Esra Ertan Yazar, Gulsah Gunluoglu, Burcu Arpinar Yigitbas, Mukadder Calikoglu, Gazi Gulbas, Nilgün Yılmaz Demirci, Nurhan Sarioglu, Fulsen Bozkus, Nevin Taci Hoca, Nalan Ogan, Seda Tural Onur, Muzaffer Onur Turan, Filiz Kosar, Evrim Eylem Akpinar, Burak Mete, Can Ozturk
Background: Several studies have shown that the risk of mortality due to COVID-19 is high in patients with COPD. However, evidence on factors predicting mortality is limited. Research Question: Are there any useful markers to predict mortality in COVID-19 patients with COPD?. Study Design and Methods: A total of 689 patients were included in this study from the COPET study, a national multicenter observational study investigating COPD phenotypes consisting of patients who were followed up with a spirometry-confirmed COPD diagnosis. Patients were also retrospectively examined in terms of COVID-19 and their outcomes. Results: Among the study patients, 105 were diagnosed with PCR-positive COVID-19, and 19 of them died. Body mass index (p= 0.01) and ADO (age, dyspnoea, airflow obstruction) index (p= 0.01) were higher, whereas predicted FEV1 (p< 0.001) and eosinophil count (p= 0.003) were lower in patients who died of COVID-19. Each 0.755 unit increase in the ADO index increased the risk of death by 2.12 times, and each 0.007 unit increase in the eosinophil count decreased the risk of death by 1.007 times. The optimum cut-off ADO score of 3.5 was diagnostic with 94% sensitivity and 40% specificity in predicting mortality. Interpretation: Our study suggested that the ADO index recorded in the stable period in patients with COPD makes a modest contribution to the prediction of mortality due to COVID-19. Further studies are needed to validate the use of the ADO index in estimating mortality in both COVID-19 and other viral respiratory infections in patients with COPD.
{"title":"Can the ADO Index Be Used as a Predictor of Mortality from COVID-19 in Patients with COPD?","authors":"Esra Ertan Yazar, Gulsah Gunluoglu, Burcu Arpinar Yigitbas, Mukadder Calikoglu, Gazi Gulbas, Nilgün Yılmaz Demirci, Nurhan Sarioglu, Fulsen Bozkus, Nevin Taci Hoca, Nalan Ogan, Seda Tural Onur, Muzaffer Onur Turan, Filiz Kosar, Evrim Eylem Akpinar, Burak Mete, Can Ozturk","doi":"10.2147/copd.s440099","DOIUrl":"https://doi.org/10.2147/copd.s440099","url":null,"abstract":"<strong>Background:</strong> Several studies have shown that the risk of mortality due to COVID-19 is high in patients with COPD. However, evidence on factors predicting mortality is limited.<br/><strong>Research Question:</strong> Are there any useful markers to predict mortality in COVID-19 patients with COPD?.<br/><strong>Study Design and Methods:</strong> A total of 689 patients were included in this study from the COPET study, a national multicenter observational study investigating COPD phenotypes consisting of patients who were followed up with a spirometry-confirmed COPD diagnosis. Patients were also retrospectively examined in terms of COVID-19 and their outcomes.<br/><strong>Results:</strong> Among the study patients, 105 were diagnosed with PCR-positive COVID-19, and 19 of them died. Body mass index (p= 0.01) and ADO (age, dyspnoea, airflow obstruction) index (p= 0.01) were higher, whereas predicted FEV<sub>1</sub> (p< 0.001) and eosinophil count (p= 0.003) were lower in patients who died of COVID-19. Each 0.755 unit increase in the ADO index increased the risk of death by 2.12 times, and each 0.007 unit increase in the eosinophil count decreased the risk of death by 1.007 times. The optimum cut-off ADO score of 3.5 was diagnostic with 94% sensitivity and 40% specificity in predicting mortality.<br/><strong>Interpretation:</strong> Our study suggested that the ADO index recorded in the stable period in patients with COPD makes a modest contribution to the prediction of mortality due to COVID-19. Further studies are needed to validate the use of the ADO index in estimating mortality in both COVID-19 and other viral respiratory infections in patients with COPD.<br/><br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lujie Wei, Pingyang Li, Xiaofeng Liu, Yuxia Wang, Zhengping Tang, Hang Zhao, Lu Yu, Kaixiu Li, Jianping Li, Min Du, Xinzhu Chen, Xin Zheng, Yixiong Zheng, Yao Luo, Jing Chen, Xiamin Jiang, Xiaobing Chen, Huaicong Long
Background: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear. Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year. Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People’s Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC). Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P< 0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663– 0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693– 0.891); sensitivity, 86.3%; specificity, 60.0%). Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.
