Respiratory Research最新文献

{"title":"CPHNet: a novel pipeline for anti-HAPE drug screening via deep learning-based Cell Painting scoring.","authors":"De-Zhi Sun, Xi-Ru Yang, Cong-Shu Huang, Zhi-Jie Bai, Pan Shen, Zhe-Xin Ni, Chao-Ji Huang-Fu, Yang-Yi Hu, Ning-Ning Wang, Xiang-Lin Tang, Yong-Fang Li, Yue Gao, Wei Zhou","doi":"10.1186/s12931-025-03173-1","DOIUrl":"10.1186/s12931-025-03173-1","url":null,"abstract":"<p><strong>Background: </strong>High altitude pulmonary edema (HAPE) poses a significant medical challenge to individuals ascending rapidly to high altitudes. Hypoxia-induced cellular morphological changes in the alveolar-capillary barrier such as mitochondrial structural alterations and cytoskeletal reorganization, play a crucial role in the pathogenesis of HAPE. These morphological changes are critical in understanding the cellular response to hypoxia and represent potential therapeutic targets. However, there is still a lack of effective and valid drug discovery strategies for anti-HAPE treatments based on these cellular morphological features. This study aims to develop a pipeline that focuses on morphological alterations in Cell Painting images to identify potential therapeutic agents for HAPE interventions.</p><p><strong>Methods: </strong>We generated over 100,000 full-field Cell Painting images of human alveolar adenocarcinoma basal epithelial cells (A549s) and human pulmonary microvascular endothelial cells (HPMECs) under different hypoxic conditions (1%~5% of oxygen content). These images were then submitted to our newly developed segmentation network (SegNet), which exhibited superior performance than traditional methods, to proceed to subcellular structure detection and segmentation. Subsequently, we created a hypoxia scoring network (HypoNet) using over 200,000 images of subcellular structures from A549s and HPMECs, demonstrating outstanding capacity in identifying cellular hypoxia status.</p><p><strong>Results: </strong>We proposed a deep neural network-based drug screening pipeline (CPHNet), which facilitated the identification of two promising natural products, ferulic acid (FA) and resveratrol (RES). Both compounds demonstrated satisfactory anti-HAPE effects in a 3D-alveolus chip model (ex vivo) and a mouse model (in vivo).</p><p><strong>Conclusion: </strong>This work provides a brand-new and effective pipeline for screening anti-HAPE agents by integrating artificial intelligence (AI) tools and Cell Painting, offering a novel perspective for AI-driven phenotypic drug discovery.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"91"},"PeriodicalIF":5.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587622","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":"Neutrophils are involved in the development and outcomes of plastic bronchitis associated with Mycoplasma pneumoniae pneumonia.","authors":"Xia Huang, Houbing Qin, Rui Zhang, Xinyi Jia, Deyu Zhao, Feng Liu","doi":"10.1186/s12931-025-03167-z","DOIUrl":"10.1186/s12931-025-03167-z","url":null,"abstract":"<p><strong>Background: </strong>Previous research has demonstrated a notable increase in neutrophil counts among pediatric patients with plastic bronchitis (PB) associated with Mycoplasma pneumoniae pneumonia (MPP). However, the role of neutrophils in MPP-associated PB remains largely elusive.</p><p><strong>Methods: </strong>This is a nested case-control study that enrolled patients diagnosed with MPP who underwent bronchoscopy in our department during the MPP pandemic from September 2023 to January 2024. We conducted an analysis of clinical characteristics, blood samples, bronchoalveolar lavage fluid (BALF), and cast specimens, correlating these factors with the development and outcomes of PB.</p><p><strong>Results: </strong>Among the 557 patients with MPP included in the study, 21 (3.8%) developed PB. The peripheral neutrophil count was identified as an independent risk factor for PB (OR = 3.113 [95%CI 1.050-9.224], P = 0.04) and exhibited strong predictive value for the condition (AUC = 0.885 [95%CI 0.796-0.975], P < 0.001). Notably, there was a marked presence of neutrophil infiltration and neutrophil extracellular traps (NETs) formation in the blood, BALF, and cast samples from patients with PB. Furthermore, the levels of neutrophils and NETs correlated significantly with clinical outcomes.