Lung最新文献

{"title":"Dasatinib-Associated Chylothorax: A Review of Cases Reported to the FDA Adverse Event Reporting System and the Published Literature.","authors":"David A Kaland, Graça M Dores, Afrouz Nayernama, S Christopher Jones","doi":"10.1007/s00408-025-00804-8","DOIUrl":"https://doi.org/10.1007/s00408-025-00804-8","url":null,"abstract":"","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"52"},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship of Lung Function and the Preserved Ratio Impaired Spirometry Pattern with Aortic and Left Ventricular Structure and Function on Magnetic Resonance Imaging: The Jackson Heart Study.","authors":"Tasnim F Imran, Gaurav Choudhary, James G Terry, Yuan-I Min, Matthew Jankowich","doi":"10.1007/s00408-025-00808-4","DOIUrl":"10.1007/s00408-025-00808-4","url":null,"abstract":"<p><strong>Introduction: </strong>Low lung function and Preserved Ratio Impaired Spirometry (PRISm) have been associated with increased co-morbid cardiovascular disease. However, the association of abnormal lung function and PRISm with imaging markers of cardiovascular dysfunction has not been well elucidated.</p><p><strong>Methods: </strong>Participants from the Jackson Heart Study who had spirometry measurements at baseline and underwent cardiac magnetic resonance (CMR) were included. Multivariable adjusted associations between forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) and markers of aortic (pulse wave velocity, aPWV, wall thickness) and cardiac function (left ventricular (LV) stroke volume, and indexed LV mass) as measured on CMR were examined using linear regression models. Study participants were then divided into three groups (normal spirometry: FEV1/FVC ≥ 0.70, FEV1 ≥ 80%, airflow obstruction: FEV1/FVC < 0.70, and PRISm: FEV1/FVC ≥ 0.70, FEV1 < 80%). We then examined the associations of spirometry pattern and markers of structure and function as dichotomous outcomes using multivariable adjusted logistic regression models.</p><p><strong>Results: </strong>A total of 1278 participants (788 women [63%]; 375 (29%) ever smokers, 612 (48%) with hypertension, 1033 [81%] with normal spirometry, 80 [6%] with airflow obstruction, and 165 (13%) with PRISm met criteria for inclusion. In a multivariable model adjusting for age, sex, BMI, smoking status, and systolic blood pressure, aPWV was significantly associated with FEV1% (-0.20 ± 0.03, p = 0.04) and those with airflow obstruction had significantly higher odds of an increased aPWV (OR 2.25, 95% CI 1.29-3.93) compared to controls with a normal spirometry pattern. In the multivariable adjusted model, those with PRISm had a higher likelihood of a reduced LV stroke volume compared to controls (OR 1.69, 95% CI 1.14-2.56).</p><p><strong>Discussion: </strong>The PRISm pattern is associated with decreased LV stroke volume. This may be a potential mechanism between PRISm pattern and incident heart failure.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"51"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Reticulocalbin 3 (RCN3) is a Novel Biomarker for the Early Diagnosis of Hepatopulmonary Syndrome in Cirrhotic Patients.","authors":"Fangping Ding, Liu Yang, Wenhui Cao, Jie Sun, Fengwei Shi, Yingfei Wang, Caixia Hu, Weiwei Kang, Jing Han, Qingkun Song, Yingmin Ma, Jiawei Jin","doi":"10.1007/s00408-025-00807-5","DOIUrl":"10.1007/s00408-025-00807-5","url":null,"abstract":"<p><strong>Background: </strong>Hepatopulmonary syndrome (HPS) is a severe complication in cirrhotic patients and characterized by abnormal intrapulmonary vasodilation (IPVD), resulting in impaired oxygenation. Recent studies highlight the pivotal role and clinical merit of Reticulocalbin 3 (RCN3) in interstitial pulmonary remodeling.</p><p><strong>Objectives: </strong>This study aimed to investigate the clinical value of plasma RCN3 for early diagnosis of HPS in cirrhotic patients.</p><p><strong>Methods: </strong>This prospective observational study on a cohort including 41 healthy control subjects and 247 cirrhotic patients with/without HPS, in which most HPS occurs in the mild stage. Plasma levels of RCN3 and key HPS-associated vasoactive factors are compared between patients with and without HPS/IPVD. The predictive value of RCN3 for the diagnosis of HPS is further analyzed.