{"title":"Multidimensional Frailty Instruments Can Predict Acute Exacerbations Within One Year in Patients with Stable Chronic Obstructive Pulmonary Disease: A Retrospective Longitudinal Study","authors":"Lujie Wei, Pingyang Li, Xiaofeng Liu, Yuxia Wang, Zhengping Tang, Hang Zhao, Lu Yu, Kaixiu Li, Jianping Li, Min Du, Xinzhu Chen, Xin Zheng, Yixiong Zheng, Yao Luo, Jing Chen, Xiamin Jiang, Xiaobing Chen, Huaicong Long","doi":"10.2147/copd.s448294","DOIUrl":"https://doi.org/10.2147/copd.s448294","url":null,"abstract":"<strong>Background:</strong> Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear.<br/><strong>Purpose:</strong> (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year.<br/><strong>Patients and methods:</strong> In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People’s Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC).<br/><strong>Results:</strong> A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (<em>P</em>< 0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663– 0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693– 0.891); sensitivity, 86.3%; specificity, 60.0%).<br/><strong>Conclusion:</strong> Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.<br/><br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhouzhou Feng, Zhengcai Han, Yaqin Wang, Hong Guo, Jian Liu
Objective: To comparison of the application of Vibrating Mesh Nebulizer and Jet Nebulizer in chronic obstructive pulmonary disease (COPD). Research Methods: This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: The amount of inhaler in the urine sample at 30 minutes after inhalation therapy (USAL0.5), The total amount of inhaler in urine sample within 24 hours (USAL24), Aerosol emitted, Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC). Results: Ten studies were included with a total of 314 study participants, including 157 subjects in the VMN group and 157 subjects in the JN group. The data analysis results of USAL0.5, MD (1.88 [95% CI, 0.95 to 2.81], P = 0.000), showed a statistically significant difference. USAL24, MD (1.61 [95% CI, 1.14 to 2.09], P = 0.000), showed a statistically significant difference. The results of aerosol emitted showed a statistically significant difference in MD (3.44 [95% CI, 2.84 to 4.04], P = 0.000). The results of FEV1 showed MD (0.05 [95% CI, − 0.24 to 0.35], P=0.716), the results were not statistically significant. The results of FVC showed MD (0.11 [95% CI, − 0.18 to 0.41], P=0.459), the results were not statistically significant. It suggests that VMN is better than JN and provides higher aerosols, but there is no difference in improving lung function between them. Conclusion: VMN is significantly better than JN in terms of drug delivery and utilization in the treatment of patients with COPD. However, in the future use of nebulizers, it is important to select a matching nebulizer based on a combination of factors such as mechanism of action of the nebulizer, disease type and comorbidities, ventilation strategies and modes, drug formulations, as well as cost-effectiveness, in order to achieve the ideal treatment of COPD.