</p><p><strong>Conclusion: </strong>A high level of neutrophils poses a risk for PB and demonstrates strong predictive value for its diagnosis. Neutrophils and NETs are closely linked to the clinical outcomes of PB in patients with MPP.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"92"},"PeriodicalIF":5.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587667","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":"Physical activity and lung cancer screening (PALS): feasibility randomised controlled trial of exercise and physical activity in lung cancer screening.","authors":"Asha Bonney, Catherine L Granger, Daniel Steinfort, Cameron Patrick, Henry M Marshall, Kwun M Fong, Renee Manser","doi":"10.1186/s12931-025-03158-0","DOIUrl":"10.1186/s12931-025-03158-0","url":null,"abstract":"<p><strong>Background: </strong>There is increasing evidence that screening provides a catalyst for behavioural change. Low physical activity (PA) levels are a potentially modifiable risk factor for developing lung cancer. This study aims to assess the feasibility and safety of a semi-supervised 8-week multi-modal exercise program to improve health-related quality of life and PA levels of participants of lung cancer screening.</p><p><strong>Methods: </strong>Participants without lung cancer from a single Australian International Lung Screen Trial (ILST; NCT02871856) site were invited to this feasibility randomised controlled trial. Enrolled participants were randomised to usual care, written material, or a home-based exercise program (in addition to written material). Assessments occurred at baseline, 9 weeks, and 6 months.</p><p><strong>Results: </strong>75 participants were enrolled over a 3-month period in 2022 (consent rate of 67%). 43% of participants were female, median age 66 years old (IQR 62, 73). Of the 25 participants randomised to the home-based exercise program, 22 participants (88%) attended > 70% of weekly sessions. 99% (74/75) of study participants attended their 9-week and 6-month follow-up assessments.</p><p><strong>Conclusions: </strong>This study confirms the feasibility and high compliance of delivering a semi-supervised 8-week multi-modal exercise program to participants of a lung cancer screening program. It was safe, with no adverse events.</p><p><strong>Clinical trial registration: </strong>Australian Clinical Trials Register https://www.australianclinicaltrials.gov.au ACTRN12622001001785.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"89"},"PeriodicalIF":5.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574293","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":"Multicentre, real-world data of next-generation computer-assisted vacuum aspiration thrombectomy in acute pulmonary embolism.","authors":"Sylwia Sławek-Szmyt, Jakub Stępniewski, Marcin Kurzyna, Jacek Klaudel, Wiktor Kuliczkowski, Maciej Lewandowski, Marek Grabka, Marek Roik, Rasa Ordiene, Stanisław Jankiewicz, Grzegorz Kopeć, Szymon Darocha, Ewa Mroczek, Katarzyna Widecka, Paweł Kurzyna, Maciej Lesiak, Piotr Pruszczyk, Aleksander Araszkiewicz","doi":"10.1186/s12931-025-03162-4","DOIUrl":"10.1186/s12931-025-03162-4","url":null,"abstract":"<p><strong>Background: </strong>Data on interventional treatment of intermediate-high (and high-risk pulmonary embolism (PE) are limited. The authors sought to evaluate the safety and efficacy of catheter-directed mechanical aspiration thrombectomy (CDMT) in a real-world PE patient population.</p><p><strong>Methods: </strong>This multicenter, prospective registry enrolled PE patients treated with CDMT using the Lightning 12 System. The primary safety endpoints included in-hospital all-cause mortality, procedure-related major bleeding, clinical deterioration, or bailout to another strategy. The primary efficacy outcomes included the reduction of pulmonary arterial pressures and change in the right-to-left ventricular (RV/LV) ratio 48 h after the CDMT. Multivariate regression analyzed characteristics associated with RV/LV improvement.</p><p><strong>Results: </strong>Our analysis included 150 patients, 72% with intermediate-high PE and 28% with high-risk PE. Systemic thrombolysis was contraindicated in 33.3%, whereas in 4% it failed. There were 2% intraprocedural deaths (1.3% due to RV failure and 0.7% due to massive interstitial bleeding), with no more deaths during follow-up. In 0.7%, CDMT was converted to open surgery, and in 0.7%, bailout systemic thrombolysis and extracorporeal oxygenation support. Major bleedings occurred in 1.3% within 48 h post CDMT. Immediate hemodynamic improvements included a mean 11.3±10 mmHg (22.1%) drop in systolic pulmonary arterial pressure (p < 0.0001) and a median 0.33 (0.25-0.45), (25.2%) drop in RV/LV ratio (p < 0.0001 for paired values), CONCLUSIONS: Aspiration thrombectomy with the Lightning 12 system characterizes an acceptable safety profile, substantial improvements in hemodynamic outcomes, and low mortality for patients with intermediate-high and high-risk PE.