Respiratory Research最新文献

{"title":"The burden of cough in idiopathic pulmonary fibrosis and other interstitial lung diseases: a systematic evidence synthesis.","authors":"Rhiannon Green, Michael Baldwin, Nick Pooley, Kate Misso, Maureen Pmh Rutten-van Mölken, Nina Patel, Marlies S Wijsenbeek","doi":"10.1186/s12931-024-02897-w","DOIUrl":"10.1186/s12931-024-02897-w","url":null,"abstract":"<p><strong>Background: </strong>Cough remains a persistent symptom in patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). To inform future research, treatment and care models, we conducted the first systematic synthesis of evidence on its associated burden.</p><p><strong>Methods: </strong>A literature search was performed for articles published between January 2010 and October 2023 using databases including Embase, MEDLINE and the Cochrane Library. Studies in patients with IPF and other ILDs reporting cough-related measures were eligible for inclusion. Included studies were categorised based on the types of ILD they examined and their design. Study details, patient characteristics and outcomes were extracted, and the risk of bias was assessed. A narrative synthesis approach was employed to interpret the findings.</p><p><strong>Results: </strong>Sixty-one studies were included: 33 in IPF, 18 in mixed-ILDs, six in connective tissue disease-associated-ILDs and four in sarcoidosis. Across the studies, a range of tools to assess cough and its impact were used. The most frequently used measures of cough were cough severity visual analogue scale (VAS) and objective cough counts, whereas the most frequently used health-related quality of life (HRQoL)/impact measures were the St. George's Respiratory Questionnaire (SGRQ) and Leicester Cough Questionnaire (LCQ). In IPF, studies consistently reported correlations between various cough and HRQoL measures, including between cough VAS scores and objective cough counts, LCQ scores and SGRQ scores. Similar correlations were observed in studies in other ILDs, but data were more limited. Qualitative studies in both IPF and other ILDs consistently highlighted the significant cough-related burden experienced by patients, including disruption of daily activities, fatigue and social embarrassment. Although there were no studies specifically investigating the economic burden of cough, one study in patients with fibrotic ILD found cough severity was associated with workplace productivity loss.</p><p><strong>Conclusions: </strong>Our study underscores the heterogeneity in assessing cough and its impact in IPF and other ILDs. The findings confirm the negative impact of cough on HRQoL in IPF and suggest a comparable impact in other ILDs. Our synthesis highlights the need for standardised assessment tools, along with dedicated studies, particularly in non-IPF ILDs and on the economic burden of cough.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082376","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":"Cobalt exposure and pulmonary function reduction in chronic obstructive pulmonary disease patients: the mediating role of club cell secretory protein.","authors":"Fei Tang, Hong-Yan Liu, Qi-Yuan He, Ying Liu, Li-Ping Lv, Jun Fei, Lin Fu","doi":"10.1186/s12931-024-02950-8","DOIUrl":"10.1186/s12931-024-02950-8","url":null,"abstract":"<p><strong>Background: </strong>Cobalt (Co) is a metal which is widely used in the industrial production. The previous studies found the toxic effects of environmental Co exposure on multiple organs. However, the correlation of blood Co concentration with lung function was inconsistent in patients with chronic obstructive pulmonary disease (COPD).</p><p><strong>Methods: </strong>All 771 stable COPD patients were recruited. Peripheral blood and clinical information were collected. The levels of blood Co and serum CC16 were measured.</p><p><strong>Results: </strong>Cross-sectional study suggested that the level of blood Co was inversely and dose-dependently related to lung function parameters. Each 1 ppm elevation of blood Co was related to 0.598 L decline in FVC, 0.465 L decline in FEV1, 6.540% decline in FEV1/FVC%, and 14.013% decline in FEV1%, respectively. Moreover, higher age, enrolled in winter, current-smoking, higher smoking amount, and inhaled corticosteroids prominently exacerbated the negative correlation between blood Co and lung function. Besides, serum CC16 content was gradually reduced with blood Co elevation in COPD patients. Besides, serum CC16 was positively correlated with lung function, and inversely related to blood Co. Additionally, decreased CC16 substantially mediated 11.45% and 6.37% Co-triggered downregulations in FEV1 and FEV1%, respectively.