Pub Date : 2025-10-29DOI: 10.1136/thorax-2025-223421
Haopu Yang, Jingen Xia, Xu Huang, Yu Bai, Dan Jin, Seyed Mehdi Nouraie, Bryan J McVerry, Alison Morris, Georgios D Kitsios, Chen Wang, Qingyuan Zhan
Purpose Subphenotype classifiers for acute respiratory distress syndrome (ARDS) dichotomise patients into hyperinflammatory versus hypoinflammatory subgroups. These models demonstrated prognostic and predictive values but were developed primarily in Caucasian populations. Generalisability of these models in Asian patients, who experience worse clinical outcomes, has not been established. We aimed to profile host responses in Asian patients with ARDS and evaluate the generalisability of established classifiers in this understudied population compared with a Caucasian cohort. Methods We prospectively enrolled patients with ARDS from medical intensive care units in Beijing, China, and Pittsburgh, Pennsylvania, USA. In the Beijing cohort, 37 protein biomarkers were measured, with 10 overlapping biomarkers measured in the Pittsburgh cohort. Six established subphenotype models were assessed for generalisability and intermodel agreement. Sensitivity analyses, including latent class analysis, were conducted to explore biological heterogeneity within Asians. Results Between 2011 and 2020, a total of 356 patients with ARDS (83% meeting the Berlin Definition; the rest on high-flow nasal cannula (HFNC) meeting the New Global Definition) were enrolled across Beijing (97% Han Asian) and Pittsburgh (90% Caucasian) sites, with comparable baseline hypoxaemia severity but disparate outcome. While the proportion of hyperinflammatory versus hypoinflammatory subphenotypes was predicted to be overall similar across different cohorts per each model, we observed poor intermodel agreement. We observed heightened inflammation in Berlin patients with ARDS compared with HFNC-ARDS within our Asian cohort. Conclusion Established subphenotype classifiers demonstrated similar distribution of subphenotypes in Asian patients with ARDS. However, poor intermodel agreement highlights the need for further investigation into model variability with models coming closer to bedside implementation. Trial registration number [NCT02975908][1]. Data are available upon reasonable request. Desensitised data for Beijing cohort, including demographics, biomarker measurement, as well as code for analyses, are available upon reasonable request (QZ (drzhanqy{at}163.com)). Pittsburgh cohort data availability as previously described. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02975908&atom=%2Fthoraxjnl%2Fearly%2F2025%2F10%2F29%2Fthorax-2025-223421.atom
{"title":"Generalisability of ARDS biological subphenotype models in Asians: an international, multicentre, prospective biomarker study","authors":"Haopu Yang, Jingen Xia, Xu Huang, Yu Bai, Dan Jin, Seyed Mehdi Nouraie, Bryan J McVerry, Alison Morris, Georgios D Kitsios, Chen Wang, Qingyuan Zhan","doi":"10.1136/thorax-2025-223421","DOIUrl":"https://doi.org/10.1136/thorax-2025-223421","url":null,"abstract":"Purpose Subphenotype classifiers for acute respiratory distress syndrome (ARDS) dichotomise patients into hyperinflammatory versus hypoinflammatory subgroups. These models demonstrated prognostic and predictive values but were developed primarily in Caucasian populations. Generalisability of these models in Asian patients, who experience worse clinical outcomes, has not been established. We aimed to profile host responses in Asian patients with ARDS and evaluate the generalisability of established classifiers in this understudied population compared with a Caucasian cohort. Methods We prospectively enrolled patients with ARDS from medical intensive care units in Beijing, China, and Pittsburgh, Pennsylvania, USA. In the Beijing cohort, 37 protein biomarkers were measured, with 10 overlapping biomarkers measured in the Pittsburgh cohort. Six established subphenotype models were assessed for generalisability and intermodel agreement. Sensitivity analyses, including latent class analysis, were conducted to explore biological heterogeneity within Asians. Results Between 2011 and 2020, a total of 356 patients with ARDS (83% meeting the Berlin Definition; the rest on high-flow nasal cannula (HFNC) meeting the New Global Definition) were enrolled across Beijing (97% Han Asian) and