Respiratory Research最新文献

{"title":"Characteristics of upper and lower respiratory tract microbiota after lung transplantation.","authors":"Yuhang Cai, Yuchen Fan, Ao Chen, Xiaohua Wang, Lulin Wang, Jiaqi Chen, Zhang Wang, Jia Li, Xinzhu Yi, Chunrong Ju","doi":"10.1186/s12931-025-03235-4","DOIUrl":"https://doi.org/10.1186/s12931-025-03235-4","url":null,"abstract":"<p><strong>Background: </strong>The composition and characteristics of airway microbiota offer critical insights for clinical decision-making. Current research on chronic lung diseases shows differences in the composition and characteristics of upper and lower respiratory tract microbiota compared with healthy individuals. However, the temporal changes of these microbial communities in lung transplant recipients remain poorly characterized.</p><p><strong>Methods: </strong>This is a longitudinal prospective study. Respiratory specimens were collected regularly from lung transplant recipients for testing and analysis. A total of 150 bronchoalveolar lavage fluid (BALF) samples, 150 throat swab samples, 51 sputum samples, and 36 lung tissue samples were collected from the recipients, at 7 days, 14 days, 1 month, 2 months, 3 months, and 6 months post-transplant for 16S rRNA gene sequencing and analysis.</p><p><strong>Results: </strong>Our study showed that there were significant differences in α-diversity and β-diversity among lung tissue, throat swab, and sputum samples, although α-diversity did not show a significant difference between lung tissue and BALF. Most amplicon sequence variants (ASVs) belonged to the families Enterobacteriaceae, Pseudomonadaceae, and Stenotrophomonas in BALF, while most ASVs belonged to the genera Streptococcus, Pseudomonadaceae, and Stenotrophomonas in sputum samples. Regarding dynamic changes, Corynebacterium and Staphylococcus were more prevalent in the early post-operative period but gradually decreased by 7 days post-operatively, while the common microbiota found in healthy populations based on literature became the most abundant ASVs at 6 months post-operatively in our study participants. Pseudomonadaceae and Stenotrophomonas contributed to the similarity in the composition of upper and lower respiratory microbiota.</p><p><strong>Conclusions: </strong>This study demonstrates that lung transplant recipients exhibit unique characteristics in their upper and lower respiratory tract microbiota, which are distinct ecological profiles, and both undergo significant changes within 6 months post-operatively. The similarity between upper and lower respiratory tract microbiota is associated with microbial diversity and taxonomic dominance.</p><p><strong>Clinical trial: </strong>The clinical trial was registered at Chinese Clinical Trial Registry (ChiCTR2200056908) in February 2022.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"160"},"PeriodicalIF":5.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018380","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":"ETS2 aggravate allergic airway inflammation by regulating ANT2-mediated cytosolic mitochondrial DsRNA levels.","authors":"Hui Jiang, Yaona Jiang, Ran Dong, Chang-Yong Fu","doi":"10.1186/s12931-025-03233-6","DOIUrl":"https://doi.org/10.1186/s12931-025-03233-6","url":null,"abstract":"<p><strong>Background: </strong>ETS2 has been identified as a pivotal regulator in the development of human inflammatory diseases. Nevertheless, the functional aspects of ETS2 in asthma remain inadequately characterized. The release of mitochondrial dsRNA is recognized as an initiator of innate immune responses and implicated in intensifying inflammation triggered by alternative immunogens. The interplay between these mechanisms remains poorly understood, and only a limited number of direct targets that underpin the pro-inflammatory role of ETS2 have been identified.</p><p><strong>Methods: </strong>The expression of ETS2 in epithelial cells under immune responses was analyzed, and its effects on asthma progression were examined through clinical specimens, human bronchial epithelial cells, and an allergic asthma mouse model. Additionally, the potential involvement of adenine nucleotide translocase-2 in mediating the immune responses regulated by ETS2 was explored.