</p><p><strong>Results: </strong>Patients with HPS had a severe condition. Plasma RCN3 was decreased in cirrhotic patients versus health control, but it is significantly higher in patients with HPS/IPVD than without non-HPS/IPVD. Notably, RCN3 level is positively correlated with P(A-a)O₂ and MELD scores as well as plasma levels of angiogenetic factors VEGF and AngII. Although the plasma levels of vasoactive factors were significantly different between HPS and non-HPS patients, only plasma RCN3 and albumin are independently associated with HPS in cirrhotic patients. Plasma RCN3 exhibits better predictive value in HPS diagnosis (RCN3, AUC = 0.657, 95% CI 0.571-0.744, p < 0.001). Interestingly, the combination of RCN3 and albumin achieves more efficiency in HPS prediction (AUC = 0.711, 95% CI 0.630-0.792, p < 0.0001).</p><p><strong>Conclusions: </strong>Circulating RCN3 is likely a relatively specific earlier biomarker for the prediction of early or latent HPS in cirrhotic patients, and the combination of RCN3-ALB can achieve more efficiency in HPS prediction.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"50"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of CFTR Modulators: A Network Meta-analysis.","authors":"Imran Hasan Iftikhar, Saad T Rao, Rufai Nadama, Ibrahim Janahi, Ahmed S BaHammam","doi":"10.1007/s00408-025-00802-w","DOIUrl":"10.1007/s00408-025-00802-w","url":null,"abstract":"<p><strong>Purpose: </strong>The objective was to study comparative efficacies of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, vanzacaftor-tezacaftor-deutivacaftor (VTD), elexacaftor-tezacaftor-ivacaftor (ETI), tezacaftor-ivacaftor (Tez-Iva), and lumacaftor-ivacaftor (Lum-Iva) in people with cystic fibrosis (pwCF), aged ≥ 12 years, carrying at least one F508del-CFTR-allele.</p><p><strong>Methods: </strong>Data from randomized controlled or randomized active comparator trials were included in this network meta-analysis which used frequentist approach for comparing the efficacy of drugs and ranking based on P-scores. Outcomes of interest were mean differences in percentage-predicted forced expiratory volume in one second (ppFEV₁), CF questionnaire-revised respiratory domain (CFQ-R) scores, sweat chloride (SwCl) levels, and odds ratios (OR) for serious adverse events (SAE).</p><p><strong>Results: </strong>Data from 13 studies were analyzed. Compared to placebo, the effects of VTD and ETI on ppFEV1 were almost quadruple of Tez-Iva and Lum-Iva (VTD: 12.78 [95% confidence intervals: 6.41; 19.15] and ETI: 11.95 [7.40; 16.50]) and almost seven times of Tez-Iva and Lum-Iva for CFQ-R (VTD: 21.23 [- 28.72; 71.18] and ETI: 19.27 [10.56; 27.98]). A statistically significant difference was noted between VTD and ETI in SwCl reduction (mean difference: - 8.59 [- 15.53; - 1.65]). There were no statistically significant ORs for SAEs for any CFTR modulators but VTD, ETI, and Tez-Iva were least associated with SAEs (ORs were 0.15 [0.01; 1.79], 0.49 [0.31; 0.78], and 0.74 [0.50; 1.09], respectively, as compared to placebo). Overall, P-score ranking ranked VTD as first and ETI as second, followed by others.</p><p><strong>Conclusion: </strong>VTD and ETI were more efficacious than Tez-Iva and Lum-Iva in pwCF with at least one F508del-CFTR-allele.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"49"},"PeriodicalIF":4.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Electronic Cigarette Vapour Exposure on Ca²⁺- and cAMP-Dependent Ion Transport in Human Airway Epithelial Cells.","authors":"Ya Niu, Chung-Yin Yip, Ke-Wu Pan, Judith Choi-Wo Mak, Wing-Hung Ko","doi":"10.1007/s00408-025-00805-7","DOIUrl":"10.1007/s00408-025-00805-7","url":null,"abstract":"<p><strong>Purpose: </strong>The popularity of electronic cigarettes (e-cigarettes) has grown exponentially over the past few years, and teenagers now prefer them to tobacco cigarettes. We determined whether exposure to e-cigarette vapour (e-vapour) adversely affects ion transport using human airway epithelial cell lines 16HBE14o- and Calu-3 and well-differentiated primary human bronchial epithelial cells (HBEs).