</p><p><strong>Conclusion: </strong>Blood Co elevation is closely related to the reductions of pulmonary function and serum CC16. CC16 exerts a significantly mediating role of Co-related to pulmonary function decrease among COPD patients.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057020","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":"Transcriptomic analysis reveals distinct effects of cigarette smoke on murine airspace and bone-marrow derived macrophages.","authors":"Lynne Faherty, William Z Zhang, Mays M Salih, Elektra K Robinson, Elizabeth Perez, Kihwan Kim, Susan Carpenter, Suzanne M Cloonan","doi":"10.1186/s12931-024-02939-3","DOIUrl":"10.1186/s12931-024-02939-3","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is an inflammatory airway disease characterized by emphysema and chronic bronchitis and a leading cause of mortality worldwide. COPD is commonly associated with several comorbid diseases which contribute to exacerbated patient outcomes. Cigarette smoke (CS) is the most prominent risk factor for COPD development and progression and is known to be detrimental to numerous effector functions of lung resident immune cells, including phagocytosis and cytokine production. However, how CS mediates the various pathologies distant from the lung in COPD, and whether CS has a similar biological effect on systemic immune cells remains unknown.</p><p><strong>Methods: </strong>C57BL/6 mice were exposed to 8 weeks of CS as an experimental model of COPD. Bone marrow cells were isolated from both CS-exposed and room air (RA) control mice and differentiated to bone marrow-derived macrophages (BMDMs). Airspace macrophages (AMs) were isolated from the same CS-exposed and RA mice and bulk RNA-Seq performed. The functional role of differentially expressed genes was assessed through gene ontology analyses. Ingenuity Pathway Analysis was used to determine the activation states of canonical pathways and upstream regulators enriched in differentially expressed genes in both cell types, and to compare the differences between the two cell types.</p><p><strong>Results: </strong>CS induced transcriptomic changes in BMDMs, including an upregulation of genes in sirtuin signalling and oxidative phosphorylation pathways and a downregulation of genes involved in histone and lysine methylation. In contrast, CS induced decreased expression of genes involved in pathogen response, phagosome formation, and immune cell trafficking in AMs. Little overlap was observed in differentially expressed protein-coding genes in BMDMs compared to AMs and their associated pathways, highlighting the distinct effects of CS on immune cells in different compartments.</p><p><strong>Conclusions: </strong>CS exposure can induce transcriptomic remodelling in BMDMs which is distinct to that of AMs. Our study highlights the ability of CS exposure to affect immune cell populations distal to the lung and warrants further investigation into the functional effects of these changes and the ensuing role in driving multimorbid disease.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057022","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":"Surgery versus intrapleural fibrinolysis for management of complicated pleural infections: a systematic review and meta-analysis.","authors":"Jaewon Chang, Ben Indja, Jesse King, Stephanie Chan, Campbell D Flynn","doi":"10.1186/s12931-024-02949-1","DOIUrl":"10.1186/s12931-024-02949-1","url":null,"abstract":"<p><strong>Background: </strong>Complicated pleural infection comprises of complex effusions and empyema. When tube thoracostomy is ineffective, treatment options include surgical drainage, deloculation and decortication or intrapleural fibrinolysis. We performed a systematic review and meta-analysis to examine which technique is superior in treating complicated pleural infections.</p><p><strong>Methods: </strong>PubMed, MEDLINE and EMBASE databases were searched for studies published between January 2000 to July 2023 comparing surgery and intrapleural fibrinolysis for treatment of complicated pleural infection. The primary outcome was treatment success. Secondary outcomes included hospital length of stay, chest drain duration and in-hospital mortality.</p><p><strong>Results: </strong>Surgical management of complicated pleural infections was more likely to be successful than intrapleural fibrinolysis (RR 1.18; 95% CI 1.02, 1.38). Surgical intervention group benefited from statistically significant shorter hospital length of stay (MD: 3.85; 95% CI 1.09, 6.62) and chest drain duration (MD: 3.42; 95% CI 1.36, 5.48). There was no observed difference between in-hospital mortality (RR: 1.00; 95% CI 0.99, 1.02).