Pub Date : 2025-01-01DOI: 10.1136/thorax-2024-222742
Alexandra Hodge
There are no licensed pharmacological treatments for obstructive sleep apnoea (OSA). Obesity is a modifiable risk factor for OSA with existing pharmacological interventions. One such treatment is tirzepatide which is a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide-1 (GLP-1) receptor agonist. Malhotra et al . (N Engl J Med 2024;391:1193–1205) reported the SURMONT-OSA phase three trials which evaluated the safety and efficacy of tirzepatide for the treatment of OSA in obese adults. SURMONT-OSA comprised of two multi-centre, international, double-blind, randomised, controlled trials conducted over 52 weeks. All participants had moderate-severe OSA. Participants were randomised to placebo or tirzepatide treatment arms. Trial one included participants unable or unwilling to use positive airway pressure (PAP) therapy (n=234) and trial two included participants using and continuing PAP therapy (n=235). The primary end-point was the change in apnoea-hypopnea index (AHI) from baseline. In trial one the mean change in AHI at week 52 was −25.3 events/hour (95% CI, −29.3 to −21.2) with tirzepatide and −5.3 events/hour (95% CI, −9.4 to −1.1) with placebo. In trial 2, after withdrawing PAP therapy, the mean change in AHI at week 52 with tirzepatide was −29.3 events/hour (95% CI, −33.2 to −25.4, p<0.001) and …
{"title":"Journal club","authors":"Alexandra Hodge","doi":"10.1136/thorax-2024-222742","DOIUrl":"https://doi.org/10.1136/thorax-2024-222742","url":null,"abstract":"There are no licensed pharmacological treatments for obstructive sleep apnoea (OSA). Obesity is a modifiable risk factor for OSA with existing pharmacological interventions. One such treatment is tirzepatide which is a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide-1 (GLP-1) receptor agonist. Malhotra et al . (N Engl J Med 2024;391:1193–1205) reported the SURMONT-OSA phase three trials which evaluated the safety and efficacy of tirzepatide for the treatment of OSA in obese adults. SURMONT-OSA comprised of two multi-centre, international, double-blind, randomised, controlled trials conducted over 52 weeks. All participants had moderate-severe OSA. Participants were randomised to placebo or tirzepatide treatment arms. Trial one included participants unable or unwilling to use positive airway pressure (PAP) therapy (n=234) and trial two included participants using and continuing PAP therapy (n=235). The primary end-point was the change in apnoea-hypopnea index (AHI) from baseline. In trial one the mean change in AHI at week 52 was −25.3 events/hour (95% CI, −29.3 to −21.2) with tirzepatide and −5.3 events/hour (95% CI, −9.4 to −1.1) with placebo. In trial 2, after withdrawing PAP therapy, the mean change in AHI at week 52 with tirzepatide was −29.3 events/hour (95% CI, −33.2 to −25.4, p<0.001) and …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"36 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873869","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 : 2025-01-01DOI: 10.1136/thoraxjnl-2015-207694corr1
BMJ Publishing Group Ltd and British Thoracic Society
Higginson J. What’s hot that the other lot got. Thorax 2015;70:1010. This Journal club article was originally published with 2 citations missing. The relevant citations have been added to the text below. The editors would like to apologise for any inconvenience caused. Zhou et al (J Clin Oncol 2015 Jul 1;33(19):2197–204) have performed a randomised, …
{"title":"Correction: What’s hot that the other lot got","authors":"BMJ Publishing Group Ltd and British Thoracic Society","doi":"10.1136/thoraxjnl-2015-207694corr1","DOIUrl":"https://doi.org/10.1136/thoraxjnl-2015-207694corr1","url":null,"abstract":"Higginson J. What’s hot that the other lot got. Thorax 2015;70:1010. This Journal club article was originally published with 2 citations missing. The relevant citations have been added to the text below. The editors would like to apologise for any inconvenience caused. Zhou et al (J Clin Oncol 2015 Jul 1;33(19):2197–204) have performed a randomised, …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"11 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874038","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 : 2024-12-31DOI: 10.1136/thorax-2024-222120
