Pub Date : 2024-06-14DOI: 10.1136/thorax-2023-220202
Sarah N Danchuk, Ori E Solomon, Thomas Andreas Kohl, Viola Dreyer, Ivan Barilar, Christian Utpatel, Stefan Niemann, Dick van Soolingen, Richard Anthony, Jakko van Ingen, Joy S Michael, Marcel A Behr
Objectives: Heteroresistant infections are defined as infections in which a mixture of drug-resistant and drug-susceptible populations are present. In Mycobacterium tuberculosis (M. tb), heteroresistance poses a challenge in diagnosis and has been linked with poor treatment outcomes. We compared the analytical sensitivity of molecular methods, such as GeneXpert and whole genome sequencing (WGS) in detecting heteroresistance when compared with the 'gold standard' phenotypic assay: the agar proportion method (APM).
Methods: Using two rounds of proficiency surveys with defined monoresistant BCG strains and mixtures of susceptible/resistant M. tb, we determined the limit of detection (LOD) of known resistance associated mutations.
Results: The LOD for rifampin-R (RIF-R) detection was 1% using APM, 60% using GeneXpert MTB/RIF, 10% using GeneXpert MTB/RIF Ultra and 10% using WGS. While WGS could detect mutations beyond those associated with RIF resistance, the LOD for these other mutations was also 10%. Additionally, we observed instances where laboratories did not report resistance in the majority population, yet the mutations were present in the raw sequence data.
Conclusion: The gold standard APM detects minority resistant populations at a lower proportion than molecular tests. Mycobacterium bovis BCG strains with defined resistance and extracted DNA from M. tb provided concordant results and can serve in quality control of laboratories offering molecular testing for resistance. Further research is required to determine whether the higher LOD of molecular tests is associated with negative treatment outcomes.
{"title":"Challenging the gold standard: the limitations of molecular assays for detection of <i>Mycobacterium tuberculosis</i> heteroresistance.","authors":"Sarah N Danchuk, Ori E Solomon, Thomas Andreas Kohl, Viola Dreyer, Ivan Barilar, Christian Utpatel, Stefan Niemann, Dick van Soolingen, Richard Anthony, Jakko van Ingen, Joy S Michael, Marcel A Behr","doi":"10.1136/thorax-2023-220202","DOIUrl":"10.1136/thorax-2023-220202","url":null,"abstract":"<p><strong>Objectives: </strong>Heteroresistant infections are defined as infections in which a mixture of drug-resistant and drug-susceptible populations are present. In <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>), heteroresistance poses a challenge in diagnosis and has been linked with poor treatment outcomes. We compared the analytical sensitivity of molecular methods, such as GeneXpert and whole genome sequencing (WGS) in detecting heteroresistance when compared with the 'gold standard' phenotypic assay: the agar proportion method (APM).</p><p><strong>Methods: </strong>Using two rounds of proficiency surveys with defined monoresistant BCG strains and mixtures of susceptible/resistant <i>M. tb</i>, we determined the limit of detection (LOD) of known resistance associated mutations.</p><p><strong>Results: </strong>The LOD for rifampin-R (RIF-R) detection was 1% using APM, 60% using GeneXpert MTB/RIF, 10% using GeneXpert MTB/RIF Ultra and 10% using WGS. While WGS could detect mutations beyond those associated with RIF resistance, the LOD for these other mutations was also 10%. Additionally, we observed instances where laboratories did not report resistance in the majority population, yet the mutations were present in the raw sequence data.</p><p><strong>Conclusion: </strong>The gold standard APM detects minority resistant populations at a lower proportion than molecular tests. <i>Mycobacterium bovis</i> BCG strains with defined resistance and extracted DNA from <i>M. tb</i> provided concordant results and can serve in quality control of laboratories offering molecular testing for resistance. Further research is required to determine whether the higher LOD of molecular tests is associated with negative treatment outcomes.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-14DOI: 10.1136/thorax-2023-221024
Alexander T Nelson, Lauren M Vasta, Dave Watson, Jung Kim, Anne K Harris, Ana F Best, Laura A Harney, Ann G Carr, Nicole Frederickson, Louis P Dehner, Christian P Kratz, Kelly N Hagedorn, William A Mize, Alexander Ling, Yoav H Messinger, D Ashley Hill, Kris Ann P Schultz, Douglas R Stewart
Background: Pleuropulmonary blastoma (PPB), the hallmark tumour associated with DICER1-related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germline DICER1 pathogenic/likely pathogenic (P/LP) variants.