</p><p><strong>Conclusion: </strong>Surgical management of complicated pleural infections results in increased likelihood of treatment success, shorter chest drain duration and hospital length of stay in the adult population compared with intrapleural fibrinolysis. In-hospital mortality did not differ. Large cohort and randomized research need to be conducted to confirm these findings.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057021","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":"Vitamin D ameliorates particulate matter induced mitochondrial damages and calcium dyshomeostasis in BEAS-2B human bronchial epithelial cells.","authors":"Ju Chang-Chien, Jing-Long Huang, Hui-Ju Tsai, Shih-Ling Wang, Ming-Ling Kuo, Tsung-Chieh Yao","doi":"10.1186/s12931-024-02951-7","DOIUrl":"10.1186/s12931-024-02951-7","url":null,"abstract":"<p><strong>Background: </strong>Mitochondria is prone to oxidative damage by endogenous and exogenous sources of free radicals, including particulate matter (PM). Given the role of mitochondria in inflammatory disorders, such as asthma and chronic obstructive pulmonary disease, we hypothesized that supplementation of vitamin D may play a protective role in PM-induced mitochondrial oxidative damages of human bronchial epithelial BEAS-2B cells.</p><p><strong>Methods: </strong>BEAS-2B cells were pretreated with 1,25(OH)₂D₃, an active form of vitamin D, for 1 h prior to 24-hour exposure to PM (SRM-1648a). Oxidative stress was measured by flow cytometry. Mitochondrial functions including mitochondrial membrane potential, ATP levels, and mitochondrial DNA copy number were analyzed. Additionally, mitochondrial ultrastructure was examined using transmission electron microscopy. Intracellular and mitochondrial calcium concentration changes were assessed using flow cytometry based on the expression of Fluo-4 AM and Rhod-2 AM, respectively. Pro-inflammatory cytokines, including IL-6 and MCP-1, were quantified using ELISA. The expression levels of antioxidants, including SOD1, SOD2, CAT, GSH, and NADPH, were determined.</p><p><strong>Results: </strong>Our findings first showed that 24-hour exposure to PM led to the overproduction of reactive oxygen species (ROS) derived from mitochondria. PM-induced mitochondrial oxidation resulted in intracellular calcium accumulation, particularly within mitochondria, and alterations in mitochondrial morphology and functions. These changes included loss of mitochondrial membrane integrity, disarrayed cristae, mitochondrial membrane depolarization, reduced ATP production, and increased mitochondrial DNA copy number. Consequently, PM-induced mitochondrial damage triggered the release of certain inflammatory cytokines, such as IL-6 and MCP-1. Similar to the actions of mitochondrial ROS inhibitor MitoTEMPO, 1,25(OH)₂D₃ conferred protective effects on mtDNA alterations, mitochondrial damages, calcium dyshomeostasis, thereby decreasing the release of certain inflammatory cytokines. We found that greater cellular level of 1,25(OH)₂D₃ upregulated the expression of enzymatic (SOD1, SOD2, and CAT) and non-enzymatic (GSH and NADPH) antioxidants to modulate cellular redox homeostasis.</p><p><strong>Conclusion: </strong>Our study provides new evidence that 1,25(OH)₂D₃ acts as an antioxidant, enhancing BEAS-2B antioxidant responses to regulate mitochondrial ROS homeostasis and mitochondrial function, thereby enhancing epithelial defense against air pollution exposure.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037503","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":"Impact of radiomics features, pulmonary emphysema score and muscle mass on the rate of pneumothorax and chest tube insertion in CT-guided lung biopsies.","authors":"Jakob Leonhardi, Ulrike Dahms, Benedikt Schnarkowski, Manuel Florian Struck, Anne-Kathrin Höhn, Sebastian Krämer, Sebastian Ebel, Gordian Prasse, Armin Frille, Timm Denecke, Hans-Jonas Meyer","doi":"10.1186/s12931-024-02936-6","DOIUrl":"10.1186/s12931-024-02936-6","url":null,"abstract":"<p><p>Iatrogenic pneumothorax is a relevant complication of computed tomography (CT)-guided percutaneous lung biopsy. The aim of the present study was to analyze the prognostic significance of texture analysis, emphysema score and muscle mass derived from CT-imaging to predict postinterventional pneumothorax after CT-guided lung biopsy. Consecutive patients undergoing CT-guided percutaneous lung biopsy between 2012 and 2021 were analyzed. Multivariate logistic regression analysis included clinical risk factors and CT-imaging features to detect associations with pneumothorax