Simone Petrarulo, Claudia Ravaglia, Maria Giulia Disanto, Sara Piciucchi, Venerino Poletti
A 25-year-old non-smoking caucasian woman, with no family history of interstitial lung disease (ILD) or consanguinity, presented with a 6-month history of progressive exertional dyspnoea, chest pain and episodes of mild haemoptysis. Her medical history was unremarkable. Physical examination revealed bibasilar crackles and digital clubbing. Blood tests showed neutrophilic leucocytosis (WBC 12 040/mm³ with neutrophils 9860/mm³) and CRP 3.8 mg/L. An autoimmunity panel and specific IgG tests for mould and avian antigens were all negative. Spirometry indicated a restrictive ventilatory defect with severe impairment of DLCO (FVC 57% predicted and DLCO 35% predicted). A high resolution CT revealed ground-glass attenuation in the peripheral regions of both lungs, with small cysts in the anterior segments of both upper lobes (figure 1). A bronchoalveolar lavage performed in the lingula showed 99% macrophages and 1% lymphocytes, and microbiology cultures for bacterial, fungal and viral pathogens were negative. After a multidisciplinary discussion, a transbronchial …
{"title":"ABCA3-related interstitial lung disease in a young woman","authors":"Simone Petrarulo, Claudia Ravaglia, Maria Giulia Disanto, Sara Piciucchi, Venerino Poletti","doi":"10.1136/thorax-2024-222120","DOIUrl":"https://doi.org/10.1136/thorax-2024-222120","url":null,"abstract":"A 25-year-old non-smoking caucasian woman, with no family history of interstitial lung disease (ILD) or consanguinity, presented with a 6-month history of progressive exertional dyspnoea, chest pain and episodes of mild haemoptysis. Her medical history was unremarkable. Physical examination revealed bibasilar crackles and digital clubbing. Blood tests showed neutrophilic leucocytosis (WBC 12 040/mm³ with neutrophils 9860/mm³) and CRP 3.8 mg/L. An autoimmunity panel and specific IgG tests for mould and avian antigens were all negative. Spirometry indicated a restrictive ventilatory defect with severe impairment of DLCO (FVC 57% predicted and DLCO 35% predicted). A high resolution CT revealed ground-glass attenuation in the peripheral regions of both lungs, with small cysts in the anterior segments of both upper lobes (figure 1). A bronchoalveolar lavage performed in the lingula showed 99% macrophages and 1% lymphocytes, and microbiology cultures for bacterial, fungal and viral pathogens were negative. After a multidisciplinary discussion, a transbronchial …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"87 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908227","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 : 2024-12-31DOI: 10.1136/thorax-2024-222606
David M Mannino
Polymorbidity is an important component of chronic obstructive pulmonary disease (COPD), with cardiovascular diseases being among the most important comorbidities.1 The development of both incident and recurrent cardiovascular events is related to the degree of lung function impairment in COPD.2 Acute exacerbations of COPD (AECOPD) are associated with a higher risk of developing an acute cardiovascular event, particularly in the first 6 months following the AECOPD.3 4 Therapies that include inhaled corticosteroids (ICS) decrease the risk of exacerbations.5 6 Thus, it would follow that therapies that decrease exacerbations, such as those include ICS, would decrease cardiovascular events. This was the topic for the Study to Understand Mortality and Morbidity in COPD trial, a 3-year trial of over 16 000 patients randomised into four groups (placebo, fluticasone furoate, vilanterol and fluticasone/vilanterol).7 The ICS-containing groups had fewer exacerbations and less lung function decline but did not significantly decrease mortality or cardiovascular events. Cardiopulmonary events are the focus for ‘A Randomised, Double-Blind, Parallel Group, Multicentre, Phase III Study to Assess the Efficacy of Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler Relative to Glycopyrronium and Formoterol Fumarate MDI on Cardiopulmonary Outcomes in COPD (THARROS)’, which is currently recruiting up to 5000 patients with an estimated completion in 2028.8 The …