</p><p><strong>Results: </strong>Increased expression of ETS2 in lung epithelial cells was observed in both asthma patients and ovalbumin (OVA)-induced asthma mice. The deficiency of ETS2 resulted in a substantial decline in inflammatory cell infiltration and markedly diminished IL-6, IL-5, and IL-13 levels in epithelial cells. Mechanistically, ETS2 overexpression was associated with elevated cytosolic mitochondrial RNA levels, whereas knockdown resulted in their suppression. Furthermore, adenine nucleotide translocase-2 (ANT2) expression was robustly upregulated by ETS2 through direct promoter binding. The advantageous effects of ETS2 on asthma development were abrogated in ANT2-deficient mice.</p><p><strong>Conclusions: </strong>The findings collectively underscore the role of ETS2 as an exacerbating factor in allergic airway inflammation during asthma progression, primarily by inducing ANT2 expression. Therapeutic targeting of epithelial ETS2 could represent a novel approach to asthma management.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"159"},"PeriodicalIF":5.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044932","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":"Serum C-C motif chemokine ligand 17 as a predictive biomarker for the progression of non-idiopathic pulmonary fibrosis interstitial lung disease.","authors":"Takatoshi Enomoto, Yoshito Takeda, Yuya Shirai, Takehiro Hasegawa, Feng Zhao, Hanna Lunding, Moritz Pohl, Ryuya Edahiro, Shigeyuki Shichino, Takahiro Kawasaki, Hanako Yoshimura, Reina Hara, Saori Amiya, Makoto Yamamoto, Daisuke Nakatsubo, Satoshi Tanizaki, Mana Nakayama, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Mari Tone, Yuko Abe, Maiko Naito, Kentaro Masuhiro, Yujiro Naito, Takayuki Shiroyama, Kotaro Miyake, Shohei Koyama, Kiyoharu Fukushima, Kota Iwahori, Haruhiko Hirata, Izumi Nagatomo, Satoshi Nojima, Masahiro Yanagawa, Yoshikazu Inoue, Atsushi Kumanogoh","doi":"10.1186/s12931-025-03237-2","DOIUrl":"https://doi.org/10.1186/s12931-025-03237-2","url":null,"abstract":"<p><strong>Background: </strong>Interstitial lung disease (ILD), represented by idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), shows poor prognosis due to progressive fibrosis. Early therapeutic intervention is required to enhance the efficacy of antifibrotic drugs, highlighting the importance of early detection of ILD progression. Although candidate biomarkers for predicting ILD progression have been recently reported through omics analyses, clinically measurable biomarkers remain unestablished. This study aimed to identify clinically measurable biomarkers that could predict the degree of ILD progression.</p><p><strong>Methods: </strong>The serum levels of 13 candidate biomarkers were prospectively measured by chemiluminescent enzyme immunoassay and the utilities for predicting ILD progression were compared in the discovery cohort (total 252 patients). Moreover, we evaluated the utility of the identified biomarker in another independent cohort (154 patients with non-IPF-ILD) and examined the dynamics of the biomarker by immunoblotting and single-cell RNA sequencing (scRNA-seq) using samples of patients and a mouse model.</p><p><strong>Results: </strong>In the discovery cohort, C-C motif chemokine ligand (CCL)17 could reliably predict ILD progression, particularly in patients with ILD other than IPF, and showed significant associations with mortality (hazard ratio [HR] 3.70; 95% confidence interval [CI] 1.19-11.49; P = 0.015; cut-off value = 418 pg/mL). Consistently, in the validation cohort, the CCL17 high group showed significantly higher mortality (HR: 2.15; 95% CI 0.99-4.69; P = 0.049), and CCL17 was identified as an independent prognostic factor from corticosteroid or immunosuppressive agents use and ILD-gender-age-physiology index. Similar to the results of serum studies, CCL17 levels in the lungs of patients with PPF and model mice were higher than those in controls. They were positively correlated with CCL17 levels in the serum, suggesting that the increased serum CCL17 levels could reflect an increase in CCL17 levels in lung tissues. The scRNA-seq analysis of lung tissues from model mice suggested that the levels of CCL17 derived primarily from conventional dendritic cells and macrophages increased, especially during the profibrotic phase.</p><p><strong>Conclusions: </strong>We identified serum CCL17 as a clinically measurable biomarker for predicting non-IPF-ILD progression. Serum CCL17 could enable the stratification of patients at risk of non-IPF-ILD progression, leading to appropriate early therapeutic intervention.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"157"},"PeriodicalIF":5.