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A structural and metabolic framework for classifying pre-clinical tuberculosis infection phenotypes using 18F-FDG PET-CT: a prospective cohort analysis following M. tuberculosis exposure. 利用 18F-FDG PET-CT 对临床前结核感染表型进行分类的结构和代谢框架:结核杆菌暴露后的前瞻性队列分析。
IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-11-14 DOI: 10.1136/thorax-2024-221470
Jee Whang Kim, Sonam Vadera, Meedya Sharifpour, Amrita Bajaj, Anver Kamil, Pranabashis Haldar

Tuberculosis (TB) control efforts are limited by ineffective characterisation of tuberculosis infection (TBI) -a heterogeneous spectrum of pre-clinical infection states, invisible to tools of routine clinical screening, that are associated with variable risk of progression to TB disease. In this prospective study, we use positron emission tomography-CT (PET-CT) as a high-resolution imaging modality to characterise and classify structural and metabolic features observed in 16 asymptomatic household TB contacts with normal chest radiographs. We identify four feature patterns that associate with distinct clinical and microbiological outcomes, supporting potential utility of PET-CT for objective classification of TBI phenotypes.

结核病(TB)控制工作因结核病感染(TBI)特征描述不清而受到限制--TBI 是临床前感染状态的一个异质性谱系,常规临床筛查工具无法发现,与结核病进展的不同风险相关。在这项前瞻性研究中,我们使用正电子发射断层扫描-计算机断层扫描(PET-CT)作为一种高分辨率成像模式,对 16 名胸片正常的无症状家庭结核病接触者的结构和代谢特征进行描述和分类。我们确定了与不同临床和微生物学结果相关的四种特征模式,支持 PET-CT 用于结核病表型客观分类的潜在用途。
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引用次数: 0
Imaging in early tuberculosis. 早期肺结核的成像
IF 11.3 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-11-14 DOI: 10.1136/thorax-2024-221993
Robert Wilkinson
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引用次数: 0
Multiple lung cyst formation caused by metastatic bladder cancer. 转移性膀胱癌导致多发性肺囊肿形成。
IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-11-14 DOI: 10.1136/thorax-2023-220573
Noriaki Nakagaki, Masashi Komori, Tatsuro Shimokama, Eiji Iwama
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引用次数: 0
Pulmonary fibrosis may begin in infancy: from childhood to adult interstitial lung disease. 肺纤维化可能始于婴儿期:从儿童期到成年期的间质性肺病。
IF 11.3 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-11-14 DOI: 10.1136/thorax-2024-221772
Matthias Griese, Geoffrey Kurland, Michal Cidon, Robin R Deterding, Ralph Epaud, Nadia Nathan, Nicolaus Schwerk, David Warburton, Jason P Weinman, Lisa R Young, Gail H Deutsch

Background: Childhood interstitial lung disease (chILD) encompasses a group of rare heterogeneous respiratory conditions associated with significant morbidity and mortality. Reports suggest that many patients diagnosed with chILD continue to have potentially progressive or fibrosing disease into adulthood. Over the last decade, the spectrum of conditions within chILD has widened substantially, with the discovery of novel entities through advanced genetic testing. However, most evidence is often limited to small case series, with reports disseminated across an array of subspecialty, clinical and molecular journals. In particular, the frequency, management and outcome of paediatric pulmonary fibrosis is not well characterised, unlike in adults, where clear diagnosis and treatment guidelines are available.

Methods and results: This review assesses the current understanding of pulmonary fibrosis in chILD. Based on registry data, we have provisionally estimated the occurrence of fibrosis in various manifestations of chILD, with 47 different potentially fibrotic chILD entities identified. Published evidence for fibrosis in the spectrum of chILD entities is assessed, and current and future issues in management of pulmonary fibrosis in childhood, continuing into adulthood, are considered.

Conclusions: There is a need for improved knowledge of chILD among pulmonologists to optimise the transition of care from paediatric to adult facilities. Updated evidence-based guidelines are needed that incorporate recommendations for the diagnosis and management of immune-mediated disorders, as well as chILD in older children approaching adulthood.