development. Overall, 479 patients (178 females, mean age 65 ± 11.7 years) underwent CT-guided percutaneous lung biopsy of which 180 patients (37.5%) developed pneumothorax including 55 patients (11.5%) requiring chest tube placement. Risk factors associated with pneumothorax were chronic-obstructive pulmonary disease (COPD) (p = 0.03), age (p = 0.02), total lung capacity (p < 0.01) and residual volume (p = 0.01) as well as interventional parameters needle length inside the lung (p < 0.001), target lesion attached to pleura (p = 0.04), and intervention duration (p < 0.001). The combined model demonstrated a prediction accuracy of the occurrence of pneumothorax with an AUC of 0.78 [95%CI: 0.70-0.86] with a resulting sensitivity 0.80 and a specificity of 0.66. In conclusion, radiomics features of the target lesion and the lung lobe CT-emphysema score are predictive for the occurrence of pneumothorax and need for chest insertion after CT-guided lung biopsy.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037491","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":"Artificial intelligence in COPD CT images: identification, staging, and quantitation.","authors":"Yanan Wu, Shuyue Xia, Zhenyu Liang, Rongchang Chen, Shouliang Qi","doi":"10.1186/s12931-024-02913-z","DOIUrl":"10.1186/s12931-024-02913-z","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) stands as a significant global health challenge, with its intricate pathophysiological manifestations often demanding advanced diagnostic strategies. The recent applications of artificial intelligence (AI) within the realm of medical imaging, especially in computed tomography, present a promising avenue for transformative changes in COPD diagnosis and management. This review delves deep into the capabilities and advancements of AI, particularly focusing on machine learning and deep learning, and their applications in COPD identification, staging, and imaging phenotypes. Emphasis is laid on the AI-powered insights into emphysema, airway dynamics, and vascular structures. The challenges linked with data intricacies and the integration of AI in the clinical landscape are discussed. Lastly, the review casts a forward-looking perspective, highlighting emerging innovations in AI for COPD imaging and the potential of interdisciplinary collaborations, hinting at a future where AI doesn't just support but pioneers breakthroughs in COPD care. Through this review, we aim to provide a comprehensive understanding of the current state and future potential of AI in shaping the landscape of COPD diagnosis and management.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037490","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":"Pulmonary adaptation to repeated poly(I:C) exposure is impaired in asthmatic mice: an observational study.","authors":"Benoit Allard, Olga Ousova, Zhanna Savitskaya, Hannah Levardon, Elise Maurat, Marilyne Campagnac, Thomas Trian, Patrick Berger","doi":"10.1186/s12931-024-02948-2","DOIUrl":"10.1186/s12931-024-02948-2","url":null,"abstract":"<p><strong>Background: </strong>While asthma exacerbations remain a major challenge in patient management, few animal models exist to explore the underlying mechanisms. Here, we established an animal model of asthma that can be used to study pathophysiological mechanisms and therapeutic strategies on asthma exacerbation.</p><p><strong>Methods: </strong>Female BALB/c mice were sensitized and exposed to PBS or Dermatophagoides pteronyssinus (DerP) extract for 11 weeks. Asthmatic phenotype was assessed through lung inflammation, bronchial hyperresponsiveness and bronchial smooth muscle remodeling. Asthmatic and control mice were exposed once or three times to poly(I:C) to simulate virus-induced inflammation.</p><p><strong>Results: </strong>Fourteen days after exposure to DerP, asthmatic mice showed resolution of inflammation with sustained bronchial hyperresponsiveness and bronchial smooth muscle remodeling compared to control. At this stage, when mice were subjected to a single exposure to poly(I:C), control and asthmatic mice were characterized by a significant increase in neutrophilic inflammation and bronchial hyperresponsiveness. When mice were repeatedly exposed to poly(I:C), control mice showed a significant decrease in neutrophilic inflammation and bronchial hyperresponsiveness, while asthmatic mice experienced worsening of these outcomes.</p><p><strong>Conclusions: </strong>This observational study report an asthmatic mouse model that can undergo exacerbation after repeated exposure to poly(I:C). Our findings on pulmonary adaptation in control mice may also pave the way for further research into the mechanism of adaptation that may be impaired in asthma and raise the question of whether asthma exacerbation may be a loss of adaptation.