{"title":"Comparison of the Application of Vibrating Mesh Nebulizer and Jet Nebulizer in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta‐analysis","authors":"Zhouzhou Feng, Zhengcai Han, Yaqin Wang, Hong Guo, Jian Liu","doi":"10.2147/copd.s452191","DOIUrl":"https://doi.org/10.2147/copd.s452191","url":null,"abstract":"<strong>Objective:</strong> To comparison of the application of Vibrating Mesh Nebulizer and Jet Nebulizer in chronic obstructive pulmonary disease (COPD).<br/><strong>Research Methods:</strong> This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: The amount of inhaler in the urine sample at 30 minutes after inhalation therapy (USAL0.5), The total amount of inhaler in urine sample within 24 hours (USAL24), Aerosol emitted, Forced expiratory volume in 1 second (FEV<sub>1</sub>), Forced vital capacity (FVC).<br/><strong>Results:</strong> Ten studies were included with a total of 314 study participants, including 157 subjects in the VMN group and 157 subjects in the JN group. The data analysis results of USAL0.5, MD (1.88 [95% CI, 0.95 to 2.81], P = 0.000), showed a statistically significant difference. USAL24, MD (1.61 [95% CI, 1.14 to 2.09], P = 0.000), showed a statistically significant difference. The results of aerosol emitted showed a statistically significant difference in MD (3.44 [95% CI, 2.84 to 4.04], P = 0.000). The results of FEV<sub>1</sub> showed MD (0.05 [95% CI, − 0.24 to 0.35], P=0.716), the results were not statistically significant. The results of FVC showed MD (0.11 [95% CI, − 0.18 to 0.41], P=0.459), the results were not statistically significant. It suggests that VMN is better than JN and provides higher aerosols, but there is no difference in improving lung function between them.<br/><strong>Conclusion:</strong> VMN is significantly better than JN in terms of drug delivery and utilization in the treatment of patients with COPD. However, in the future use of nebulizers, it is important to select a matching nebulizer based on a combination of factors such as mechanism of action of the nebulizer, disease type and comorbidities, ventilation strategies and modes, drug formulations, as well as cost-effectiveness, in order to achieve the ideal treatment of COPD.<br/><br/><strong>Keywords:</strong> chronic obstructive pulmonary disease, aerosol, vibrating mesh nebulizers, jet nebulizers, meta-analysis<br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140314580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah N Miller, Michelle Nichols, Ronald J Teufel II, Erin P Silverman, Marta Walentynowicz
Abstract: Dyspnea is an unpredictable and distressing symptom of chronic obstructive pulmonary disease (COPD). Dyspnea is challenging to measure due to the heterogeneity of COPD and recall bias associated with retrospective reports. Ecological Momentary Assessment (EMA) is a technique used to collect symptoms in real-time within a natural environment, useful for monitoring symptom trends and risks of exacerbation in COPD. EMA can be integrated into mobile health (mHealth) platforms for repeated data collection and used alongside physiological measures and behavioral activity monitors. The purpose of this paper is to discuss the use of mHealth and EMA for dyspnea measurement, consider clinical implications of EMA in COPD management, and identify needs for future research in this area.
Keywords: COPD, ecological momentary assessment, mobile health, dyspnea, mHealth, telehealth
摘要：呼吸困难是慢性阻塞性肺疾病（COPD）的一种难以预测且令人痛苦的症状。由于慢性阻塞性肺病的异质性和回顾性报告的回忆偏差，呼吸困难的测量具有挑战性。生态瞬间评估（EMA）是一种用于在自然环境中实时收集症状的技术，可用于监测慢性阻塞性肺病的症状趋势和恶化风险。EMA 可集成到移动医疗（mHealth）平台中进行重复数据收集，并与生理测量和行为活动监测器一起使用。本文旨在讨论移动医疗和 EMA 在呼吸困难测量中的应用，考虑 EMA 在慢性阻塞性肺病管理中的临床意义，并确定该领域未来研究的需求：慢性阻塞性肺病、生态瞬间评估、移动医疗、呼吸困难、移动医疗、远程医疗
{"title":"Use of Ecological Momentary Assessment to Measure Dyspnea in COPD","authors":"Sarah N Miller, Michelle Nichols, Ronald J Teufel II, Erin P Silverman, Marta Walentynowicz","doi":"10.2147/copd.s447660","DOIUrl":"https://doi.org/10.2147/copd.s447660","url":null,"abstract":"<strong>Abstract:</strong> Dyspnea is an unpredictable and distressing symptom of chronic obstructive pulmonary disease (COPD). Dyspnea is challenging to measure due to the heterogeneity of COPD and recall bias associated with retrospective reports. Ecological Momentary Assessment (EMA) is a technique used to collect symptoms in real-time within a natural environment, useful for monitoring symptom trends and risks of exacerbation in COPD. EMA can be integrated into mobile health (mHealth) platforms for repeated data collection and used alongside physiological measures and behavioral activity monitors. The purpose of this paper is to discuss the use of mHealth and EMA for dyspnea measurement, consider clinical implications of EMA in COPD management, and identify needs for future research in this area.<br/><br/><strong>Keywords:</strong> COPD, ecological momentary assessment, mobile health, dyspnea, mHealth, telehealth<br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140314911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Menghong Wan, Chen Wang, Jiamin Cui, Qing Xia, Lei Zhang