</p><p><strong>Trial registration: </strong>NCT04879069 - date of registration 04.05.2021.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"87"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568609","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":"Disproportionately raised risk of adverse outcomes in patients with COPD and comorbid type 2 diabetes or depression: Swedish register-based cohort study.","authors":"Carolina Smith, Mikael Hasselgren, Hanna Sandelowsky, Björn Ställberg, Ayako Hiyoshi, Scott Montgomery","doi":"10.1186/s12931-025-03160-6","DOIUrl":"10.1186/s12931-025-03160-6","url":null,"abstract":"<p><strong>Background: </strong>We aimed to examine if patients with COPD and comorbid type 2 diabetes, or COPD with comorbid depression or anxiety, had disproportionally raised excess risks of subsequent cardiovascular disease and mortality.</p><p><strong>Methods: </strong>This general population-based cohort study used data from Swedish national registers, with follow-up during 2005-2018. Cox regression estimated risks of cardiovascular disease or mortality, producing hazard ratios (HR) with (95% confidence intervals). Interaction testing quantified disproportionally increased excess risks.</p><p><strong>Results: </strong>Among 5,624,306 individuals, 332,549 had a COPD diagnosis. Compared with individuals who did not have COPD or type 2 diabetes, all-cause mortality risk was higher for individuals who had either COPD or type 2 diabetes, with HR 2.68 (2.66-2.69) and 1.70 (1.69-1.71), respectively. Having both conditions produced an HR of 3.72 (3.68-3.76). Among cardiovascular outcomes, the highest risks were found for chronic heart failure: COPD only, HR 2.87 (2.84-2.90); type 2 diabetes only, 1.86 (1.84-1.88); and both, 4.55 (4.46-4.64). Having both COPD and type 2 diabetes was associated with disproportionally higher excess risks than expected from the sum of the individual diseases, except for cerebrovascular disease or ischemic heart disease. For COPD and depression/anxiety, all-cause mortality risk was associated with COPD only, HR 2.74 (2.72-2.76); depression/anxiety only, 2.39 (2.38-2.40); and both 4.72 (4.68-4.75). Chronic heart failure was associated with COPD only, HR 2.74 (2.71-2.78); depression/anxiety only, 1.31 (1.30-1.32); and both, 3.45 (3.40-3.50). This disease combination was associated with disproportionally higher excess risks than expected, except for atrial fibrillation.</p><p><strong>Conclusions: </strong>Type 2 diabetes or depression/anxiety in COPD patients were associated with disproportionally excess risks for cardiovascular disease and mortality. It is important for clinicians to be aware of these greater than expected risks, to prevent further cardiovascular morbidity and mortality.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"84"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568287","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":"Early bacterial co-infections and ventilator-associated lower respiratory tract infections among intubated patients during the first and second COVID-19 waves: a European comparative cohort study.","authors":"Anahita Rouze, Pedro Povoa, Ignacio Martin-Loeches, Ouriel Saura, Julien Maizel, Olivier Pouly, Demosthenes Makris, Damien Du Cheyron, Fabienne Tamion, Marie Labruyere, Laurent Argaud, Fabien Lambiotte, Elie Azoulay, Martine Nyunga, Matthieu Turpin, Mehdi Imouloudene, Nicolas Weiss, Arnaud W Thille, Bruno Megarbane, Eleni Magira, Iliana Ioannidou, Gaëtan Plantefeve, Flavia Galli, Emili Diaz, Armand Mekontso Dessap, Pierre Asfar, Alexandre Boyer, Alexandra Beurton, Ariane Gavaud, Charlotte Larrat, Jean Reignier, Alexandre Pierre, Christophe Vinsonneau, Pierre-Edouard Floch, Adrian Ceccato, Antonio Artigas, Alexandre Iellatchitch, Julien Labreuche, Saad Nseir","doi":"10.1186/s12931-025-03148-2","DOIUrl":"10.1186/s12931-025-03148-2","url":null,"abstract":"<p><strong>Background: </strong>The management of severe SARS-CoV-2 pneumonia, alongside logistical constraints, evolved between the first and subsequent COVID-19 waves. This study aimed to compare the prevalence of early bacterial pulmonary co-infections and the incidence of ventilator-associated lower respiratory tract infections (VA-LRTI) across the first and second waves of the pandemic, and to characterize their microbiology.