Respiratory Research最新文献

{"title":"Assessing the comparative effects of interventions in COPD: a tutorial on network meta-analysis for clinicians.","authors":"Katrin Haeussler, Afisi S Ismaila, Mia Malmenäs, Stephen G Noorduyn, Nathan Green, Chris Compton, Lehana Thabane, Claus F Vogelmeier, David M G Halpin","doi":"10.1186/s12931-024-03056-x","DOIUrl":"10.1186/s12931-024-03056-x","url":null,"abstract":"<p><p>To optimize patient outcomes, healthcare decisions should be based on the most up-to-date high-quality evidence. Randomized controlled trials (RCTs) are vital for demonstrating the efficacy of interventions; however, information on how an intervention compares to already available treatments and/or fits into treatment algorithms is sometimes limited. Although different therapeutic classes are available for the treatment of chronic obstructive pulmonary disease (COPD), assessing the relative efficacy of these treatments is challenging. Synthesizing evidence from multiple RCTs via meta-analysis can help provide a comprehensive assessment of all available evidence and a \"global summary\" of findings. Pairwise meta-analysis is a well-established method that can be used if two treatments have previously been examined in head-to-head clinical trials. However, for some comparisons, no head-to-head studies are available, for example the efficacy of single-inhaler triple therapies for the treatment of COPD. In such cases, network meta-analysis (NMA) can be used, to indirectly compare treatments by assessing their effects relative to a common comparator using data from multiple studies. However, incorrect choice or application of methods can hinder interpretation of findings or lead to invalid summary estimates. As such, the use of the GRADE reporting framework is an essential step to assess the certainty of the evidence. With an increasing reliance on NMAs to inform clinical decisions, it is now particularly important that healthcare professionals understand the appropriate usage of different methods of NMA and critically appraise published evidence when informing their clinical decisions. This review provides an overview of NMA as a method for evidence synthesis within the field of COPD pharmacotherapy. We discuss key considerations when conducting an NMA and interpreting NMA outputs, and provide guidance on the most appropriate methodology for the data available and potential implications of the incorrect application of methods. We conclude with a simple illustrative example of NMA methodologies using simulated data, demonstrating that when applied correctly, the outcome of the analysis should be similar regardless of the methodology chosen.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"438"},"PeriodicalIF":5.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NCAM1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension.","authors":"Yunwei Chen, Ningxin Liu, Yunjing Yang, Lingzhi Yang, Yan Li, Zhuo Qiao, Yumin Zhang, Ailing Li, Rui Xiang, Li Wen, Wei Huang","doi":"10.1186/s12931-024-03068-7","DOIUrl":"10.1186/s12931-024-03068-7","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a malignant vascular disease characterized by pulmonary arterial remodeling. Neural cell adhesion molecule 1 (NCAM1) is a cell surface glycoprotein that is involved in a variety of diseases, including cardiovascular disease. However, the role of NCAM1 in PH remains underexplored.</p><p><strong>Methods: </strong>Pulmonary hypertension models were established using monocrotaline in rats and hypoxia in mice. NCAM1 protein levels in plasma from patients and rats were measured by ELISA. Expression of NCAM1 in rat lung tissues were evaluated using qRT-PCR, Western blotting, and immunofluorescence. The effects of NCAM1 on rat pulmonary artery smooth muscle cells were studied by stimulating these cells with PDGF-BB.</p><p><strong>Results: </strong>Elevated levels of NCAM1 protein and mRNA were observed in both PH patients and monocrotaline-induced PH rats. NCAM1 knockdown ameliorated hypoxia-induced PH, highlighting its role in pulmonary artery remodeling. In PASMCs, NCAM1 expression was upregulated by PDGF-BB stimulation, enhancing cell proliferation and migration. This effect was attenuated by NCAM1 knockdown but partially restored by an ERK1/2 pathway activator (tert-butylhydroquinone, TBHQ), suggesting NCAM1's involvement in PASMC dynamics through the ERK1/2 signaling pathway.