Methods: Individuals were enrolled in the National Cancer Institute Natural History of DICER1 Syndrome study, the International PPB/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germline DICER1 P/LP variant with first chest CT at 12 years of age or older were selected for this analysis.
Results: In the combined databases, 110 individuals with a germline DICER1 P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB.
Conclusion: Lung cysts are common in adolescents and adults with germline DICER1 variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention.
{"title":"Prevalence of lung cysts in adolescents and adults with a germline <i>DICER1</i> pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/<i>DICER1</i> Registry.","authors":"Alexander T Nelson, Lauren M Vasta, Dave Watson, Jung Kim, Anne K Harris, Ana F Best, Laura A Harney, Ann G Carr, Nicole Frederickson, Louis P Dehner, Christian P Kratz, Kelly N Hagedorn, William A Mize, Alexander Ling, Yoav H Messinger, D Ashley Hill, Kris Ann P Schultz, Douglas R Stewart","doi":"10.1136/thorax-2023-221024","DOIUrl":"10.1136/thorax-2023-221024","url":null,"abstract":"<p><strong>Background: </strong>Pleuropulmonary blastoma (PPB), the hallmark tumour associated with <i>DICER1</i>-related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germline <i>DICER1</i> pathogenic/likely pathogenic (P/LP) variants.</p><p><strong>Methods: </strong>Individuals were enrolled in the National Cancer Institute Natural History of <i>DICER1</i> Syndrome study, the International PPB/<i>DICER1</i> Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germline <i>DICER1</i> P/LP variant with first chest CT at 12 years of age or older were selected for this analysis.</p><p><strong>Results: </strong>In the combined databases, 110 individuals with a germline <i>DICER1</i> P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB.</p><p><strong>Conclusion: </strong>Lung cysts are common in adolescents and adults with germline <i>DICER1</i> variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-14DOI: 10.1136/thorax-2023-220227
Chuanjia Gu, Haibin Yuan, Chi Yang, Fangfang Xie, Junxiang Chen, Lei Zhu, Yifeng Jiang, Jiayuan Sun
Background: Transbronchial cryoablation shows potential as a local therapy for inoperable peripheral lung cancer. However, its clinical application for peripheral pulmonary lesions has not been reported yet.
Methods: An improved cryoprobe with an 8-mm-long, 1.9-mm-wide cryotip was used. Initially, the safety and effectiveness of this cryoprobe were assessed in an in vivo porcine model. Transbronchial cryoablation with 2 or 3 freeze-thaw cycles (10 min or 15 min in each freezing time) was performed in 18 pigs under CT monitoring. Radiological and pathological examinations were performed to evaluate the extent of cryoablation. Subsequently, nine patients with stage IA peripheral lung cancer or metastases underwent transbronchial cryoablation with this cryoprobe under the guidance of navigation bronchoscopy and cone-beam CT. Technical success, safety and outcomes were assessed.
Results: 36 cryoablation procedures were performed successfully without any major complications in the porcine model. The extent of cryoablation increased with freezing time and the number of freeze-thaw cycles, which peaked at 24 hours and then gradually decreased. Pathological results showed a change from massive haemorrhage at 24 hours to fibrous hyperplasia with chronic inflammation after 4 weeks. In the clinical trial, 10 cryoablations were performed on 9 tumours with a technical success rate of 100%. One mild treatment-related complication occurred. Of the nine tumours, seven achieved complete ablation, while two exhibited incomplete ablation and subsequent local progression at 6 months.
