{"title":"Impacts of COPD exacerbation history on mortality and severe cardiovascular events among patients with COPD in China: a retrospective cohort study.","authors":"Dongni Hou, Zhike Liu, Xinli Li, Peng Shen, Wenhao Li, Meng Zhang, IokFai Cheang, Hongbo Lin, Siyan Zhan, Feng Sun, Yan Chen, Yuanlin Song","doi":"10.1186/s12931-025-03316-4","DOIUrl":"10.1186/s12931-025-03316-4","url":null,"abstract":"<p><strong>Background: </strong>Chronic Obstructive Pulmonary Disease (COPD) exacerbations are associated with increased mortality and cardiovascular events. However, there is limited evidence on the relationship between COPD exacerbations and mortality and cardiovascular outcomes in China.</p><p><strong>Methods: </strong>This retrospective cohort study included Chinese patients with COPD aged ≥ 40 years from the Yinzhou regional electronic health records database. Patients were screened for eligibility between 1 Jan 2014 and 1 Mar 2022, with the index date being the first identified COPD diagnosis within this timeframe. Patient characteristics and frequency and severity of COPD exacerbations were collected during the 24-month baseline period prior to the index date. Outcomes included all-cause mortality and severe cardiovascular events. The incidence of death and first severe cardiovascular event was reported overall, and by baseline exacerbation history. Cox proportional hazards models were employed to identify the association between baseline COPD exacerbation history and all-cause death.</p><p><strong>Results: </strong>A total of 14,713 patients with COPD were included, with a median follow-up duration of 41.3 months. During the follow-up period, 20.1% of patients died, with a crude incidence rate of 5.17 (95% CI: 4.98, 5.36) per 100 person-years. Additionally, 20.1% of patients experienced severe cardiovascular events. The incidence of severe cardiovascular events numerically increased with higher frequency and severity of baseline COPD exacerbations. Patients with history of severe COPD exacerbations exhibited an increased risk (adjusted HR: 1.26, 95%CI: 1.14, 1.38) of all-cause death compared with patients with no exacerbations.</p><p><strong>Conclusions: </strong>This study found that severe COPD exacerbations significantly increased mortality risk in Chinese patients with COPD. Patients with a history of severe exacerbations also reported a higher incidence rate of severe cardiovascular events. These findings emphasize the need for improved exacerbation prevention strategies in COPD management.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"252"},"PeriodicalIF":5.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700192","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":"Open-access ultrasonic diaphragm dataset and an automatic diaphragm measurement using deep learning network.","authors":"Zhifei Li, Lin Mao, Fan Jia, Shaohui Zhang, Cuiping Han, Shuiqiao Fu, Yueying Zheng, Yonghua Chu, Zuobing Chen, Daming Wang, Huilong Duan, Yinfei Zheng","doi":"10.1186/s12931-025-03325-3","DOIUrl":"10.1186/s12931-025-03325-3","url":null,"abstract":"<p><strong>Background: </strong>The assessment of diaphragm function is crucial for effective clinical management and the prevention of complications associated with diaphragmatic dysfunction. However, current measurement methodologies rely on manual techniques that are susceptible to human error: How does the performance of an automatic diaphragm measurement system based on a segmentation neural network focusing on diaphragm thickness and excursion compare with existing methodologies?</p><p><strong>Methods: </strong>The proposed system integrates segmentation and parameter measurement, leveraging a newly established ultrasound diaphragm dataset. This dataset comprises B-mode ultrasound images and videos for diaphragm thickness assessment, as well as M-mode images and videos for movement measurement. We introduce a novel deep learning-based segmentation network, the Multi-ratio Dilated U-Net (MDRU-Net), to enable accurate diaphragm measurements. The system additionally incorporates a comprehensive implementation plan for automated measurement.