for FEV1% and FVC%. TCTSS exhibited stronger negative correlations with FEV1%, FVC%, DLCO, and 6MWT% compared to Scadding staging. Conversely, the Scadding stage correlated more strongly with FVC (liters), FEV1 (liters), FEV1/FVC, DLCO/VA, initial SpO2, final SpO2, and 6MWT distance. Desaturation showed similar low-to-moderate positive correlations with both staging systems.

Conclusions: This study demonstrates that TCTSS significantly correlates with most functional parameters, exhibiting stronger correlations for key measures (FVC%, FEV1%, DLCO, and 6MWT%) compared to the Scadding staging system. TCTSS is a valuable tool that warrants consideration in the follow-up of sarcoidosis patients. Our findings suggest that TCTSS could serve as a potential alternative or complementary system to the Scadding classification, potentially informing the development of a modified combined staging approach. Larger, multicenter studies are necessary to confirm these findings and further explore the role of TCTSS in sarcoidosis management.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease with a poor prognosis and no effective pharmacological treatments. Cytokines are a class of small-molecule proteins with diverse biological activities. Many cytokines-most notably transforming growth factor β-have been demonstrated to play an important role in IPF. However, a few studies have systematically described the relationship between cytokines and IPF.

Methods: Lung tissues from controls and patients with IPF were collected during lung transplantation. The expression profiles of 440 cytokines in lung tissues were obtained using protein microarrays. Proteomic analysis was performed, and differentially expressed proteins (DEPs) were identified. Furthermore, an integrative bioinformatics analysis was performed and included functional enrichment analysis, protein-protein interaction (PPI) network construction, hub protein determination, immune cell infiltration analysis, potential drug prediction, and single-cell analysis. The hub protein expression was validated through Gene Expression Omnibus (GEO) database evaluation and immunochemical analysis.

Results: 32 DEPs were identified from the two groups. They were mainly enriched in cell chemotaxis, basal part of cell, and growth factor binding and were involved in PI3K-Akt signaling. The PPI network was constructed for the DEPs, and five hub proteins (FGF2, HGF, HBEGF, ERBB3, and ANGPT2) were identified. The immune infiltration analysis demonstrated a significantly higher percentage of resting NK cells in IPF lung tissue. The drug prediction analyses identified 13 potential candidates targeting the five hub proteins. The single-cell analysis predicted the cellular localization of each key cytokine.

Conclusions: Using protein microarrays, we obtained comprehensive cytokine expression profiles in control and IPF lung tissues and conducted an integrated bioinformatics analysis of the proteomic data. Our findings may improve the comprehension of the role of cytokines in IPF and the underlying mechanisms. Moreover, they provide novel targets for developing safe and efficacious drugs for treating IPF.

Objective: This study aims to investigate the relationship between the difference in hematocrit and albumin (HCT-ALB) and ventilator-associated pneumonia (VAP) among patients undergoing continuous mechanical ventilation.

Methods: This research utilized the data from the Medical Information Mart for Intensive Care IV database. The primary outcome was VAP occurred. HCT-ALB levels were divided into three groups according to the quantile: < -1.10; -1.10-5.30; ≥ 5.30. All patients with continuous mechanical ventilation were categorized into two groups: those who developed VAP and those who did not. Univariate and multivariate logistic regression analyses were used to assess the relationship between HCT-ALB and VAP risk. Receiver operating characteristic (ROC) curves were used to evaluate the predictive ability. To further assess the robustness of the findings, subgroup analyses were performed.

Results: In our study, a total of 3021 patients were enrolled, and among them, 361 patients experienced VAP. Multivariate logistic regression showed that taking HCT-ALB < -1.10 as reference, HCT-ALB ≥ 5.30 was linked to an increased risk of VAP in patients undergoing continuous mechanical ventilation (odds ratio = 1.36, 95% confidence interval: 1.02-1.81). The ROC curve demonstrated approximately moderate predictive ability. This association remained robust in subgroups of male, quick Sepsis-Related Organ Failure Assessment score ≤ 2, not using antibiotics, having oral care, and no history of trauma injury, chronic obstructive pulmonary disease, or respiratory failure.

Conclusion: HCT-ALB, as an easily measurable indicator, was associated with the risk of VAP in patients with continuous mechanical ventilation.

Objective: This study aimed to explore the potential of LINC01214 in providing prognostic and therapeutic insights, thereby offering valuable references for the research of non-small cell lung cancer (NSCLC).

Methods: 122 NSCLC subjects were recruited. The molecular level was quantified by qPCR and WB. Kaplan-Meier estimated the prognostic effects and Cox regression analyses the hazard ratio. The cell activities including proliferation, apoptosis, and migration/invasion were evaluated by CCK-8, flow cytometry, and Transwell. The regulatory axis of LINC01214/miR-497-3p/HSP90AB1 was verified by the dual luciferase reporter assay and rescue experiments.