</p><p><strong>Conclusion: </strong>Our findings confirm the role of NCAM1 in pulmonary arterial hypertension and demonstrate its promotion of PASMC proliferation and migration through the ERK1/2 signaling pathway.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"435"},"PeriodicalIF":5.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal anemia status and risk for adverse outcomes in former smokers with COPD.","authors":"Yukiko Kunitomo, Han Woo, Aparna Balasubramanian, Ashraf Fawzy, Cheng Ting Lin, Sarath Raju, Daniel C Belz, Meredith C McCormack, Kirsten Koehler, Nadia N Hansel, Nirupama Putcha","doi":"10.1186/s12931-024-03071-y","DOIUrl":"10.1186/s12931-024-03071-y","url":null,"abstract":"<p><strong>Background: </strong>Anemia is a prevalent comorbidity in COPD associated with increased morbidity. However, the significance of longitudinal anemia status and variation in anemia status trends over time in COPD are not known. Furthermore, individuals with COPD and smoking history often have multiple comorbidities, in particular cardiovascular disease. The objective of this study was to evaluate the association between longitudinal anemia status and COPD outcomes, accounting for comorbid cardiovascular disease.</p><p><strong>Methods: </strong>Serial hemoglobin measures and clinical outcomes were obtained in former smokers with moderate to severe COPD from two clinical studies over a 6-to-9-month period. In the first analysis, the association between repeated measures of time-varying anemia status and outcomes was assessed by generalized estimating equations adjusted for covariates including cardiovascular disease. In the second analysis, each participant's anemia risk profile during the study period was characterized as high versus low anemia risk-growth rate. Mean differences in the progression of COPD outcomes over time between the two groups were assessed using a generalized linear mixed model. Effect modification by baseline coronary artery calcium (CAC) burden was explored.</p><p><strong>Results: </strong>There were 159 individuals with mean age of 66.5 years (± 8.3) and mean FEV₁% predicted of 51.4% (± 17.0), of which 41% were ever-anemic during the study period. Repeated measures of anemia status were associated with higher St. George's Respiratory Questionnaire (SGRQ) scores (β 2.5, 95% CI: 0.1,4.8, p = 0.04), lower 6-minute walk distance (6MWD) (β -38.6, 95% CI: -67.7,-7.4, p = 0.02), and higher rate of moderate-to-severe exacerbations over the prospective follow-up period (IRR 1.8, 95% CI: 1.1,2.8, p = 0.02). There was effect modification by CAC burden such that with higher burden the mean difference in COPD outcome by anemia status was greater for a subset of symptom scores. Participants with profiles of increasing anemia risk had higher estimated rates of decline in the FEV₁% predicted and 6MWD and increase in SGRQ scores compared to those with stable or decreasing anemia risk.</p><p><strong>Conclusions: </strong>Longitudinal anemia status trends may be predictive of COPD disease trajectory. Anemia status by repeated measures analysis is associated with COPD morbidity with potentially stronger associations in the setting of high CAC burden.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"437"},"PeriodicalIF":5.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The F508del-CFTR trafficking correctors elexacaftor and tezacaftor are CFTR-independent Ca²⁺-mobilizing agonists normalizing abnormal Ca²⁺ levels in human airway epithelial cells.","authors":"Manuella Lévêque, Sandra Mirval, Christine Barrault, Isabelle Fixe, Christelle Coraux, Edouard Sage, Frédéric Becq, Clarisse Vandebrouck","doi":"10.1186/s12931-024-03059-8","DOIUrl":"10.1186/s12931-024-03059-8","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel. For people with CF (pwCF) affected by the most common pathogenic variant F508del, a tritherapy, named Trikafta/Kaftrio (ETI: elexacaftor (VX-445) /tezacaftor (VX-661) / ivacaftor (VX-770)) was successfully developed. However, in CF airway epithelial cells the calcium homeostasis is also disturbed; it is observed an increased calcium mobilization in CF cells compared to non-CF cells. Here, we studied the effects of ETI on intracellular calcium levels in F508del-CFTR airway epithelial cells to determine whether these compounds, individually or collectively, could normalize intracellular calcium levels.