</p><p><strong>Results: </strong>Automatic measurement results are compared against manual assessments conducted by clinicians, revealing an average error of 8.12% in diaphragm thickening fraction measurements and a mere 4.3% average relative error in diaphragm excursion measurements. The results indicate overall minor discrepancies and enhanced potential for clinical detection of diaphragmatic conditions. Additionally, we design a user-friendly automatic measurement system for assessing diaphragm parameters and an accompanying method for measuring ultrasound-derived diaphragm parameters.</p><p><strong>Conclusions: </strong>In this paper, we constructed a diaphragm ultrasound dataset of thickness and excursion. Based on the U-Net architecture, we developed an automatic diaphragm segmentation algorithm and designed an automatic parameter measurement scheme. A comparative error analysis was conducted against manual measurements. Overall, the proposed diaphragm ultrasound segmentation algorithm demonstrated high segmentation performance and efficiency. The automatic measurement scheme based on this algorithm exhibited high accuracy, eliminating subjective influence and enhancing the automation of diaphragm ultrasound parameter assessment, thereby providing new possibilities for diaphragm evaluation.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"251"},"PeriodicalIF":5.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668756","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}
Longfei Ji, Binyu Wang, Danfei Shi, Weiyun Shen, Xinmin Li, Yong Li
{"title":"Single-cell RNA sequencing technology was employed to construct a risk prediction model for genes associated with pyroptosis and ferroptosis in lung adenocarcinoma.","authors":"Longfei Ji, Binyu Wang, Danfei Shi, Weiyun Shen, Xinmin Li, Yong Li","doi":"10.1186/s12931-025-03323-5","DOIUrl":"10.1186/s12931-025-03323-5","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is one of the most common subtypes of non-small cell lung cancer, and its mortality rate remains high. As a programmed cell death mode closely related to inflammation, pyroptosis has been found to play an important regulatory role in the tumor immune microenvironment and tumor progression in recent years. However, the characteristics and prognostic value of apoptosis in different cell types in LUAD have not been systematically elucidated.</p><p><strong>Method: </strong>This study integrated single-cell RNA sequencing (scRNA seq), bulk transcriptome data, and clinical information to comprehensively analyze the expression patterns and functional roles of pyroptosis related genes (PRGs) in LUAD. We conducted high-resolution clustering analysis on the GSE189357 single-cell dataset, constructed a protein interaction network, and established a prognostic model in conjunction with iron death related genes. Experimental validation of key genes through RNA sequencing and qPCR.</p><p><strong>Result: </strong>This study identified 17 different cell types, among which the pyroptosis activity of myeloid dendritic cells and neutrophils was significantly increased. Differentially expressed PRGs are enriched in immune related pathways, such as inflammasome assembly and NOD like receptor signaling pathways. The seven gene prognostic model we constructed (CXCL2, SLC7A5, CAV1, IFNG, EPAS1, TNFAIP3, CYBB) can effectively distinguish high-risk LUAD patients. Functional enrichment analysis revealed that the IL-17 signaling pathway is active in high-risk populations, suggesting that apoptosis may promote the progression of LUAD through immune dysfunction. Immune infiltration and pseudo time trajectory analysis further reveal the close correlation between PRGs expression and the dynamic state of immune cells. RNA sequencing and qPCR confirmed the differential expression of core genes in tumor tissues.</p><p><strong>Conclusion: </strong>This study developed a single-cell atlas of pyroptosis in LUAD and identified prognostic biomarkers with potential translational value. Our findings reveal the interaction mechanism between pyroptosis, ferroptosis, and tumor immunity, providing new ideas and targets for precise treatment of LUAD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"249"},"PeriodicalIF":5.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668817","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}