Background: The incidence of chronic obstructive pulmonary disease (COPD) is increasing year by year. Kruppel-like factor 6 (KLF6) plays an important role in inflammatory diseases. However, the regulatory role of KLF6 in COPD has not been reported so far. Methods: The viability of human bronchial epithelial cells BEAS-2B induced by cigarette smoke extract (CSE) was detected by CCK-8 assay. The protein expression of KLF6 and sirtuin 4 (SIRT4) was appraised with Western blot. RT-qPCR and Western blot were applied to examine the transfection efficacy of sh-KLF6 and Oe-KLF6. Cell apoptosis was detected using flow cytometry. The levels of inflammatory factors IL-6, TNF-α and IL-1β were assessed with ELISA assay. DCFH-DA staining was employed for the detection of ROS activity and the levels of oxidative stress markers SOD, CAT and MDA were estimated with corresponding assay kits. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content and Complex I activity were evaluated with JC-1 staining, ATP colorimetric/fluorometric assay kit and Complex I enzyme activity microplate assay kit. With the application of mitochondrial permeability transition pore detection kit, mPTP opening was measured. Luciferase report assay was employed to evaluate the activity of SIRT4 promoter and chromatin immunoprecipitation (ChIP) to verify the binding ability of KLF6 and SIRT4 promoter. Results: KLF6 expression was significantly elevated in CSE-induced cells. KLF6 was confirmed to suppress SIRT4 transcription. Interference with KLF6 expression significantly inhibited cell viability damage, cell apoptosis, inflammatory response, oxidative stress and mitochondrial dysfunction in CSE-induced BEAS-2B cells, which were all reversed by SIRT4 overexpression. Conclusion: Silencing KLF6 alleviated CSE-induced mitochondrial dysfunction in bronchial epithelial cells by SIRT4 upregulation.
{"title":"Silencing KLF6 Alleviates Cigarette Smoke Extract-Induced Mitochondrial Dysfunction in Bronchial Epithelial Cells by SIRT4 Upregulation","authors":"Menghong Wan, Chen Wang, Jiamin Cui, Qing Xia, Lei Zhang","doi":"10.2147/copd.s451264","DOIUrl":"https://doi.org/10.2147/copd.s451264","url":null,"abstract":"<strong>Background:</strong> The incidence of chronic obstructive pulmonary disease (COPD) is increasing year by year. Kruppel-like factor 6 (KLF6) plays an important role in inflammatory diseases. However, the regulatory role of KLF6 in COPD has not been reported so far.<br/><strong>Methods:</strong> The viability of human bronchial epithelial cells BEAS-2B induced by cigarette smoke extract (CSE) was detected by CCK-8 assay. The protein expression of KLF6 and sirtuin 4 (SIRT4) was appraised with Western blot. RT-qPCR and Western blot were applied to examine the transfection efficacy of sh-KLF6 and Oe-KLF6. Cell apoptosis was detected using flow cytometry. The levels of inflammatory factors IL-6, TNF-α and IL-1β were assessed with ELISA assay. DCFH-DA staining was employed for the detection of ROS activity and the levels of oxidative stress markers SOD, CAT and MDA were estimated with corresponding assay kits. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content and Complex I activity were evaluated with JC-1 staining, ATP colorimetric/fluorometric assay kit and Complex I enzyme activity microplate assay kit. With the application of mitochondrial permeability transition pore detection kit, mPTP opening was measured. Luciferase report assay was employed to evaluate the activity of SIRT4 promoter and chromatin immunoprecipitation (ChIP) to verify the binding ability of KLF6 and SIRT4 promoter.<br/><strong>Results:</strong> KLF6 expression was significantly elevated in CSE-induced cells. KLF6 was confirmed to suppress SIRT4 transcription. Interference with KLF6 expression significantly inhibited cell viability damage, cell apoptosis, inflammatory response, oxidative stress and mitochondrial dysfunction in CSE-induced BEAS-2B cells, which were all reversed by SIRT4 overexpression.<br/><strong>Conclusion:</strong> Silencing KLF6 alleviated CSE-induced mitochondrial dysfunction in bronchial epithelial cells by SIRT4 upregulation.<br/><br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140201187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meilan Xian, Jiaoyuan Xu, Yamei Zheng, Lei Zhang, Jie Zhao, Jie Chen, Siguang Li, Lingsang Lin, Yi Zhong, Zehua Yang, Tian Xie, Linhui Huang, Yipeng Ding
Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder in pulmonology. Chuanbeimu (CBM) is a traditional Chinese medicinal herb for treating COPD and has been widely utilized in clinical practice. However, the mechanism of CBM in the treatment of COPD remains incompletely understood. This study aims to investigate the underlying therapeutic mechanism of CBM for COPD using network pharmacology and experimental approaches. Methods: Active ingredients and their targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database. COPD-associated targets were retrieved from the GeneCards database. The common targets for CBM and COPD were identified through Venn diagram analysis. Protein-protein interaction (PPI) networks and disease-herb-ingredient-target networks were constructed. Subsequently, the results of the network pharmacology were validated by molecular docking and in vitro experiments. Results: Seven active ingredients and 32 potential targets for CBM were identified as closely associated with COPD. The results of the disease-herb-ingredient-target network and PPI network showed that peimisine emerged as the core ingredient, and SRC, ADRB2, MMP2, and NOS3 were the potential targets for CBM in treating COPD. Molecular docking analysis confirmed that peimisine exhibited high binding affinity with SRC, ADRB2, MMP2, and NOS3. In vitro experiments demonstrated that peimisine significantly upregulated the expression of ADRB2 and NOS3 and downregulated the expression of SRC and MMP2. Conclusion: These findings indicate that CBM may modulate the expression of SRC, ADRB2, MMP2, and NOS3, thereby exerting a protective effect against COPD.
{"title":"Network Pharmacology and Experimental Verification Reveal the Regulatory Mechanism of Chuanbeimu in Treating Chronic Obstructive Pulmonary Disease","authors":"Meilan Xian, Jiaoyuan Xu, Yamei Zheng, Lei Zhang, Jie Zhao, Jie Chen, Siguang Li, Lingsang Lin, Yi Zhong, Zehua Yang, Tian Xie, Linhui Huang, Yipeng Ding","doi":"10.2147/copd.s442191","DOIUrl":"https://doi.org/10.2147/copd.s442191","url":null,"abstract":"<strong>Background:</strong> Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder in pulmonology. Chuanbeimu (CBM) is a traditional Chinese medicinal herb for treating COPD and has been widely utilized in clinical practice. However, the mechanism of CBM in the treatment of COPD remains incompletely understood. This study aims to investigate the underlying therapeutic mechanism of CBM for COPD using network pharmacology and experimental approaches.<br/><strong>Methods:</strong> Active ingredients and their targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database. COPD-associated targets were retrieved from the GeneCards database. The common targets for CBM and COPD were identified through Venn diagram analysis. Protein-protein interaction (PPI) networks and disease-herb-ingredient-target networks were constructed. Subsequently, the results of the network pharmacology were validated by molecular docking and in vitro experiments.<br/><strong>Results:</strong> Seven active ingredients and 32 potential targets for CBM were identified as closely associated with COPD. The results of the disease-herb-ingredient-target network and PPI network showed that peimisine emerged as the core ingredient, and <em>SRC, ADRB2, MMP2</em>, and <em>NOS3</em> were the potential targets for CBM in treating COPD. Molecular docking analysis confirmed that peimisine exhibited high binding affinity with <em>SRC, ADRB2, MMP2</em>, and <em>NOS3</em>. In vitro experiments demonstrated that peimisine significantly upregulated the expression of <em>ADRB2</em> and <em>NOS3</em> and downregulated the expression of <em>SRC</em> and <em>MMP2</em>.<br/><strong>Conclusion:</strong> These findings indicate that CBM may modulate the expression of <em>SRC, ADRB2, MMP2</em>, and <em>NOS3</em>, thereby exerting a protective effect against COPD.<br/><br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140200959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Here, we studied the pharmacological effect of P22077 on airway inflammation induced by lipopolysaccharide and cigarette smoke and explored the therapeutic mechanism of P22077 in COPD model RAT. Patients and Methods: The COPD model was established by lipopolysaccharide combined with fumigation; animals were treated with vehicle or P22077. Serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for analysis. Results: Our results showed that P22077 treatment significantly improved the airway inflammation of COPD model RAT and reduced the recruitment of leukocytes in BALF, and hypersecretion of interleukin-18 (IL-18), interleukin-1β (IL-1β) in BALF and serum. H&E staining showed that P22077 treatment could effectively reduce emphysema, immune cell infiltration and airway wall destruction. PAS staining showed that The proliferation of cup cells in the airway wall and the number of bronchial cup cells were significantly reduced in rats treated with P22077. In addition, we found that P22077 treatment suppressed the generation of the NLRP3/ASC/Caspase 1 inflammasome complex to inhibit the inflammatory response caused by IL-1β and IL-18. Conclusion: Conclusion: P22077 inhibits expression of NLRP3 pathway-related inflammatory factors and proteins and reduces the airway inflammatory response and inflammatory cell aggregation in COPD rats. The underlying mechanism may be related to the down-regulation of NLRP3 inflammatory vesicle signaling pathway expression.