Conclusion: Our initial experience indicated that transbronchial cryoablation was a safe and feasible procedure for non-surgical peripheral stage IA lung cancer or pulmonary metastases.
{"title":"Transbronchial cryoablation in peripheral lung parenchyma with a novel thin cryoprobe and initial clinical testing.","authors":"Chuanjia Gu, Haibin Yuan, Chi Yang, Fangfang Xie, Junxiang Chen, Lei Zhu, Yifeng Jiang, Jiayuan Sun","doi":"10.1136/thorax-2023-220227","DOIUrl":"10.1136/thorax-2023-220227","url":null,"abstract":"<p><strong>Background: </strong>Transbronchial cryoablation shows potential as a local therapy for inoperable peripheral lung cancer. However, its clinical application for peripheral pulmonary lesions has not been reported yet.</p><p><strong>Methods: </strong>An improved cryoprobe with an 8-mm-long, 1.9-mm-wide cryotip was used. Initially, the safety and effectiveness of this cryoprobe were assessed in an in vivo porcine model. Transbronchial cryoablation with 2 or 3 freeze-thaw cycles (10 min or 15 min in each freezing time) was performed in 18 pigs under CT monitoring. Radiological and pathological examinations were performed to evaluate the extent of cryoablation. Subsequently, nine patients with stage IA peripheral lung cancer or metastases underwent transbronchial cryoablation with this cryoprobe under the guidance of navigation bronchoscopy and cone-beam CT. Technical success, safety and outcomes were assessed.</p><p><strong>Results: </strong>36 cryoablation procedures were performed successfully without any major complications in the porcine model. The extent of cryoablation increased with freezing time and the number of freeze-thaw cycles, which peaked at 24 hours and then gradually decreased. Pathological results showed a change from massive haemorrhage at 24 hours to fibrous hyperplasia with chronic inflammation after 4 weeks. In the clinical trial, 10 cryoablations were performed on 9 tumours with a technical success rate of 100%. One mild treatment-related complication occurred. Of the nine tumours, seven achieved complete ablation, while two exhibited incomplete ablation and subsequent local progression at 6 months.</p><p><strong>Conclusion: </strong>Our initial experience indicated that transbronchial cryoablation was a safe and feasible procedure for non-surgical peripheral stage IA lung cancer or pulmonary metastases.</p><p><strong>Trial registration number: </strong>ChiCTR2200061544.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-14DOI: 10.1136/thorax-2024-221459
Eric Santoni-Rugiu
{"title":"To progress or not to progress: new insights into the evolution of pleuropulmonary blastomas come from studying lung cysts in adolescents and adults with <i>DICER1</i>-related tumour predisposition.","authors":"Eric Santoni-Rugiu","doi":"10.1136/thorax-2024-221459","DOIUrl":"10.1136/thorax-2024-221459","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319272","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 : 2024-06-14DOI: 10.1136/thorax-2022-219839
Yun-Jiang Yu, Tong Zheng, Jennifer L Perret, Yajing Han, Hongyan Li, Wenjie Meng, Dinh Bui, Qi-Zhen Wu, Chenyin Dong, Qiu-Ling Fang, Zhenchi Li, Hongxuan Kuang, Xiaowen Chen, Mingdeng Xiang, Xiaodi Qin, Shyamali C Dharmage, Guang-Hui Dong, Yang Zhou
Background: There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation.
Methods: A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively.
Results: Overall, there were negative associations between forced expiratory volume in 1 s (FEV1) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV1/FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV1 (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV1 and FVC within the model, respectively.
Conclusion: Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health.