Vickram Tejwani, Nirupama Putcha, Han Woo, Chen Liu, David Lafon, Neil E Alexis, Antoine Azar, R Graham Barr, Igor Barjaktarevic, Russell P Bowler, Alejandro Comellas, David J Couper, Ashraf Fawzy, MeiLan K Han, Nadia N Hansel, Robert J Kaner, Jerry A Krishnan, Nathaniel Marchetti, Fernando J Martinez, Jill Ohar, Wanda O'Neal, Victor E Ortega, Robert Paine Iii, Tess D Pottinger, Martin Stämpfli, Lisa Ruvuna, Prescott G Woodruff, Christine M Freeman, Yvonne J Huang, Jeffrey L Curtis
{"title":"Associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbations.","authors":"Vickram Tejwani, Nirupama Putcha, Han Woo, Chen Liu, David Lafon, Neil E Alexis, Antoine Azar, R Graham Barr, Igor Barjaktarevic, Russell P Bowler, Alejandro Comellas, David J Couper, Ashraf Fawzy, MeiLan K Han, Nadia N Hansel, Robert J Kaner, Jerry A Krishnan, Nathaniel Marchetti, Fernando J Martinez, Jill Ohar, Wanda O'Neal, Victor E Ortega, Robert Paine Iii, Tess D Pottinger, Martin Stämpfli, Lisa Ruvuna, Prescott G Woodruff, Christine M Freeman, Yvonne J Huang, Jeffrey L Curtis","doi":"10.1186/s12931-025-03310-w","DOIUrl":"10.1186/s12931-025-03310-w","url":null,"abstract":"<p><strong>Rationale: </strong>Immunoglobulins (Ig) protect against pathogens frequently implicated in COPD exacerbations. We previously demonstrated an association of low-normal serum IgA and IgG concentrations with prospective exacerbation risk, but responsible mechanisms are undefined. Here, we examined associations of lower respiratory tract bacterial diversity to Ig levels in serum and bronchoalveolar lavage (BAL) and to the memory phenotypes of blood and BAL B cells.</p><p><strong>Methods: </strong>We analyzed data from phase I of SPIROMICS, an observational cohort study of smoking-related COPD. A subset of participants completed comprehensive research bronchoscopies, including analysis of BAL bacterial microbiota by 16 S rRNA gene (V4 region) sequencing and of blood and BAL B-cells by 12-color flow cytometry. In some participants, we also analyzed serum and BAL Ig levels by ELISA. We constructed linear regression models including either serum or BAL (albumin-corrected) Ig measurements as the independent variable and separate dependent variables, including B-cell subsets, BAL bacterial diversity metrics (Faith phylogenetic diversity, inverse Simpson, and richness indices), and clinical measures (FEV<sub>1</sub>% predicted, risk of prospective exacerbations), adjusted by age, sex, race, educational attainment, smoking status, and use of inhaled corticosteroids.</p><p><strong>Results: </strong>Serum IgG and IgA (n = 66 participants) were 1,486.1 ± 510.6 mg/dL [mean ± standard deviation (SD)] and 237.7 ± 131.6 mg/dL, respectively. Albumin-corrected BAL IgG and IgA (n = 117) were 0.03 ± 0.02 mg/dL and 0.01 ± 0.01 mg/dL, respectively. B-cells (n = 82) comprised 3.5 ± 3.0% of blood leukocytes. Serum IgA was associated with higher blood switched memory (IgD- CD27+) B-cell percentages (β 6.06, p = 0.01) and inversely associated with blood double-negative (IgD-CD27-) B-cell percentages (β - 9.96, p = 0.02). Available BAL microbiome data (n = 107) showed that reduced lung bacterial diversity associated with lower serum IgG, but not with serum IgA, BAL IgA, or BAL IgG concentrations. Neither BAL IgG nor IgA were associated with lung function or exacerbations.</p><p><strong>Conclusions: </strong>These results demonstrate an association of low serum IgG with reduced lung bacterial diversity, a feature of dysbiosis that may predispose to exacerbation. Defining the role of Ig in specific anatomic compartments is relevant to designing vaccine strategies.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"250"},"PeriodicalIF":5.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668755","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}
