Respiratory Research最新文献

{"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":"All-cause and cause-specific mortality in respiratory symptom clusters: a population-based multicohort study.","authors":"Daniil Lisik, Helena Backman, Hannu Kankaanranta, Rani Basna, Linnea Hedman, Linda Ekerljung, Fredrik Nyberg, Anne Lindberg, Göran Wennergren, Eva Rönmark, Bright Nwaru, Lowie Vanfleteren","doi":"10.1186/s12931-025-03224-7","DOIUrl":"https://doi.org/10.1186/s12931-025-03224-7","url":null,"abstract":"<p><strong>Background: </strong>Respiratory symptoms are common in the general adult population. Increased burden of respiratory symptoms may increase the risk of mortality. We assessed the association between respiratory symptom clusters and mortality.</p><p><strong>Methods: </strong>Participants were derived from two population-based Swedish adult cohorts (N = 63,060). Cluster analysis was performed with Locality Sensitive Hashing (LSH)-k-prototypes in subjects with ≥ 1 self-reported respiratory symptom. Linked mortality register data (up to 21 years of follow-up, > 600,000 person-years) were used. Associations between clusters and all-cause/cause-specific mortality were assessed using asymptomatic subjects as reference.</p><p><strong>Results: </strong>Over 60% reported ≥ 1 respiratory symptom and ~ 30% reported ≥ 5 respiratory symptoms. Five clusters were identified, partly overlapping with established respiratory disease phenotypes but many individuals were undiagnosed: (1) \"low-symptomatic\" (30.3%); (2) \"allergic nasal symptoms\" (10.7%); (3) \"allergic nasal symptoms, wheezing, and dyspnea attacks\" (4.7%); (4) \"wheezing and dyspnea attacks\" (6.6%); (5) \"recurrent productive cough and wheezing\" (4.1%). All but Cluster 2 were associated with all-cause mortality, highest risk for Cluster 3 (hazard ratio 1.4, 95% confidence interval 1.13-1.73) and Cluster 5 (1.4, 1.22-1.61). Comparable associations were seen for cardiovascular mortality. For respiratory mortality, Cluster 4 (2.02, 1.18-3.46) and Cluster 5 (1.89, 1.1-3.25) were most strongly associated.</p><p><strong>Conclusions: </strong>Respiratory symptoms are common in the general adult population, with identifiable clusters. These clusters have clinical relevancy as they are differentially associated with mortality and relatively weakly correlated with diagnosed respiratory disease.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"150"},"PeriodicalIF":5.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993147","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}

{"title":"The association and impact of radiographic, pathological emphysema and spirometric airway obstruction on patients with resectable lung adenocarcinoma.","authors":"Yixiao Zhang, Lu Lang, Xiaojuan Guo, Kewu Huang, Jiawen Yi, Yuan Yuan, Min Zhu, Shu Zhang, Bin Hu, Xue Li, Yuhui Zhang","doi":"10.1186/s12931-025-03225-6","DOIUrl":"https://doi.org/10.1186/s12931-025-03225-6","url":null,"abstract":"<p><strong>Background: </strong>Destruction of alveoli structure and lung function are interrelated, however, their correlation and clinical significance have been not well defined in patients with lung cancer. Thus, this study aimed to examine the association among radiographic, pathological emphysema and spirometric airway obstruction in patients with resectable lung cancer as well as explore their impact on postoperative pulmonary complications (PPCs) and long-term prognosis.</p><p><strong>Methods: </strong>Lung adenocarcinoma (LUAD) patients who performed chest CT, spirometry, and curative resection were included from a prospective three-institution database. CT-defined emphysema at baseline was assessed visually and quantitatively, pathological emphysema was reviewed on postoperative specimen. Multivariable regression models, propensity score matching, stratified analysis, and subgroup analysis were adopted to reduce selection bias.</p><p><strong>Results: </strong>Our cohort included 902 patients, with a median follow-up of 5.6 years. CT-defined emphysema was present in 163 patients (18.1%) and most of them (86.5%) were validated with pathological evidence. 169 had spirometric airway obstruction, while only 29.6% patients overlapped with CT-defined emphysema. Multivariable logistic regression models showed CT-defined emphysema, not airway obstruction, was associated with an increased risk of PPCs (adjusted odds ratio, 2.35; 95% CI, 1.40-3.93; P = 0.001). After adjusting for age, sex, body mass index, smoking history, tumour stage, vascular invasion, pleural invasion, multivariate cox analysis identified CT-defined emphysema, not airway obstruction, as an independent prognostic factor for OS (adjusted hazard ratio, 1.44; 95%CI, 1.05-1.97; P = 0.022). Patients with both radiographic and pathological emphysema experienced worse OS (log-rank P < 0.001). In the propensity score-matched cohort, stratified analysis, and never-smokers subgroup analysis, CT-defined emphysema remained a strong and statistically significant factor related to poor survival.</p><p><strong>Conclusions: </strong>The presence of radiological and pathological emphysema in resectable LUAD was associated with frequent PPCs and decreased survival.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"151"},"PeriodicalIF":5.