{"title":"Do inhaled corticosteroids decrease the risk of cardiovascular outcomes in patients with chronic obstructive pulmonary disease?","authors":"David M Mannino","doi":"10.1136/thorax-2024-222606","DOIUrl":"https://doi.org/10.1136/thorax-2024-222606","url":null,"abstract":"Polymorbidity is an important component of chronic obstructive pulmonary disease (COPD), with cardiovascular diseases being among the most important comorbidities.1 The development of both incident and recurrent cardiovascular events is related to the degree of lung function impairment in COPD.2 Acute exacerbations of COPD (AECOPD) are associated with a higher risk of developing an acute cardiovascular event, particularly in the first 6 months following the AECOPD.3 4 Therapies that include inhaled corticosteroids (ICS) decrease the risk of exacerbations.5 6 Thus, it would follow that therapies that decrease exacerbations, such as those include ICS, would decrease cardiovascular events. This was the topic for the Study to Understand Mortality and Morbidity in COPD trial, a 3-year trial of over 16 000 patients randomised into four groups (placebo, fluticasone furoate, vilanterol and fluticasone/vilanterol).7 The ICS-containing groups had fewer exacerbations and less lung function decline but did not significantly decrease mortality or cardiovascular events. Cardiopulmonary events are the focus for ‘A Randomised, Double-Blind, Parallel Group, Multicentre, Phase III Study to Assess the Efficacy of Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler Relative to Glycopyrronium and Formoterol Fumarate MDI on Cardiopulmonary Outcomes in COPD (THARROS)’, which is currently recruiting up to 5000 patients with an estimated completion in 2028.8 The …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"71 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908225","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 : 2024-12-25DOI: 10.1136/thorax-2024-222636
Narat Srivali, Federica De Giacomi, Teng Moua, Jay H Ryu
Introduction Acute exacerbation of interstitial lung disease (AE-ILD) often results in death and poses significant challenges in clinical management. While corticosteroids are frequently employed, the optimal regimen and their clinical efficacy remain uncertain. To address this knowledge gap, we undertook a systematic review to evaluate the impact of steroid therapy on clinical outcomes in patients experiencing AE-ILD. Method Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically searched multiple databases, identifying 12 454 articles. After removing duplicates and screening titles and abstracts, 447 articles were selected for full-text review. Ultimately, nine studies met inclusion criteria, comparing high-dose corticosteroids with low-dose or non-steroidal interventions in treating AE-ILD. Key outcomes included in-hospital and long-term mortality, as well as AE recurrence. Results Analysis of nine studies (total n=18 509) revealed differential treatment effects based on the ILD subtype. In non-idiopathic pulmonary fibrosis (IPF) ILD, high-dose corticosteroid therapy (>1.0 mg/kg prednisolone) demonstrated improved survival (adjusted HR 0.221, 95% CI 0.102 to 0.480, p<0.001) and reduced 90-day mortality. Early tapering of high-dose corticosteroids (>10% reduction within 2 weeks) reduced in-hospital mortality (adjusted HR 0.37, 95% CI 0.14 to 0.99). Higher cumulative doses in the first 30 days (5185±2414 mg/month vs 3133±1990 mg/month) were associated with lower recurrence rates (adjusted HR 0.61, 95% CI 0.41 to 0.90, p=0.02). In IPF patients, however, high-dose therapy showed inconsistent benefits, with some studies reporting increased mortality risk (OR 1.075, 95% CI 1.044 to 1.107, p<0.001). Conclusion This review emphasises the potential benefits of individualised treatment approaches for AE-ILD but highlights the need for caution in making definitive recommendations. Although high-dose corticosteroids may show promise, particularly in non-IPF cases, the current evidence is inconsistent, and the lack of robust supporting literature makes it difficult to draw firm conclusions. Further research through randomised controlled trials is necessary to refine and optimise therapeutic strategies for AE-ILD. Data sharing not applicable as no datasets generated and/or analysed for this study.