{"title":"Inhibitory Effect of P22077 on Airway Inflammation in Rats with COPD and Its Mechanism","authors":"Di Zeng, Wenbo Zhang, Xiaoju Chen, Guochun Ou, Yuewei Huang, Chengxiu Yu","doi":"10.2147/copd.s451244","DOIUrl":"https://doi.org/10.2147/copd.s451244","url":null,"abstract":"<strong>Purpose:</strong> Here, we studied the pharmacological effect of P22077 on airway inflammation induced by lipopolysaccharide and cigarette smoke and explored the therapeutic mechanism of P22077 in COPD model RAT.<br/><strong>Patients and Methods:</strong> The COPD model was established by lipopolysaccharide combined with fumigation; animals were treated with vehicle or P22077. Serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for analysis.<br/><strong>Results:</strong> Our results showed that P22077 treatment significantly improved the airway inflammation of COPD model RAT and reduced the recruitment of leukocytes in BALF, and hypersecretion of interleukin-18 (IL-18), interleukin-1β (IL-1β) in BALF and serum. H&E staining showed that P22077 treatment could effectively reduce emphysema, immune cell infiltration and airway wall destruction. PAS staining showed that The proliferation of cup cells in the airway wall and the number of bronchial cup cells were significantly reduced in rats treated with P22077. In addition, we found that P22077 treatment suppressed the generation of the NLRP3/ASC/Caspase 1 inflammasome complex to inhibit the inflammatory response caused by IL-1β and IL-18.<br/><strong>Conclusion:</strong> Conclusion: P22077 inhibits expression of NLRP3 pathway-related inflammatory factors and proteins and reduces the airway inflammatory response and inflammatory cell aggregation in COPD rats. The underlying mechanism may be related to the down-regulation of NLRP3 inflammatory vesicle signaling pathway expression.<br/><br/><strong>Keywords:</strong> COPD, ubiquitinase inhibitors, P22077, airway inflammation, NLRP3<br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140172263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Circular RNAs (circRNAs) are newly identified endogenous non-coding RNAs that function as crucial gene modulators in the development of several diseases. By assessing the expression levels of circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD), this study attempted to find new biomarkers for COPD screening. Patients and Methods: We confirmed altered circRNA expression in PBMCs of COPD (n=41) vs controls (n=29). Further analysis focused on the highest and lowest circRNA expression levels. The T-test is used to assess the statistical variances in circRNAs among COPD patients in the smoking and non-smoking cohorts. Additionally, among smokers, the Spearman correlation test assesses the association between circRNAs and clinical indicators. Results: Two circRNAs, hsa_circ_0042590 and hsa_circ_0049875, that were highly upregulated and downregulated in PBMCs from COPD patients were identified and verified. Smokers with COPD had lower hsa_circ_0042590 and higher hsa_circ_0049875, in comparison to non-smokers. There was a significant correlation (r=0.52, P< 0.01) between the number of acute exacerbations (AEs) that smokers with COPD experienced in the previous year and the following year (r=0.67, P< 0.001). Moreover, hsa_circ_0049875 was connected to the quantity of AEs in the year prior (r=0.68, P< 0.0001) as well as the year after (r=0.72, P< 0.0001). AUC: 0.79, 95% CI: 0.1210– 0.3209, P< 0.0001) for hsa_circ_0049875 showed a strong diagnostic value for COPD, according to ROC curve analysis. Hsa_circ_0042590 showed a close second with an AUC of 0.83 and 95% CI: − 0.1972--0.0739 (P < 0.0001). Conclusion: This research identified a strong correlation between smoking and hsa_circ_0049875 and hsa_circ_0042590 in COPD PBMCs. The number of AEs in the preceding and succeeding years was substantially linked with the existence of hsa_circ_0042590 and hsa_circ_0049875 in COPD patients who smoke. Additionally, according to our research, hsa_circ_0049875 and hsa_circ_0042590 may be valuable biomarkers for COPD diagnosis.
