Pub Date : 2025-12-12DOI: 10.1136/thorax-2024-221988
Jorge I F Salluh,Filipe Amado,Luigi Pisani,Amanda Quintairos,Antonio Paulo Nassar,Bruno Besen,Cornelius Sendagire,Daniela C Souza,Fernando Bozza,Gaston Burghi,Hem Raj Paneru,Leonardo S L Bastos,Maria Del Pilar Arias López,Moses Siaw-Frimpong,Pedro Kurtz,Regis Goulart Rosa,Renato Daltro de Oliveira,Vanessa Soares Lanziotti,Juliana Carvalho Ferreira,Otavio T Ranzani
Critical illness poses a significant global health challenge, disproportionately affecting low- and middle-income countries (LMICs) and other low-resource settings, where healthcare resources and infrastructure are often limited. This narrative review explores the multifaceted dynamics of critical care research in low-resource settings, focusing on socioeconomic, demographic and structural barriers that impact the delivery of intensive care services and its consequences for clinical research. Research is a cornerstone in addressing these challenges. Locally relevant evidence is crucial for informing healthcare policies and clinical guidelines, particularly in adapting high-income country recommendations to resource-constrained contexts. This review describes research challenges and findings on several fields of critical care in LMICs. It underscores the pressing need for sustained investment in critical care research and infrastructure in LMICs to overcome health disparities and improve outcomes for critically ill patients.
{"title":"Critical care research in low- and middle-income countries: a narrative review.","authors":"Jorge I F Salluh,Filipe Amado,Luigi Pisani,Amanda Quintairos,Antonio Paulo Nassar,Bruno Besen,Cornelius Sendagire,Daniela C Souza,Fernando Bozza,Gaston Burghi,Hem Raj Paneru,Leonardo S L Bastos,Maria Del Pilar Arias López,Moses Siaw-Frimpong,Pedro Kurtz,Regis Goulart Rosa,Renato Daltro de Oliveira,Vanessa Soares Lanziotti,Juliana Carvalho Ferreira,Otavio T Ranzani","doi":"10.1136/thorax-2024-221988","DOIUrl":"https://doi.org/10.1136/thorax-2024-221988","url":null,"abstract":"Critical illness poses a significant global health challenge, disproportionately affecting low- and middle-income countries (LMICs) and other low-resource settings, where healthcare resources and infrastructure are often limited. This narrative review explores the multifaceted dynamics of critical care research in low-resource settings, focusing on socioeconomic, demographic and structural barriers that impact the delivery of intensive care services and its consequences for clinical research. Research is a cornerstone in addressing these challenges. Locally relevant evidence is crucial for informing healthcare policies and clinical guidelines, particularly in adapting high-income country recommendations to resource-constrained contexts. This review describes research challenges and findings on several fields of critical care in LMICs. It underscores the pressing need for sustained investment in critical care research and infrastructure in LMICs to overcome health disparities and improve outcomes for critically ill patients.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"35 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732753","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 : 2025-12-12DOI: 10.1136/thorax-2025-223967
Christopher Farley,Anastasia N L Newman,Stuart M Phillips,Jenna Smith-Turchyn,Dina Brooks
BACKGROUNDThe sit-to-stand (STS) test can assess physical function in people with chronic obstructive pulmonary disease (COPD); however, there are multiple versions. No study has used current guidelines to assess the measurement properties of the STS tests in people with COPD.METHODSWe conducted a systematic review using current COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. Full text peer-reviewed publications were included if they assessed the measurement properties (validity, reliability and/or responsiveness) of at least one STS test among community-dwelling people with COPD. We searched six databases and imported results into Covidence where title/abstract screening and full text selection was completed independently and in duplicate. Extraction was conducted independently and in duplicate using the COSMIN extraction file. We assessed study risk of bias (very good, adequate, doubtful or inadequate), measurement property quality (sufficient, indeterminate or insufficient) and overall certainty of evidence (high, moderate, low or very low) using the COSMIN recommended tools.RESULTSWe assessed 2577 titles/abstracts and 102 full texts for inclusion; 30 publications met eligibility. Seven unique STS tests were located with the most common being the 1 min STS test (n=14, 39%), 5-repetition STS test (n=10, 28%) and the 30 s STS test (n=8, 22%). Where assessed, reliability was sufficient for the 1 min, the 5-repetition and the 30 s STS tests. Only the 1 min STS test had high-quality evidence of sufficient construct validity, while the 30 s STS test was the sole test with at least moderate quality evidence of sufficient responsiveness.CONCLUSIONSThe 1 min STS test has the most robust measurement properties for cross-sectional assessments while the 30 s STS test is more robust to assess change.