</p><p><strong>Methods: </strong>Latter part of a multicenter retrospective European cohort analysis conducted in 35 ICUs. Adult patients admitted for SARS-CoV-2 pneumonia and requiring invasive mechanical ventilation ≥ 48 h were consecutively included from both waves (February-May 2020 for period 1, October 2020-April 2021 for period 2). Co-infections were defined by bacterial isolation in respiratory secretions or blood cultures, or a positive pneumococcal urinary antigen test, within 48 h after intubation. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. The 28-day cumulative incidence of first VA-LRTI episodes was estimated using the Kalbfleisch and Prentice method, with co-infection prevalence and VA-LRTI incidence compared using multivariable logistic regression and Fine-and-Gray models, respectively.</p><p><strong>Results: </strong>The study included 1,154 patients (558 in period 1 and 596 in period 2). Co-infection prevalence significantly rose from 9.7% in period 1 to 14.9% in period 2 (adjusted odds ratio (95% confidence interval) 1.52 (1.04-2.22), p = 0.03). Gram-positive cocci dropped from 59 to 48% of co-infections between periods 1 and 2. The overall incidence of VA-LRTI was similar across periods (50.4% and 53.9%, adjusted sub distribution hazard ratio (sHR) 1.14 (0.96-1.35), p = 0.11), with a significant increase in VAP incidence in period 2 (36% to 44.8%, adjusted sHR 1.37 (1.12-1.66), p = 0.001), predominantly occurring within the initial 14 days after intubation, and a concurrent significant decrease in VAT incidence (14.3% to 9.1%, adjusted sHR 0.61 (0.42-0.88), p = 0.007). Gram-negative bacilli, led by Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp., were responsible for 89% and 84% of VA-LRTI in periods 1 and 2, respectively.</p><p><strong>Conclusions: </strong>Between the first and second COVID-19 waves, the prevalence of early bacterial pulmonary co-infections significantly increased among intubated patients. Although the overall incidence of VA-LRTI remained stable, there was a significant shift from VAT to VAP episodes.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"83"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568363","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":"Addition of thoracic radiotherapy to a PD-L1 inhibitor plus chemotherapy regimen delays brain metastasis onset in extensive-stage small cell lung cancer patients without baseline brain metastasis.","authors":"Baiyang Huang, Senyuan Liu, Kaiyue Wang, Jiarui Zhao, Min Li, Xingpeng Wang, Weiqing Wang, Xiaohan Wang, Jinming Yu, Xue Meng, Guoxin Cai","doi":"10.1186/s12931-025-03157-1","DOIUrl":"10.1186/s12931-025-03157-1","url":null,"abstract":"<p><strong>Background: </strong>With the application of immune checkpoint inhibitors (ICIs) and the discovery of the synergistic effect of radiotherapy and immunotherapy, the intracranial benefit of thoracic radiotherapy (TRT) is receiving signiffcant clinical attention. The purpose of this study was to analyze the cranial benefits of ICIs and TRT in patients with extensive-stage small cell lung cancer (ES-SCLC) without baseline brain metastases (BMs).</p><p><strong>Materials and methods: </strong>From August 2019 to August 2022, data from patients diagnosed with ES-SCLC without baseline BMs were retroactively recorded. The Kaplan‒Meier method was used to calculate overall survival (OS), progression-free survival (PFS), and brain metastasis-free survival (BMFS), and the differences between the treatment groups were compared with the log-rank test. Risk factors associated with OS were analyzed via the Cox regression model.</p><p><strong>Results: </strong>A total of 216 patients were included, with a median follow-up of 24.73 months. Among these patients, 137 (63.4%) received first-line ICIs combined with chemotherapy (ChT), including 32 patients treated with anti-programmed death 1 antibody (αPD-1) and 105 patients treated with anti-programmed death-ligand 1 antibody (αPD-L1), and 79 patients (36.6%) received first-line ChT alone. Compared with the ChT-alone group, the ICI + ChT group demonstrated significantly improved PFS (8.07 vs. 6.87 months; p < 0.001) and OS (19.83 vs. 13.80 months; p = 0.001). The addition of ICIs to the ChT regimen did not significantly delay the onset of BMs compared to that with ChT alone (16.93 vs. 12.67 months; p = 0.379). Notably, the addition of TRT to the αPD-L1 + ChT regimen significantly prolonged BMFS compared to that without TRT (20.27 vs. 8.80 months; p = 0.045).