背景:儿童间质性肺病(childhood interstitial lung disease,chILD)是一组罕见的异质性呼吸系统疾病,发病率和死亡率都很高。报告显示,许多确诊为儿童间质性肺病的患者在成年后仍有潜在的进展性或纤维化疾病。在过去的十年中,通过先进的基因检测发现了一些新的实体,从而大大拓宽了 chILD 的病症范围。然而,大多数证据往往局限于小型病例系列,报告散见于一系列亚专科、临床和分子杂志。特别是,儿科肺纤维化的发病率、管理和治疗效果还没有得到很好的描述,不像成人有明确的诊断和治疗指南:本综述评估了目前对儿童期肺纤维化的认识。根据登记数据,我们初步估算了各种表现形式的儿童慢性阻塞性肺疾病的肺纤维化发生率,共发现了47种不同的可能发生肺纤维化的儿童慢性阻塞性肺疾病。我们评估了已发表的有关chILD实体纤维化的证据,并考虑了儿童期肺纤维化管理的当前和未来问题,这些问题将持续到成年期:结论:需要提高肺科医生对chILD的认识,以优化从儿科到成人设施的护理过渡。需要更新以证据为基础的指南,将免疫介导疾病的诊断和管理建议以及即将成年的大龄儿童的 chILD 纳入其中。
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引用次数: 0
Associations of pulmonary microvascular blood volume with per cent emphysema and CT emphysema subtypes in the community: the MESA Lung study. 肺微血管血容量与肺气肿百分比和社区 CT 肺气肿亚型的关系:MESA 肺研究。
IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-11-04 DOI: 10.1136/thorax-2024-222002
Emilia A Hermann, Amin Motahari, Eric A Hoffman, Yifei Sun, Norrina Allen, Elsa D Angelini, Alain G Bertoni, David A Bluemke, Sarah E Gerard, Junfeng Guo, David W Kaczka, Andrew Laine, Erin Michos, Prashant Nagpal, James S Pankow, Coralynn S Sack, Benjamin Smith, Karen Hinckley Stukovsky, Karol E Watson, Artur Wysoczanski, R Graham Barr

Background: Pulmonary microvasculature alterations are implicated in emphysema pathogenesis, but the association between pulmonary microvascular blood volume (PMBV) and emphysema has not been directly assessed at scale, and prior studies have used non-specific measures of emphysema.

Methods: The Multi-Ethnic Study of Atherosclerosis Lung Study invited participants recruited from the community without renal impairment to undergo contrast-enhanced dual-energy CT. Pulmonary blood volume was calculated by material decomposition; PMBV was defined as blood volume in the peripheral 2 cm of the lung. Non-contrast CT was acquired to assess per cent emphysema and novel CT emphysema subtypes, which include the diffuse emphysema subtype and small-airways-related combined bronchitic-apical emphysema subtype. Generalised linear regression models included age, sex, race/ethnicity, body size, smoking, total lung volume and small airway count.

Results: Among 495 participants, 53% were never-smokers and the race/ethnic distribution was 35% white, 31% black, 15% Hispanic and 18% Asian. Mean PMBV was 352±120 mL; mean per cent emphysema was 4.95±4.75%. Lower PMBV was associated with greater per cent emphysema (-0.90% per 100 mL PMBV, 95% CI: -1.29 to -0.51). The association was of larger magnitude in participants with 10 or more pack-years smoking and airflow obstruction, but present among participants with no smoking history or airflow limitation, and was specific to the diffuse CT emphysema subtype (-1.48% per 100 mL PMBV, 95% CI: -2.31 to -0.55).

Conclusion: In this community-based study, lower PMBV was associated with greater per cent emphysema, including in participants without a smoking history or airflow limitation, and was specific to the diffuse CT emphysema subtype.

