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IF 1 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-08-01 DOI: 10.1136/thorax-2024-222131
Zin Nge Nge Sein
Treatment recommendations for primary spontaneous pneumothorax (PSP) have changed significantly in recent years. The latest guideline by the British Thoracic Society (BTS) has shifted towards ambulatory and conservative management, following the publication of two robust randomised controlled trials (RCTs). Keijzers and colleagues have published a further post-hoc analysis from one of these RCTs, demonstrating that conservative management can safely treat a large primary spontaneous pneumothorax (European Respiratory Journal, 2024; DOI: 10.1183/13993003.00429–2024). This study used the Collins method to determine the size of the pneumothorax. Patients with a sum of interpleural distance>16 cm, equating to≥80% collapse, were defined as having large/complete collapse, and patients with an interpleural distance of 6–16 cm, equating to 32–80% as having medium (<80%) collapse. The primary outcome for conservative vs intervention (radiographic resolution at 8 weeks) was 71% vs 95% in large/complete, and 87% vs 93% in medical-sized pneumothorax (OR 1.8 vs 4.5, P-interaction: 0.10). Adverse events were higher with intervention (41/154) than with conservative (13/162) management, but where not statistically significantly different based on pneumothorax size. This study showed that most patients with a large/complete pneumothorax allocated to conservative management recovered symptomatically and radiographically with shorter hospital length of stay (0.8 …
近年来,原发性自发性气胸(PSP)的治疗建议发生了很大变化。在两项可靠的随机对照试验(RCT)发表后,英国胸科学会(BTS)的最新指南已转向非卧床保守治疗。Keijzers 及其同事发表了对其中一项随机对照试验的进一步事后分析,证明保守治疗可以安全地治疗大面积原发性自发性气胸(《欧洲呼吸杂志》,2024 年;DOI: 10.1183/13993003.00429-2024)。这项研究采用柯林斯法确定气胸的大小。胸膜间距离总和>16厘米(相当于塌陷≥80%)的患者被定义为大/完全塌陷,胸膜间距离为6-16厘米(相当于32-80%)的患者被定义为中等(<80%)塌陷。保守治疗与干预治疗的主要结果(8周时的放射学分辨率)分别为:大型/完全型气胸的71%对95%,医源性大型气胸的87%对93%(OR 1.8对4.5,P-交互作用:0.10)。干预治疗的不良事件发生率(41/154)高于保守治疗的不良事件发生率(13/162),但根据气胸大小的不同,不良事件发生率在统计学上没有显著差异。这项研究表明,大多数接受保守治疗的大气胸/完全性气胸患者在症状和影像学方面都得到了恢复,住院时间更短(0.8 天)。
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引用次数: 0
CD206+ macrophages are relevant non-invasive imaging biomarkers and therapeutic targets in experimental lung fibrosis CD206+ 巨噬细胞是实验性肺纤维化的相关非侵入性成像生物标记物和治疗靶标
IF 1 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-07-20 DOI: 10.1136/thorax-2023-221168
Lenny Pommerolle, Guillaume Beltramo, Leo Biziorek, Marin Truchi, Alexandre Magno Maneschy Dias, Lucile Dondaine, Julie Tanguy, Nicolas Pernet, Victor Goncalves, Alexanne Bouchard, Marie Monterrat, Grégoire Savary, Nicolas Pottier, Kjetil Ask, Martin R J Kolb, Bernard Mari, Carmen Garrido, Bertrand Collin, Philippe Bonniaud, Olivier Burgy, Françoise Goirand, Pierre-Simon Bellaye
Background Interstitial lung diseases (ILDs) include a large number of diseases associated with progressive pulmonary fibrosis (PPF), including idiopathic pulmonary fibrosis (IPF). Despite the rarity of each of the fibrotic ILDs individually, they cumulatively affect a considerable number of patients. PPF is characterised by an excessive collagen deposition leading to functional decline. Objectives Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression. CD206-expressing M2 macrophages are involved in fibrosis progression, and whether they may be relevant therapeutic targets or biomarkers remains an open question. Results In our study, CD206+ lung macrophages were monitored in bleomycin-induced lung fibrosis in mice by combining flow cytometry, scRNAseq and in vivo molecular imaging using a single photon emission computed tomography (SPECT) radiopharmaceutical, 99mTc-tilmanocept. The antifibrotic effect of the inhibition of M2 macrophage polarisation with a JAK inhibitor, tofacitinib, was assessed in vivo. We demonstrate that CD206-targeted in vivo SPECT imaging with 99mTc-tilmanocept was able to accurately detect and quantify the increase in CD206+ macrophages from early to advanced stages of experimental fibrosis and ex vivo in lung biopsies from patients with IPF. CD206-targeted imaging also specifically detected a decrease in CD206+ lung macrophages on nintedanib and tofacitinib treatment. Importantly, early in vivo imaging of CD206+ macrophages allowed the prediction of experimental lung fibrosis progression as well as nintedanib and tofacitinib efficacy. Conclusions These findings indicate that M2 macrophages may be relevant theranostic targets for personalised medicine for patients with PPF. Data are available upon reasonable request.