</p><p><strong>Conclusion: </strong>In patients with ES-SCLC without baseline BMs, first-line chemoimmunotherapy significantly improves PFS and OS. However, it does not delay intracranial metastasis. The addition of TRT to αPD-L1 + ChT therapy significant delays the development of BMs.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"85"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568285","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":"Increased autophagy activity regulated by LC3B gene promoter DNA methylation is associated with progression to active pulmonary tuberculosis disease.","authors":"Yung-Che Chen, Ying-Tang Fang, Chao-Chien Wu, Tung-Ying Chao, Yi-Hsi Wang, Chia-Cheng Tseng, Sum-Yee Leung, Chiu-Ping Lee, Ting-Ya Wang, Po-Yuan Hsu, Jen-Chieh Chang, Meng-Chih Lin, Chang-Chun Hsiao","doi":"10.1186/s12931-025-03149-1","DOIUrl":"10.1186/s12931-025-03149-1","url":null,"abstract":"<p><strong>Background: </strong>This study aims to explore the role of autophagy-associated genes (ATG) and their epigenetic markers in the progression of mycobacterium tuberculosis (M. tb) infection, and to test the effects of de-methylation agents on macrophage functions against TB.</p><p><strong>Methods: </strong>ATG expressions and their gene promoter DNA methylation levels of blood immune cells were measured in 60 patients with active pulmonary TB disease, 31 subjects with latent TB infection (LTBI), and 15 non-infected healthy subjects (NIHS). An in vitro monocytic THP-1 cell culture model under M. tb-specific antigen stimuli was applied.</p><p><strong>Results: </strong>LC3B protein expression of blood M1/M2a monocyte, ATG5 protein expression of M2a, and mean DNA methylation levels of the LC3B gene promoter region of peripheral blood mononuclear cells were all increased in active TB patients versus either LTBI or NIHS group. The LC3B methylation levels were negatively correlated with its protein expressions. The discrimination of active TB disease from LTBI or NIHS was optimally captured by prediction scores, which combined LC3B (+) percentage of blood M1/M2a monocyte, LC3B gene promoter DNA methylation level, male gender, and body mass index. LC3B and ATG5 expressions of both blood M2a and neutrophil were decreased after 6-month anti-TB therapy, but hypermethylated LC3B gene promoter persisted. In vitro 5-Aza-2'-deoxycytidine treatment improved bactericidal, apoptosis and phagocytosis functions through augmenting autophagy flux via mechanisms other than demethylation of the LC3B gene promoter in THP-1 cells.</p><p><strong>Conclusions: </strong>Increased LC3B expression and LC3B gene promoter hypermethylation may serve as biomarkers for progression of M. tb infection, while use of de-methylation agent may be a potential approach to host-directed immunotherapy in active TB disease.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"86"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568526","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":"Exposure to volatile organic compounds and chronic respiratory disease mortality, a case-cohort study.","authors":"Mahdi Nalini, Hossein Poustchi, Deepak Bhandari, Benjamin C Blount, Brandon M Kenwood, Cindy M Chang, Amy Gross, Christopher Ellison, Masoud Khoshnia, Akram Pourshams, Mitchell H Gail, Barry I Graubard, Sanford M Dawsey, Farin Kamangar, Paolo Boffetta, Paul Brennan, Christian C Abnet, Reza Malekzadeh, Neal D Freedman, Arash Etemadi","doi":"10.1186/s12931-025-03165-1","DOIUrl":"10.1186/s12931-025-03165-1","url":null,"abstract":"<p><strong>Background: </strong>Chronic respiratory diseases (CRDs) are the third leading cause of death worldwide. Data of the associations between specific volatile organic compounds (VOCs), a major component of air pollution and tobacco smoke, and subsequent CRD mortality in the general population are scarce.