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Neutrophil extracellular traps are associated with airways inflammation and increased severity of lung disease in Cystic Fibrosis 中性粒细胞胞外捕获物与囊性纤维化患者气道炎症和肺病严重程度增加有关
Pub Date : 2024-07-18 DOI: 10.1183/23120541.00312-2024
S. Law, G. Hardisty, J. Gillan, Nicola J Robinson, Donald J Davidson, Moira KB Whyte, Ian Dransfield, Robert D Gray
Cystic Fibrosis (CF) is characterised by inflammatory lung disease and large numbers of airways neutrophils. In health, neutrophils undergo apoptosis and removal from the airway. Since CF neutrophils are known to engage in apoptosis less efficiently, we wanted to assess whether alternative forms of neutrophil clearance such as NETosis were prominent in the CF airway.Sputum and blood were collected from 45 CF and 15 healthy control (HC) participants. Neutrophil morphology and biochemical properties were assessed in CF and HC sputum. Neutrophil Extracellular Traps (NETs) were measured by a novel histone-calprotectin ELISA. NET levels were compared to established measurements of airway inflammation. CF participants were followed up for one year and number of exacerbations recorded. Neutrophil and macrophage co-culture experiments were undertaken with cells from CF and HC.Neutrophil numbers were significantly higher in CF and associated with abnormal morphology. Several inflammatory mediators were elevated in CF sputum, as was cell-free DNA. This was highly correlated with sputum calprotectin, a known NET associated protein. Using a Histone/Calprotectin NETs ELISA, we demonstrated higher levels of NETs in the CF airway. CF participants treated with DNase had less sputum NETs, and in neutrophil/macrophage co-culture experiments, DNase effectively attenuated the pro-inflammatory potential of NETs, suggesting a previously unrecognised anti-inflammatory role for this treatment.NETs in the CF airway are associated with increased levels of inflammatory mediators and more severe lung disease. NETs effects on macrophages can be blocked by DNase, suggesting an anti-inflammatory role for this treatment in CF.
囊性纤维化(CF)的特征是肺部炎症和大量气道中性粒细胞。在健康状态下,中性粒细胞会发生凋亡并从气道中清除。众所周知,CF 中性粒细胞凋亡的效率较低,因此我们希望评估中性粒细胞清除的替代形式(如NETosis)在 CF 气道中是否突出。我们收集了 45 名 CF 患者和 15 名健康对照组(HC)患者的痰液和血液,对 CF 和 HC 痰液中的中性粒细胞形态和生化特性进行了评估。中性粒细胞胞外捕获物(NET)通过新型组蛋白-钙保护蛋白 ELISA 进行测量。NET水平与气道炎症的既定测量结果进行了比较。对 CF 参与者进行了为期一年的随访,并记录了病情恶化的次数。用来自CF和HC的细胞进行了中性粒细胞和巨噬细胞共培养实验。CF 痰中的几种炎症介质以及细胞游离 DNA 均升高。这与痰中的钙蛋白高度相关,钙蛋白是一种已知的NET相关蛋白。通过组蛋白/钙蛋白 NET 酶联免疫吸附试验,我们发现 CF 气道中的 NET 水平较高。在中性粒细胞/巨噬细胞共培养实验中,DNase 能有效减弱 NETs 的促炎潜能,这表明这种治疗方法具有以前未被发现的抗炎作用。CF 气道中的 NETs 与炎症介质水平升高和更严重的肺部疾病有关。NETs对巨噬细胞的影响可被DNase阻断,这表明这种疗法在CF中具有抗炎作用。
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引用次数: 0
Pulmonary fibrosis in patients with auto-immune pulmonary alveolar proteinosis: a retrospective nationwide cohort study 自身免疫性肺泡蛋白沉积症患者的肺纤维化:一项全国性回顾性队列研究
Pub Date : 2024-07-18 DOI: 10.1183/23120541.00314-2024
Yoann Guirriec, D. Luque-Paz, Gontran Bernard, Axelle Mabo, M. Kerjouan, Cédric Ménard, Delphine Monnier, Hilario Nunes, Yurdagul Uzunhan, M. Reynaud-Gaubert, J. Bermudez, Raphaël Borie, B. Crestani, J. Traclet, L. Wémeau-Stervinou, Cécile Chenivesse, E. Gomez, G. Prévôt, Arnaud Bourdin, B. Bondue, Anne Bergeron, Vincent Cottin, Mathieu Lederlin, S. Jouneau