背景:肺微血管的改变与肺气肿的发病机制有关,但肺微血管血容量(PMBV)与肺气肿之间的关系尚未得到直接的大规模评估,之前的研究使用的是非特异性的肺气肿测量方法:方法:多种族动脉粥样硬化肺研究邀请从社区招募的无肾功能损害的参与者接受对比增强双能 CT 检查。通过材料分解计算肺血容量;PMBV 被定义为肺外围 2 厘米处的血容量。采用非对比 CT 评估肺气肿的百分比和新的 CT 肺气肿亚型,其中包括弥漫性肺气肿亚型和小气道相关性合并支气管尖锐性肺气肿亚型。广义线性回归模型包括年龄、性别、种族/民族、体型、吸烟、肺总量和小气道数量:在 495 名参与者中,53% 的人从不吸烟,种族/族裔分布为白人 35%、黑人 31%、西班牙裔 15%、亚裔 18%。平均肺活量(PMBV)为(352±120)毫升;平均肺气肿百分比为(4.95±4.75)%。较低的 PMBV 与较高的肺气肿百分比相关(每 100 mL PMBV -0.90%,95% CI:-1.29 至 -0.51)。这种关联在吸烟10包年或更多且气流阻塞的参与者中表现得更为明显,但在无吸烟史或气流受限的参与者中也存在这种关联,而且这种关联是弥漫性CT肺气肿亚型所特有的(每100毫升PMBV-1.48%,95% CI:-2.31至-0.55):在这项以社区为基础的研究中,较低的PMBV与较高的肺气肿百分比相关,包括在无吸烟史或气流受限的参与者中,并且与弥漫性CT肺气肿亚型相关。
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引用次数: 0
Journal club 期刊俱乐部
IF 1 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-11-01 DOI: 10.1136/thorax-2024-222463
Anthony W Martinelli
The ACCESS trial ( Lancet Respir Med 2024;12(4):294–304) provides new evidence supporting the use of macrolides in community-acquired pneumonia (CAP). In this prospective, double-blind study, Giamarellos-Bourboulis and colleagues randomised patients admitted with CAP and receiving intravenous antibiotics to addition of either oral clarithromycin or placebo for 7 days. Participants from 18 Greek hospitals were enrolled, with CAP defined as consolidation on chest radiograph with compatible auscultatory findings or consolidation on CT, though a pathogen was only identified in 55% of the study population (most commonly Staphylococcus aureus ). Inclusion criteria limited the study to a subset of hospital patients with systemic inflammation, requiring two positive criteria of systemic inflammatory response syndrome, a sequential organ failure assessment (SOFA) score of≥2, and a procalcitonin of≥0.25 ng/mL. The primary outcome was achievement at day 4 of both an ‘early clinical response’ (≥50% decrease in respiratory symptom score) and an ‘early inflammatory response’ (≥30% decrease in SOFA score and/or procalcitonin decrease by≥80% or to<0.25 ng/mL). This endpoint was met in 68% (n=91) of patients treated with clarithromycin, compared with 38% (n=51) in the placebo group (OR 3.40 (95% CI 2.06 to 5.63), p<0.0001). Secondary analyses revealed that clarithromycin significantly reduced the rate of progression to organ dysfunction and recurrent sepsis, and shortened time to hospital …
ACCESS 试验(Lancet Respir Med 2024;12(4):294-304)提供了支持在社区获得性肺炎(CAP)中使用大环内酯类药物的新证据。在这项前瞻性的双盲研究中,Giamarellos-Bourboulis及其同事将入院接受静脉注射抗生素治疗的CAP患者随机分组,让他们在7天内口服克拉霉素或安慰剂。研究对象来自 18 家希腊医院,CAP 的定义是胸片上的合并症与听诊结果相符或 CT 上的合并症,但只有 55% 的研究对象确定了病原体(最常见的是金黄色葡萄球菌)。纳入标准将研究对象限制在有全身炎症的住院患者中,要求有两个全身炎症反应综合征阳性标准、序贯器官功能衰竭评估(SOFA)评分≥2分、降钙素原≥0.25纳克/毫升。主要结果是在第4天达到 "早期临床反应"(呼吸道症状评分下降≥50%)和 "早期炎症反应"(SOFA评分下降≥30%和/或降钙素原下降≥80%或<0.25纳克/毫升)。在接受克拉霉素治疗的患者中,有68%(91人)达到了这一终点,而在安慰剂组中,只有38%(51人)达到了这一终点(OR 3.40 (95% CI 2.06 to 5.63),P<0.0001)。二次分析表明,克拉霉素能显著降低器官功能障碍和败血症复发率,并缩短住院时间...
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引用次数: 0
Community-based approaches to improve tuberculosis services: observations from preintervention and postintervention surveys in a high TB burden disadvantaged community in India 改善结核病服务的社区方法:从印度一个结核病负担沉重的弱势社区的干预前和干预后调查中观察到的问题
IF 1 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-10-26 DOI: 10.1136/thorax-2024-221446