背景：坐立测试（STS）可以评估慢性阻塞性肺疾病（COPD）患者的身体功能；然而，有多个版本。没有研究使用目前的指南来评估STS测试在COPD患者中的测量特性。方法采用现行的基于共识的健康测量仪器选择标准（COSMIN）指南进行系统评价。如果在社区COPD患者中评估了至少一项STS测试的测量特性（效度、信度和/或反应性），则纳入全文同行评审出版物。我们检索了6个数据库，并将结果导入covid - ence，其中标题/摘要筛选和全文选择独立完成，一式两份。使用COSMIN提取文件独立进行提取，一式两份。我们使用COSMIN推荐的工具评估了研究偏倚风险（非常好、充分、可疑或不充分）、测量属性质量（充分、不确定或不充分）和证据的总体确定性（高、中、低或极低）。结果共纳入2577篇题目/摘要和102篇全文；30份出版物符合资格。7种独特的STS测试，最常见的是1分钟STS测试（n=14, 39%）， 5次重复STS测试（n=10, 28%）和30秒STS测试（n=8, 22%）。经评估，1分钟、5次重复和30秒STS测试的可靠性是足够的。只有1分钟STS测试具有足够的结构效度的高质量证据，而30分钟STS测试是唯一具有足够反应性的至少中等质量证据的测试。结论1 min STS测试对横断面评估的稳健性最强，而30 s STS测试对变化的稳健性更强。
{"title":"Measurement properties of the sit-to-stand test in community-dwelling people with chronic obstructive pulmonary disease: a COSMIN systematic review.","authors":"Christopher Farley,Anastasia N L Newman,Stuart M Phillips,Jenna Smith-Turchyn,Dina Brooks","doi":"10.1136/thorax-2025-223967","DOIUrl":"https://doi.org/10.1136/thorax-2025-223967","url":null,"abstract":"BACKGROUNDThe sit-to-stand (STS) test can assess physical function in people with chronic obstructive pulmonary disease (COPD); however, there are multiple versions. No study has used current guidelines to assess the measurement properties of the STS tests in people with COPD.METHODSWe conducted a systematic review using current COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. Full text peer-reviewed publications were included if they assessed the measurement properties (validity, reliability and/or responsiveness) of at least one STS test among community-dwelling people with COPD. We searched six databases and imported results into Covidence where title/abstract screening and full text selection was completed independently and in duplicate. Extraction was conducted independently and in duplicate using the COSMIN extraction file. We assessed study risk of bias (very good, adequate, doubtful or inadequate), measurement property quality (sufficient, indeterminate or insufficient) and overall certainty of evidence (high, moderate, low or very low) using the COSMIN recommended tools.RESULTSWe assessed 2577 titles/abstracts and 102 full texts for inclusion; 30 publications met eligibility. Seven unique STS tests were located with the most common being the 1 min STS test (n=14, 39%), 5-repetition STS test (n=10, 28%) and the 30 s STS test (n=8, 22%). Where assessed, reliability was sufficient for the 1 min, the 5-repetition and the 30 s STS tests. Only the 1 min STS test had high-quality evidence of sufficient construct validity, while the 30 s STS test was the sole test with at least moderate quality evidence of sufficient responsiveness.CONCLUSIONSThe 1 min STS test has the most robust measurement properties for cross-sectional assessments while the 30 s STS test is more robust to assess change.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"11 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732754","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 : 2025-12-10DOI: 10.1136/thorax-2025-223625
Jacob C Taylor,Kirk U Knowlton,Thomas C Wilson,Mark W Dodson
{"title":"Recurrent right atrial myxoma presenting as pulmonary hypertension and peripheral pulmonary artery aneurysms.","authors":"Jacob C Taylor,Kirk U Knowlton,Thomas C Wilson,Mark W Dodson","doi":"10.1136/thorax-2025-223625","DOIUrl":"https://doi.org/10.1136/thorax-2025-223625","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"18 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717631","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}
BACKGROUNDPneumocystis jirovecii pneumonia (PcP) in HIV-negative patients is associated with high mortality rates. While early adjunctive corticosteroid (AC) therapy benefits HIV-positive patients with severe PcP, its efficacy and safety in HIV-negative patients remain poorly investigated.METHODSThis multicentre retrospective observational study included consecutive patients diagnosed with proven or probable PcP, from January 2011 to January 2021. This study assessed the prognostic impact and safety of early AC in HIV-negative patients with PcP. To address baseline characteristic imbalances between patients, a non-parsimonious propensity matching analysis was performed with a 1/1 ratio. Survival analysis, day-90 mortality rate and healthcare-associated infections (HCAI) were compared using Cox and logistic regressions.RESULTS350 consecutive HIV-negative patients with proven or probable PcP were included. Of these, 116 (33.1%) received early AC within 5 days of anti-PcP therapy initiation. The median arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ratio was 224 (114-229). The 90-day mortality rate was 29.4% (103/350). There was no significant difference in 90-day mortality according to AC, both in overall and matched populations (OR 1.27 (0.78-2.05); p=0.336 and 0.92 (0.52-1.62); p=0.772, respectively). HCAI incidences appeared similar between groups. In the matched population, a higher proportion of AC patients required high-flow oxygen therapy (OR 2.15 (1.17-4.05); p=0.015) and mechanical ventilation duration was higher in corticosteroid recipients (OR 1.04 (1.01-1.09); p=0.048).CONCLUSIONEarly AC therapy was not associated with reduced 90-day mortality in HIV-negative PcP patients. Although recommended in hypoxemic HIV-positive PcP patients, the benefit of this strategy in HIV-negative patients remains to be proven.