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005681","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":"Assessment and monitoring of lung disease in patients with severe alpha 1 antitrypsin deficiency: a european delphi consensus of the EARCO group.","authors":"Marc Miravitlles, Alice M Turner, Maria Sucena, Jean-François Mornex, Timm Greulich, Marion Wencker, N Gerard McElvaney","doi":"10.1186/s12931-024-02929-5","DOIUrl":"10.1186/s12931-024-02929-5","url":null,"abstract":"<p><strong>Background: </strong>Currently, there is conflicting information and guidance on the effective management of Alpha 1 Antitrypsin Deficiency (AATD). Establishing a consensus of assessment and disease management specific to AATD is important for achieving a standardized treatment pathway and for improving patient outcomes. Here, we aim to utilize the Delphi method to establish a European consensus for the assessment and management of patients with severe AATD.</p><p><strong>Methods: </strong>Two rounds of a Delphi survey were completed online by members of the European Alpha-1 Research Collaboration (EARCO). Respondents were asked to indicate their agreement with proposed statements for patients with no respiratory symptoms, stable respiratory disease, and worsening respiratory disease using a Likert scale of 1-7. Levels of agreement between respondents were calculated using a weighted average.</p><p><strong>Results: </strong>Round 1 of the Delphi survey was sent to 103 members of EARCO and 38/103 (36.9%) pulmonologists from across 15 countries completed all 109 questions. Round 2 was sent to all who completed Round 1 and 36/38 (94.7%) completed all 79 questions. Responses regarding spirometry, body plethysmography, high-resolution computed tomography, and the initiation of augmentation therapy showed little variability among physicians, but there was discordance among other aspects, such as the use of low-dose computed tomography in both a research setting and routine clinical care.</p><p><strong>Conclusions: </strong>These results provide expert opinions for the assessment and monitoring of patients with severe AATD, which could be used to provide updated recommendations and standardized treatment pathways for patients across Europe.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005677","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":"Levosimendan mediates the BMP/Smad axis through upregulation of circUSP34-targeted miR-1298 to alleviate pulmonary hypertension.","authors":"Qiang Meng, Linhong Song, Hui Wang, Gang Wang, Gengxu Zhou","doi":"10.1186/s12931-024-02945-5","DOIUrl":"10.1186/s12931-024-02945-5","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a long-term disease that impacts approximately 1% of the world's population. Currently, levosimendan (Lev) is proposed for PH treatment. However, the mechanism of Lev in the treatment of PH is unknown.</p><p><strong>Methods: </strong>We used hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) to establish a PH cell model. A number of cell biology methods were performed to assay alterations in cell proliferation, migration and apoptosis after Lev treatment. qRT-PCR and WB were performed to test the levels of circUSP34 and miR-1298, and BMP/Smad protein respectively. In addition, the regulatory relationship between circUSP34 or BMPR2 with miR-1298 was verified through the use of double luciferase as well as RIP assay. In addition, we explored the regulatory effect of Lev on the circUSP34/miR-1298/BMP/Smad axis using a rat PH model.</p><p><strong>Results: </strong>Our results demonstrate that Lev inhibited PASMCs cell proliferation, migration and promoted apoptosis exposed to hypoxia. In hypoxia-treated PASMCs, circUSP34 expression got downregulated while miR-1298 upregulated, whereas the addition with Lev resulted in upregulation of circUSP34 expression and downregulation of miR-1298 expression, indicating that circUSP34 can target and regulate miR-1298. In addition, miR-1298 targets and regulates the expression of BMPR2. In a rat PH model induced by hypoxia combined with SU5416, Lev upregulated circUSP34 targeting miR-1298-mediated BMP/Smad axis to alleviate the PH phenotype.</p><p><strong>Conclusion: </strong>We have shown that Lev can be used as a therapeutic drug for PH patients, which works through the circUSP34/miR-1298/BMP/Smad axis to alleviate PH symptoms.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005680","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}