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034512","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 longitudinal impact of low-dose morphine on diurnal cortisol profiles in people with chronic breathlessness and chronic obstructive pulmonary disease (COPD): an exploratory study.","authors":"Diana H Ferreira, Richella Ryan, Nina Smyth, Angela Clow, David C Currow","doi":"10.1186/s12931-025-03230-9","DOIUrl":"https://doi.org/10.1186/s12931-025-03230-9","url":null,"abstract":"<p><strong>Introduction: </strong>Stress activates the hypothalamic-pituitary-adrenal (HPA) axis of which cortisol is an end product. 'Allostatic load' is where systems including the HPA axis are exposed to high, cumulative, physiologic burdens (such as chronic breathlessness) leading to flatter diurnal cortisol slopes and poorer health outcomes. The aim of this hypothesis-generating study explored longitudinal changes in cortisol secretion and any associated changes in breathlessness after introducing regular, low dose morphine or placebo.</p><p><strong>Methods: </strong>This was an optional, hypothesis-generating sub-study embedded in a multi-site, randomised, double-blind, placebo-controlled trial (RCT) of regular, low-dose morphine for chronic breathlessness and chronic obstructive pulmonary disease. In a blinded dose-increment algorithm by week three, doses were 0 mg-32 mg. Participants in the RCT could elect to continue in a six-month blinded extension. This sub-study excluded people who used non-inhaled corticosteroids in the previous month or were on subcutaneous insulin. Participants collected saliva for cortisol assays for two days at baseline, and ends of weeks 1, 3 and 12 at 3,6 and 12 h after waking, generating sufficient data to calculate diurnal cortisol slopes and areas under the curve (AUC). Samples were analysed using ELISA. Correlations between diurnal cortisol profiles (slope and AUC) and a range of measures were explored.</p><p><strong>Results: </strong>Twenty mostly female former smokers were in this sub-study. At baseline and the end of week 1, one-way ANOVA between-group analyses showed no significant differences in the log-transformed cortisol slope or ln-AUC. There was a strong correlation between the age-adjusted Charlson Comorbidity Index (CCI) and ln-AUC (r=-0.70, p < 0.001) and moderate correlation with age (r=-0.43, p = 0.06). In the blinded extension study, there was a self-selecting blinded group (n = 7) all on active medication. Global impression of change (GIC) was highly correlated with the diurnal cortisol slope (rs = 0.98, p = 0.01), and with decrease in average breathlessness (r = 0.89, p = 0.04).</p><p><strong>Discussion: </strong>This hypothesis-generating study did not show a relationship between the diurnal cortisol profile and morphine in people with chronic breathlessness and COPD. For the sub-group still on study at 12weeks, the cortisol curves became steeper as average breathlessness decreased and as global impression of change (GIC) improved, suggesting that reducing breathlessness may potentially positively impact the HPA axis in a sub-group of people.</p><p><strong>Trial registration: </strong>Registration Number NCT02720822 date registered 28/03/2016.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"156"},"PeriodicalIF":5.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993367","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":"An integrated machine learning model of transcriptomic genes in multi-center chronic obstructive pulmonary disease reveals the causal role of TIMP4 in airway epithelial cell.","authors":"Erkang Yi, Haiqing Li, Yu Liu, Qingyang Li, Chengshu Xie, Ruining Sun, Fan Wu, Zhishan Deng, Kunning Zhou, Hairong Wang, Xinru Ran, Yumin Zhou, Pixin Ran","doi":"10.1186/s12931-025-03238-1","DOIUrl":"10.1186/s12931-025-03238-1","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome, resulting in inconsistent findings across studies. Identifying a core set of genes consistently involved in COPD pathogenesis, independent of patient variability, is essential.</p><p><strong>Methods: </strong>We integrated lung tissue sequencing data from patients with COPD across two centers. We used weighted gene co-expression network analysis and machine learning to identify 13 potential pathogenic genes common to both centers. Additionally, a gene-based model was constructed to distinguish COPD at the molecular level and validated in independent cohorts. Gene expression in specific cell types was analyzed, and Mendelian randomization was used to confirm associations between candidate genes and lung function/COPD. Preliminary in vitro functional validation was performed on prioritized core candidate genes.