</p><p><strong>Methods: </strong>We measured intracellular calcium variations using human airway epithelial cells (hAEC) from pwCF, human bronchial epithelial CFBE41o- F508del-CFTR cells and Chinese Hamster Ovary (CHO) cells using the fluorescent probe Fluo4-AM, in the presence or absence of extracellular calcium. The rescue to the plasma membrane of F508del-CFTR protein by ETI was determined by western blot. The SarcoEndoplasmic Reticulum Calcium ATPase (SERCA), was also analysed by western blotting and by interference assay.</p><p><strong>Results: </strong>We show that ETI normalizes calcium homeostasis in our cellular models. However, we also found that (1) each ETI-corrector compound is capable of mobilizing calcium acutely in the absence of CFTR, and (2) tezacaftor mobilizes calcium from the endoplasmic reticulum (ER) probably via inhibition of the SERCA pump.</p><p><strong>Conclusions: </strong>We show that ETI not only corrects the abnormal trafficking and function of F508del-CFTR but also normalizes calcium homeostasis in our cellular models. Finally, we identified SERCA as a potential intracellular target for tezacaftor.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"436"},"PeriodicalIF":5.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and prognostic implications of family history of fibrotic interstitial lung diseases.","authors":"D Duminy-Luppi, A Alcaide-Aldeano, L Planas-Cerezales, G Bermudo, V Vicens-Zygmunt, P Luburich, B Del Río-Carrero, R Llatjós, L Pijuan, I Escobar, F Rivas, A Montes-Worboys, Y Gutiérrez-Rodríguez, D Rodríguez-Plaza, A Padró-Miquel, A Esteve-Garcia, B Fernández-Varas, C Flores, M Fuentes, J Dorca, S Santos, R Perona, A Günther, J Shull, M Molina-Molina","doi":"10.1186/s12931-024-03063-y","DOIUrl":"10.1186/s12931-024-03063-y","url":null,"abstract":"<p><strong>Background: </strong>Patients with familial fibrotic interstitial lung disease (ILD) experience worse survival than patients with sporadic disease. Current guidelines do not consider family aggregation or genetic information in the diagnostic algorithm for idiopathic pulmonary fibrosis or other fibrotic ILDs. Better characterizing familial cases could help in diagnostic and treatment decision-making.</p><p><strong>Methods: </strong>This retrospective cohort study included 222 patients with fibrotic ILD (104 familial and 118 sporadic) from Bellvitge University Hospital. Clinical, radiological, pulmonary functional tests (PFT), and histological evaluations were performed at diagnosis and follow-up. Telomere shortening and disease-associated variants (DAVs) in telomerase-related genes were analysed in familial patients and sporadic patients with telomeric clinical signs. Primary outcomes were the presence of a UIP histological pattern and disease progression.</p><p><strong>Results: </strong>Patients with idiopathic pulmonary fibrosis (IPF) (52%), fibrotic hypersensitivity pneumonitis (23%), and other fibrotic ILDs (25%) were included. 42% of patients underwent lung biopsy. Patients with family aggregation were younger and less frequently associated comorbidities, male sex, and smoking history. However, usual interstitial pneumonia (UIP) was more frequent on pathology (p = 0.005; OR 3.37), especially in patients with indeterminate or non-UIP radiological patterns. Despite similar PFT results at diagnosis, familial patients were more likely to present with progressive disease (p = 0.001; OR 3.75). Carrying a DAV increased the risk of fibrotic progression in familial and sporadic patients (p = 0.029, OR 5.01).</p><p><strong>Discussion: </strong>Familial patients diagnosed with different fibrotic ILDs were more likely to exhibit a histological UIP pattern and disease progression than sporadic patients, independent of radiological findings and pulmonary function at diagnosis.</p><p><strong>Conclusion: </strong>Considering the diagnostic likelihood of the histological UIP pattern and disease outcome, the presence of family aggregation would be useful in the decision making of multidisciplinary committees.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"433"},"PeriodicalIF":5.