肺间质性疾病（AE-ILD）急性加重常导致死亡，给临床治疗带来重大挑战。虽然经常使用皮质类固醇，但最佳方案及其临床疗效仍不确定。为了解决这一知识差距，我们进行了一项系统综述，以评估类固醇治疗对AE-ILD患者临床结果的影响。方法根据系统评价和荟萃分析指南的首选报告项目，我们系统地检索了多个数据库，确定了12454篇文章。在剔除重复、筛选标题和摘要后，我们选择了447篇文章进行全文审查。最终，9项研究符合纳入标准，比较了高剂量皮质类固醇与低剂量或非类固醇干预治疗AE-ILD的效果。主要结局包括住院和长期死亡率，以及AE复发。结果9项研究（总n= 18509）的分析揭示了基于ILD亚型的不同治疗效果。在非特发性肺纤维化（IPF） ILD中，高剂量皮质类固醇治疗（bbb1.0 mg/kg泼尼松龙）可改善生存率（调整后危险度0.221,95% CI 0.102至0.480,2周内降低10%）降低住院死亡率（调整后危险度0.37,95% CI 0.14至0.99）。前30天较高的累积剂量（5185±2414 mg/月vs 3133±1990 mg/月）与较低的复发率相关（调整后危险度0.61,95% CI 0.41 ~ 0.90, p=0.02）。然而，在IPF患者中，高剂量治疗显示出不一致的益处，一些研究报告死亡风险增加（OR 1.075, 95% CI 1.044至1.107,p<0.001）。结论：本综述强调了AE-ILD个体化治疗方法的潜在益处，但也强调了在提出明确建议时需要谨慎。尽管大剂量皮质类固醇可能显示出希望，特别是在非ipf病例中，但目前的证据并不一致，而且缺乏有力的支持文献，因此很难得出确切的结论。有必要通过随机对照试验进行进一步研究，以完善和优化AE-ILD的治疗策略。数据共享不适用，因为没有为本研究生成和/或分析数据集。
{"title":"Corticosteroid therapy for treating acute exacerbation of interstitial lung diseases: a systematic review","authors":"Narat Srivali, Federica De Giacomi, Teng Moua, Jay H Ryu","doi":"10.1136/thorax-2024-222636","DOIUrl":"https://doi.org/10.1136/thorax-2024-222636","url":null,"abstract":"Introduction Acute exacerbation of interstitial lung disease (AE-ILD) often results in death and poses significant challenges in clinical management. While corticosteroids are frequently employed, the optimal regimen and their clinical efficacy remain uncertain. To address this knowledge gap, we undertook a systematic review to evaluate the impact of steroid therapy on clinical outcomes in patients experiencing AE-ILD. Method Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically searched multiple databases, identifying 12 454 articles. After removing duplicates and screening titles and abstracts, 447 articles were selected for full-text review. Ultimately, nine studies met inclusion criteria, comparing high-dose corticosteroids with low-dose or non-steroidal interventions in treating AE-ILD. Key outcomes included in-hospital and long-term mortality, as well as AE recurrence. Results Analysis of nine studies (total n=18 509) revealed differential treatment effects based on the ILD subtype. In non-idiopathic pulmonary fibrosis (IPF) ILD, high-dose corticosteroid therapy (>1.0 mg/kg prednisolone) demonstrated improved survival (adjusted HR 0.221, 95% CI 0.102 to 0.480, p<0.001) and reduced 90-day mortality. Early tapering of high-dose corticosteroids (>10% reduction within 2 weeks) reduced in-hospital mortality (adjusted HR 0.37, 95% CI 0.14 to 0.99). Higher cumulative doses in the first 30 days (5185±2414 mg/month vs 3133±1990 mg/month) were associated with lower recurrence rates (adjusted HR 0.61, 95% CI 0.41 to 0.90, p=0.02). In IPF patients, however, high-dose therapy showed inconsistent benefits, with some studies reporting increased mortality risk (OR 1.075, 95% CI 1.044 to 1.107, p<0.001). Conclusion This review emphasises the potential benefits of individualised treatment approaches for AE-ILD but highlights the need for caution in making definitive recommendations. Although high-dose corticosteroids may show promise, particularly in non-IPF cases, the current evidence is inconsistent, and the lack of robust supporting literature makes it difficult to draw firm conclusions. Further research through randomised controlled trials is necessary to refine and optimise therapeutic strategies for AE-ILD. Data sharing not applicable as no datasets generated and/or analysed for this study.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"8 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886832","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 : 2024-12-25DOI: 10.1136/thorax-2024-222113
Anne E Ioannides, Constantinos Kallis, Hannah R Whittaker, Jennifer K Quint