{"title":"Prognostic impact and safety of early adjunctive corticosteroid therapy in HIV-negative severe pneumocystis pneumonia: a propensity-matched multicentre study.","authors":"Florian Reizine,Vicky Stiegler,Romain Lecuyer,Benoit Tessoulin,Guillaume Rieul,Fabrice Camou,Florent Morio,Anne Cady,Frederic Gabriel,Emmanuel Canet,François Raffi,David Boutoille,Nahéma Issa,Benjamin Jean Gaborit, ","doi":"10.1136/thorax-2025-223504","DOIUrl":"https://doi.org/10.1136/thorax-2025-223504","url":null,"abstract":"BACKGROUNDPneumocystis jirovecii pneumonia (PcP) in HIV-negative patients is associated with high mortality rates. While early adjunctive corticosteroid (AC) therapy benefits HIV-positive patients with severe PcP, its efficacy and safety in HIV-negative patients remain poorly investigated.METHODSThis multicentre retrospective observational study included consecutive patients diagnosed with proven or probable PcP, from January 2011 to January 2021. This study assessed the prognostic impact and safety of early AC in HIV-negative patients with PcP. To address baseline characteristic imbalances between patients, a non-parsimonious propensity matching analysis was performed with a 1/1 ratio. Survival analysis, day-90 mortality rate and healthcare-associated infections (HCAI) were compared using Cox and logistic regressions.RESULTS350 consecutive HIV-negative patients with proven or probable PcP were included. Of these, 116 (33.1%) received early AC within 5 days of anti-PcP therapy initiation. The median arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ratio was 224 (114-229). The 90-day mortality rate was 29.4% (103/350). There was no significant difference in 90-day mortality according to AC, both in overall and matched populations (OR 1.27 (0.78-2.05); p=0.336 and 0.92 (0.52-1.62); p=0.772, respectively). HCAI incidences appeared similar between groups. In the matched population, a higher proportion of AC patients required high-flow oxygen therapy (OR 2.15 (1.17-4.05); p=0.015) and mechanical ventilation duration was higher in corticosteroid recipients (OR 1.04 (1.01-1.09); p=0.048).CONCLUSIONEarly AC therapy was not associated with reduced 90-day mortality in HIV-negative PcP patients. Although recommended in hypoxemic HIV-positive PcP patients, the benefit of this strategy in HIV-negative patients remains to be proven.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"18 4 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717630","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}
BACKGROUNDTuberculous pleurisy (TBP) is a leading aetiology of exudative pleural effusion in tuberculosis (TB)-endemic regions and poses significant diagnostic challenges due to its paucibacillary nature of Mycobacterium tuberculosis (MTB) in pleural fluid. This study aims to characterise MTB-derived cell-free DNA (cfDNA) in pleural effusion and to develop an optimised molecular assay to improve TBP diagnostic accuracy.METHODSWe quantified MTB cfDNA/genomic DNA (gDNA) concentrations and characterised cfDNA fragment profiles in pleural effusion specimens using ddPCR. A multiplex droplet digital PCR (ddPCR) assay was developed, targeting two insertion sequences (IS6110 and IS1081) using ultra-short amplicons (49-59 bp) to enhance detection efficiency. Diagnostic performance was prospectively evaluated in 356 consecutive adults with radiologically confirmed pleural effusion, using composite microbiological criteria as the reference standard.RESULTSMTB cfDNA exhibited significantly higher detection rates than gDNA in definite TBP cases (p=0.0006), with dominant fragment lengths of 60-80 bp. The multiplex ddPCR assay demonstrated a limit of detection of 0.2 genome equivalents per reaction. Among microbiologically confirmed TBP cases (n=69), the assay achieved a sensitivity of 94.2%, significantly outperforming Xpert MTB/RIF (52.0%, p<0.0001) and liquid culture (35.3%, p<0.0001). Specificity remained high at 97.0% among cases of non-TB effusion (n=208).CONCLUSIONSOur findings establish MTB cfDNA as the predominant nucleic acid form in tuberculous pleural effusion. The optimised multiplex ddPCR platform, leveraging multicopy targets and fragment-length-adapted amplification, achieves improved diagnostic sensitivity without compromising specificity in a high-prevalence TB setting. This approach may help address key limitations of TBP diagnostics and shows promise for clinical implementation.