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A worldwide assessment of the mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease. Analysis of the VENTILAGROUP over time. A retrospective, multicenter study.","authors":"Oscar Peñuelas, Laura Del Campo-Albendea, Luis Morales-Quinteros, Alfonso Muriel, Nicolás Nin, Arnaud Thille, Bin Du, Bruno Pinheiro, Fernando Ríos, María Carmen Marín, Salvatore Maggiore, Konstantinos Raymondos, Marco González, Andrew Bersten, Pravin Amin, Nahit Cakar, Gee Young Suh, Fekri Abroug, Manuel Jibaja, Dimitros Matamis, Amine Ali Zeggwagh, Yuda Sutherasan, Antonio Artigas, Antonio Anzueto, Andrés Esteban, Fernando Frutos-Vivar, Lorenzo Del Sorbo","doi":"10.1186/s12931-024-03037-0","DOIUrl":"10.1186/s12931-024-03037-0","url":null,"abstract":"<p><strong>Background: </strong>The trend over time and across different geographical areas of outcomes and management with noninvasive ventilation or invasive mechanical ventilation in patients admitted for acute exacerbations of chronic obstructive pulmonary disease and treated with ventilatory support is unknown. The purpose of this study was to describe outcomes and identify variables associated with survival for patients admitted to an intensive care unit (ICU) with acute exacerbation of chronic obstructive pulmonary disease [aeCOPD] who received noninvasive or invasive mechanical ventilation worldwide.</p><p><strong>Methods: </strong>Retrospective, multi-national, and multicenter studies, including four observational cohort studies, were carried out in 1998, 2004, 2010, and 2016 for the VENTILAGROUP following the same methodology.</p><p><strong>Results: </strong>A total of 1,848 patients from 1,253 ICUs in 38 countries admitted for aeCOPD and need of ventilatory support were identified in the four study cohorts and included in the study. The overall incidence of aeCOPD as a cause for ventilatory support at ICU admission significantly decreased over time and varied widely according to the gross national income. The mortality of patients admitted to ICU for aeCOPD and ventilatory support significantly decreased over time regardless of the geographical area and gross national income; however, there is a remarkable variability in ICU mortality according to geographical area and gross national income. The use of NPPV as the first attempt at ventilatory support has significantly increased over time, with a parallel reduction of invasive mechanical ventilation regardless of gross national income.</p><p><strong>Conclusion: </strong>In this worldwide observational study, including four sequential cohorts of patients over 18 years from 1998 to 2016, the mortality of patients admitted to ICU for aeCOPD and ventilatory support significantly decreased regardless of the geographical area and gross national income. Future research will need to investigate the reason for the remarkable variability in ICU mortality according to the geographical area, gross national income, and methods to select patients for the appropriate ventilatory support.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"434"},"PeriodicalIF":5.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"A systematic literature review of the epidemiology, clinical, economic and humanistic burden in recurrent respiratory papillomatosis\".","authors":"Olga Ovcinnikova, Kayla Engelbrecht, Meenu Verma, Rishabh Pandey, Edith Morais","doi":"10.1186/s12931-024-03057-w","DOIUrl":"10.1186/s12931-024-03057-w","url":null,"abstract":"<p><strong>Introduction: </strong>Recurrent respiratory papillomatosis (RRP) is a chronic disease caused by human papillomavirus (HPV), characterized by recurrent papillomas in the respiratory tract. Presenting as either juvenile-onset RRP (JoRRP) or adult-onset RRP (AoRRP), the severity of the disease is subjective and unpredictable. Lack of curative therapies necessitates disease management involving repeated surgical removal of lesions. The review aimed to assess the clinical, humanistic and economic burden associated with RRP.</p><p><strong>Methods: </strong>Systematic literature reviews of Embase^®, MEDLINE^® and Cochrane databases were conducted for epidemiology, clinical, humanistic, and economic burden, from database inception to November 30, 2022. Conference abstracts were also searched (2019-2022). Key inclusion criteria consisted of juveniles or adults with RRP/laryngeal papillomatosis, with no restriction on study country, interventions, or comparators. Outcomes of interest included incidence, prevalence, risk factors, symptomatic presentation, HPV genotype, cost burden, resource use and health related quality of life (HRQoL).