</p><p><strong>Methods: </strong>We concurrently measured fluorescent signals and short-circuit current (I_SC), an indicator of electrogenic ion transport, in polarised epithelia. The P2Y receptor-mediated signalling pathway was used to induce an increase in intracellular calcium concentration ([Ca²⁺]_i) and I_SC. We used a single-polypeptide fluorescence resonance energy transfer reporter based on exchange proteins directly activated by cAMP (Epac) to measure forskolin-induced changes in cAMP and I_SC.</p><p><strong>Results: </strong>We compared the effects of e-vapour to those of traditional cigarette smoke (CS) on the human airway cell models. In all three cell types, e-vapour, similar to CS, significantly reduced agonist-induced increases in Ca²⁺ or cAMP signalling and I_SC. However, reductions in the epithelial electrolyte transport activities did not correlate with any changes in the protein levels of various ion channels and transporters.</p><p><strong>Conclusion: </strong>Our data suggest that e-vapour is not harmless and causes ion transport dysfunction similar to CS, thereby predisposing e-cigarette users to vaping-induced lung injury.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"48"},"PeriodicalIF":4.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657666","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 Role of HDAC3 in Pulmonary Diseases.","authors":"Leyu Hong, Ming Ni, Fei Xue, Tao Jiang, Xuanpeng Wu, Chenxi Li, Shuhao Liang, Tianhao Chen, Chao Luo, Qifei Wu","doi":"10.1007/s00408-025-00798-3","DOIUrl":"10.1007/s00408-025-00798-3","url":null,"abstract":"<p><p>Histone deacetylases (HDACs), a class of enzymes involved in epigenetic modifications, play a pivotal role in modulating chromatin structure and gene expression. Among these, histone deacetylase 3 (HDAC3) has emerged as a key regulator in diverse cellular pathophysiological processes. The remarkable therapeutic potential of HDAC inhibitors in lung cancer has intensified research into the role of HDAC3 in pulmonary diseases. Through deacetylating histones and non-histone proteins, HDAC3 has been increasingly recognized for its critical involvement in regulating inflammatory responses, fibrotic processes, and oncogenic signaling pathways, positioning it as a compelling therapeutic target. This review systematically examines the structural and functional features of HDAC3 and discusses its multifaceted contributions to pulmonary pathologies, including lung injury, pulmonary fibrosis, and lung cancer. Additionally, we critically evaluate advances in HDAC inhibitor-based therapies for lung cancer, with emphasis on the development of HDAC3-targeted therapies. As a promising therapeutic target for pulmonary diseases, HDAC3 needs to be further investigated to elucidate its regulatory mechanisms and facilitate the development of selective inhibitors for clinical translation.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"47"},"PeriodicalIF":4.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIP-3-Alpha and MIP-3-Beta as Early Predictors of Pneumonia in Polytraumatized Patients.","authors":"Gregor Wollner, Florian Hruska, Paul Ettel, Thomas Weichhart, Felix R M Koenig, Lukas L Negrin","doi":"10.1007/s00408-025-00799-2","DOIUrl":"10.1007/s00408-025-00799-2","url":null,"abstract":"<p><strong>Introduction: </strong>Pneumonia is one of the most common complications in patients suffering multiple traumas and is associated with an exceptionally high mortality rate. MIP-3-alpha and MIP-3-beta are pro-inflammatory chemokines expressed in the pulmonary mucosa and are reported to play a crucial role in inflammation. Thus, the present study aimed to investigate whether there is an association between MIP-3-alpha- and MIP-3-beta expression and manifestation of pneumonia in patients suffering polytrauma.</p><p><strong>Material and methods: </strong>This prospective outcome study was conducted at our level I trauma center, and 110 polytraumatized patients (Injury Severity Score ≥ 16, ≥ 2 body regions) were prospectively enrolled (median age, 39 years; median Injury Severity Score (ISS), 33; 70.9% male) over four years. Protein levels were assessed at admission (day 0) and subsequently on days 1, 3, 5, 7, and 10 during routine blood draws, utilizing one separation gel tube for each measurement. Furthermore, the correlation between MIP-3-alpha- and MIP-3-beta expression and the manifestation of pneumonia was calculated.