{"title":"Enhanced diagnosis of tuberculous pleurisy using a multiplex droplet digital PCR assay targeting circulating mycobacterial DNA.","authors":"Siqi Zhang,Ye Xu,Mingxiang Huang,Yuying Pan,Jichang Shangguan,Rui Peng,Xiaoman Hu,Fang Zheng,Na Luo,Xiaohong Chen,Qingge Li","doi":"10.1136/thorax-2025-223553","DOIUrl":"https://doi.org/10.1136/thorax-2025-223553","url":null,"abstract":"BACKGROUNDTuberculous pleurisy (TBP) is a leading aetiology of exudative pleural effusion in tuberculosis (TB)-endemic regions and poses significant diagnostic challenges due to its paucibacillary nature of Mycobacterium tuberculosis (MTB) in pleural fluid. This study aims to characterise MTB-derived cell-free DNA (cfDNA) in pleural effusion and to develop an optimised molecular assay to improve TBP diagnostic accuracy.METHODSWe quantified MTB cfDNA/genomic DNA (gDNA) concentrations and characterised cfDNA fragment profiles in pleural effusion specimens using ddPCR. A multiplex droplet digital PCR (ddPCR) assay was developed, targeting two insertion sequences (IS6110 and IS1081) using ultra-short amplicons (49-59 bp) to enhance detection efficiency. Diagnostic performance was prospectively evaluated in 356 consecutive adults with radiologically confirmed pleural effusion, using composite microbiological criteria as the reference standard.RESULTSMTB cfDNA exhibited significantly higher detection rates than gDNA in definite TBP cases (p=0.0006), with dominant fragment lengths of 60-80 bp. The multiplex ddPCR assay demonstrated a limit of detection of 0.2 genome equivalents per reaction. Among microbiologically confirmed TBP cases (n=69), the assay achieved a sensitivity of 94.2%, significantly outperforming Xpert MTB/RIF (52.0%, p<0.0001) and liquid culture (35.3%, p<0.0001). Specificity remained high at 97.0% among cases of non-TB effusion (n=208).CONCLUSIONSOur findings establish MTB cfDNA as the predominant nucleic acid form in tuberculous pleural effusion. The optimised multiplex ddPCR platform, leveraging multicopy targets and fragment-length-adapted amplification, achieves improved diagnostic sensitivity without compromising specificity in a high-prevalence TB setting. This approach may help address key limitations of TBP diagnostics and shows promise for clinical implementation.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"139 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710902","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 : 2025-12-09DOI: 10.1136/thorax-2025-223687
Rachel L Eddy,Vanessa M Diamond,Josie Chrenek,Girija Bhatnagar,David Sag,Rana Ghadymimahani,Amreen Aulakh,Britney X Ha,Bradley S Quon,Jonathan H Rayment
BACKGROUNDPersonalised management of cystic fibrosis (CF) lung disease in the era of CF transmembrane conductance regulator (CFTR) modulator therapy will require novel approaches to assess treatment response and monitor longitudinal progression.METHODSWe evaluated the heterogeneity of short-term response to elexacaftor-tezacaftor-ivacaftor (ETI) using 129Xe MRI, multiple breath washout (MBW) and spirometry. For CFTR modulator-naïve people ≥6 years old starting commercial ETI, we measured same-day 129XeMRI ventilation defect per cent (VDP), lung clearance index (LCI), forced expiratory volume in 1 s (FEV1) and CF Questionnaire-Revised respiratory-domain (CFQ-R(R)) at pre-ETI baseline and up to 4 months post-ETI. Baseline versus follow-up measures were compared using Wilcoxon-signed-rank tests with r effect size coefficients. Abnormal follow-up measures determined using z-scores and upper/lower limits of normal; correlations evaluated using Spearman ρ coefficients.RESULTSVDP, FEV1, LCI and CFQ-R(R) significantly improved in the total group (n=40; all p<0.001, r=0.69, r=0.79, r=0.70, r=0.77) and both ≥12-year-old subgroups (n=15 FEV1<80%, p=0.005/r=0.69, p<0.001/r=0.87, p=0.004/r=0.70, p<0.001/r=0.88; n=17 FEV1≥80%, p=0.003/r=0.54, p=0.003/r=0.74, p=0.01/r=0.56, p=0.006/r=0.73). VDP (p=0.008/r=0.89), LCI (p=0.03/r=0.83) and percent-predicted FEV1 (p=0.03/r=0.83) significantly improved in the 6-11-year-old subgroup, with VDP having the greatest effect size in children. VDP remained abnormal at follow-up in 21 participants with normal FEV1, whereas LCI was abnormal in 12. Baseline VDP (ρ=0.39/p=0.01) and LCI (ρ=0.43/p=0.008) were significantly correlated with the change in CFQ-R(R).CONCLUSIONThough all outcome measures showed a positive response, response to ETI was heterogeneous between individuals and between 129XeMRI, MBW and spirometry. Leveraging the rich information provided by multimodal tools will be critical to understanding the nature of CF lung disease and measuring response to future therapies in the era of CFTR modulators.