</p><p><strong>Results: </strong>In JoRRP, the incidence rate ranged from 0.2-2.1 per 100,000 and the prevalence rate ranged from 0.8-4.3 per 100,000. Incidence and prevalence of AoRRP were 0.2-3.9 and 0.4-8.4 per 100,000, respectively. Limited studies reported the subsequent impact of introducing national prophylactic HPV immunisation programs on JoRRP epidemiology, but where available, they were associated with significantly reduced incidence rates. Symptomatic presentations were diverse, with voice impact and breathing difficulties commonly reported. More aggressive disease was linked to earlier age of onset and HPV11 genotype. Healthcare utilisation was largely driven by surgical interventions, due to lack of curative treatments. Cost burden was substantial, with JoRRP associated with triple the costs of AoRRP in the US. Patients with JoRRP and AoRRP experienced considerable HRQoL impairment, particularly relating to voice disorder.</p><p><strong>Conclusion: </strong>Extensive clinical, humanistic and economic disease burden was reported for both JoRRP and AoRRP, as it is a chronic condition, with propensity to recur and spread. Feasibility of improving HPV prophylactic vaccination coverage against HPV6/HPV11 should be explored to reduce incidence, alongside efforts to improve treatment of JoRRP and AoRRP patients. Despite the existing literature, RRP remains a poorly understood disease, and future research on risk factors and medical options are needed.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"430"},"PeriodicalIF":5.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bexarotene ameliorated the pulmonary inflammation and M1 polarization of alveolar macrophages induced by cigarette smoke via PPARγ/HO-1.","authors":"Haoshen Feng, Zhe Li, Rui Zheng","doi":"10.1186/s12931-024-03064-x","DOIUrl":"10.1186/s12931-024-03064-x","url":null,"abstract":"<p><strong>Background: </strong>Alveolar macrophages (AMs) modulate pulmonary inflammation in chronic obstructive pulmonary disease (COPD), contributing to its progression. The PPARγ/RXRα heterodimer influences AM polarization induced by cigarette smoke (CS). Although PPARγ agonists suppress CS-induced M1 macrophage polarization, the impact of RXRα agonists on this process has not been determined. This study explored the effects and mechanisms of the RXRα agonist bexarotene on macrophage polarization in a COPD mouse model.</p><p><strong>Methods: </strong>C57BL/6 mice were assigned to the control, model, bexarotene, or model + bexarotene group. The COPD model was induced by CS exposure and intraperitoneal injection of cigarette smoke extract (CSE), followed by intraperitoneal administration of bexarotene. Additionally, MH-S cells were exposed to CSE and bexarotene. Lung tissues were subjected to hematoxylin-eosin staining, and emphysema and inflammatory scores were assessed. Cytokine levels and cell differentials in bronchoalveolar lavage fluid were measured, and macrophage polarization was evaluated using immunohistochemistry, flow cytometry, and qPCR.</p><p><strong>Results: </strong>Bexarotene effectively reduced inflammatory scores, cytokine levels, and neutrophil counts and ameliorated emphysema and M1 polarization of AMs in COPD model mice. Furthermore, while CSE exposure reduced PPARγ expression and the transcriptional activity of AMs, bexarotene enhanced the transcriptional response of PPARγ to CSE. HO-1 was identified as a potential target of PPARγ; its levels were assessed in AMs, revealing that bexarotene mitigated the CSE-induced reduction in HO-1. Notably, the effect of bexarotene was partially inhibited by the PPARγ inhibitor.</p><p><strong>Conclusions: </strong>Our results indicated that bexarotene may curb inflammation and M1 polarization in COPD through activation of the PPARγ/HO-1 pathway.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"431"},"PeriodicalIF":5.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a Prediction Model for Chronic Thromboembolic Pulmonary Disease.","authors":"Guixiang Liu, Jing Wen, Chunyi Lv, Mingjie Liu, Min Li, Kexia Fang, Jianwen Fei, Nannan Zhang, Xuehua Li, Huarui Wang, Yuanyuan Sun, Ling Zhu","doi":"10.1186/s12931-024-03067-8","DOIUrl":"10.1186/s12931-024-03067-8","url":null,"abstract":"<p><strong>Background: </strong>Acute pulmonary embolism (APE) is a critical disease with a high mortality rate, some of the surviving patients may develop chronic thromboembolic pulmonary disease (CTEPD), which affects the patient's prognosis. However, the research on the early diagnosis of CTEPD is limited. This study aimed to establish a prediction model for earlier identification of CTEPD.