</p><p><strong>Results: </strong>Tissue inhibitor of metalloproteinase 4 (TIMP4) was identified as a key pathogenic gene and validated in COPD cohorts. Further analysis using single-cell sequencing from mice and patients with COPD revealed that TIMP4 is involved in ciliated cells. In primary human airway epithelial cells cultured at the air-liquid interface, TIMP4 overexpression reduced ciliated cell numbers.</p><p><strong>Conclusions: </strong>We developed a 13-gene model for distinguishing COPD at the molecular level and identified TIMP4 as a potential hub pathogenic gene. This finding provides insights into shared disease mechanisms and positions TIMP4 as a promising therapeutic target for further investigation.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"158"},"PeriodicalIF":5.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027587","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":"Proteogenomic verifies targets underlying erythromycin alleviate neutrophil extracellular traps-induced inflammation.","authors":"Nan Ma, Xiao Na Liang, Quan Fang Chen, Mei Hua Li, Guang Sheng Pei, Xiao Fei Yi, Li Yan Guo, Fu Gang Chen, Zhi Yi He","doi":"10.1186/s12931-025-03226-5","DOIUrl":"https://doi.org/10.1186/s12931-025-03226-5","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil Extracellular Traps (NETs) are closely related to the progression of inflammation in Chronic Obstructive Pulmonary Disease (COPD). Erythromycin (EM) has been shown to inhibit inflammation in COPD, but its molecular mechanisms is still unclear. The aim of our study is investigate the molecular mechanisms of EM's anti-inflammatory effects in NETs-induced inflammation.</p><p><strong>Methods: </strong>Transcriptomics and proteomics data were obtained from U937 cells treated with NETs and EM. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were identified using R software. Pathway enrichment analyses, were employed to identify inflammation-related pathways. Cytoscape were utilized to construct network of hub targets regulated by EM which related with oxidative stress and inflammation. Additionally, Cytoscape and STRING were used to construct protein-protein interaction (PPI) network of key targets regulated by EM. The expression levels of key targets were further confirmed through WB and PCR experiments.</p><p><strong>Results: </strong>Both transcriptomics and proteomics indicate that EM decrease NETs -induced AKT1 expression. Enrichment analysis of DEGs and DEPs reveal multiple common pathways involved in EM's regulation inflammation, including the PI3K/AKT pathway, response to oxidative stress, IKK/NF-κB signaling and PTEN signaling pathway. Nine key targets in PI3K/AKT-related inflammatory pathways regulated by EM and ten targets of EM-regulated oxidative stress were identified. WB and PCR results confirmed that EM reversing the NETs-induced inflammation by modulating the activity of these targets. Furthermore, clinical samples and vitro experiments confirm that EM alleviates NETs-induced glucocorticoid resistance via inhibiting PI3K/AKT, thereby repressing inflammation.</p><p><strong>Conclusions: </strong>Our study provides a comprehensive proteogenomic characterization of how EM alleviates NET-related inflammation, and identify PI3K/AKT play a critical role in the mechanism by which EM inhibits inflammation.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"155"},"PeriodicalIF":5.8,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065051","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":"Pleural fluid agitation for improving the microbiologic diagnostic yield in pleural infection: a feasibility study.","authors":"Ahmed Sadaka, Reda Said, Heba Ashmawy, Hadir Okasha, Heba Gharraf","doi":"10.1186/s12931-025-03208-7","DOIUrl":"https://doi.org/10.1186/s12931-025-03208-7","url":null,"abstract":"<p><strong>Background: </strong>Pleural infection is a commonly encountered respiratory disease but in > 40% the underlying microbiologic etiology is unknown. This feasibility study aims to investigate whether pleural fluid agitation prior to sample aspiration is safe and can improve the diagnostic yield of microbiologic analysis.</p><p><strong>Methods: </strong>Thirty adult patients with pleural infection, based on clinical, imaging and biochemical evidence, were included in this feasibility study. Ultrasound guided thoracentesis was performed with an initial standard aspiration sampling technique, followed by pleural fluid agitation into the pleural cavity for 3-5 cycles before collecting the agitated fluid. Coded samples were sent for biochemical and microbiologic analysis with culture in aerobic and anaerobic media.