背景：在囊性纤维化（CF）肺疾病的跨膜传导调节剂（CFTR）治疗时代，个体化管理将需要新的方法来评估治疗反应和监测纵向进展。方法采用129Xe MRI、多次呼吸冲洗法（MBW）和肺活量测定法评估提取因子-干扰素-干扰素（ETI）短期疗效的异质性。对于CFTR modulator-naïve≥6岁开始商业ETI的患者，我们在ETI前基线和ETI后4个月测量了当天129XeMRI通气缺陷百分比（VDP）、肺清除率指数（LCI）、1秒内用力呼气量（FEV1）和CF问卷-修订呼吸域（CFQ-R(R)）。基线和随访测量比较使用具有r效应大小系数的Wilcoxon-signed-rank检验。使用z分数和正常上/下限确定异常随访措施；用斯皮尔曼ρ系数评估相关性。结果vdp、FEV1、LCI、CFQ-R(R)在总组（n=40，均p<0.001, R =0.69, R =0.79, R =0.70, R =0.77）及≥12岁亚组（n=15, FEV1<80%, p=0.005/ R =0.69, p<0.001/ R =0.87, p=0.004/ R =0.70, p<0.001/ R =0.88; n=17, FEV1≥80%,p=0.003/ R =0.54, p=0.003/ R =0.74, p=0.01/ R =0.56, p=0.006/ R =0.73）均有显著改善。VDP （p=0.008/r=0.89）、LCI （p=0.03/r=0.83）和百分比预测FEV1 （p=0.03/r=0.83）在6-11岁亚组均显著改善，其中VDP在儿童中的效应量最大。21名FEV1正常的参与者在随访中VDP仍异常，而12名LCI异常。基线VDP （ρ=0.39/p=0.01）和LCI （ρ=0.43/p=0.008）与CFQ-R(R)变化显著相关。结论：虽然所有结局指标均显示阳性反应，但个体之间以及129XeMRI、MBW和肺活量测定之间对ETI的反应存在异质性。在CFTR调节剂时代，利用多模式工具提供的丰富信息对于理解CF肺病的性质和衡量对未来治疗的反应至关重要。
{"title":"Heterogeneity of short-term elexacaftor-tezacaftor-ivacaftor response in cystic fibrosis using 129Xe MRI.","authors":"Rachel L Eddy,Vanessa M Diamond,Josie Chrenek,Girija Bhatnagar,David Sag,Rana Ghadymimahani,Amreen Aulakh,Britney X Ha,Bradley S Quon,Jonathan H Rayment","doi":"10.1136/thorax-2025-223687","DOIUrl":"https://doi.org/10.1136/thorax-2025-223687","url":null,"abstract":"BACKGROUNDPersonalised management of cystic fibrosis (CF) lung disease in the era of CF transmembrane conductance regulator (CFTR) modulator therapy will require novel approaches to assess treatment response and monitor longitudinal progression.METHODSWe evaluated the heterogeneity of short-term response to elexacaftor-tezacaftor-ivacaftor (ETI) using 129Xe MRI, multiple breath washout (MBW) and spirometry. For CFTR modulator-naïve people ≥6 years old starting commercial ETI, we measured same-day 129XeMRI ventilation defect per cent (VDP), lung clearance index (LCI), forced expiratory volume in 1 s (FEV1) and CF Questionnaire-Revised respiratory-domain (CFQ-R(R)) at pre-ETI baseline and up to 4 months post-ETI. Baseline versus follow-up measures were compared using Wilcoxon-signed-rank tests with r effect size coefficients. Abnormal follow-up measures determined using z-scores and upper/lower limits of normal; correlations evaluated using Spearman ρ coefficients.RESULTSVDP, FEV1, LCI and CFQ-R(R) significantly improved in the total group (n=40; all p<0.001, r=0.69, r=0.79, r=0.70, r=0.77) and both ≥12-year-old subgroups (n=15 FEV1<80%, p=0.005/r=0.69, p<0.001/r=0.87, p=0.004/r=0.70, p<0.001/r=0.88; n=17 FEV1≥80%, p=0.003/r=0.54, p=0.003/r=0.74, p=0.01/r=0.56, p=0.006/r=0.73). VDP (p=0.008/r=0.89), LCI (p=0.03/r=0.83) and percent-predicted FEV1 (p=0.03/r=0.83) significantly improved in the 6-11-year-old subgroup, with VDP having the greatest effect size in children. VDP remained abnormal at follow-up in 21 participants with normal FEV1, whereas LCI was abnormal in 12. Baseline VDP (ρ=0.39/p=0.01) and LCI (ρ=0.43/p=0.008) were significantly correlated with the change in CFQ-R(R).CONCLUSIONThough all outcome measures showed a positive response, response to ETI was heterogeneous between individuals and between 129XeMRI, MBW and spirometry. Leveraging the rich information provided by multimodal tools will be critical to understanding the nature of CF lung disease and measuring response to future therapies in the era of CFTR modulators.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"166 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710903","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 : 2025-12-03DOI: 10.1136/thorax-2025-223961
Anthony Yii,Tunn Ren Tay,Ken Cheah Hooi Lee,Si Yuan Chew,Nicole Yu-Fang Sieow,Xue Ning Choo,Ming Ren Toh,Sean Chee Hong Loh,Pei Yee Tiew,Jansen Meng Kwang Koh,Augustine K H Tee,Mariko Siyue Koh