Background Whether inhaled corticosteroids (ICSs) reduce major adverse cardiovascular events (MACEs) in people with chronic obstructive pulmonary disease (COPD) is debated. Objectives To establish, within people with COPD, (1) whether ICS reduced MACE rates (acute coronary syndrome (ACS), heart failure (HF), ischaemic strokes or cardiovascular-specific death) compared with long-acting bronchodilators; and (2) whether drug class, incident usership or patient cardiovascular history influenced the ICS-MACE relationship. Methods We conducted a cohort study including patients with COPD in England, using Clinical Practice Research Datalink Aurum data, linked with Hospital Episode Statistics and Office of National Statistics death data, between 1 January 2010 and 31 December 2019. We implemented Cox proportional hazard regressions, adjusting for time interactions or using propensity score-adjusted models, as necessary. Our exposures included prescriptions of any ICS (vs any long-acting bronchodilators) and triple therapy (vs combination long-acting bronchodilators), determined during the year prior to follow-up. The outcomes of interest were MACE collectively and individual MACE subtypes. Measurements and main results Among 113 353 people with COPD (mean age 67.9 years old, 53.3% male), ICS prescription was not associated with MACE (adjusted HR (95% CI)=0.98 (0.95, 1.02), p=0.41) but was associated with reduced HF, specifically, until year 6 of follow-up (average adjusted HR (95% CI)=0.91 (0.86, 0.96), p<0.001). HF reduction was driven by the ICS group containing mometasone furoate, beclomethasone, budesonide or ciclesonide (HR (95% CI)=0.89 (0.84, 0.94), p<0.001). Incident ICS use was associated with increased ACS (HR (95% CI)=1.27 (1.09, 1.47), p<0.001) but was not sustained beyond incident use. There was no association between triple therapy and MACE. Results did not differ by cardiovascular history. Conclusions ICS did not reduce MACE, except HF, likely by reducing misclassified COPD exacerbations. Data may be obtained from a third party and are not publicly available. Data sets generated and/or analysed in this study are not publicly available, however, data are available on request from the CPRD. Their provision requires the purchase of a license and this license does not permit the authors to make them publicly available to all. This work used data from the version collected in May 2022 and has clearly specified the data selected in the Methods section. To allow identical data to be obtained by others, via the purchase of a license, the code lists will be provided upon request. Licenses are available from the CPRD (): The Clinical Practice Research Datalink Group, The Medicines and Healthcare products Regulatory Agency, 10 South Colonnade, Canary Wharf, London E14 4PU.
背景：吸入皮质类固醇（ICSs）是否能减少慢性阻塞性肺疾病（COPD）患者的主要不良心血管事件（mace）尚存争议。目的：在COPD患者中，(1)与长效支气管扩张剂相比，ICS是否降低了MACE（急性冠脉综合征（ACS）、心力衰竭（HF）、缺血性中风或心血管特异性死亡）的发生率；(2)药物类别、事件使用者或患者心血管病史是否影响ICS-MACE关系。方法：我们在2010年1月1日至2019年12月31日期间，使用临床实践研究数据链Aurum数据，与医院事件统计和国家统计局死亡数据相关联，对英国COPD患者进行了一项队列研究。我们实施了Cox比例风险回归，调整了时间相互作用或必要时使用倾向评分调整模型。我们的暴露包括在随访前一年确定的任何ICS（与任何长效支气管扩张剂相比）和三联治疗（与联合长效支气管扩张剂相比）的处方。我们关注的结果是总体MACE和个体MACE亚型。在113353例COPD患者（平均年龄67.9岁，53.3%为男性）中，ICS处方与MACE无关(调整HR (95% CI)=0.98 (0.95, 1.02), p=0.41)，但与HF降低相关，特别是，直到随访第6年(平均调整HR (95% CI)=0.91 (0.86, 0.96), p)：临床实践研究数据链组，药物和保健产品监管机构，10 South Colonnade, Canary Wharf, London E14 4PU。
{"title":"Inhaled corticosteroids and major cardiovascular events in people with chronic obstructive pulmonary disease","authors":"Anne E Ioannides, Constantinos Kallis, Hannah R Whittaker, Jennifer K Quint","doi":"10.1136/thorax-2024-222113","DOIUrl":"https://doi.org/10.1136/thorax-2024-222113","url":null,"abstract":"Background Whether inhaled corticosteroids (ICSs) reduce major adverse cardiovascular events (MACEs) in people with chronic obstructive pulmonary disease (COPD) is debated. Objectives To establish, within people with COPD, (1) whether ICS reduced MACE rates (acute coronary syndrome (ACS), heart failure (HF), ischaemic strokes or cardiovascular-specific death) compared with long-acting bronchodilators; and (2) whether drug class, incident usership or patient cardiovascular history influenced the ICS-MACE relationship. Methods We conducted a cohort study including patients with COPD in England, using Clinical Practice Research Datalink Aurum data, linked with Hospital Episode Statistics and Office of National Statistics death data, between 1 January 2010 and 31 December 2019. We implemented Cox proportional hazard regressions, adjusting for time interactions or using propensity