Jyothi Bhat, Ravendra Kumar Sharma, Rajiv Yadav, M Muniyandi, Prashant Mishra, Samridhi Nigam, Mercy Aparna Latha Lingala, Vikas Gangadhar Rao
An alarmingly high prevalence of tuberculosis (TB) was reported among the Saharia tribe in Madhya Pradesh, India. A community-based intervention study was undertaken to improve TB case finding during 2018–2021. The interventions mainly comprised active case detection through village TB volunteers using advocacy, communication and social mobilisation activities. A preintervention and postintervention survey design was adopted to assess the impact of intervention. The prevalence declined from 1357 (95% CI 1206 to 1527) to 752 (95% CI 646 to 875) per 100 000 population (p<0.001). The study findings highlight the importance of innovative community-based approaches in controlling TB in high burden areas.
据报道,印度中央邦萨哈里亚(Saharia)部落的结核病(TB)发病率高得惊人。在 2018-2021 年期间,开展了一项基于社区的干预研究,以改善结核病病例发现情况。干预措施主要包括通过乡村结核病志愿者利用宣传、沟通和社会动员活动积极发现病例。采用干预前和干预后调查设计来评估干预的影响。干预后,每 10 万人口中的结核病发病率从 1357 例(95% CI 1206 至 1527 例)下降到 752 例(95% CI 646 至 875 例)(p<0.001)。研究结果凸显了以社区为基础的创新方法在高负担地区控制结核病的重要性。
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引用次数: 0
Collagen neoepitopes in sarcoidosis: what do they tell us? 肉样瘤病中的胶原新表位:它们能告诉我们什么?
IF 1 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-10-22 DOI: 10.1136/thorax-2024-222276
Daniel A Culver, Pauline Teresa Lukey
Fibrosis is scarring due to the replacement of tissue architecture by extracellular matrix (ECM), which consists largely of collagen. Scarring progressively destroys organ structure and thereby impairs function. Accumulation of collagen is thought to be due to an increase in production, a reduction in degradation of collagen or a combination of both.1 If so, we might expect the ratio of production to degradation to increase with increasing fibrosis. Biomarkers of type III and VI collagen production (PRO-C3 and PRO-C6) and degradation (C3M and C6M), called neoepitopes, have been developed to measure these processes.1 In diseases such as idiopathic pulmonary fibrosis, where fibrosis is the dominant pathophysiological feature, neoepitope levels align closely with disease progression.2 Whether these collagen markers are relevant in other diseases has been less well explored. In sarcoidosis, fibrosis in affected organs, especially the lungs and heart, accounts for most of the long-term morbidity and mortality that is directly attributable to sarcoidosis itself (rather than due to attempts to treat the disease). Fibrosis in sarcoidosis is thought to occur in the setting of persistent granulomatous inflammation but is likely modulated by other factors besides duration of disease alone since not all patients with chronic sarcoidosis develop substantial fibrosis. A major clinical challenge is to identify whether the dysfunction of an affected organ is predominantly due to granulomatous inflammation or fibrosis. Thus, a blood marker of sarcoidosis fibrosis would be an extremely helpful clinical tool. Recently, Sand and co-workers3 hypothesised that patients with sarcoidosis may have increased plasma levels of collagen neoepitopes and that …