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease that may progress toward pulmonary fibrosis. Data about fibrosis prevalence and risk factors are lacking.In this retrospective multicentric nationwide cohort, we included patients newly diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected from medical record, using a standardized questionnaire.Sixty-one patients were included in the final analysis. We identified 5 patients (8%) with fibrosis on initial CT and 16 patients (26%) with fibrosis on final CT after a median time of 3.6 years. Dust exposure was associated with pulmonary fibrosis occurrence (OR=4.3; p=0.038).aPAP patients treated with whole lung lavage (WLL), rituximab, or GM-CSF therapy did not have more fibrotic evolution than patients who did not receive these treatments (n=25/45, 57%versusn=10/16, 62%, p=0.69). All-cause mortality was significantly higher in fibrotic than in non-fibrotic cases: n=4/16, 25%versusn=2/45, 4.4%, p=0.036 respectively.In our population, a quarter of aPAP patients progressed toward pulmonary fibrosis. Dust exposure seems to be an important factor associated with this complication. More studies are needed to analyse precisely the impact of dust exposure impact, especially silica, in patients with aPAP.
自身免疫性肺泡蛋白沉着症(aPAP)是一种罕见疾病,可发展为肺纤维化。在这项回顾性多中心全国性队列研究中,我们纳入了2008年至2018年间在法国和比利时新诊断出的aPAP患者。通过标准化问卷从病历中收集数据。我们发现5名患者(8%)在初次CT检查中发现肺纤维化,16名患者(26%)在中位3.6年后的最终CT检查中发现肺纤维化。接受全肺灌洗(WLL)、利妥昔单抗或 GM-CSF 治疗的 aPAP 患者与未接受这些治疗的患者相比,其纤维化演变程度并不更高(n=25/45,57%vsn=10/16,62%,p=0.69)。纤维化病例的全因死亡率明显高于非纤维化病例:分别为 n=4/16、25%versn=2/45、4.4%,p=0.036。粉尘暴露似乎是导致这种并发症的一个重要因素。需要进行更多的研究,以准确分析粉尘暴露(尤其是二氧化硅)对心肺复苏患者的影响。
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引用次数: 0
The prevalence and implications of depression and anxiety in patients with bronchiectasis: a systematic review and meta-analysis 支气管扩张患者抑郁和焦虑的患病率及其影响:系统回顾和荟萃分析
Pub Date : 2024-07-18 DOI: 10.1183/23120541.00248-2024
Min-Seok Chang, Hyun-Jung Kim, Ji-Ho Lee
Comorbidities significantly affect bronchiectasis prognosis. Depression and anxiety are frequently encountered psychological comorbidities that have the greatest impact on bronchiectasis. This review aimed to identify the prevalence of depression and anxiety and describe their implications on bronchiectasis.Three databases were searched from inception to October 2023 for studies reporting the prevalence and/or clinical implications of depression and anxiety in patients with bronchiectasis. Two independent reviewers rated the quality of the evidence presented in the studies using the risk of bias tool for prevalence studies.Of the 50 studies identified, 17 studies with 2637 patients were included. The overall risk of bias was classified as low (10 studies) or moderate (seven studies). The pooled prevalence of depression and anxiety was 31% (95% CI: 24%–38%) and 34% (95% CI: 28%–40%), respectively. Depression was significantly higher in female compared to male patients (risk difference: 10%; 95% CI: 0%–21%) and associated with bronchiectasis exacerbation (adjusted odds ratio: 1.72; 95% CI: 1.28–2.15). Depression and anxiety are closely associated with poor health-related quality of life (HRQOL). However, clinical outcomes including dyspnea symptoms, severity index, computed tomography score, lung function, and physical activity were not associated with depression or anxiety.This study revealed a high prevalence of depression and anxiety among patients with bronchiectasis. Depression was more prevalent in females and is significantly associated with bronchiectasis exacerbation. Depression and anxiety were associated with poor HRQOL.