{"title":"Comprehensive analysis of environmental exposure to hazardous trace elements and lung function: a national cross-sectional study.","authors":"Yun-Jiang Yu, Tong Zheng, Jennifer L Perret, Yajing Han, Hongyan Li, Wenjie Meng, Dinh Bui, Qi-Zhen Wu, Chenyin Dong, Qiu-Ling Fang, Zhenchi Li, Hongxuan Kuang, Xiaowen Chen, Mingdeng Xiang, Xiaodi Qin, Shyamali C Dharmage, Guang-Hui Dong, Yang Zhou","doi":"10.1136/thorax-2022-219839","DOIUrl":"10.1136/thorax-2022-219839","url":null,"abstract":"<p><strong>Background: </strong>There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation.</p><p><strong>Methods: </strong>A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively.</p><p><strong>Results: </strong>Overall, there were negative associations between forced expiratory volume in 1 s (FEV<sub>1</sub>) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV<sub>1</sub>/FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV<sub>1</sub> (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV<sub>1</sub> and FVC within the model, respectively.</p><p><strong>Conclusion: </strong>Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933033","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 : 2024-06-02DOI: 10.1136/thorax-2024-221747
Andrew Fisher, Jasvir Parmar
We read with interest the paper from Roussel et al .1 In this study, the authors examine the outcomes for lung transplant recipients who were allocated donor organs in two very different healthcare systems. Their findings raise the complex and vexed question of what the fairest system for the allocation donor lungs is, especially for those candidates identified as being at the highest risk of waiting list mortality. There are a myriad of different allocation systems in operation across the world, which highlights the complex interplay between medical need, the ethical, legal and societal issues that shape national organ allocation policies.2 3 The paper examines two large national databases over a 10-year period to compare lung transplant outcomes in the French and US systems. The French national lung allocation programme is similar to the UK lung allocation …
{"title":"Lung allocation: a vexed, complex multifaceted challenge","authors":"Andrew Fisher, Jasvir Parmar","doi":"10.1136/thorax-2024-221747","DOIUrl":"https://doi.org/10.1136/thorax-2024-221747","url":null,"abstract":"We read with interest the paper from Roussel et al .1 In this study, the authors examine the outcomes for lung transplant recipients who were allocated donor organs in two very different healthcare systems. Their findings raise the complex and vexed question of what the fairest system for the allocation donor lungs is, especially for those candidates identified as being at the highest risk of waiting list mortality. There are a myriad of different allocation systems in operation across the world, which highlights the complex interplay between medical need, the ethical, legal and societal issues that shape national organ allocation policies.2 3 The paper examines two large national databases over a 10-year period to compare lung transplant outcomes in the French and US systems. The French national lung allocation programme is similar to the UK lung allocation …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141235974","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 : 2024-06-01DOI: 10.1136/thorax-2023-btsabstracts-corr1
BMJ Publishing Group Ltd and British Thoracic Society