</p><p><strong>Results: </strong>We observed significantly higher levels of MIP-3-beta expression over the entire time course in the pneumonia cohort. MIP-3-alpha levels were elevated on days 3, 5, 7, and 10 post-trauma in patients suffering from pneumonia. In contrast, no comparable pattern was observed for other pro- and anti-inflammatory cytokines (e.g., IL-6 or TNF-alpha). A peak of serum level expression was documented on day 5 in both biomarkers (MIP-3-alpha 51.8 pg/mL; MIP-3-beta 328.0 pg/mL). ROC analysis provided a cut-off value of 19.3 pg/mL (sensitivity 0.87, specificity 0.33; AUC 0.757) for MIP-3-alpha, whereas a cut-off value of 209.5 pg/mL (sensitivity 0.78, specificity 0.34; AUC 0.757) was determined for MIP-3-beta on day 5.</p><p><strong>Conclusion: </strong>The present study demonstrated elevated MIP-3-alpha and MIP-3-beta levels as sensitive pneumonia predictors in patients with multiple traumas. These biomarkers allow for identifying patients at high risk of developing pneumonia at an early stage.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"44"},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Soluble Toll-Like Receptor 4 is a Predictive Biomarker for Acute Exacerbation and Prognosis of Idiopathic Pulmonary Fibrosis: A Retrospective Study.","authors":"Erika Kitadai, Kakuhiro Yamaguchi, Hiroshi Iwamoto, Kiyofumi Shimoji, Shinjiro Sakamoto, Yasushi Horimasu, Takeshi Masuda, Taku Nakashima, Shinichiro Ohshimo, Hironobu Hamada, Noboru Hattori","doi":"10.1007/s00408-025-00800-y","DOIUrl":"10.1007/s00408-025-00800-y","url":null,"abstract":"<p><strong>Purpose: </strong>Toll-like receptor 4 (TLR4) is a transmembrane receptor promoting pro-inflammatory signalling, that is associated with the pathogenesis of pulmonary fibrosis. TLR4 is abundantly expressed on monocytes and the acceleration of TLR4 signalling induces the secretion of soluble TLR4 isoforms (sTLR4) in circulation. The aim of study was to evaluate the association of serum levels of sTLR4 with acute exacerbation (AE) and prognosis of patients with idiopathic pulmonary fibrosis (IPF).</p><p><strong>Methods: </strong>This retrospective cohort study included 97 patients with IPF and 76 healthy participants. The association of serum sTLR4 levels with the onset of AE and the prognosis in 97 patients with IPF was analyzed.</p><p><strong>Results: </strong>No significant difference in sTLR4 serum level was observed between the patients with IPF and healthy participants. Kaplan-Meier curves showed that patients with sTLR4 ≥ 2.2 ng/mL had a significantly higher incidence of AE-IPF and a significantly lower 5-year survival rate. Univariate and multivariate Cox hazard analyses demonstrated that sTLR4 ≥ 2.2 ng/mL was significantly associated with higher incidence of AE and poorer survival. In an exploratory analysis, a weak correlation was observed between sTLR4 levels and monocyte counts, and the incidence of AE-IPF was the highest in the patients with sTLR4 ≥ 2.2 ng/mL and monocyte counts ≥ 381/μL.</p><p><strong>Conclusion: </strong>High sTLR4 level is associated with an increased incidence of AE-IPF and poor prognosis in patients with IPF. The combination of sTLR4 level and monocyte count might be used to stratify patients with IPF according to the risk for AE via reflecting monocyte activation.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"43"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615829","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":"Supratherapeutic Inhaled Corticosteroid Use in Patients Initiating on Biologic Therapies for Severe Asthma: A Nationwide Cohort Study.","authors":"Frederikke Hjortdahl, Marianne Baastrup Soendergaard, Susanne Hansen, Anne-Sofie Bjerrum, Anna von Bülow, Ole Hilberg, Barbara Bonnesen, Claus Rikard Johnsen, Sofie Lock Johansson, Linda Makowska Rasmussen, Johannes Martin Schmid, Charlotte Suppli Ulrik, Anne Byriel Walls, Celeste Porsbjerg, Kjell Erik Julius Håkansson","doi":"10.1007/s00408-025-00796-5","DOIUrl":"10.1007/s00408-025-00796-5","url":null,"abstract":"<p><strong>Background: </strong>In severe asthma, intensive (\"supratherapeutic\") doses of inhaled corticosteroids (ICS) are often used. The prevalence of supratherapeutic ICS use and its impact on corticosteroid-related comorbidities is poorly understood. We aimed to describe the prevalence of supratherapeutic ICS use in severe asthma, its relation to corticosteroid-related comorbidities, and changes in prescribed and redeemed ICS dose after 12 months of biologic therapy.