</p><p><strong>Methods: </strong>In a case-cohort analysis within the population-based Golestan cohort study (n = 50045, aged 40-75 years, 58% women, enrollment: 2004-2008, northeastern Iran), we included all participants who died from CRD during follow-up through 2018 (n = 242) as cases and stratified them into 16 strata defined by age, sex, residence, and tobacco smoking. Subcohort participants (n = 610) were randomly selected from all eligible cohort participants in each stratum, and sampling fractions were calculated. Baseline urine samples were used to measure 20 VOCs using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. After excluding participants with previous history of CRDs, we used stratified Cox regression models weighted by the inverse sampling fractions (i.e. inverse probability weighting) adjusted for potential confounders, including urinary cotinine and pack-years of smoking, to calculate hazard ratios (HR) for the associations between biomarker tertiles and CRD mortality.</p><p><strong>Results: </strong>Data from 545 non-case, sub-cohort participants and 149 cases (69.1% chronic obstructive pulmonary disease, 13.4% asthma, 17.5% other CRDs) were assessed in this study. During a follow-up of 10.5 years, associations [2nd and 3rd vs. 1st tertiles, HR (95% confidence interval), p for trend] were observed between metabolites of acrolein [1.56 (0.64,3.79), 3.53 (1.53,8.16), 0.002] and styrene/ethylbenzene [1.17 (0.53,2.60), 3.24 (1.37,7.66), 0.005] and CRD mortality, which persisted after excluding the first four years of follow-up.</p><p><strong>Conclusion: </strong>Our findings support prior research suggesting respiratory toxicity of VOCs. Further investigation and monitoring of these compounds, especially acrolein and styrene/ethylbenzene, as CRD risk factors, are recommended.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"88"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568335","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":"Aerosolized nicotine-free e-liquid base constituents exacerbates mitochondrial dysfunction and endothelial glycocalyx shedding via the AKT/GSK3β-mPTP pathway in lung injury models.","authors":"Ziyu Dai, Bin Xie, Chen Jiang, Yun Peng, Jianing Lin, Qiong Chen, Jingyi Sun","doi":"10.1186/s12931-025-03155-3","DOIUrl":"10.1186/s12931-025-03155-3","url":null,"abstract":"<p><p>Smoking has been recognized as a risk factor of cancer, heart disease, stroke, diabetes, and lung diseases such as chronic obstructive pulmonary disease, and nicotine appears to be the responsible component of tobacco smoke that affects lung development. While nicotine-free electronic cigarettes (e-cigarettes) are often promoted as a safer alternative to traditional smoking, recent evidence suggests that they might pose significant health risks. This study investigates the effects of nicotine-free e-cigarette vapor (ECV) on lung tissue and endothelial function. A mouse model of ECV-induced lung injury and human pulmonary microvascular endothelial cells (HPMVECs) were utilized to evaluate the impact of ECV exposure on mitochondrial function, endothelial cell viability, and glycocalyx shedding. ECV exposure significantly damages lung tissue, characterized by alveolar enlargement, inflammation, and vascular remodeling, indicative of emphysematous changes. In vitro, HPMVECs exposed to nicotine-free e-cigarette extract (ECE) demonstrated dose-dependent increases in mitochondrial reactive oxygen species (ROS), mitochondrial membrane depolarization, mPTP opening, and reduced ATP production, leading to enhanced endothelial permeability and glycocalyx degradation. The inhibition of mPTP opening with Cyclosporin A (CsA) was found to mitigate the mitochondrial dysfunction and glycocalyx damage induced by ECE, indicating a protective role of mPTP inhibition in preserving endothelial integrity. The AKT/GSK3β signaling pathway was identified as a key regulator of these processes, with ECE exposure downregulating p-AKT and p-GSK3β, thereby promoting mPTP opening. Activation of AKT signaling partially reversed these effects, highlighting the potential of targeting the AKT/GSK3β-mPTP axis to mitigate the adverse effects of e-cigarette exposure on lung and endothelial function. These findings underscore the potential risks associated with nicotine-free e-cigarettes and suggest novel therapeutic targets for preventing lung injury progression.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"82"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537991","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}