Pittsburgh (90% Caucasian) sites, with comparable baseline hypoxaemia severity but disparate outcome. While the proportion of hyperinflammatory versus hypoinflammatory subphenotypes was predicted to be overall similar across different cohorts per each model, we observed poor intermodel agreement. We observed heightened inflammation in Berlin patients with ARDS compared with HFNC-ARDS within our Asian cohort. Conclusion Established subphenotype classifiers demonstrated similar distribution of subphenotypes in Asian patients with ARDS. However, poor intermodel agreement highlights the need for further investigation into model variability with models coming closer to bedside implementation. Trial registration number [NCT02975908][1]. Data are available upon reasonable request. Desensitised data for Beijing cohort, including demographics, biomarker measurement, as well as code for analyses, are available upon reasonable request (QZ (drzhanqy{at}163.com)). Pittsburgh cohort data availability as previously described. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02975908&atom=%2Fthoraxjnl%2Fearly%2F2025%2F10%2F29%2Fthorax-2025-223421.atom","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"61 30 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDNumerous studies have found associations between parental socio-economic position (SEP) and offspring asthma. Obesity and tobacco smoking during pregnancy (SDP) are more prevalent in lower SEP groups and have been identified as risk factors for childhood asthma.AIMThe aim of this study was to explore and quantify the role of the modifiable risk factors-obesity, body mass index (BMI) and SDP-in the association between maternal SEP and offspring asthma.METHODSThis Swedish register-based cohort study included n=1 265 933 children born between 2006 and 2018, with information on asthma during the third and sixth years of life obtained from the National Patient Register and the Swedish Prescribed Drug Register. Maternal education was used as a measure of SEP. We used logistic regression to estimate exposure-outcome associations and applied the counterfactual approach to mediation analysis to estimate the proportion of the maternal SEP-offspring asthma association that could be explained by maternal obesity, BMI and SDP, with and without adjustment for birth year.RESULTThe OR was 1.15 (95% CI 1.13 to 1.16) for the association between maternal education and asthma during the third year of life and slightly lower during the sixth year (OR 1.09, 95% CI 1.07 to 1.10). Out of the excess risks, 20%-30% could be explained by obesity or BMI through mediation and mediated interaction, while 15%-20% could be explained by SDP.CONCLUSIONOur results indicate that supporting young women and mothers-to-be to healthy weight and to abstain from tobacco smoking, in particular during pregnancy, could reduce child morbidity and improve health equity in childhood.
大量研究发现父母社会经济地位（SEP）与后代哮喘之间存在关联。妊娠期肥胖和吸烟（SDP）在低SEP组中更为普遍，并已被确定为儿童哮喘的危险因素。目的探讨肥胖、体重指数（BMI）和sdp这三个可改变的危险因素在母亲SEP与后代哮喘的关系中所起的作用。方法：这项以瑞典登记为基础的队列研究纳入了2006年至2018年间出生的n= 1265933名儿童，其生命第3年和第6年的哮喘信息来自国家患者登记和瑞典处方药登记。我们使用母亲受教育程度作为SEP的衡量标准。我们使用逻辑回归来估计暴露与结果的关联，并应用反事实方法进行中介分析，以估计母亲肥胖、BMI和SDP可以解释的母亲SEP与后代哮喘的关联比例，无论是否对出生年份进行调整。结果母亲教育程度与出生后第3年哮喘相关的OR为1.15 (95% CI 1.13 ~ 1.16)，第6年的OR略低（OR 1.09, 95% CI 1.07 ~ 1.10）。在过量风险中，20%-30%可由肥胖或BMI通过中介和介导的相互作用解释，15%-20%可由SDP解释。结论支持年轻妇女和准妈妈保持健康体重和戒烟，特别是在怀孕期间，可以降低儿童发病率，改善儿童健康公平。
{"title":"Maternal BMI and smoking partly explain the association between maternal socio-economic position and offspring asthma.","authors":"Cecilia Lundholm,Emma Caffrey Osvald,Samuel Rhedin,Catarina Almqvist","doi":"10.1136/thorax-2025-223330","DOIUrl":"https://doi.org/10.1136/thorax-2025-223330","url":null,"abstract":"BACKGROUNDNumerous studies have found associations between parental socio-economic position (SEP) and offspring asthma. Obesity and tobacco smoking during pregnancy (SDP) are more prevalent in lower SEP groups and have been identified as risk factors for childhood asthma.AIMThe aim of this study was to explore and quantify the role of the modifiable risk factors-obesity, body mass index (BMI) and SDP-in the association between maternal SEP and offspring asthma.METHODSThis Swedish register-based cohort study included n=1 265 933 children born between 2006 and 2018, with information