Abstract withdrawn as it was not presented at the Meeting S45 - Forced Oscillometry Technique in Children with Preschool Wheeze: Feasibility and Relationship to Clinical Parameters P89 - The burden and impact of NTM-LD and perspectives on care, UK data from a European patient survey (ENPADE) P97 - CPET’s utility in understanding unexplained exertional dyspnoea in military personnel. Amendments to author list M7 – Improving the use of Treatment Escalation Plans in the care of respiratory inpatients in a large tertiary centre. R Meharry, K Hamilton. Queen Elizabeth University Hospital, Glasgow, UK. Amendment to text in abstract P43 – …
{"title":"Correction: British Thoracic Society Winter Meeting 2023","authors":"BMJ Publishing Group Ltd and British Thoracic Society","doi":"10.1136/thorax-2023-btsabstracts-corr1","DOIUrl":"https://doi.org/10.1136/thorax-2023-btsabstracts-corr1","url":null,"abstract":"Abstract withdrawn as it was not presented at the Meeting S45 - Forced Oscillometry Technique in Children with Preschool Wheeze: Feasibility and Relationship to Clinical Parameters P89 - The burden and impact of NTM-LD and perspectives on care, UK data from a European patient survey (ENPADE) P97 - CPET’s utility in understanding unexplained exertional dyspnoea in military personnel. Amendments to author list M7 – Improving the use of Treatment Escalation Plans in the care of respiratory inpatients in a large tertiary centre. R Meharry, K Hamilton. Queen Elizabeth University Hospital, Glasgow, UK. Amendment to text in abstract P43 – …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074272","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 : 2024-06-01DOI: 10.1136/thorax-2024-221678
Neda Akhtar Hasan
IPF is a progressive fibrotic lung disease with a median survival of 3–5 years post-diagnosis. Fifty cases are diagnosed per 100 000 people in the UK. The incidence has been rising over the last two decades, with no cure at present. Furthermore, considerable heterogeneity exists within the disease course, making management and prognostication challenging. Kraven et al (DOI: 10.1136/thoraxjnl-2021–218563) have identified 3 IPF endotypes, termed clusters, that exhibit statistically significant differences in the GAP index (gender-age-physiology index), mortality and gas transfer (DLCO). 220 patients were identified from three pooled, publicly available blood transcriptomic datasets found on the Gene Expression Omnibus, where intermittently, data such as force vital capacity (FVC) was missing. Cluster one heavily displayed genes correlating to electron transport, cellular respiration and TGFβ. Cluster two demonstrated genes related to DNA repair, cell cycle, and apoptosis. Cluster three expressed genes corresponding to immune responses. Cluster 2 patients had the most favourable outcomes, achieving higher DLCO values, and lower GAP scores. Cluster one had the highest GAP score. Cluster three had the poorest prognosis, being 3.59 times more likely to die than patients in cluster 2. Following this discovery phase, the authors created a validated …
IPF 是一种进行性纤维化肺病,确诊后的中位生存期为 3-5 年。在英国,每 10 万人中就有 50 例确诊病例。在过去的二十年里,发病率一直在上升,目前还没有治愈的方法。此外,病程中存在相当大的异质性,使得管理和预后具有挑战性。Kraven 等人(DOI: 10.1136/thoraxjnl-2021-218563)发现了 3 种 IPF 内型,称为群组,它们在 GAP 指数(性别-年龄-生理学指数)、死亡率和气体转移(DLCO)方面表现出显著的统计学差异。我们从基因表达总库(Gene Expression Omnibus)上公开发布的三个集合血液转录组数据集中确定了 220 名患者,这些数据集间歇性地缺失了力量生命容量(FVC)等数据。第一组大量显示了与电子传递、细胞呼吸和 TGFβ 相关的基因。第二组显示了与 DNA 修复、细胞周期和细胞凋亡有关的基因。第三组显示了与免疫反应相关的基因。第二组患者的预后最理想,DLCO值较高,GAP评分较低。第一组的 GAP 评分最高。第三组患者的预后最差,死亡几率是第二组患者的 3.59 倍。在这一发现阶段之后,作者创建了一个经过验证的...