OBJECTIVESystemic corticosteroids for 5-7 days are standard care for asthma exacerbations, but the optimal duration and potential for precision prescribing remain unclear. Biomarker-guided approaches could reduce corticosteroid exposure without compromising outcomes. We aimed to evaluate whether the blood eosinophil count can be used to safely reduce systemic corticosteroid exposure in hospitalised asthma exacerbations.METHODSIn this open-label, two-centre randomised trial, adults hospitalised for asthma exacerbation were assigned 1:1 to usual care (5 days prednisolone) or eosinophil-guided care using blood eosinophil counts obtained prior to corticosteroid administration (3 days if eosinophils <300 cells/µL; 5 days if ≥300 cells/µL). The primary outcome was non-inferiority of treatment failure rates (composite of extension of steroid duration, mechanical ventilation or death), with a prespecified 20% non-inferiority margin.RESULTSAmong 110 randomised patients (55 per group), 60% were eosinophilic, and 40% non-eosinophilic. Treatment failure occurred in 6/55 (10.9%) of eosinophil-guided versus 4/55 (7.3%) of usual care patients, with a 3.6% absolute difference (95% CI -8.9% to 16.2%), meeting non-inferiority. Cumulative corticosteroid dose per patient was similar between groups but significantly lower for non-eosinophilic than eosinophilic exacerbations in the eosinophil-guided group (136 vs 214 mg; p=0.0004), a difference not observed in usual care (186 vs 211 mg; p=0.18). Length of stay, Asthma Control Questionnaire-5 change, additional steroid bursts at 14 days or time to next exacerbation up to 1 year showed no significant differences.CONCLUSIONEosinophil-guided therapy safely reduced systemic corticosteroid exposure in non-eosinophilic exacerbations while maintaining non-inferior outcomes in this proof-of-concept trial.TRIAL REGISTRATION NUMBERNCT05417906.
目的：5-7天的全身皮质类固醇治疗是哮喘加重的标准治疗，但最佳持续时间和精确处方的潜力尚不清楚。生物标志物引导的方法可以减少皮质类固醇暴露而不影响结果。我们的目的是评估血嗜酸性粒细胞计数是否可以安全地用于减少住院哮喘发作时全身皮质类固醇暴露。方法在这项开放标签、双中心随机试验中，因哮喘加重住院的成年人按1:1分配到常规护理（5天强的松龙）或嗜酸性粒细胞引导护理（使用皮质类固醇前获得的血液嗜酸性粒细胞计数）（嗜酸性粒细胞<300细胞/µL 3天；≥300细胞/µL 5天）。主要结局是治疗失败率的非劣效性（类固醇持续时间延长、机械通气或死亡的综合因素），预设的非劣效性范围为20%。结果在110例随机患者中（每组55例），60%为嗜酸性粒细胞，40%为非嗜酸性粒细胞。嗜酸性粒细胞引导组治疗失败的发生率为6/55(10.9%)，而常规治疗组为4/55(7.3%)，绝对差异为3.6% (95% CI -8.9% ~ 16.2%)，符合非劣效性。每名患者的累积皮质类固醇剂量在两组之间相似，但非嗜酸性粒细胞组明显低于嗜酸性粒细胞引导组的嗜酸性粒细胞加重（136 vs 214 mg, p=0.0004），在常规护理中未观察到差异（186 vs 211 mg, p=0.18）。住院时间、哮喘控制问卷-5的改变、第14天额外的类固醇爆发或下一次发作的时间长达1年，没有显着差异。结论：在这项概念验证试验中，嗜酸性粒细胞引导的治疗可以安全地减少非嗜酸性粒细胞加重患者的全身皮质类固醇暴露，同时保持非不良结局。试验注册号：05417906。
{"title":"Blood eosinophil-guided systemic corticosteroid duration in adults hospitalised for asthma exacerbation: a randomised, controlled, open-label, non-inferiority trial.","authors":"Anthony Yii,Tunn Ren Tay,Ken Cheah Hooi Lee,Si Yuan Chew,Nicole Yu-Fang Sieow,Xue Ning Choo,Ming Ren Toh,Sean Chee Hong Loh,Pei Yee Tiew,Jansen Meng Kwang Koh,Augustine K H Tee,Mariko Siyue Koh","doi":"10.1136/thorax-2025-223961","DOIUrl":"https://doi.org/10.1136/thorax-2025-223961","url":null,"abstract":"OBJECTIVESystemic corticosteroids for 5-7 days are standard care for asthma exacerbations, but the optimal duration and potential for precision prescribing remain unclear. Biomarker-guided approaches could reduce corticosteroid exposure without compromising outcomes. We aimed to evaluate whether the blood eosinophil count can be used to safely reduce systemic corticosteroid exposure in hospitalised asthma exacerbations.METHODSIn this open-label, two-centre randomised trial, adults hospitalised for asthma exacerbation were assigned 1:1 to usual care (5 days prednisolone) or eosinophil-guided care using blood eosinophil counts obtained prior to corticosteroid administration (3 days if