背景间质性肺疾病(ILD)包括大量与进行性肺纤维化(PPF)相关的疾病,其中包括特发性肺纤维化(IPF)。尽管每种纤维化 ILD 单独发病的情况并不多见,但它们累积起来会影响相当多的患者。PPF 的特点是胶原过度沉积,导致功能衰退。治疗目标 治疗方案仅限于宁替达尼(nintedanib)和吡非尼酮(pirfenidone),这两种药物只能缓解纤维化的进展。表达 CD206 的 M2 巨噬细胞参与了纤维化的进展,它们是否可能成为相关的治疗靶点或生物标志物仍是一个未决问题。结果 我们的研究结合流式细胞术、scRNAseq 和使用单光子发射计算机断层扫描(SPECT)放射性药物 99mTc-tilmanocept 的体内分子成像,监测了博莱霉素诱导的小鼠肺纤维化过程中的 CD206+ 肺巨噬细胞。我们在体内评估了 JAK 抑制剂托法替尼抑制 M2 巨噬细胞极化的抗纤维化效果。我们证明,使用99m锝-替曼诺受体的CD206靶向体内SPECT成像能够准确检测和量化从实验性纤维化早期到晚期的CD206+巨噬细胞的增加情况,以及IPF患者肺活检组织的体内外情况。CD206靶向成像还特异性地检测到了宁替尼和托法替尼治疗后CD206+肺巨噬细胞的减少。重要的是,CD206+巨噬细胞的早期体内成像可以预测实验性肺纤维化的进展以及宁替尼和托法替尼的疗效。结论 这些研究结果表明,M2巨噬细胞可能是PPF患者个性化用药的相关治疗靶点。如有合理要求,可提供相关数据。
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引用次数: 0
Non-cigarette tobacco products, aryl-hydrocarbon receptor repressor gene methylation and smoking-related health outcomes 非卷烟烟草制品、芳基烃受体抑制基因甲基化与吸烟相关的健康后果
IF 1 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-07-20 DOI: 10.1136/thorax-2023-220731
Christina M Eckhardt, Pallavi Balte, Jack E Morris, Surya P Bhatt, David Couper, Jessica Fetterman, Neal Freedman, David R Jacobs, Lifang Hou, Ravi Kalhan, Yongmei Liu, Laura Loehr, Pamela L Lutsey, Joseph E Schwartz, Wendy White, Sachin Yende, Stephanie J London, Tiffany R Sanchez, Elizabeth C Oelsner
Introduction Cigarette smoking leads to altered DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) gene. However, it remains unknown whether pipe or cigar smoking is associated with AHRR methylation. We evaluated associations of non-cigarette tobacco use with AHRR methylation and determined if AHRR methylation was associated with smoking-related health outcomes. Methods Data were pooled across four population-based cohorts that enrolled participants from 1985 to 2002. Tobacco exposures were evaluated using smoking questionnaires. AHRR cg05575921 methylation was measured in peripheral blood leucocyte DNA. Spirometry and respiratory symptoms were evaluated at the time of methylation measurements and in subsequent visits. Vital status was monitored using the National Death Index. Results Among 8252 adults (mean age 56.7±10.3 years, 58.1% women, 40.6% black), 4857 (58.9%) participants used cigarettes and 634 (7.7%) used non-cigarette tobacco products. Exclusive use of non-cigarette tobacco products was independently associated with lower AHRR methylation (−2.44 units, 95% CI −4.42 to −0.45), though to a lesser extent than exclusive use of cigarettes (−6.01 units, 95% CI −6.01 to −4.10). Among participants who exclusively used non-cigarette tobacco products, reduced AHRR methylation was associated with increased respiratory symptom burden (OR 1.60, 95% CI 1.03 to 2.68) and higher all-cause mortality (log-rank p=0.02). Conclusion Pipe and cigar smoking were independently associated with lower AHRR methylation in a multiethnic cohort of US adults. Among users of non-cigarette tobacco products, lower AHRR methylation was associated with poor respiratory health outcomes and increased mortality. AHRR methylation may identify non-cigarette tobacco users with an increased risk of adverse smoking-related health outcomes. Data are available on reasonable request.