{"title":"Journal club","authors":"Neda Akhtar Hasan","doi":"10.1136/thorax-2024-221678","DOIUrl":"https://doi.org/10.1136/thorax-2024-221678","url":null,"abstract":"IPF is a progressive fibrotic lung disease with a median survival of 3–5 years post-diagnosis. Fifty cases are diagnosed per 100 000 people in the UK. The incidence has been rising over the last two decades, with no cure at present. Furthermore, considerable heterogeneity exists within the disease course, making management and prognostication challenging. Kraven et al (DOI: 10.1136/thoraxjnl-2021–218563) have identified 3 IPF endotypes, termed clusters, that exhibit statistically significant differences in the GAP index (gender-age-physiology index), mortality and gas transfer (DLCO). 220 patients were identified from three pooled, publicly available blood transcriptomic datasets found on the Gene Expression Omnibus, where intermittently, data such as force vital capacity (FVC) was missing. Cluster one heavily displayed genes correlating to electron transport, cellular respiration and TGFβ. Cluster two demonstrated genes related to DNA repair, cell cycle, and apoptosis. Cluster three expressed genes corresponding to immune responses. Cluster 2 patients had the most favourable outcomes, achieving higher DLCO values, and lower GAP scores. Cluster one had the highest GAP score. Cluster three had the poorest prognosis, being 3.59 times more likely to die than patients in cluster 2. Following this discovery phase, the authors created a validated …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074136","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 : 2024-05-20DOI: 10.1136/thorax-2022-219958
Mircea Gabriel Stoleriu, Meshal Ansari, Maximilian Strunz, Andrea Schamberger, Motaharehsadat Heydarian, Yaobo Ding, Carola Voss, Juliane Josephine Schneider, Michael Gerckens, Gerald Burgstaller, Alejandra Castelblanco, Teresa Kauke, Jan Fertmann, Christian Schneider, Juergen Behr, Michael Lindner, Elvira Stacher-Priehse, Martin Irmler, Johannes Beckers, Oliver Eickelberg, Benjamin Schubert, Stefanie M Hauck, Otmar Schmid, Rudolf A Hatz, Tobias Stoeger, Herbert B Schiller, Anne Hilgendorff
Introduction: Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised.
Methods: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4). After nanoparticle exposure of pHBECs at air-liquid interface, cell cultures were characterised by functional assays, transcriptome and protein analysis, complemented by single-cell analysis in serial samples of pHBEC cultures focusing on basal cell differentiation.
Results: COPD-IV was characterised by a prosecretory phenotype (twofold increase in MUC5AC+) at the expense of the multiciliated epithelium (threefold reduction in Ac-Tub+), resulting in an increased resilience towards particle-induced cell damage (fivefold reduction in transepithelial electrical resistance), as exemplified by environmentally abundant doses of zinc oxide nanoparticles. Exposure of COPD-II cultures to cigarette smoke extract provoked the COPD-IV characteristic, prosecretory phenotype. Time-resolved single-cell transcriptomics revealed an underlying COPD-IV unique basal cell state characterised by a twofold increase in KRT5+ (P=0.018) and LAMB3+ (P=0.050) expression, as well as a significant activation of Wnt-specific (P=0.014) and Notch-specific (P=0.021) genes, especially in precursors of suprabasal and secretory cells.
Conclusion: We identified COPD stage-specific gene alterations in basal cells that affect the cellular composition of the bronchial elevator and may control disease-specific epithelial resilience mechanisms in response to environmental nanoparticles. The identified phenomena likely inform treatment and prevention strategies.