score-adjusted models, as necessary. Our exposures included prescriptions of any ICS (vs any long-acting bronchodilators) and triple therapy (vs combination long-acting bronchodilators), determined during the year prior to follow-up. The outcomes of interest were MACE collectively and individual MACE subtypes. Measurements and main results Among 113 353 people with COPD (mean age 67.9 years old, 53.3% male), ICS prescription was not associated with MACE (adjusted HR (95% CI)=0.98 (0.95, 1.02), p=0.41) but was associated with reduced HF, specifically, until year 6 of follow-up (average adjusted HR (95% CI)=0.91 (0.86, 0.96), p<0.001). HF reduction was driven by the ICS group containing mometasone furoate, beclomethasone, budesonide or ciclesonide (HR (95% CI)=0.89 (0.84, 0.94), p<0.001). Incident ICS use was associated with increased ACS (HR (95% CI)=1.27 (1.09, 1.47), p<0.001) but was not sustained beyond incident use. There was no association between triple therapy and MACE. Results did not differ by cardiovascular history. Conclusions ICS did not reduce MACE, except HF, likely by reducing misclassified COPD exacerbations. Data may be obtained from a third party and are not publicly available. Data sets generated and/or analysed in this study are not publicly available, however, data are available on request from the CPRD. Their provision requires the purchase of a license and this license does not permit the authors to make them publicly available to all. This work used data from the version collected in May 2022 and has clearly specified the data selected in the Methods section. To allow identical data to be obtained by others, via the purchase of a license, the code lists will be provided upon request. Licenses are available from the CPRD (<http://www.cprd.com>): The Clinical Practice Research Datalink Group, The Medicines and Healthcare products Regulatory Agency, 10 South Colonnade, Canary Wharf, London E14 4PU.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"41 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886833","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}
A 48-year-old woman reported a 1-year history of breathlessness, persistent cough and recurrent chest infections. She was a former smoker with a medical history of nasal polyps and asthma since childhood. She was managed as a case of worsening bronchial asthma, until a CT scan was performed to investigate anaemia, incidentally identified an obstructing lesion in her left main bronchus (figure 1). She was referred to our specialist interventional bronchoscopy unit for further investigation and management. A review of her imaging disclosed a pedunculated soft tissue lesion obstructing the distal left main bronchus and presence of left-to-right axis switching of the aorta and inferior vena cava with polysplenia (figure 1). All abdominal organs were normally sited. Figure 1 (A) Chest x-ray showing dextrocardia and partial left lower lobe collapse (B) CT chest with contrast demonstrating left hilar lesion on axial view (see arrow & red circle) (C) Coronal view showing lesion in distal …
{"title":"Endobronchial obstruction of the left middle lobe","authors":"Hardeep Singh Kalsi, Rimsha Khan, Reena Khiroya, Neal Navani, Ricky Thakrar","doi":"10.1136/thorax-2024-221955","DOIUrl":"https://doi.org/10.1136/thorax-2024-221955","url":null,"abstract":"A 48-year-old woman reported a 1-year history of breathlessness, persistent cough and recurrent chest infections. She was a former smoker with a medical history of nasal polyps and asthma since childhood. She was managed as a case of worsening bronchial asthma, until a CT scan was performed to investigate anaemia, incidentally identified an obstructing lesion in her left main bronchus (figure 1). She was referred to our specialist interventional bronchoscopy unit for further investigation and management. A review of her imaging disclosed a pedunculated soft tissue lesion obstructing the distal left main bronchus and presence of left-to-right axis switching of the aorta and inferior vena cava with polysplenia (figure 1). All abdominal organs were normally sited. Figure 1 (A) Chest x-ray showing dextrocardia and partial left lower lobe collapse (B) CT chest with contrast demonstrating left hilar lesion on axial view (see arrow & red circle) (C) Coronal view showing lesion in distal …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"25 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886834","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 : 2024-12-25DOI: 10.1136/thorax-2024-222412