</p><p><strong>Results: </strong>No complications were encountered with the pleural fluid agitation technique. Overall, 14 (46.6%) of patients had a positive pleural fluid culture. No yield discordance was noted between the standard and the agitated pleural fluid sampling techniques except for 1 extra agitated sample growing klebsiella pneumoniae and another agitated sample with mixed infection showing an additional anaerobic bacterial growth. Four (30.8%) of the 13 concordantly positive samples showed heavier bacterial growth in the agitated samples using semi-quantitative culture scoring.</p><p><strong>Conclusion: </strong>Pleural fluid agitation was safe but didn't significantly add to the microbiologic yield in pleural infection. However, higher bacterial growth in almost one third of positive samples suggests a potential effect for further investigation in a larger study. Despite being safe, pleural fluid agitation resulted in no significant improvement in the microbiologic yield among pleural infection. However, agitated samples grew more bacteria in almost a third of the positive samples suggesting a signal for further investigation in a larger study.</p><p><strong>Study registration: </strong>Clinicaltrials.gov - NCT05702580, 23/12/2022.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"154"},"PeriodicalIF":5.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058181","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 pleural thickness on the sensitivity of computed tomography scan-guided cutting-needle pleural biopsy in diagnosing unexplained exudative pleural effusion.","authors":"Rui Xu, Ling Zuo, Chiyong Yang, Li Jiang, Ying Liu, Ping Fan, Kaige Wang, Dan Liu","doi":"10.1186/s12931-025-03229-2","DOIUrl":"https://doi.org/10.1186/s12931-025-03229-2","url":null,"abstract":"<p><strong>Background: </strong>In most cases, patients with pleural effusion require a pleural biopsy to confirm the diagnosis, due to the low diagnostic sensitivity of thoracentesis. Among the different biopsy modalities, real time computed tomography scan-guided cutting-needle pleural biopsy (CT-CNPB) ensures high sensitivity and accessibility. However, there is no study investigating the difference in the diagnostic sensitivity of CT-CNPB for lesions with variable pleural thickness in effusions of different types.</p><p><strong>Methods: </strong>Of the 303 patients who underwent CT-CNPB, 218 met the eligibility criteria and were retrospectively analyzed from November 2021 to June 2024. Patients were divided into malignant pleural effusion (MPE), tuberculosis pleural effusion (TPE), and non-tuberculous benign pleural effusion (BPE) groups according to the diagnosis with a minimum follow-up of 6 months. Pleural thickness was defined as the length of the portion of the puncture needle that passes through the thickened parietal pleura or the pleural lesion (nodule/mass). In further analysis, we compare the differences in sensitivity between subgroups with different pleural thicknesses in each group.</p><p><strong>Results: </strong>The overall diagnostic sensitivity is 74.3%. The sensitivity in MPE, TPE, and BPE is 75.7%, 78.6%, and 67.8%, respectively. There was a significant difference in sensitivity between the < 5 mm and ≥ 5 mm groups in MPE and BPE groups but was not observed in the TPE group. In the further analysis, there was a significant difference in sensitivity between < 3 mm and 3-5 mm groups in TPE (p = 0.046) and a significant difference in sensitivity between 3 and 5 mm and 5-10 mm groups in MPE (p = 0.017), but a significant difference was not observed in BPE group.</p><p><strong>Conclusion: </strong>CT-CNPB may serve as a preferred diagnostic approach in suspected TPE with pleural thickening ≥ 3 mm and suspected MPE with thickening ≥ 5 mm on chest CT. Where MT is unavailable, CT-CNPB is a viable alternative for suspected MPE or TPE patients with pleural thickening, nodularity, or mass lesions observed on CT. However, in suspected BPE, CT-CNPB alone is often insufficient; integrated clinical, laboratory, and imaging evaluation remains essential.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"153"},"PeriodicalIF":5.