Elizabeth Dort, Hannah Rud, Taylor Billion, Abubakar Tauseef
{"title":"Trends in pulmonary embolism mortality in cancer patients in the United States from 1999-2022- A CDC Wonder database study.","authors":"Elizabeth Dort, Hannah Rud, Taylor Billion, Abubakar Tauseef","doi":"10.1186/s12931-025-03319-1","DOIUrl":"10.1186/s12931-025-03319-1","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary embolism (PE) is the third leading cause of cardiovascular death in the United States (Thromb Res. 2023;223:53-60) and presides as a major cause of morbidity and mortality among cancer patients. We investigated the trends of PE-related mortality in cancer patients over the last two decades.</p><p><strong>Methods: </strong>This retrospective analysis of the Centers for Disease Control's Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database focused on PE-related mortality in cancer patients across the United States from 1999 to 2022. Mortality in adults with PE and cancer was analyzed. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) and average annual percent changes (AAPCs) were calculated and reported.</p><p><strong>Results: </strong>There were 214,756 total deaths due to PEs in cancer patients in the United States between 1999-2022. The overall mortality trend increased over time, with an annual percent change increase from 0.61 (95% CI 0.29 to 0.88)* from 1999-2016 to 5.77 (95% CI 4.68 to 7.41)* in 2016-2022 and an average annual percent change (AAPC) of 1.93 (95% CI 1.72 to 2.13). A notable mortality increase was seen across gender, race/ethnicity, age, and regional factors beginning in 2016 and continuing through 2022. Additionally, PE-related mortality was significantly higher in the male, Black, and 85 + years old populations. The Midwest and rural regions had the highest PE-related mortality rates as well.</p><p><strong>Conclusion: </strong>There is an overall increasing trend in PE-related mortality for cancer patients, with a remarkable increase in 2016. This study highlights the specific populations and regions most affected by PE-related mortality emphasizing the need to increase education, timely management, and address disparities for these patients.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"248"},"PeriodicalIF":5.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650970","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}
Matthew Moll, Brian D Hobbs, Katherine A Pratte, Chengyue Zhang, Auyon J Ghosh, Russell P Bowler, David A Lomas, Edwin K Silverman, Dawn L DeMeo
{"title":"Assessing inflammatory protein biomarkers in COPD subjects with and without alpha-1 antitrypsin deficiency.","authors":"Matthew Moll, Brian D Hobbs, Katherine A Pratte, Chengyue Zhang, Auyon J Ghosh, Russell P Bowler, David A Lomas, Edwin K Silverman, Dawn L DeMeo","doi":"10.1186/s12931-025-03320-8","DOIUrl":"10.1186/s12931-025-03320-8","url":null,"abstract":"<p><strong>Rationale: </strong>Individuals homozygous for the Alpha-1 Antitrypsin (AAT) Z allele (Pi*ZZ) exhibit heterogeneity in COPD risk. COPD occurrence in non-smokers with AAT deficiency (AATD) suggests that inflammatory processes may contribute to COPD risk independently of smoking. We hypothesized that inflammatory protein biomarkers in non-AATD COPD are associated with moderate-to-severe COPD in AATD individuals, after accounting for clinical factors.</p><p><strong>Methods: </strong>Participants from the COPDGene (Pi*MM) and AAT Genetic Modifiers Study (Pi*ZZ) were included. Proteins associated with FEV<sub>1</sub>/FVC were identified, adjusting for confounders and familial relatedness. Lung-specific protein-protein interaction (PPI) networks were constructed. Proteins associated with AAT augmentation therapy were identified, and drug repurposing analyses performed. A protein risk score (protRS) was developed in COPDGene and validated in AAT GMS using AUROC analysis. Machine learning ranked proteomic predictors, adjusting for age, sex, and smoking history.