导言 吸烟会导致芳基烃受体抑制因子(AHRR)基因的 DNA 甲基化发生改变。然而,吸烟斗或雪茄是否与 AHRR 甲基化有关仍是未知数。我们评估了非卷烟烟草使用与 AHRR 甲基化的关系,并确定 AHRR 甲基化是否与吸烟相关的健康结果有关。方法 我们对 1985 年至 2002 年间四个人群队列的数据进行了汇总。使用吸烟调查问卷评估烟草暴露。对外周血白细胞 DNA 中的 AHRR cg05575921 甲基化进行了测量。在甲基化测量时和随后的访问中对肺活量和呼吸道症状进行了评估。使用国家死亡指数监测生命状态。结果 在 8252 名成人(平均年龄为 56.7±10.3 岁,58.1% 为女性,40.6% 为黑人)中,4857 人(58.9%)使用香烟,634 人(7.7%)使用非香烟烟草制品。完全使用非卷烟烟草制品与较低的 AHRR 甲基化(-2.44 个单位,95% CI -4.42 至 -0.45)独立相关,但程度低于完全使用卷烟(-6.01 个单位,95% CI -6.01 至 -4.10)。在完全使用非卷烟烟草制品的参与者中,AHRR甲基化程度降低与呼吸道症状负担加重(OR 1.60,95% CI 1.03 至 2.68)和全因死亡率升高(对数秩 p=0.02)有关。结论 在美国多种族成年人队列中,吸烟烟和抽雪茄与较低的 AHRR 甲基化程度有独立关联。在非卷烟烟草制品使用者中,AHRR甲基化水平较低与呼吸系统健康状况较差和死亡率增加有关。AHRR甲基化可识别吸烟相关不良健康后果风险增加的非卷烟烟草使用者。如有合理要求,可提供相关数据。
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引用次数: 0
Refractory granulomatous Pneumocystis jirovecii pneumonia masquerading as malignancy 伪装成恶性肿瘤的难治性肉芽肿性肺孢子虫肺炎
IF 1 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-07-20 DOI: 10.1136/thorax-2024-221457
Chi Wan Koo, Ananya Panda, Jennifer Boland Froemming
An elderly female, lifelong non-smoker, with rheumatoid arthritis treated with methotrexate and prednisone for 10 years was referred for evaluation of incidentally detected, randomly distributed pulmonary nodules on a CT performed for pleuritic chest pain and dyspnoea (figure 1A). Subsequent [18F]fluoro-d-glucose (FDG)-positron emission tomography (PET) showed the nodules had increased in size and were FDG-avid (figure 1B). Patient underwent percutaneous biopsy at an external institution with pathology reported to be highly suspicious for lung adenocarcinoma. Figure 1 (A) CT angiogram performed for evaluation of pleuritic chest pain and dyspnoea demonstrated incidental solid, non-calcified left lower lobe subpleural predominant pulmonary nodules (arrow, additional nodules not shown). Note dependent atelectasis presenting as ground-glass opacities. (B) [18F]fluoro-d-glucose (FDG)-positron emission tomography performed 4 months later showed these nodules had more than doubled in size and were FDG-avid (arrow). No additional FDG avidity was detected elsewhere. After an unrevealing bronchoscopy with bronchoalveolar lavage, the patient was referred to our institution for further care. Re-evaluation of the previous percutaneous …
一名终生不吸烟的老年女性,患有类风湿性关节炎,接受甲氨蝶呤和泼尼松治疗 10 年,因胸膜炎性胸痛和呼吸困难而进行 CT 检查,偶然发现随机分布的肺部结节(图 1A)。随后进行的[18F]氟-d-葡萄糖(FDG)-正电子发射断层扫描(PET)显示,结节增大且与 FDG 相关(图 1B)。患者在一家外部机构接受了经皮活检,病理报告高度怀疑为肺腺癌。图 1 (A) 为评估胸膜炎性胸痛和呼吸困难而进行的 CT 血管造影显示,患者左下叶胸膜下偶见实性、非钙化的肺结节(箭头,其他结节未显示)。注意依赖性肺不张表现为磨玻璃不透光。(B) 4 个月后进行的[18F]氟-d-葡萄糖(FDG)-正电子发射断层扫描显示,这些结节的大小增加了一倍多,并且与 FDG 相关(箭头)。其他部位未检测到额外的 FDG 阳性。在进行支气管镜检查和支气管肺泡灌洗未发现异常后,患者被转到我院接受进一步治疗。重新评估之前的经皮...
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引用次数: 0
Integrated disease management: good news but more work to do. 综合疾病管理:好消息,但还有更多工作要做。
IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-07-16 DOI: 10.1136/thorax-2024-221754
Christine R Jenkins
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引用次数: 0
Respiratory rescue is the new frontier. 呼吸救援是新领域。
IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-07-16 DOI: 10.1136/thorax-2024-221830
Sarath Ranganathan
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引用次数: 0
Quantifying sustained health system benefits of primary care-based integrated disease management for COPD: a 6-year interrupted time series study. 量化基于初级保健的慢性阻塞性肺病综合疾病管理对医疗系统的持续益处:一项为期 6 年的间断时间序列研究。
IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-07-16 DOI: 10.1136/thorax-2023-221211
Christopher Licskai, Anna Hussey, Véronique Rowley, Madonna Ferrone, Zihang Lu, Kimball Zhang, Emilie Terebessy, Andrew Scarffe, Shannon Sibbald, Cathy Faulds, Tim O'Callahan, Teresa To

Background: Severe exacerbation of chronic obstructive pulmonary disease (COPD) is a trajectory-changing life event for patients and a major contributor to health system costs. This study evaluates the real-world impact of a primary care, integrated disease management (IDM) programme on acute health service utilisation (HSU) in the Canadian health system.

Methods: Interrupted time series analysis using retrospective health administrative data, comparing monthly HSU event rates 3 years prior to and 3 years following the implementation of COPD IDM. Primary outcomes were COPD-related hospitalisation and emergency department (ED) visits. Secondary outcomes included hospital bed days and all-cause HSU.

Results: There were 2451 participants. COPD-related and all-cause HSU rates increased in the 3 years prior to IDM implementation. With implementation, there was an immediate decrease (month 1) in COPD-related hospitalisation and ED visit rates of -4.6 (95% CI: -7.76 to -1.39) and -6.2 (95% CI: -11.88, -0.48) per 1000 participants per month, respectively, compared with the counterfactual control group. After 12 months, COPD-related hospitalisation rates decreased: -9.1 events per 1000 participants per month (95% CI: -12.72, -5.44) and ED visits -19.0 (95% CI: -25.50, -12.46). This difference nearly doubled by 36 months. All-cause HSU also demonstrated rate reductions at 12 months, hospitalisation was -10.2 events per 1000 participants per month (95% CI: -15.79, -4.44) and ED visits were -30.4 (95% CI: -41.95, -18.78).

Conclusions: Implementation of COPD IDM in a primary care setting was associated with a changed trajectory of COPD-related and all-cause HSU from an increasing year-on-year trend to sustained long-term reductions. This highlights a substantial real-world opportunity that may improve health system performance and patient outcomes.