eosinophils <300 cells/µL; 5 days if ≥300 cells/µL). The primary outcome was non-inferiority of treatment failure rates (composite of extension of steroid duration, mechanical ventilation or death), with a prespecified 20% non-inferiority margin.RESULTSAmong 110 randomised patients (55 per group), 60% were eosinophilic, and 40% non-eosinophilic. Treatment failure occurred in 6/55 (10.9%) of eosinophil-guided versus 4/55 (7.3%) of usual care patients, with a 3.6% absolute difference (95% CI -8.9% to 16.2%), meeting non-inferiority. Cumulative corticosteroid dose per patient was similar between groups but significantly lower for non-eosinophilic than eosinophilic exacerbations in the eosinophil-guided group (136 vs 214 mg; p=0.0004), a difference not observed in usual care (186 vs 211 mg; p=0.18). Length of stay, Asthma Control Questionnaire-5 change, additional steroid bursts at 14 days or time to next exacerbation up to 1 year showed no significant differences.CONCLUSIONEosinophil-guided therapy safely reduced systemic corticosteroid exposure in non-eosinophilic exacerbations while maintaining non-inferior outcomes in this proof-of-concept trial.TRIAL REGISTRATION NUMBERNCT05417906.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"1 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663901","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 : 2025-12-02DOI: 10.1136/thorax-2025-223718
Maja Popovic,Milena Maule,Chiara Moccia,Elena Isaevska,Demetris Avraam,Tim Cadman,Ahmed Elhakeem,Veit Grote,Kathrin Guerlich,Sido Haakma,Jennifer Ruth Harris,Pauline W Jansen,Johanna Lucia Thorbjørnsrud Nader,Angela Pinot de Moira,Katrine Strandberg-Larsen,Morris Swertz,Marieke Welten,Tiffany Yang,Vincent Jaddoe,Liesbeth Duijts,Lorenzo Richiardi
BACKGROUNDWhile maternal depression and anxiety have been linked to adverse childhood respiratory outcomes, the role of eating disorders (EDs) remains less understood. This study examined associations between maternal EDs and offspring respiratory outcomes, considering ED subtypes, exposure windows and comorbid depression/anxiety.METHODSData from 131 495 mother-child pairs across seven cohorts from the EU Child Cohort Network were analysed. Primary analyses assessed associations between maternal pre-pregnancy EDs and preschool wheezing and school-age asthma. Secondary analyses explored associations in women without comorbid depression/anxiety, specific ED subtypes (anorexia nervosa, bulimia nervosa), exposure periods (pregnancy, post-pregnancy) and - within two cohorts - school-age lung function. Logistic regression models were fitted for each cohort, and results pooled using random-effects meta-analysis.RESULTSMaternal pre-pregnancy ED prevalence ranged from 0.8% (health records) to 17.0% (self-reported lifetime EDs). Preschool wheezing prevalence ranged from 20.7% to 49.6%, and school-age asthma from 2.1% to 17.3%. Pre-pregnancy EDs were associated with preschool wheezing (OR: 1.25, 95% CI: 1.06 to 1.47, I2: 74%) and school-age asthma (OR: 1.26, 95% CI: 1.10 to 1.46, I2: 9%). These estimates were slightly attenuated but remained directionally consistent with the main analyses after exclusion of mothers with depression/anxiety. There was evidence of a weak positive association with lung function. Associations across ED subtypes were largely consistent with the pre-pregnancy any ED estimate, while no clear pattern emerged by timing of exposure.CONCLUSIONSMaternal EDs are associated with a higher risk of wheezing and asthma in children, independently of comorbid depression/anxiety. These findings highlight the need to understand mechanisms and long-term respiratory consequences of maternal EDs to inform interventions for improving offspring respiratory health.