</p><p><strong>Results: </strong>Among 4,446 Pi*MM and 352 Pi*ZZ individuals, sixteen blood proteins were associated with airflow obstruction, fourteen of which were highly expressed in lung. PPI networks implicated regulation of immune system function, cytokine and interleukin signaling, and matrix metalloproteinases. Eleven proteins, including IL4R, were linked to augmentation therapy. Drug repurposing identified antibiotics, thyroid medications, hormone therapies, and antihistamines as potential adjunctive AATD treatments. Adding protRS improved COPD prediction in AAT GMS (AUROC 0.86 vs. 0.80, p = 0.0001). AGER was the top-ranked protein predictor of COPD.</p><p><strong>Conclusions: </strong>Sixteen proteins are associated with COPD and inflammatory processes that predict airflow obstruction in AATD after accounting for age and smoking. Immune activation and inflammation are modulators of COPD risk in AATD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"247"},"PeriodicalIF":5.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643977","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}
Kaitlyn Kuntzman, Kjell Erik Julius Håkansson, Charlotte Suppli Ulrik, Deepa Rastogi
{"title":"Impact of natal and childhood metabolic markers on childhood asthma burden - a nationwide cohort study.","authors":"Kaitlyn Kuntzman, Kjell Erik Julius Håkansson, Charlotte Suppli Ulrik, Deepa Rastogi","doi":"10.1186/s12931-025-03321-7","DOIUrl":"10.1186/s12931-025-03321-7","url":null,"abstract":"<p><strong>Background: </strong>Pediatric obesity, a risk factor for asthma, is increasing in prevalence. Obesity-mediated metabolic abnormalities are one of the mechanisms that link asthma and obesity. While maternal obesity contributes to obesity and respiratory morbidity in the child, the contribution of paternal obesity and parental metabolic abnormalities to the child's asthma is not known.</p><p><strong>Methods: </strong>To quantify the impact of parental and child's body weight and metabolic traits, including elevated HbA1c, and blood cholesterol levels based on national, age-specific cut-off values, on asthma exacerbations, control, and severity, in a Danish nationwide cohort of 29,851 children aged 2-17 years with inhaled corticosteroid-treated asthma during 2015-17.</p><p><strong>Results: </strong>Among the 29,851 children, 1,430 had severe asthma, 4,750 had poor asthma control, and 2,353 had exacerbating asthma. Elevated LDL in the child was associated with 2.2-fold higher odds of severe asthma and elevated triglycerides with 1.5-fold higher odds of exacerbating asthma, while reduced HDL was associated with 1.5-fold higher odds of poor control. Both triglycerides and HDL were associated with 1.5-fold higher odds of exacerbating asthma. Maternal parameters including elevated LDL cholesterol, triglycerides, and HbA1C were associated with 1.2 to 1.4-fold higher odds of uncontrolled asthma in the child. Elevated paternal HbA1C was associated with exacerbating asthma.</p><p><strong>Conclusion: </strong>Dyslipidemia, including elevated LDL and decreased HDL, in the child and their parents was associated with high asthma burden in a Danish pediatric cohort with persistent asthma. These observations highlight the need to investigate the underlying mechanisms driven by fat metabolism that are transgenerational.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"246"},"PeriodicalIF":5.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638553","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}
Lu Sun, Haobo Li, Xincheng Li, Yuhan Li, Min Liu, Han Tian, Jixiang Liu, Ran Miao, Yu Zhang, Qiang Huang, Zhu Zhang, Ximei Niu, Shuai Zhang, Wanmu Xie, Shiqing Xu, Peiran Yang, Zhenguo Zhai