背景:慢性阻塞性肺病(COPD)的严重恶化是改变患者生活轨迹的事件,也是医疗系统成本的主要来源。本研究评估了初级保健、综合疾病管理(IDM)计划对加拿大医疗系统中急性医疗服务利用率(HSU)的实际影响:方法:使用回顾性健康管理数据进行间断时间序列分析,比较慢性阻塞性肺病综合疾病管理计划实施前 3 年和实施后 3 年的每月医疗服务使用率。主要结果是慢性阻塞性肺病相关的住院和急诊就诊。次要结果包括住院天数和全因 HSU:共有 2451 名参与者。在实施 IDM 之前的 3 年中,慢性阻塞性肺病相关住院率和全因 HSU 率均有所上升。与反事实对照组相比,实施 IDM 后,慢性阻塞性肺病相关住院率和急诊室就诊率立即下降(第 1 个月),分别为每月每 1000 名参与者-4.6(95% CI:-7.76 至-1.39)和-6.2(95% CI:-11.88,-0.48)。12 个月后,慢性阻塞性肺病相关住院率有所下降:与慢性阻塞性肺病相关的住院率在 12 个月后有所下降:每 1000 名参与者每月的住院率为-9.1(95% CI:-12.72, -5.44),急诊室就诊率为-19.0(95% CI:-25.50, -12.46)。这一差异在 36 个月后几乎翻了一番。12 个月后,全因 HSU 的发病率也有所下降,每 1000 名参与者每月的住院率为-10.2(95% CI:-15.79, -4.44),急诊室就诊率为-30.4(95% CI:-41.95, -18.78):在基层医疗机构实施慢性阻塞性肺疾病 IDM 与慢性阻塞性肺疾病相关和全因 HSU 的变化轨迹有关,即从逐年增加的趋势转变为持续的长期减少。这凸显出现实世界中存在着巨大的机会,可以改善医疗系统的绩效和患者的预后。
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引用次数: 0
Physical activity and body mass related to catch-up lung function growth in childhood: a population-based accelerated cohort study. 体力活动和体重与儿童期肺功能追赶性增长的关系:一项基于人群的加速队列研究。
IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-07-16 DOI: 10.1136/thorax-2022-219666
Sarah Koch, Gabriela Prado Peralta, Anne-Elie Carsin, Alicia Abellan, Celine Roda, Maties Torrent, Carmen Iñiguez, Ferran Ballester, Amparo Ferrero, Carlos Zabaleta, Aitana Lertxundi, Mònica Guxens, Martine Vrijheid, Jordi Sunyer, Maribel Casas, Judith Garcia-Aymerich

Objective: The existence of catch-up lung function growth and its predictors is uncertain. We aimed to identify lung function trajectories and their predictors in a population-based birth cohort.

Methods: We applied group-based trajectory modelling to z-scores of forced expiratory volume in 1 second (zFEV1) and z-scores of forced vital capacity (zFVC) from 1151 children assessed at around 4, 7, 9, 10, 11, 14 and 18 years. Multinomial logistic regression models were used to test whether potential prenatal and postnatal predictors were associated with lung function trajectories.

Results: We identified four lung function trajectories: a low (19% and 19% of the sample for zFEV1 and zFVC, respectively), normal (62% and 63%), and high trajectory (16% and 13%) running in parallel, and a catch-up trajectory (2% and 5%) with catch-up occurring between 4 and 10 years. Fewer child allergic diseases and higher body mass index z-score (zBMI) at 4 years were associated with the high and normal compared with the low trajectories, both for zFEV1 and zFVC. Increased children's physical activity during early childhood and higher zBMI at 4 years were associated with the catch-up compared with the low zFEV1 trajectory (relative risk ratios: 1.59 per physical activity category (1.03-2.46) and 1.47 per zBMI (0.97-2.23), respectively). No predictors were identified for zFVC catch-up growth.

Conclusion: We found three parallel-running and one catch-up zFEV1 and zFVC trajectories, and identified physical activity and body mass at 4 years as predictors of zFEV1 but not zFVC catch-up growth.