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041642","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":"Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVID.","authors":"Tamara Cruz, Núria Albacar, Estibaliz Ruiz, Gema M Lledo, Lídia Perea, Alba Puebla, Alejandro Torvisco, Núria Mendoza, Pau Marrades, Jacobo Sellares, Alvar Agustí, Odette Viñas, Oriol Sibila, Rosa Faner","doi":"10.1186/s12931-025-03200-1","DOIUrl":"https://doi.org/10.1186/s12931-025-03200-1","url":null,"abstract":"<p><strong>Introduction: </strong>Most patients recover fully after an acute infection by SARS-CoV-2. Some, however, may develop pulmonary sequelae (PS) and/or long COVID (LC). However, whether these two clinical conditions have similar or different pathogenic mechanisms is unknown.</p><p><strong>Methods: </strong>The levels of autoantibodies and 184 inflammatory and organ damage associated proteins in plasma were determined (by immunofluorescence and Olink panels, respectively) 1 year after an acute infection by SARS-CoV-2 in 51 patients with PS (DLCO < 80% ref), 31 patients with LC and 31 patients fully recovered (Rec). PS was defined by the presence of reduced carbon monoxide diffusing capacity (DLCO) lower than 80% ref. LC was defined by the presence of chronic symptoms in the absence of an alternative diagnosis.</p><p><strong>Results: </strong>We found that patients with PS or LC both showed increased levels than Rec of anti-microbial, immune cell activation and recruitment related proteins. Patients with PS showed higher levels of anti-nuclear autoantibodies, whereas LC patients had increased levels of organ-damage associated proteins. In patients with PS most of the elevated proteins correlate with the impairment of lung function (DLCO). Finally, in PS we additionally performed the determinations at an earlier time point (6 months) and showed that the expression of CCL20 and IFN-ɣ was already higher at 6 months, while CCL3 and CCL19 increase from 6 to 12 months, suggesting a pathogenic role in PS persistence.</p><p><strong>Conclusions: </strong>Patients with PS or LC have abnormal but different persistent circulatory immune and organ damage biomarkers, suggesting different underlying biology of both post-COVID conditions.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"152"},"PeriodicalIF":5.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048570","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 transcription factor PITX1 cooperates with super-enhancers to regulate the expression of DUSP4 and inhibit pyroptosis in pulmonary artery smooth muscle cells.","authors":"Jingya Zhang, Yuyu Song, Xinru Wang, Xu Wang, Songyue Li, Xinyue Song, Chong Zhao, Jing Qi, Yunyun Tian, Baoshan Zhao, Xiaodong Zheng, Yan Xing","doi":"10.1186/s12931-025-03222-9","DOIUrl":"https://doi.org/10.1186/s12931-025-03222-9","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a highly fatal pathophysiological syndrome. The group 1 pulmonary arterial hypertension (PAH) is characterized by acute pulmonary vasoconstriction and chronic vascular remodeling caused by hyperplasia and hypertrophy of pulmonary artery smooth muscle cells (PASMCs) and chronic inflammation. Pyroptosis is an inflammatory mode of cell death that is regulated by super-enhancers (SEs) and occurs in the setting of tumors and cardiovascular diseases. However, whether SEs are involved in the pathological process of pyroptosis in PAH and the specific mechanism involved remain unclear.</p><p><strong>Methods: </strong>Here, we identified the SE target gene DUSP4 via ChIP-seq with an anti-H3K27ac antibody, and bioinformatics predictions revealed that the transcription factor PITX1 can bind to the promoter and SE sequences of DUSP4. The AAV5 vector was used to deliver shRNAs targeting PITX1 and DUSP4 to PASMCs.</p><p><strong>Results: </strong>PITX1 overexpression reversed the increase in right ventricular systolic pressure and pulmonary vascular remodeling, restored the PAAT/PAVTI ratio in hypoxic pulmonary hypertension (HPH, Group 3 PH) and SuHx PAH (Group 1 PAH) mice, and suppressed pyroptosis in pulmonary vascular cells. However, knockdown of DUSP4 counteracted the effects of PITX1 overexpression. Similar results were obtained in cultured PASMCs. In addition, treatment with the SE inhibitors JQ1 and iBET decreased the transcription of DUSP4 and increased the expression of hypoxia-induced pyroptosis proteins in PASMCs.</p><p><strong>Conclusion: </strong>We confirmed that PITX1 can promote DUSP4 expression by binding to the DUSP4 promoter and SE to reduce pyroptosis in hypoxic PASMCs, providing new insights into the role of SEs and pyroptosis in pulmonary vascular remodeling and a theoretical basis for the treatment of PAH and related diseases.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"149"},"PeriodicalIF":5.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055273","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}