{"title":"COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors.","authors":"Mircea Gabriel Stoleriu, Meshal Ansari, Maximilian Strunz, Andrea Schamberger, Motaharehsadat Heydarian, Yaobo Ding, Carola Voss, Juliane Josephine Schneider, Michael Gerckens, Gerald Burgstaller, Alejandra Castelblanco, Teresa Kauke, Jan Fertmann, Christian Schneider, Juergen Behr, Michael Lindner, Elvira Stacher-Priehse, Martin Irmler, Johannes Beckers, Oliver Eickelberg, Benjamin Schubert, Stefanie M Hauck, Otmar Schmid, Rudolf A Hatz, Tobias Stoeger, Herbert B Schiller, Anne Hilgendorff","doi":"10.1136/thorax-2022-219958","DOIUrl":"10.1136/thorax-2022-219958","url":null,"abstract":"<p><strong>Introduction: </strong>Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised.</p><p><strong>Methods: </strong>We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4). After nanoparticle exposure of pHBECs at air-liquid interface, cell cultures were characterised by functional assays, transcriptome and protein analysis, complemented by single-cell analysis in serial samples of pHBEC cultures focusing on basal cell differentiation.</p><p><strong>Results: </strong>COPD-IV was characterised by a prosecretory phenotype (twofold increase in MUC5AC<sup>+</sup>) at the expense of the multiciliated epithelium (threefold reduction in Ac-Tub<sup>+</sup>), resulting in an increased resilience towards particle-induced cell damage (fivefold reduction in transepithelial electrical resistance), as exemplified by environmentally abundant doses of zinc oxide nanoparticles. Exposure of COPD-II cultures to cigarette smoke extract provoked the COPD-IV characteristic, prosecretory phenotype. Time-resolved single-cell transcriptomics revealed an underlying COPD-IV unique basal cell state characterised by a twofold increase in KRT5<sup>+</sup> (<i>P</i>=0.018) and LAMB3<sup>+</sup> (<i>P</i>=0.050) expression, as well as a significant activation of Wnt-specific (<i>P</i>=0.014) and Notch-specific (<i>P</i>=0.021) genes, especially in precursors of suprabasal and secretory cells.</p><p><strong>Conclusion: </strong>We identified COPD stage-specific gene alterations in basal cells that affect the cellular composition of the bronchial elevator and may control disease-specific epithelial resilience mechanisms in response to environmental nanoparticles. The identified phenomena likely inform treatment and prevention strategies.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-20DOI: 10.1136/thorax-2023-220877
Panayiotis Kouis, Emmanouil Galanakis, Eleni Michaelidou, Paraskevi Kinni, Antonis Michanikou, Constantinos Pitsios, Julietta Perez, Souzana Achilleos, Nicos Middleton, Pinelopi Anagnostopoulou, Helen Dimitriou, Efstathios Revvas, Gerasimos Stamatelatos, Haris Zacharatos, Chrysanthos Savvides, Emily Vasiliadou, Nikos Kalivitis, Andreas Chrysanthou, Filippos Tymvios, Stefania I Papatheodorou, Petros Koutrakis, Panayiotis K Yiallouros
Introduction: Elevated particulate matter (PM) concentrations of anthropogenic and/or desert dust origin are associated with increased morbidity among children with asthma.
Objective: The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches randomised controlled trial assessed the impact of exposure reduction recommendations, including indoor air filtration, on childhood asthma control during high desert dust storms (DDS) season in Cyprus and Greece.
Design, participants, interventions and setting: Primary school children with asthma were randomised into three parallel groups: (a) no intervention (controls); (b) outdoor intervention (early alerts notifications, recommendations to stay indoors and limit outdoor physical activity during DDS) and (c) combined intervention (same as (b) combined with indoor air purification with high efficiency particulate air filters in children's homes and school classrooms. Asthma symptom control was assessed using the childhood Asthma Control Test (c-ACT), spirometry (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)) and fractional exhaled nitric oxide (FeNO).
Results: In total, 182 children with asthma (age; mean=9.5, SD=1.63) were evaluated during 2019 and 2021. After three follow-up months, the combined intervention group demonstrated a significant improvement in c-ACT in comparison to controls (β=2.63, 95% CI 0.72 to 4.54, p=0.007), which was more profound among atopic children (β=3.56, 95% CI 0.04 to 7.07, p=0.047). Similarly, FEV1% predicted (β=4.26, 95% CI 0.54 to 7.99, p=0.025), the need for any asthma medication and unscheduled clinician visits, but not FVC% and FeNO, were significantly improved in the combined intervention compared with controls.
Conclusion: Recommendations to reduce exposure and use of indoor air filtration in areas with high PM pollution may improve symptom control and lung function in children with asthma.
Trial registration number: NCT03503812.