Results: LINC01214 increased both in the malignant tissues and cell lines of NSCLC. Mortality was increased in NSCLC patients with high LINC01214 levels. LINC01214 was an independent risk predictor of prognosis in NSCLC. Silencing of LINC01214 inhibited the NSCLC cell proliferation, migration, and invasion and promoted apoptosis. The abundance of miR-497-3p showed an opposite trend to LINC01214. LINC01214 could target miR-497-3p and negatively correlate with miR-497-3p. The inhibitory effect of LINC01214 on cell activity was reversed by miR-497-3p. HSP90AB1 was predicted and further confirmed as the target of miR-497-3p. The LINC01214/miR-497-3p/HSP90AB1 axis regulated NSCLC cell proliferation, migration, and invasion.

Conclusion: LINC01214, a potential biomarker, contributed to the progression of NSCLC through the miR-497-3p/HSP90AB1 axis by promoting cell proliferation and motility.

Background: Lung cancer is the predominant cause of cancer-related mortality globally. Computed tomography (CT) scanning is employed to enhance the early diagnosis of lung cancer by screening for risk factors. This study aimed to examine the impact of CT scanning on the incidence of lung cancer detection in a group with unidentified risk factors for the disease.

Methods: Data from two patient cohorts were analyzed: the "study group," comprising individuals with a CT-detected pulmonary nodule of ≥ 8 mm and unknown lung cancer risk factors, and the "control group," consisting of individuals with a pulmonary nodule of ≥ 8 mm identified by CT scan due to known lung cancer risk factors.

Results: No significant difference was seen between the groups regarding malignancy frequency (p=0.155) and early-stage occurrence (p=0.842).

Conclusions: The incidence of lung cancer in pulmonary nodules measuring ≥ 8 mm is not influenced by the presence of lung cancer risk factors.

Background: In 2022, new guidelines for the diagnosis and treatment of pulmonary hypertension (PH) revised the hemodynamic definition, reducing the mean pulmonary artery pressure threshold from ≥ 25 to > 20 mmHg. The optimal threshold of transthoracic echocardiography (TTE) parameters and the predictive capability require further validation. This study aims to investigate the diagnostic value of TTE parameters under the new hemodynamic criteria.

Methods: Retrospective analysis of PH patients who underwent right heart catheterization and TTE examination between 2017 and 2022 in a single center. Logistic regression was employed to ascertain the predictive capacity of parameters across various conditions. Receiver operating characteristic curves were used to determine the optimal cutoff values based on the new criteria.

Results: In a cohort of 213 patients, the optimal cutoff values identified were a tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary arterial pressure (sPAP) ratio of < 0.50 mm/mmHg, a right ventricular outflow tract acceleration time (RVOT-AT) of < 93 ms, and a right atrial area (RAA) > of 14.5 cm². Regardless of the inclusion of tricuspid regurgitation velocity (TRV) and related parameters, RVOT-AT < 93 ms manifested as an effective predictive parameter. A combination of RVOT-AT < 93 ms, main pulmonary artery diameter > 25 mm and RAA > 14.5 cm² exhibited better specificity.

Conclusion: The threshold values for TAPSE/sPAP, RVOT-AT, and RAA should be adjusted to improve the predictive capacity of PH based on revised criteria in this single-center dataset. RVOT-AT was a promising indirect parameter, and the utilization of combined indirect indicators may enhance diagnostic accuracy, particularly in instances where satisfactory TRV measurements are unavailable.

Hypoxic pulmonary hypertension (HPH) lacks effective treatments. The research is designed to examine the effectiveness of Notoginsenoside R1 (NGR1) in addressing HPH and to explore its molecular mechanisms. Under hypoxic conditions, we created a rat model of HPH and treated the animals with NGR1. We assessed the therapeutic effects of NGR1 on HPH through hemodynamic measurements and pulmonary artery vascular remodeling. We employed transcriptomic analysis to evaluate gene expression changes in HPH rats. We conducted untargeted metabolomics to examine how NGR1 influences the metabolic profile of HPH rats. NGR1 treatment significantly improved hemodynamic parameters and ameliorated pulmonary artery vascular remodeling in HPH rats. Transcriptomic analysis identified Pck1 as the most significantly altered gene. NGR1 intervention significantly improved the expression of vascular remodeling-related proteins. NGR1 reversed the expression of glycolysis-related genes. NGR1 reduced the levels of glycolysis-related metabolites. Further analysis revealed that NGR1 treatment decreased PFKL, HK2, and LDHA protein expression and lowered lactate levels in lung tissue. Our findings demonstrate that NGR1 effectively alleviates the pathological features of HPH in rats. NGR1 inhibits hypoxia-induced glycolysis-mediated pulmonary artery remodeling, mitigates vascular endothelial damage, and suppresses the abnormal proliferation of smooth muscle cells and fibroblasts.