{"title":"Dysregulation of immune cells and platelet-monocyte aggregates in chronic thromboembolic pulmonary hypertension.","authors":"Lu Sun, Haobo Li, Xincheng Li, Yuhan Li, Min Liu, Han Tian, Jixiang Liu, Ran Miao, Yu Zhang, Qiang Huang, Zhu Zhang, Ximei Niu, Shuai Zhang, Wanmu Xie, Shiqing Xu, Peiran Yang, Zhenguo Zhai","doi":"10.1186/s12931-025-03284-9","DOIUrl":"10.1186/s12931-025-03284-9","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and immunological dysregulation are involved in the uncommon pulmonary thromboembolism (PTE) consequence known as chronic thromboembolic pulmonary hypertension (CTEPH). Although tissue samples are provided by pulmonary endarterectomy (PEA), accessibility is restricted by its technical complexity. Immune cells found in peripheral blood may provide information on how a disease develops.</p><p><strong>Methods: </strong>We developed a 7-color flow cytometry method using 200 µl of peripheral blood to analyze immune cell subpopulations and platelet immune cell aggregates in CTEPH. PEA tissues were used for immunofluorescence validation. We employed correlation analysis and linear regression to examine the relationships between immune cell dysregulation and the severity of CTEPH.</p><p><strong>Results: </strong>There were 36 age- and sex-matched healthy controls, 10 patients with other subtypes of pulmonary hypertension (PH) except CTEPH, 20 PTE patients, and 62 CTEPH patients. CTEPH patients had markedly dysregulated immune cell subpopulations. There was an increase in T lymphocytes from 60.59 ± 9.94% to 69.05 ± 4.90% (p < 0.0001) in CTEPH patients. Classical monocytes decreased (87.94 ± 9.93% vs. 82.02 ± 9.92%, p < 0.0001), while non-classical monocytes increased (3.69 ± 5.42% vs. 8.44 ± 5.91%, p = 0.02) in CTEPH patients. The same trend was also observed in PH group. Dysregulated immune cells were primarily localized in thrombus and neointima regions. Platelet-monocyte aggregates (PMAs) and their subpopulations were positively correlated with hemodynamic and ultrasound indicators. PTE patients had greater levels of PMAs than CTEPH patients (p = 0.0007), and these levels decreased during treatment (p = 0.0168).</p><p><strong>Conclusion: </strong>Immune cell subpopulations in CTEPH can be efficiently analyzed using the low blood volume flow cytometry approach. Peripheral blood immune cell dysregulation points to an active immune response in CTEPH. Insights into the pathophysiology of CTEPH may be gained by using PMA as a biomarker for assessing the severity and treatment outcomes of CTEPH. However, more research is needed to determine PMA's role in CTEPH for disease diagnosis assessment and pathogenesis.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"245"},"PeriodicalIF":5.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620991","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}
Celia Vidal, Jean-Pierre Mallet, Sarah Skinner, Raphael Gilson, Olivier Gaubert, Arnaud Prigent, Frédéric Gagnadoux, Arnaud Bourdin, Nicolas Molinari, Dany Jaffuel
{"title":"Concerns arising from the calculation of the apnea-hypopnea index during CPAP-telemonitoring of patients with obstructive sleep apnea.","authors":"Celia Vidal, Jean-Pierre Mallet, Sarah Skinner, Raphael Gilson, Olivier Gaubert, Arnaud Prigent, Frédéric Gagnadoux, Arnaud Bourdin, Nicolas Molinari, Dany Jaffuel","doi":"10.1186/s12931-025-03324-4","DOIUrl":"10.1186/s12931-025-03324-4","url":null,"abstract":"<p><strong>Background: </strong>Continuous Positive Airway Pressure (CPAP) telemonitoring is increasingly important in managing obstructive sleep apnea (OSA). The Apnea-Hypopnea Index reported by CPAP devices (AHI<sub>flow</sub>) is used as a key indicator of treatment effectiveness. However, discrepancies in AHI<sub>flow</sub> calculation rules between manufacturers may affect clinical decision-making. No prior studies have investigated whether manufacturers' choices to exclude certain apnea-hypopnea events from the AHI<sub>flow</sub> calculation may influence the number of patients presenting an AHI<sub>flow</sub> alert. The aim of this proof-of-concept study was not to compare the manufacturers with each other, but to evaluate, for each manufacturer, how the different possible ways of calculating AHI<sub>flow</sub> influence the percentage of alert cases.