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056216","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":"Advances and applications of biosensors in pulmonary hypertension.","authors":"Zhi Liu, Zhuojun Bai, Xiang Chen, Yajie Chen, Zhu Chen, Li Wang, Yi He, Yuan Guo","doi":"10.1186/s12931-025-03221-w","DOIUrl":"https://doi.org/10.1186/s12931-025-03221-w","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a serious disease characterized by elevated pulmonary artery pressure, with its prevalence and incidence continuously increasing, posing a threat to the lives of many patients worldwide. Due to the complex etiology of PH and the lack of specificity in clinical manifestations, there is currently a lack of effective and specific methods for early diagnosis in clinical practice. Biosensors hold significant promise for the early detection, therapeutic monitoring, prognostic evaluation, and personalized treatment of PH, owing to their rapid, sensitive, and highly selective characteristics. The rapid development of various types of biosensors, such as electrochemical biosensors, optical biosensors, microfluidic biosensors, and wireless biosensors, combined with the use of nanomaterials, makes the rapid and accurate detection of PH-related biomarkers possible. Despite the broad application prospects of biosensors in the field of PH, challenges remain in terms of sensitivity, selectivity, stability, and regulation. This article reviews the main pathophysiological mechanisms and commonly used biomarkers of PH, the types and principles of biosensors, and summarizes the progress of biosensors in PH research as well as the current challenges, in order to promote further in-depth research and the development of biosensor technology, thereby improving the diagnosis and treatment effects of PH. Clinical trial number: Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"147"},"PeriodicalIF":5.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992211","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":"Altered maturation and activation state of circulating monocytes is associated with their enhanced recruitment in pulmonary arterial hypertension.","authors":"Rebecca L Harper, Xin Zhou, David P Marciano, Aiqin Cao, Lingli Wang, Guibin Chen, Mir S Adil, Wenyu Zhou, Peter Maguire, Shanthi Deivanayagam, Quan Yu, Vignesh Viswanathan, Dan Yang, Marcy Martin, Sarasa Isobe, Shoichiro Otsuki, Jordan Burgess, Audrey Inglis, Devon Kelley, Patricia A Del Rosario, Andrew Hsi, Francois Haddad, Roham T Zamanian, Manfred Boehm, Michael P Snyder, Marlene Rabinovitch","doi":"10.1186/s12931-025-03182-0","DOIUrl":"https://doi.org/10.1186/s12931-025-03182-0","url":null,"abstract":"<p><strong>Background: </strong>It is well-established that patients with pulmonary arterial hypertension (PAH) exhibit increased recruitment of circulating monocytes to their pulmonary arteries. However, it remains unclear whether these monocytes have intrinsic abnormalities that contribute to their recruitment and to PAH pathogenesis. This study aimed to characterize the gene expression profiles of circulating classical, intermediate, and non-classical monocytes and assess their maturation trajectory in patients with idiopathic (I) PAH compared to control subjects. Additionally, it sought to explore the relationship between the observed IPAH abnormalities and deficiencies in bone morphogenetic receptor 2 (BMPR2), the most frequently mutated gene in PAH, and to assess adhesion and transendothelial migration, key processes in monocyte infiltration of pulmonary arteries.</p><p><strong>Methods: </strong>Differentially expressed genes and maturation trajectories of circulating monocytes from patients with IPAH vs. control subjects were compared using single cell RNA sequencing (scRNAseq), followed by FACS analysis. Observations from IPAH and control cells were related to reduced BMPR2 using a THP1 monocyte cell line with BMPR2 reduced by siRNA as well as induced pluripotent stem cell (iPSC) derived monocytes (iMono) from hereditary (H) PAH patients with a BMPR2 mutation and monocytes from mice with Bmpr2 deleted (MON-Bmpr2^-/-).</p><p><strong>Results: </strong>Classical IPAH monocytes have decreased CD14 mRNA leading to a deviation in their maturation trajectory and early terminal fate, which is not rescued by cytokine treatment. Monocytes that evade early cell death show elevated STAT1, PPDPF and HLA-B, and an interferon (IFN) signature indicative of an altered activation state. A strong link between decreased BMPR2 and CD14 was observed in THP1 cells and in HPAH iMono with a BMPR2 mutation associated with STAT1 and IFN related genes, and in monocytes from MON-Bmpr2^-/- mice. Increased adhesion to iPSC-derived endothelial cells (iECs) in HPAH-BMPR2 mutant iMono was associated with elevated ICAM1 expression. Enhanced transendothelial migration of these cells was associated with the reduction in endothelial VE-cadherin (CDH5).</p><p><strong>Conclusions: </strong>IPAH monocytes exhibit an altered activation state associated with reduced BMPR2 and CD14, along with elevated STAT1-IFN expression. These changes are linked to intrinsic functional abnormalities that contribute to the monocytes' increased propensity to invade the pulmonary circulation.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"148"},"PeriodicalIF":5.