目的:是否存在肺功能追赶性增长及其预测因素尚不确定。我们旨在确定基于人群的出生队列中的肺功能轨迹及其预测因素:我们对 1151 名分别在 4、7、9、10、11、14 和 18 岁左右接受评估的儿童的 1 秒用力呼气容积 (zFEV1) z 值和用力肺活量 (zFVC) z 值进行了分组轨迹建模。我们使用多叉逻辑回归模型来检验潜在的产前和产后预测因素是否与肺功能轨迹相关:我们发现了四种肺功能轨迹:低轨迹(zFEV1和zFVC分别占样本的19%和19%)、正常轨迹(62%和63%)和高轨迹(16%和13%)并行,以及追赶轨迹(2%和5%),追赶发生在4至10岁之间。就 zFEV1 和 zFVC 而言,高轨迹和正常轨迹与低轨迹相比,儿童过敏性疾病较少,4 岁时体重指数 z 值(zBMI)较高。与低zFEV1轨迹相比,儿童早期体力活动的增加和4岁时较高的zBMI与追赶轨迹相关(相对风险比:1.59/体力活动类别(zBMI)):每个体力活动类别的相对风险比为 1.59(1.03-2.46),每个 zBMI 的相对风险比为 1.47(0.97-2.23))。没有发现zFVC追赶增长的预测因素:我们发现了三个并行和一个追赶的 zFEV1 和 zFVC 增长轨迹,并确定了 4 年时体力活动和体重是 zFEV1 增长的预测因素,但不是 zFVC 追赶增长的预测因素。
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引用次数: 0
Children’s interstitial lung disease (chILD): less rare than we thought? 儿童间质性肺病 (chILD):没有我们想象的那么罕见?
IF 1 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-07-16 DOI: 10.1136/thorax-2024-221951
Andrew Bush, Lawrence Nogee
The presentation of childhood interstitial lung disease (chILD) is non-specific,1 and chILD is usually low on the list of diagnoses in children with combinations of respiratory symptoms, feeding difficulties and failure to thrive. However, if a diagnosis is not considered, it will never be made. In this issue of the Journal , Fletcher et al describe nearly 800 French children, suggesting that chILD may not be as rare as once thought.2 The French RespiRare network has long been systematically collecting incidence and prevalence data of rare diseases, and in this excellent publication, they report a chILD prevalence of 44/million children (95% CI 40.76 to 47.46) and thus a computed incidence of 4.4/million children (95% CI 3.44 to 5.56). This is similar to a recent Spanish study,3 and far greater than previous studies,4 5 which were likely underestimated due to incomplete ascertainment. The major strength of the present study is the collection of data from a well-organised network spanning the whole of France, with multiple different ways of ensuring chILDs were captured. Despite this, cases may still have been missed. For example, it is a surprise that they reported not a single ILD related to e-cigarettes.6 Newborns with rapidly progressive disease due to …
儿童间质性肺病(children interstitial lung disease,chILD)的表现无特异性1,对于合并呼吸道症状、喂养困难和发育不良的儿童,chILD 通常在诊断名单中排名靠后。然而,如果不考虑诊断,就永远不会做出诊断。法国RespiRare网络长期以来一直在系统地收集罕见病的发病率和流行率数据,在这篇出色的文章中,他们报告了罕见病的流行率为44/百万儿童(95% CI 40.76-47.46),因此计算出的发病率为4.4/百万儿童(95% CI 3.44-5.56)。这与西班牙最近的一项研究3 相似,也远远高于之前的研究4 5 ,而之前的研究很可能由于不完全确定而低估了发病率。本研究的主要优势在于从一个覆盖全法国的组织良好的网络中收集数据,并通过多种不同方式确保chILDs被采集到。尽管如此,仍有可能遗漏病例。例如,令人惊讶的是,他们没有报告一起与电子烟有关的 ILD。
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引用次数: 0
Undertreating cardiovascular disease in people with chronic obstructive pulmonary disease (COPD). 对慢性阻塞性肺病(COPD)患者的心血管疾病治疗不足。
IF 9 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2024-07-16 DOI: 10.1136/thorax-2023-221141
Andrea S Gershon, Alina Blazer, Dennis Ko
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引用次数: 0
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Thorax
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