{"title":"Circular RNA Expression of Peripheral Blood Mononuclear Cells Associated with Risk of Acute Exacerbation in Smoking Chronic Obstructive Pulmonary Disease","authors":"Xu-Rui Shen, Ying-Ying Liu, Rui-Qi Qian, Wei-Yun Zhang, Jian-An Huang, Xiu-Qin Zhang, Da-Xiong Zeng","doi":"10.2147/copd.s448759","DOIUrl":"https://doi.org/10.2147/copd.s448759","url":null,"abstract":"<strong>Purpose:</strong> Circular RNAs (circRNAs) are newly identified endogenous non-coding RNAs that function as crucial gene modulators in the development of several diseases. By assessing the expression levels of circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD), this study attempted to find new biomarkers for COPD screening.<br/><strong>Patients and Methods:</strong> We confirmed altered circRNA expression in PBMCs of COPD (n=41) vs controls (n=29). Further analysis focused on the highest and lowest circRNA expression levels. The <em>T</em>-test is used to assess the statistical variances in circRNAs among COPD patients in the smoking and non-smoking cohorts. Additionally, among smokers, the Spearman correlation test assesses the association between circRNAs and clinical indicators.<br/><strong>Results:</strong> Two circRNAs, hsa_circ_0042590 and hsa_circ_0049875, that were highly upregulated and downregulated in PBMCs from COPD patients were identified and verified. Smokers with COPD had lower hsa_circ_0042590 and higher hsa_circ_0049875, in comparison to non-smokers. There was a significant correlation (r=0.52, P< 0.01) between the number of acute exacerbations (AEs) that smokers with COPD experienced in the previous year and the following year (r=0.67, P< 0.001). Moreover, hsa_circ_0049875 was connected to the quantity of AEs in the year prior (r=0.68, P< 0.0001) as well as the year after (r=0.72, P< 0.0001). AUC: 0.79, 95% CI: 0.1210– 0.3209, P< 0.0001) for hsa_circ_0049875 showed a strong diagnostic value for COPD, according to ROC curve analysis. Hsa_circ_0042590 showed a close second with an AUC of 0.83 and 95% CI: − 0.1972--0.0739 (P < 0.0001).<br/><strong>Conclusion:</strong> This research identified a strong correlation between smoking and hsa_circ_0049875 and hsa_circ_0042590 in COPD PBMCs. The number of AEs in the preceding and succeeding years was substantially linked with the existence of hsa_circ_0042590 and hsa_circ_0049875 in COPD patients who smoke. Additionally, according to our research, hsa_circ_0049875 and hsa_circ_0042590 may be valuable biomarkers for COPD diagnosis.<br/><br/><strong>Keywords:</strong> chronic obstructive pulmonary disease, circular RNAs, smoking, acute exacerbation, biomarker<br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140172265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madalina Macrea, Atul Malhotra, Richard ZuWallack, Krisann Oursler, Richard Casaburi
Abstract: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Overlap Syndrome (OS), the co-occurrence of Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease. Clustering of patients in subgroups with similar pre-clinical manifestations (ie, endothelial dysfunction) may identify relevant therapeutic phenotype categories for patients with OS who are at high risk of CVD. We therefore conducted a cross-sectional pilot study of endothelial function in 7 patients with OS (Forced Expiratory Volume in 1 second/Forced Vital Capacity < 0.7) on continuous positive airway pressure therapy (n = 7) to assess the relationship between FMD and physical activity. We found a strong association between FMD and step counts (rho = 0.77, p = 0.04); and FMD and moderate physical activity (rho = 0.9, p = 0.005). Further, larger studies are needed to confirm that FMD may identify patients with OS at high risk of CVD who benefit from increased physical activity.