Matthew J Cummings, Julius J Lutwama, Alin S Tomoiaga, Nicholas Owor, Xuan Lu, Jesse E Ross, Moses Muwanga, Christopher Nsereko, Irene Nayiga, Kai Nie, John Kayiwa, Xiaoyu Che, Misaki Wayengera, Seunghee Kim-Schulze, W Ian Lipkin, Max R O’Donnell, Barnabas Bakamutumaho
The generalisability of critical illness molecular phenotypes to low- and middle-income countries (LMICs) is unknown. We show that molecular phenotypes derived in high-income countries (hyperinflammatory and hypoinflammatory, reactive and uninflamed) stratify sepsis patients in Uganda by physiological severity, mortality risk and dysregulation of key pathobiological domains. A classifier model including data available at the LMIC bedside modestly discriminated phenotype assignment (area under the receiver operating characteristic curve (AUROC) 0.80, 95% CI 0.71 to 0.90 for hyperinflammatory vs hypoinflammatory; AUROC 0.74, 95% CI 0.65 to 0.83 for reactive vs uninflamed). Our findings highlight the potential for a globally relevant, clinicomolecular classification of critical illness and may support the inclusion of diverse populations in phenotype-targeted critical care trials. Improved laboratory capacity and access to rapid biomarker assays are likely necessary to optimise phenotype stratification in LMIC settings.
危重疾病分子表型在低收入和中等收入国家（LMICs）的普遍性尚不清楚。我们发现，来自高收入国家的分子表型（高炎症和低炎症，反应性和非炎症）通过生理严重程度，死亡风险和关键病理生物学域的失调对乌干达败血症患者进行分层。包括LMIC床边可用数据的分类器模型适度区分表型分配(接受者工作特征曲线下面积（AUROC） 0.80，高炎症与低炎症的95% CI 0.71至0.90；AUROC为0.74,95% CI为0.65 - 0.83（反应性与非炎症性）。我们的研究结果强调了全球相关的危重疾病临床分子分类的潜力，并可能支持将不同人群纳入以表型为目标的危重护理试验。提高实验室能力和获得快速生物标志物检测可能是优化低mic环境中表型分层的必要条件。
{"title":"Molecular phenotypes of critical illness confer prognostic and biological enrichment in sub-Saharan Africa: a prospective cohort study from Uganda","authors":"Matthew J Cummings, Julius J Lutwama, Alin S Tomoiaga, Nicholas Owor, Xuan Lu, Jesse E Ross, Moses Muwanga, Christopher Nsereko, Irene Nayiga, Kai Nie, John Kayiwa, Xiaoyu Che, Misaki Wayengera, Seunghee Kim-Schulze, W Ian Lipkin, Max R O’Donnell, Barnabas Bakamutumaho","doi":"10.1136/thorax-2024-222412","DOIUrl":"https://doi.org/10.1136/thorax-2024-222412","url":null,"abstract":"The generalisability of critical illness molecular phenotypes to low- and middle-income countries (LMICs) is unknown. We show that molecular phenotypes derived in high-income countries (hyperinflammatory and hypoinflammatory, reactive and uninflamed) stratify sepsis patients in Uganda by physiological severity, mortality risk and dysregulation of key pathobiological domains. A classifier model including data available at the LMIC bedside modestly discriminated phenotype assignment (area under the receiver operating characteristic curve (AUROC) 0.80, 95% CI 0.71 to 0.90 for hyperinflammatory vs hypoinflammatory; AUROC 0.74, 95% CI 0.65 to 0.83 for reactive vs uninflamed). Our findings highlight the potential for a globally relevant, clinicomolecular classification of critical illness and may support the inclusion of diverse populations in phenotype-targeted critical care trials. Improved laboratory capacity and access to rapid biomarker assays are likely necessary to optimise phenotype stratification in LMIC settings.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"11 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886837","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 : 2024-12-23DOI: 10.1136/thorax-2024-221906
Alex E Henney, David R Riley, Theresa J Hydes, Matthew Anson, Gema H Ibarburu, Frederick Frost, Uazman Alam, Daniel J Cuthbertson
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are treatments for type 2 diabetes (T2D). Beyond glucose-lowering and cardiorenal protection, these drugs may protect against pneumonia and sepsis.