</p><p><strong>Methods: </strong>This prospective study included 464 consecutive patients with APE confirmed between January 2020 and September 2023, at 7 centers from China. After follow-up for at least 3 months, the patients were divided into the CTEPD and non-CTEPD groups based on symptoms and computed tomography pulmonary angiography (CTPA) or pulmonary ventilation perfusion (V/Q) scans showing residual thrombosis. The independent risk factors for CTEPD were identified via univariate and multivariate logistic regression analyses. Next, a nomogram of predictive model was established, and validation was completed via decision curve analysis (DCA) and receiver operating characteristic curve analysis.</p><p><strong>Result: </strong>In total, 130 (28%) patients presented with CTEPD, 17% (22/130) of CTEPD patients developed chronic thromboembolic pulmonary hypertension (CTEPH). Based on the multivariate analysis, a time interval from symptoms onset to diagnosis (time-to-diagnosis) ≥ 15 days (95% confidence interval [CI]: 3.392-14.972, p < 0.001), recurrent pulmonary embolism (RPE) (95%CI: 1.560-17.300, p = 0.007), right ventricular dysfunction (RVD) (95%CI: 1.042-6.437, p = 0.040), central embolus (95%CI: 1.776-7.383, p < 0.001) and residual pulmonary vascular obstruction (RPVO) > 10% (95%CI: 4.884-21.449, p < 0.001) were identified as the independent predictors of CTEPD. Then, A prediction model with a C-index of 0.895 (95% CI 0.863-0.927) was established for high-risk patients. The nomogram had an excellent predictive performance for earlier identification of CTEPD, with an area under the curve of 0.908 (95%CI: 0.875-0.941) in the training cohort and 0.875 (95%CI: 0.803-0.947) in the validation cohort.</p><p><strong>Conclusion: </strong>The current study established and validated a reliable nomogram for predicting CTEPD, which would assist clinicians identify the high-risk patients for CTEPD earlier.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"432"},"PeriodicalIF":5.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing SMAD4 inhibits inflammation and ferroptosis in asthma by blocking the IL-17A signaling pathway.","authors":"Xingyu Rao, Hong Luo, Kaiyuan Luo, Chaohua Hu","doi":"10.1186/s12931-024-03052-1","DOIUrl":"10.1186/s12931-024-03052-1","url":null,"abstract":"<p><strong>Background: </strong>The TGF-β/SMAD signaling pathway is crucial in the pathogenesis of asthma. However, SMAD family member 4 (SMAD4), a key mediator of TGF-β, its roles and underlying mechanisms in asthma remain unclear.</p><p><strong>Methods: </strong>The in vivo and in vitro roles of SMAD4 in asthma were investigated through an ovalbumin (OVA)-induced mouse model and an interleukin-13 (IL-13)-induced cell model. The molecular mechanism of SMAD4 influenced asthma was examined using transcriptome sequencing, followed by feedback experiments involving recombinant human interleukin 17 A (rhIL-17 A), an IL-17 A signaling pathway activator.</p><p><strong>Results: </strong>SMAD4 was highly expressed in the asthma models. SMAD4 silencing alleviated damage to lung tissue and decreased inflammatory infiltration. Expression levels of Caspase-3, IgG, and inflammatory factors were reduced after silencing SMAD4. Silencing SMAD4 suppressed ferroptosis. Silencing SMAD4 also enhanced IL-13-induced BEAS-2B cell proliferation and suppressed apoptosis. Furthermore. IL-17 A signaling pathway was promoted in the asthma models, as evidenced by elevated IL-17RA, IL-17 A, and Act1 protein levels. SMAD4 silencing inhibited the expression levels of these IL-17 A pathway-associated proteins. Moreover, rhIL-17 A treatment notably reversed the impacts of SMAD4 silencing on asthma in the IL-13-induced cell model and OVA-induced mouse model, indicating that silencing SMAD4 inhibited inflammation and ferroptosis in asthma by blocking the IL-17 A signaling pathway.</p><p><strong>Conclusion: </strong>Silencing SMAD4 prevents inflammation and ferroptosis in asthma by inhibiting the IL-17 pathway, which provides a novel potential approach for asthma therapy.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"429"},"PeriodicalIF":5.8,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}