on asthma during the third and sixth years of life obtained from the National Patient Register and the Swedish Prescribed Drug Register. Maternal education was used as a measure of SEP. We used logistic regression to estimate exposure-outcome associations and applied the counterfactual approach to mediation analysis to estimate the proportion of the maternal SEP-offspring asthma association that could be explained by maternal obesity, BMI and SDP, with and without adjustment for birth year.RESULTThe OR was 1.15 (95% CI 1.13 to 1.16) for the association between maternal education and asthma during the third year of life and slightly lower during the sixth year (OR 1.09, 95% CI 1.07 to 1.10). Out of the excess risks, 20%-30% could be explained by obesity or BMI through mediation and mediated interaction, while 15%-20% could be explained by SDP.CONCLUSIONOur results indicate that supporting young women and mothers-to-be to healthy weight and to abstain from tobacco smoking, in particular during pregnancy, could reduce child morbidity and improve health equity in childhood.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"356 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1136/thorax-2025-224041
Van Le Hong,C Louise Thwaites
{"title":"Acute breathlessness in resource-limited settings: diagnostic gaps and treatment challenges.","authors":"Van Le Hong,C Louise Thwaites","doi":"10.1136/thorax-2025-224041","DOIUrl":"https://doi.org/10.1136/thorax-2025-224041","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"29 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1136/thorax-2025-223477
Na Wang,Wei Cheng,Yun Long,Huaiwu He,Yan Shi
{"title":"Mycelial growth in the bronchial lumen of a patient with acute promyelocytic leukaemia.","authors":"Na Wang,Wei Cheng,Yun Long,Huaiwu He,Yan Shi","doi":"10.1136/thorax-2025-223477","DOIUrl":"https://doi.org/10.1136/thorax-2025-223477","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"101 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1136/thorax-2025-223722
Bin Zeng,Binglin Lai
{"title":"Unicentric Castleman disease presenting as a right lung mass in an 18-year-old man.","authors":"Bin Zeng,Binglin Lai","doi":"10.1136/thorax-2025-223722","DOIUrl":"https://doi.org/10.1136/thorax-2025-223722","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"108 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-20DOI: 10.1136/thorax-2025-222970
David Hui,Soraira Pacheco,Linh Nguyen,Kristofer Jennings,Vera de la Cruz,Penny Stanton,Raul Laureano,Amy Ontai,Donald Mahler,Eduardo Bruera
INTRODUCTIONExertional dyspnoea is highly debilitating. Previous single-dose studies found that prophylactic administration of fentanyl buccal tablet (FBT) improved exertional dyspnoea. In this randomised trial, we compared daily use of prophylactic FBT, oral morphine and placebo on exertional dyspnoea over 14 days.METHODSThis parallel, double-blind, randomised clinical trial enrolled opioid-tolerant patients with cancer and exertional dyspnoea. After a 5-day observation period, patients were randomised (1:1:1) to receive FBT, morphine or placebo 30 min before daily structured activity for 14 days. Shuttle walk tests (SWTs) were conducted on days 1/5/8/12/15/19. The primary outcome was change in modified Borg Scale dyspnoea intensity during SWTs from day 5 to day 19, analysed using a mixed effects model with treatment, time and treatment×time interaction. SWT distance was a key secondary outcome.RESULTS67 patients were enrolled and 56 (84%) were randomised. Over the 14-day blinded phase, we observed a significant decrease in the magnitude of dyspnoea intensity change during the SWTs in all three groups, with no significant difference by treatment group (slope change from day 5 to day 19: FBT -2.2 (95% CI -2.9 to -1.6); morphine -1.9 (95% CI -2.7 to -1.2); placebo -2.2 (95% CI -3 to -1.4); time effect p<0.001, treatment×time effect p=0.79). SWT distance increased significantly over time (FBT +93 m; morphine +84 m; placebo +76 m) but did not differ by treatment (p=0.71). Few adverse events were reported.CONCLUSIONAll three groups reported less dyspnoea while walking farther; however, no difference was detected between opioids and placebo. These findings should be considered preliminary given the underpowered sample.TRIAL REGISTRATION NUMBERNCT04188418.