Aims: This study assesses the impact of SGLT2i and GLP-1 RAs on the risk of incident pneumonia and severe sepsis.
Methods: A retrospective cohort study was conducted using anonymised electronic medical records from TriNetX, a global federated database. Two intention-to-treat analyses were performed, each with two cohorts of adult T2D patients. The first analysis compared individuals prescribed SGLT2i, and the second individuals prescribed GLP-1 RAs, with those prescribed dipeptidyl peptidase-4 inhibitors (DPP-4i). An active comparator new user design was used, with outcomes defined as time-to-incident pneumonia and severe sepsis. Propensity score matching (1:1) was applied to control for potential confounders, and patients were followed for 12 months. Secondary analyses compared SGLT2i and GLP-1 RAs against other glucose-lowering therapies.
Results: After propensity score matching, 352 687 patients were included in the SGLT2i versus DPP-4i comparison. SGLT2i treatment was associated with a risk reduction in incident pneumonia (HR 0.75 (95% CI 0.73, 0.78)) and severe sepsis (0.75 (0.73, 0.77)). In the GLP-1 RA versus DPP-4i comparison, 331 863 patients were included. GLP-1 RA treatment was associated with a risk reduction in incident pneumonia (0.60 (0.58, 0.62)) and severe sepsis (0.61 (0.59, 0.63)).
Conclusion: SGLT2i and GLP-1 RAs are associated with a reduced risk of incident pneumonia and severe sepsis in patients with T2D. Further research and focused randomised controlled trials are warranted to explore the broader clinical implications of these treatments.
{"title":"Comparative estimate of glucose-lowering therapies on risk of incident pneumonia and severe sepsis: an analysis of real-world cohort data.","authors":"Alex E Henney, David R Riley, Theresa J Hydes, Matthew Anson, Gema H Ibarburu, Frederick Frost, Uazman Alam, Daniel J Cuthbertson","doi":"10.1136/thorax-2024-221906","DOIUrl":"10.1136/thorax-2024-221906","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are treatments for type 2 diabetes (T2D). Beyond glucose-lowering and cardiorenal protection, these drugs may protect against pneumonia and sepsis.</p><p><strong>Aims: </strong>This study assesses the impact of SGLT2i and GLP-1 RAs on the risk of incident pneumonia and severe sepsis.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using anonymised electronic medical records from TriNetX, a global federated database. Two intention-to-treat analyses were performed, each with two cohorts of adult T2D patients. The first analysis compared individuals prescribed SGLT2i, and the second individuals prescribed GLP-1 RAs, with those prescribed dipeptidyl peptidase-4 inhibitors (DPP-4i). An active comparator new user design was used, with outcomes defined as time-to-incident pneumonia and severe sepsis. Propensity score matching (1:1) was applied to control for potential confounders, and patients were followed for 12 months. Secondary analyses compared SGLT2i and GLP-1 RAs against other glucose-lowering therapies.</p><p><strong>Results: </strong>After propensity score matching, 352 687 patients were included in the SGLT2i versus DPP-4i comparison. SGLT2i treatment was associated with a risk reduction in incident pneumonia (HR 0.75 (95% CI 0.73, 0.78)) and severe sepsis (0.75 (0.73, 0.77)). In the GLP-1 RA versus DPP-4i comparison, 331 863 patients were included. GLP-1 RA treatment was associated with a risk reduction in incident pneumonia (0.60 (0.58, 0.62)) and severe sepsis (0.61 (0.59, 0.63)).</p><p><strong>Conclusion: </strong>SGLT2i and GLP-1 RAs are associated with a reduced risk of incident pneumonia and severe sepsis in patients with T2D. Further research and focused randomised controlled trials are warranted to explore the broader clinical implications of these treatments.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"32-41"},"PeriodicalIF":9.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792586","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}
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