</p><p><strong>Methods: </strong>Patients from the nationwide Danish Severe Asthma Register (DSAR) receiving biologic therapy > 12 months were included. Supratherapeutic doses were defined as > 1600 µg budesonide daily. Baseline characteristics, comorbidity burden, and change in ICS use after 12 months of biologic therapy was stratified according to ICS use at baseline.</p><p><strong>Results: </strong>We included 652 patients in our analyses and 156 (24%) were supratherapeutic ICS users prior to initiation of biologic therapy. Supratherapeutic ICS users had a higher baseline prevalence of cataracts at 14 vs 8.1%; p = 0.025. No differences in other corticosteroid-related comorbidities were observed. No change in prevalence of prescribed supratherapeutic ICS was seen after 12 months of biologic therapy. However, a reduction in ICS adherence among supratherapeutic users was observed with 72% of patients demonstrating > 80% adherence at 12 months, compared to 83% at baseline (p < 0.001).</p><p><strong>Conclusion: </strong>Supratherapeutic doses of ICS were used by almost one-fourth of the patients prior to initiation of biologic therapy and were associated with a higher prevalence of cataracts. Physician-driven ICS reduction was rare, yet supratherapeutic ICS users were found to self-regulate ICS therapy when treated with biologic therapy.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"42"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605291","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":"SIRT2 Regulates Apoptosis Signaling in Hyperoxic Acute Lung Injury.","authors":"Yu Jin Lee, Mi Na Kim, Eun Gyul Kim, Chang Hyun Park, Joo Yeon Cho, Byung Chan Ko, Min Jung Kim, Yoon Hee Kim, Soon Min Lee, Kyung Won Kim, Tae Won Song, Myung Hyun Sohn","doi":"10.1007/s00408-025-00794-7","DOIUrl":"10.1007/s00408-025-00794-7","url":null,"abstract":"<p><strong>Purpose: </strong>Oxygen therapy is helpful for patients with breathing difficulties; however, sustained supplementation with high-concentration oxygen can cause hyperoxic acute lung injury. Sirtuin 2 (SIRT2), a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, has been shown to be involved in pulmonary fibrosis, apoptosis, and inflammation. Here, we elucidated the role of SIRT2 in hyperoxic acute lung injury.</p><p><strong>Methods: </strong>Wild-type (WT) mice and SIRT2-deficient (SIRT2^-/-) mice were exposed to room air or hyperoxia for 72 h. Thereafter, changes in hyperoxia-induced responses were evaluated in WT and SIRT2^-/- mice.</p><p><strong>Results: </strong>SIRT2 expression was elevated in WT mice after hyperoxic exposure. We also observed that the levels of SIRT2 were higher in tracheal aspirates from newborns with bronchopulmonary dysplasia (BPD) than in those without BPD. Hyperoxia-induced inflammation and apoptosis were more considerably attenuated in SIRT2^-/- mice than in WT mice. We also observed an interaction between SIRT2 and forkhead box O3 (FOXO3), and that SIRT2 deficiency was associated with altered acetylation levels of FOXO3 and changes in the expression of its downstream targets. Further investigation of the therapeutic effect of SIRT2 showed that hyperoxic acute lung injury was alleviated when AGK2, a SIRT2 inhibitor, was administered.</p><p><strong>Conclusion: </strong>Taken together, SIRT2 plays a critical role in the pathogenesis of hyperoxic acute lung injury by regulating apoptotic signaling. These findings indicated that SIRT2 is potentially a novel therapeutic strategy for hyperoxic acute lung injury.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"41"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}