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055260","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 prevalence of pathogenic variants in the BMPR2 gene in patients with the idiopathic pulmonary arterial hypertension in the Russian population: sequencing data and meta-analysis.","authors":"Galina Okhrimenko, Irina Borovikova, Elena Dankovtseva, Vladimir Zamyatin, Dmitry Nikulin, Ekaterina Zobova, Anna Lyzhenkova, Anna Danilova, Natalia Osipova, Larisa Minushkina, Dmitry Zateyshchikov, Maria Poptsova","doi":"10.1186/s12931-025-03214-9","DOIUrl":"https://doi.org/10.1186/s12931-025-03214-9","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary arterial hypertension (IPAH) is a rare and severe form of pulmonary hypertension, with a genetic basis most commonly associated with mutations in the BMPR2 gene. However, no genetic testing has been reported for IPAH patients in the Russian population, nor have systematic studies been conducted to assess the frequency of pathogenic variants in this group.</p><p><strong>Methods: </strong>The study cohort included 105 IPAH patients, consisting of 23 males and 82 females, who were managed at the PH care center in Moscow, Russia, from 2014 to 2024. Genetic testing was performed using whole-genome sequencing. Variant identification and annotation were conducted using GATK, DeepVariant, VEP, sv-callers and AnnotSV. A meta-analysis, performed with MOOSE, included 24 studies involving 3124 IPAH patients and 470 P/LP variants. Pathogenicity reassessment was carried out using InterVar, which incorporates ACMG criteria.</p><p><strong>Results: </strong>Analysis of 105 adult IPAH patients in Russia revealed 11 patients (10.48%) as carriers of pathogenic or likely pathogenetic (P/LP) BMPR2 variants. As the result of reassessment, the number of P/LP BMPR2 variants raised from 394 (59%) to 445 (67%) with 80 pathogenic variants became of uncertain significance, and 152 unclassified variants became P/LP. The meta-analysis of these reevaluated pathogenic variants showed that while the frequency of P/LP variants in our cohort (10.48%) is lower than the overall average of 17.75% from the meta-analysis, the difference is not statistically significant (p = 0.062). Additionally, we report three P/LP BMPR2 variants, not reported in literature, with one being structural, and four P/LP variants in TBX4, ATP13A3 and AQP1 genes from 27 IPAH genes in 3 patients.</p><p><strong>Conclusions: </strong>For the first time, we present the results of genetic testing in IPAH patients from the Russian population. Despite the considerable heterogeneity in the world-wide data, the prevalence of pathogenic BMPR2 mutations in IPAH patients from the Russian population does not significantly differ from the overall average in the meta-analysis. It is crucial to periodically reassess the pathogenicity of published variants, as half of the pathogenic BMPR2 IPAH variants were reclassified as LP or of uncertain significance.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"146"},"PeriodicalIF":5.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A LncRNA panel within EpCAM-specific exosomes for noninvasive early diagnosing non-small cell lung cancer.","authors":"Linyuan Liu, Danlei Li, Amei Zhuo, Jiachun Lu, Jianjun Zou, Guitian Huang, Zhaoting Hu, Zili Zhang, Yibin Deng, Lei Yang","doi":"10.1186/s12931-025-03220-x","DOIUrl":"https://doi.org/10.1186/s12931-025-03220-x","url":null,"abstract":"<p><strong>Background: </strong>Plasma tumor-associated exosomes represent a promising source for cancer biomarkers; however, the role of long non-coding RNAs (lncRNAs) within these exosomes is not well-defined in non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>We identified a panel of NSCLC-specific lncRNAs within plasma EpCAM-specific exosomes (Epexo) through a comparative analysis of lncRNA profiles between plasma Epexo and lung tissues. The panel's diagnostic value was firstly evaluated in a retrospective cohort of 210 NSCLC patients and 245 healthy controls, and validated in a prospective cohort of 192 patients with pulmonary nodules (nodule size < 3 cm in diameter). The evaluation utilized the area under the ROC curve (AUC) based on a random forest model. For precision, repeat testing was conducted with 31 randomly selected samples. Additionally, 39 paired tissue-plasma samples were employed to assess the concordance of lncRNA expression between tissue and plasma within the same individuals.</p><p><strong>Results: </strong>The panel, including linc01125, HNF1A-AS1, MIR100HG, linc01160, and ZNRF3-AS1, demonstrated superior capability in distinguishing early-stage NSCLC patients from controls, achieving AUC values of 0.805 and 0.856 in the discovery and validation set, respectively. The panel also showed potential for differentiating adenocarcinoma and squamous cell carcinoma. Repeat sample testing showed a consistency of 90.3% for this panel. The expression levels of MIR100HG and HNF1A-AS1 showed significant correlations between plasma Epexo and cancerous tissues.</p><p><strong>Conclusions: </strong>The identified lncRNA panel, consisting of linc01125, HNF1A-AS1, MIR100HG, linc01160, and ZNRF3-AS1, presents a promising diagnostic tool for NSCLC.</p><p><strong>Clinical trial number: </strong>not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"144"},"PeriodicalIF":5.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008998","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}