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 13,764 CPAP-treated OSA patients monitored on October 2, 2023. AHI<sub>flow</sub> calculations were evaluated according to manufacturer-specific rules. When possible, we assessed the impact of excluding central hypopneas, events during major leaks, and/or ramp periods on the percentage of patients crossing the consensual AHI<sub>flow</sub> alert threshold of ≥ 10 events/h.</p><p><strong>Results: </strong>We identified significant disparities in AHI<sub>flow</sub> calculations between manufacturers, which lead to significant differences in the number of patients flagged as being in an alert state. Excluding central hypopneas reduced the number of alert cases by 50%, while excluding apneas/hypopneas during major leaks or ramp periods reduced alerts by 20%.</p><p><strong>Conclusions: </strong>Our proof-of-concept study highlights inconsistencies in AHI<sub>flow</sub> calculations among CPAP manufacturers, raising concerns about patient care. Establishing standardized AHI<sub>flow</sub> calculation criteria is essential to ensuring accurate monitoring and optimal patient safety.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"244"},"PeriodicalIF":5.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620990","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}
Vickram Tejwani, Yifan Wang, Lauren Munoz Tremblay, Elizabeth Azzato, Arianne K Baldomero, Christine Wendt, Amy Attaway, Russell Bowler, Umur Hatipoglu, Rebecca Hutton, Charlie Strange, Xiaofeng Wang, Victor E Ortega, Joe Zein, James K Stoller
{"title":"Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis.","authors":"Vickram Tejwani, Yifan Wang, Lauren Munoz Tremblay, Elizabeth Azzato, Arianne K Baldomero, Christine Wendt, Amy Attaway, Russell Bowler, Umur Hatipoglu, Rebecca Hutton, Charlie Strange, Xiaofeng Wang, Victor E Ortega, Joe Zein, James K Stoller","doi":"10.1186/s12931-025-03322-6","DOIUrl":"10.1186/s12931-025-03322-6","url":null,"abstract":"<p><strong>Background: </strong>The best described endotype of COPD is alpha-1 antitrypsin (AAT) deficiency, due to a genetic abnormality in the SERPINA1 gene. Common deficient PI variants are the Z and S variants. Homozygotes for the Z allele (PI*ZZ individuals) carry the genotype most commonly associated with severe AAT deficiency (AATD), but a highly prevalent endotype is the heterozygous state (PI*MZ individuals). The effect of PI*MZ status on exacerbations and health care utilization is unknown.</p><p><strong>Study design and methods: </strong>Cleveland electronic health record data was examined to compare healthcare utilization between PI*MZ and PI*MM individuals. Three outcomes were assessed: moderate COPD exacerbation (defined as short-term steroid prescription), any emergent care (defined as an express care, urgent care, or emergency department visit), and any hospitalization. Models were adjusted for age, sex, race, BMI, smoking status, comorbidity count, liver disease, zip code median income.</p><p><strong>Results: </strong>4,148 individuals had the PI*MM genotype and 308 PI*MZ. PI*MZ was associated with increased risk for moderate COPD exacerbations (HR [95% CI]: 1.66 [1.27, 2.17]) and hospitalizations (HR [95% CI]: 1.44 [1.19, 1.75]) compared to PI*MM. The risk of hospitalization was higher among PI*MZ individuals with AAT levels < 90 mg/dL (HR [95% CI]: 1.59 [1.14, 2.23]) but not in those with AAT levels > 90 mg/dL, as compared to PI*MM.</p><p><strong>Interpretation: </strong>Given the high prevalence, PI*MZ represents a COPD phenotype that is associated with worse outcomes, inviting additional investigation to identify predictive biomarkers of worse disease and treatable traits. Future prospective studies to better characterize the longitudinal course and healthcare utilization among individuals with a PI*MZ genotype.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"243"},"PeriodicalIF":5.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620992","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}