{"title":"A Cross-Sectional Study Evaluating the Association of Brachial Artery Flow Mediated Vasodilation with Physical Activity Measured by Accelerometry in Patients with the Overlap of Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease","authors":"Madalina Macrea, Atul Malhotra, Richard ZuWallack, Krisann Oursler, Richard Casaburi","doi":"10.2147/copd.s432243","DOIUrl":"https://doi.org/10.2147/copd.s432243","url":null,"abstract":"<strong>Abstract:</strong> Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Overlap Syndrome (OS), the co-occurrence of Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease. Clustering of patients in subgroups with similar pre-clinical manifestations (ie, endothelial dysfunction) may identify relevant therapeutic phenotype categories for patients with OS who are at high risk of CVD. We therefore conducted a cross-sectional pilot study of endothelial function in 7 patients with OS (Forced Expiratory Volume in 1 second/Forced Vital Capacity < 0.7) on continuous positive airway pressure therapy (n = 7) to assess the relationship between FMD and physical activity. We found a strong association between FMD and step counts (rho = 0.77, p = 0.04); and FMD and moderate physical activity (rho = 0.9, p = 0.005). Further, larger studies are needed to confirm that FMD may identify patients with OS at high risk of CVD who benefit from increased physical activity.<br/><br/><strong>Keywords:</strong> flow-mediated dilation, chronic obstructive pulmonary disease, obstructive sleep apnea, physical activity<br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140172267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: The heterogeneity of clinical features in COPD at stable state has been associated with airway microbiota. Blood eosinophil count (BEC) represents a biomarker for a pejorative evolution of COPD, including exacerbations and accelerated FEV1 decline. We aimed to analyse the associations between BEC and airway microbiota in COPD at stable state. Patients and Methods: Adult COPD patients at stable state (RINNOPARI cohort) were included and characterised for clinical, functional, biological and morphological features. BEC at inclusion defined 2 groups of patients with low BEC < 300/mm3 and high BEC ≥ 300/mm3. Sputa were collected and an extended microbiological culture was performed for the identification of viable airway microbiota. Results: Fifty-nine subjects were included. When compared with the low BEC (n=40, 67.8%), the high BEC group (n=19, 32.2%) had more frequent exacerbations (p< 0.001) and more pronounced cough and sputum (p< 0.05). The global composition, the number of bacteria per sample and the α-diversity of the microbiota did not differ between groups, as well as the predominant phyla (Firmicutes), or the gender repartition. Conclusion: In our study, high BEC in COPD at stable state was associated with a clinical phenotype including frequent exacerbation, but no distinct profile of viable airway microbiota compared with low BEC.
{"title":"High Blood Eosinophil Count at Stable State is Not Associated with Airway Microbiota Distinct Profile in COPD","authors":"Jeanne-Marie Perotin, Anaëlle Muggeo, Quentin Lecomte-Thenot, Audrey Brisebarre, Sandra Dury, Claire Launois, Julien Ancel, Valérian Dormoy, Thomas Guillard, Gaëtan Deslee","doi":"10.2147/copd.s453526","DOIUrl":"https://doi.org/10.2147/copd.s453526","url":null,"abstract":"<strong>Purpose:</strong> The heterogeneity of clinical features in COPD at stable state has been associated with airway microbiota. Blood eosinophil count (BEC) represents a biomarker for a pejorative evolution of COPD, including exacerbations and accelerated FEV<sub>1</sub> decline. We aimed to analyse the associations between BEC and airway microbiota in COPD at stable state.<br/><strong>Patients and Methods:</strong> Adult COPD patients at stable state (RINNOPARI cohort) were included and characterised for clinical, functional, biological and morphological features. BEC at inclusion defined 2 groups of patients with low BEC < 300/mm<sup>3</sup> and high BEC ≥ 300/mm<sup>3</sup>. Sputa were collected and an extended microbiological culture was performed for the identification of viable airway microbiota.<br/><strong>Results:</strong> Fifty-nine subjects were included. When compared with the low BEC (n=40, 67.8%), the high BEC group (n=19, 32.2%) had more frequent exacerbations (p< 0.001) and more pronounced cough and sputum (p< 0.05). The global composition, the number of bacteria per sample and the α-diversity of the microbiota did not differ between groups, as well as the predominant phyla (Firmicutes), or the gender repartition.<br/><strong>Conclusion:</strong> In our study, high BEC in COPD at stable state was associated with a clinical phenotype including frequent exacerbation, but no distinct profile of viable airway microbiota compared with low BEC.<br/><br/><strong>Keywords:</strong> COPD, eosinophil, sputum, microbiota<br/>","PeriodicalId":13792,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140149854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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