纤维化是由于细胞外基质(ECM)取代了组织结构而形成的瘢痕,细胞外基质主要由胶原蛋白组成。瘢痕会逐渐破坏器官结构,从而损害功能。胶原蛋白的积累被认为是由于胶原蛋白的生成增加、降解减少或两者的共同作用1。1 在特发性肺纤维化等以纤维化为主要病理生理特征的疾病中,新表位水平与疾病的进展密切相关2。在肉样瘤病中,受影响器官(尤其是肺部和心脏)的纤维化是直接归因于肉样瘤病(而非试图治疗疾病)的长期发病率和死亡率的主要原因。肉样瘤病的纤维化被认为是在肉芽肿炎症持续存在的情况下发生的,但除了病程长短之外,还可能受到其他因素的影响,因为并非所有慢性肉样瘤病患者都会出现实质性纤维化。临床面临的一大挑战是如何确定受影响器官的功能障碍主要是由肉芽肿炎症还是纤维化引起的。因此,肉样瘤病纤维化的血液标志物将是一种非常有用的临床工具。最近,桑德和合作者3 假设肉样瘤病患者的血浆中胶原新表位水平可能会升高,并且...
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引用次数: 0
Inequalities in care and the burden of wheeze and asthma in young children from diverse socioeconomic and ethnic backgrounds. 来自不同社会经济和种族背景的幼儿在护理方面的不平等以及喘息和哮喘的负担。
IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-10-16 DOI: 10.1136/thorax-2024-222111
Björn Nordlund
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引用次数: 0
Added complexity to genotype–phenotype relationships in primary ciliary dyskinesia: TAS2R38 as a gene modifier 原发性睫状肌运动障碍基因型与表型关系的复杂性增加:TAS2R38 是一个基因修饰因子
IF 1 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-10-16 DOI: 10.1136/thorax-2024-222333
Katherine Alexandra Despotes, Stephanie D Davis
Primary ciliary dyskinesia (PCD), an inherited motile ciliopathy, is characterised by recurrent upper and lower respiratory tract infections, organ laterality defects, subfertility and neonatal respiratory distress due to impaired ciliary function.1 Over 50 PCD disease-causing genes have been identified that impact the structure and function of the cilia (figure 1, originally in Despotes et al 1). Significant clinical heterogeneity is associated with PCD, in part driven by genotype; genotype–phenotype relationships are an emerging area of great importance within this rare disease.2–4 However, clinical heterogeneity has also been reported among patients with the same genetic variants,3 suggesting that genetic modifiers may play an important role in disease manifestations. In their Thorax paper, Pifferi and colleagues have helped uncover our incomplete understanding of this heterogeneity by evaluating the impact of TAS2R38 polymorphisms within specific PCD genotypes. The authors specifically explored the impact of these polymorphisms on Pseudomonas aeruginosa (PA) infections, lung function and nasal nitric oxide (nNO) levels.5 Figure 1 : The location and function of the 54 currently known disease-causing genes implicated in PCD, originally published in Despotes et al (1). Panel A: Respiratory Epithelial Cell. * DNAH9 and DNAH11 are represented twice (panel A and panel C) as these genes are important in ODA structure at different locations along the axoneme length, as demonstrated in panel A. Panel B: Cilium and Intraflageller Transport. Panel C: Axoneme (in cross-section). The outer doublet A and B microtubules are labeled. The cross-section of the axoneme shows the “9 + …
原发性纤毛运动障碍(PCD)是一种遗传性纤毛运动病,其特点是由于纤毛功能受损而导致反复发生上下呼吸道感染、器官侧位缺陷、不育和新生儿呼吸窘迫。PCD 具有显著的临床异质性,部分原因在于基因型;基因型与表型的关系是这一罕见疾病中一个非常重要的新兴领域。2-4 然而,也有报道称,具有相同基因变异的患者之间也存在临床异质性,3 这表明基因修饰因子可能在疾病表现中起着重要作用。在他们的 Thorax 论文中,Pifferi 及其同事通过评估特定 PCD 基因型中 TAS2R38 多态性的影响,揭示了我们对这种异质性的不完全理解。作者特别探讨了这些多态性对铜绿假单胞菌 (PA) 感染、肺功能和鼻腔一氧化氮 (nNO) 水平的影响。面板 A:呼吸道上皮细胞。* DNAH9 和 DNAH11 表示了两次(A 组和 C 组),因为这些基因在轴丝长度的不同位置对 ODA 结构非常重要,如 A 组所示。面板 C:轴丝(横截面)。外层双微管 A 和 B 已标记。轴丝的横截面显示了 "9 + ...
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引用次数: 0
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Thorax
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