导言:人为和/或沙漠沙尘造成的颗粒物(PM)浓度升高与哮喘儿童发病率增加有关:利用减少接触方法减轻沙漠沙尘暴对健康的影响随机对照试验评估了减少接触建议(包括室内空气过滤)对塞浦路斯和希腊沙漠沙尘暴高发季节儿童哮喘控制的影响:患有哮喘的小学生被随机分为三个平行组:(a) 无干预组(对照组);(b) 户外干预组(早期警报通知,建议在沙漠沙尘暴期间待在室内并限制户外体育活动);(c) 综合干预组(与(b)组相同,同时在儿童家中和学校教室使用高效微粒空气过滤器进行室内空气净化)。哮喘症状控制情况通过儿童哮喘控制测试(c-ACT)、肺活量测定(1 秒内用力呼气容积(FEV1)、用力肺活量(FVC))和呼出一氧化氮分数(FeNO)进行评估:在2019年和2021年期间,共对182名哮喘儿童(平均年龄=9.5岁,SD=1.63)进行了评估。经过三个月的随访,与对照组相比,联合干预组的 c-ACT 有显著改善(β=2.63,95% CI 0.72 至 4.54,p=0.007),特应性儿童的改善幅度更大(β=3.56,95% CI 0.04 至 7.07,p=0.047)。同样,与对照组相比,联合干预措施显著改善了预测 FEV1%(β=4.26,95% CI 0.54 至 7.99,p=0.025)、对任何哮喘药物的需求和非计划就诊率,但 FVC% 和 FeNO 没有改善:结论:建议在可吸入颗粒物污染严重的地区减少接触并使用室内空气滤清,可改善哮喘儿童的症状控制和肺功能:NCT03503812。
{"title":"Improved childhood asthma control after exposure reduction interventions for desert dust and anthropogenic air pollution: the MEDEA randomised controlled trial.","authors":"Panayiotis Kouis, Emmanouil Galanakis, Eleni Michaelidou, Paraskevi Kinni, Antonis Michanikou, Constantinos Pitsios, Julietta Perez, Souzana Achilleos, Nicos Middleton, Pinelopi Anagnostopoulou, Helen Dimitriou, Efstathios Revvas, Gerasimos Stamatelatos, Haris Zacharatos, Chrysanthos Savvides, Emily Vasiliadou, Nikos Kalivitis, Andreas Chrysanthou, Filippos Tymvios, Stefania I Papatheodorou, Petros Koutrakis, Panayiotis K Yiallouros","doi":"10.1136/thorax-2023-220877","DOIUrl":"10.1136/thorax-2023-220877","url":null,"abstract":"<p><strong>Introduction: </strong>Elevated particulate matter (PM) concentrations of anthropogenic and/or desert dust origin are associated with increased morbidity among children with asthma.</p><p><strong>Objective: </strong>The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches randomised controlled trial assessed the impact of exposure reduction recommendations, including indoor air filtration, on childhood asthma control during high desert dust storms (DDS) season in Cyprus and Greece.</p><p><strong>Design, participants, interventions and setting: </strong>Primary school children with asthma were randomised into three parallel groups: (a) no intervention (controls); (b) outdoor intervention (early alerts notifications, recommendations to stay indoors and limit outdoor physical activity during DDS) and (c) combined intervention (same as (b) combined with indoor air purification with high efficiency particulate air filters in children's homes and school classrooms. Asthma symptom control was assessed using the childhood Asthma Control Test (c-ACT), spirometry (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)) and fractional exhaled nitric oxide (FeNO).</p><p><strong>Results: </strong>In total, 182 children with asthma (age; mean=9.5, SD=1.63) were evaluated during 2019 and 2021. After three follow-up months, the combined intervention group demonstrated a significant improvement in c-ACT in comparison to controls (β=2.63, 95% CI 0.72 to 4.54, p=0.007), which was more profound among atopic children (β=3.56, 95% CI 0.04 to 7.07, p=0.047). Similarly, FEV1% predicted (β=4.26, 95% CI 0.54 to 7.99, p=0.025), the need for any asthma medication and unscheduled clinician visits, but not FVC% and FeNO, were significantly improved in the combined intervention compared with controls.</p><p><strong>Conclusion: </strong>Recommendations to reduce exposure and use of indoor air filtration in areas with high PM pollution may improve symptom control and lung function in children with asthma.</p><p><strong>Trial registration number: </strong>NCT03503812.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933035","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}