{"title":"Maternal eating disorders and respiratory outcomes in childhood: findings from the EU Child Cohort Network.","authors":"Maja Popovic,Milena Maule,Chiara Moccia,Elena Isaevska,Demetris Avraam,Tim Cadman,Ahmed Elhakeem,Veit Grote,Kathrin Guerlich,Sido Haakma,Jennifer Ruth Harris,Pauline W Jansen,Johanna Lucia Thorbjørnsrud Nader,Angela Pinot de Moira,Katrine Strandberg-Larsen,Morris Swertz,Marieke Welten,Tiffany Yang,Vincent Jaddoe,Liesbeth Duijts,Lorenzo Richiardi","doi":"10.1136/thorax-2025-223718","DOIUrl":"https://doi.org/10.1136/thorax-2025-223718","url":null,"abstract":"BACKGROUNDWhile maternal depression and anxiety have been linked to adverse childhood respiratory outcomes, the role of eating disorders (EDs) remains less understood. This study examined associations between maternal EDs and offspring respiratory outcomes, considering ED subtypes, exposure windows and comorbid depression/anxiety.METHODSData from 131 495 mother-child pairs across seven cohorts from the EU Child Cohort Network were analysed. Primary analyses assessed associations between maternal pre-pregnancy EDs and preschool wheezing and school-age asthma. Secondary analyses explored associations in women without comorbid depression/anxiety, specific ED subtypes (anorexia nervosa, bulimia nervosa), exposure periods (pregnancy, post-pregnancy) and - within two cohorts - school-age lung function. Logistic regression models were fitted for each cohort, and results pooled using random-effects meta-analysis.RESULTSMaternal pre-pregnancy ED prevalence ranged from 0.8% (health records) to 17.0% (self-reported lifetime EDs). Preschool wheezing prevalence ranged from 20.7% to 49.6%, and school-age asthma from 2.1% to 17.3%. Pre-pregnancy EDs were associated with preschool wheezing (OR: 1.25, 95% CI: 1.06 to 1.47, I2: 74%) and school-age asthma (OR: 1.26, 95% CI: 1.10 to 1.46, I2: 9%). These estimates were slightly attenuated but remained directionally consistent with the main analyses after exclusion of mothers with depression/anxiety. There was evidence of a weak positive association with lung function. Associations across ED subtypes were largely consistent with the pre-pregnancy any ED estimate, while no clear pattern emerged by timing of exposure.CONCLUSIONSMaternal EDs are associated with a higher risk of wheezing and asthma in children, independently of comorbid depression/anxiety. These findings highlight the need to understand mechanisms and long-term respiratory consequences of maternal EDs to inform interventions for improving offspring respiratory health.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"6 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656838","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 : 2025-12-01DOI: 10.1136/thorax-2025-224421
Andrew Harries
Following critical illness requiring intubation, a key step in recovery is liberation from mechanical ventilation. There is a risk during this process of developing postextubation acute respiratory failure (PRF) leading to reintubation. The WIN IN WEAN multicentre randomised controlled trial (Rouby et al. JAMA 2025 doi:10.1001/jama.2024.15815) used a lung ultrasound score (LUS) to characterise the risk of PRF. They identified high risk patients (lung ultrasound score>14) and randomised to receiving intermittent HFNO and NIV (intervention) or conventional oxygen (control) on extubation in the hope of preventing PRF. Importantly the authors excluded patients with known COPD and attempted to optimise other patient characteristics that are known to influence extubation success (successful spontaneous breathing trial, pleural effusion management, fluid balance management, suction of secretions and analysis for bacterial infection.) The intervention arm included 134 patients with 106 in the control group. The primary outcome was met and the incidence of PRF was significantly reduced in the intervention group (28% vs 19%, p = 0.01). The secondary outcomes of reduction in intubation rates and mortality were not met; the study was powered to see a difference in PRF and may have been underpowered to see differences in these outcomes. Rescue …
在需要插管的危重疾病之后，恢复的关键步骤是从机械通气中解放出来。在此过程中存在发生拔管后急性呼吸衰竭（PRF）导致重新插管的风险。WIN IN断奶多中心随机对照试验（Rouby et al.）。JAMA 2025 doi:10.1001/ JAMA .2024.15815)使用肺超声评分（LUS）来表征PRF的风险。他们确定了高风险患者（肺超声评分为bbbb14），并随机分为两组，在拔管时接受间歇性HFNO和NIV（干预）或常规氧（控制），以期预防PRF。重要的是，作者排除了已知的COPD患者，并试图优化已知影响拔管成功的其他患者特征（成功的自主呼吸试验、胸腔积液管理、液体平衡管理、分泌物吸引和细菌感染分析）。干预组包括134例患者，对照组106例。干预组达到主要终点，PRF发生率显著降低（28% vs 19%, p = 0.01）。降低插管率和死亡率的次要结局未达到；这项研究被用来观察PRF的差异，但可能没有足够的证据来观察这些结果的差异。救援……
{"title":"Journal club","authors":"Andrew Harries","doi":"10.1136/thorax-2025-224421","DOIUrl":"https://doi.org/10.1136/thorax-2025-224421","url":null,"abstract":"Following critical illness requiring intubation, a key step in recovery is liberation from mechanical ventilation. There is a risk during this process of developing postextubation acute respiratory failure (PRF) leading to reintubation. The WIN IN WEAN multicentre randomised controlled trial (Rouby et al. JAMA 2025 doi:10.1001/jama.2024.15815) used a lung ultrasound score (LUS) to characterise the risk of PRF. They identified high risk patients (lung ultrasound score>14) and randomised to receiving intermittent HFNO and NIV (intervention) or conventional oxygen (control) on extubation in the hope of preventing PRF. Importantly the authors excluded patients with known COPD and attempted to optimise other patient characteristics that are known to influence extubation success (successful spontaneous breathing trial, pleural effusion management, fluid balance management, suction of secretions and analysis for bacterial infection.) The intervention arm included 134 patients with 106 in the control group. The primary outcome was met and the incidence of PRF was significantly reduced in the intervention group (28% vs 19%, p = 0.01). The secondary outcomes of reduction in intubation rates and mortality were not met; the study was powered to see a difference in PRF and may have been underpowered to see differences in these outcomes. Rescue …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"54 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145509296","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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