劳累性呼吸困难是非常虚弱的。先前的单剂量研究发现，预防性服用芬太尼口腔片（FBT）可改善运动性呼吸困难。在这项随机试验中，我们比较了每天使用预防性FBT、口服吗啡和安慰剂治疗劳累性呼吸困难的14天。方法：这项平行、双盲、随机临床试验招募了阿片类药物耐受的癌症和用力性呼吸困难患者。在5天的观察期后，患者被随机分配（1:1:1），在每天有组织的活动前30分钟接受FBT、吗啡或安慰剂治疗，持续14天。穿梭行走测试（SWTs）在1/5/8/12/15/19天进行。主要终点是SWTs期间第5天至第19天改良博格量表呼吸困难强度的变化，使用治疗、时间和treatment×time相互作用的混合效应模型进行分析。SWT距离是一个关键的次要指标。结果纳入67例患者，56例（84%）随机分组。在14天的盲法阶段，我们观察到三组在SWTs期间呼吸困难强度变化的幅度显着下降，各组间无显着差异(从第5天到第19天斜率变化：FBT -2.2 (95% CI -2.9至-1.6)；吗啡-1.9 (95% CI -2.7 ~ -1.2)；安慰剂-2.2 (95% CI -3 ~ -1.4)；时间效应p<0.001， treatment×time效应p=0.79)。SWT距离随时间显著增加（FBT +93 m；吗啡+84 m；安慰剂+76 m），但不同治疗间无差异（p=0.71）。几乎没有不良事件的报道。结论：行走距离越远，三组患者呼吸困难越少；然而，在阿片类药物和安慰剂之间没有发现差异。这些发现应该被认为是初步的，因为样本的动力不足。试验注册号：04188418。
{"title":"Efficacy of fentanyl buccal tablet and morphine for exertional dyspnoea in patients with cancer: a double-blind, placebo-controlled, randomised clinical trial.","authors":"David Hui,Soraira Pacheco,Linh Nguyen,Kristofer Jennings,Vera de la Cruz,Penny Stanton,Raul Laureano,Amy Ontai,Donald Mahler,Eduardo Bruera","doi":"10.1136/thorax-2025-222970","DOIUrl":"https://doi.org/10.1136/thorax-2025-222970","url":null,"abstract":"INTRODUCTIONExertional dyspnoea is highly debilitating. Previous single-dose studies found that prophylactic administration of fentanyl buccal tablet (FBT) improved exertional dyspnoea. In this randomised trial, we compared daily use of prophylactic FBT, oral morphine and placebo on exertional dyspnoea over 14 days.METHODSThis parallel, double-blind, randomised clinical trial enrolled opioid-tolerant patients with cancer and exertional dyspnoea. After a 5-day observation period, patients were randomised (1:1:1) to receive FBT, morphine or placebo 30 min before daily structured activity for 14 days. Shuttle walk tests (SWTs) were conducted on days 1/5/8/12/15/19. The primary outcome was change in modified Borg Scale dyspnoea intensity during SWTs from day 5 to day 19, analysed using a mixed effects model with treatment, time and treatment×time interaction. SWT distance was a key secondary outcome.RESULTS67 patients were enrolled and 56 (84%) were randomised. Over the 14-day blinded phase, we observed a significant decrease in the magnitude of dyspnoea intensity change during the SWTs in all three groups, with no significant difference by treatment group (slope change from day 5 to day 19: FBT -2.2 (95% CI -2.9 to -1.6); morphine -1.9 (95% CI -2.7 to -1.2); placebo -2.2 (95% CI -3 to -1.4); time effect p<0.001, treatment×time effect p=0.79). SWT distance increased significantly over time (FBT +93 m; morphine +84 m; placebo +76 m) but did not differ by treatment (p=0.71). Few adverse events were reported.CONCLUSIONAll three groups reported less dyspnoea while walking farther; however, no difference was detected between opioids and placebo. These findings should be considered preliminary given the underpowered sample.TRIAL REGISTRATION NUMBERNCT04188418.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"20 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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