合并症严重影响支气管扩张症的预后。抑郁和焦虑是常见的心理并发症,对支气管扩张症的影响最大。本综述旨在确定抑郁和焦虑的患病率,并描述其对支气管扩张症的影响。从开始到2023年10月,我们在三个数据库中检索了报告支气管扩张症患者抑郁和焦虑患病率和/或临床影响的研究。两位独立审稿人使用流行病学研究的偏倚风险工具对研究中提供的证据进行了质量评级。在确定的 50 项研究中,共纳入了 17 项研究,涉及 2637 名患者。总体偏倚风险分为低度(10 项研究)或中度(7 项研究)。抑郁和焦虑的汇总患病率分别为 31% (95% CI: 24%-38%) 和 34% (95% CI: 28%-40%) 。与男性患者相比,女性患者的抑郁症发病率明显更高(风险差异:10%;95% CI:0%-21%),并且与支气管扩张加重有关(调整后的几率比:1.72;95% CI:1.28-2.15)。抑郁和焦虑与健康相关生活质量(HRQOL)低下密切相关。然而,包括呼吸困难症状、严重程度指数、计算机断层扫描评分、肺功能和体力活动在内的临床结果与抑郁或焦虑无关。该研究显示,支气管扩张患者中抑郁和焦虑的发病率较高,女性抑郁患者较多,且抑郁与支气管扩张加重有显著相关性。抑郁和焦虑与不良的 HRQOL 有关。
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引用次数: 0
Long-term dupilumab efficacy in type 2 asthma regardless of baseline characteristics 2型哮喘的长期杜匹单抗疗效与基线特征无关
Pub Date : 2024-07-18 DOI: 10.1183/23120541.00188-2024
Michael E. Wechsler, L. Rogers, G. Canonica, Arnaud Bourdin, A. Altincatal, Megan Hardin, X. Soler, Paul J. Rowe, Y. Deniz, H. Sacks, J. Jacob-Nara
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引用次数: 0
Barriers and enablers of physical activity and its association with daily steps after hospitalisation for a COPD exacerbation: what patients say matters 慢性阻塞性肺疾病加重住院后体育锻炼的障碍和促进因素及其与每日步数的关系:患者的意见很重要
Pub Date : 2024-07-11 DOI: 10.1183/23120541.00216-2024
Beatriz Valeiro, Esther Rodríguez, Jaume Ferrer, A. Pasarín, Jordi Ibañez, M. Ramon
Exacerbations of chronic obstructive pulmonary disease (COPD) decrease physical activity (PA). PA interventions after these events are desirable but have had mixed results. Understanding the barriers and enablers of PA may help to improve their results. We aimed to assess the barriers and enablers of PA after COPD exacerbation and its association with daily steps.Cross-sectional analysis of patients with COPD enrolled during a hospitalisation for an exacerbation. PA was measured with an accelerometer for 7 days after discharge. Patients completed an ad-hoc 6-point Likert-scale questionnaire about 13 barriers and 9 enablers of PA. We analysed the association between each item and patients’ daily step counts.46 patients with FEV1%pred (mean (sd)) of 48.6 (15.9) completed the assessments. They were 65 (10) years old, spent 8 (2) days hospitalised, and walked 5633 (3314) steps·day−1after discharge. The patients who reported “breathlessness” (median (p25-p75)) (3813 (2664–5639)versus5549 (3692–9984), p 0.034) and “low mood” (3813 (2456–5471)versus5426 (3612–8942), p 0.047) as barriers(yes (≥2/6) versus no (<2/6) responders, respectively)took statistically fewer daily steps; whereas if they considered “PA as healthy” as an enabler walked statically more (5085 (3538–8703)versus2760 (2271–5298), p 0.031).some barriers and enablers of PA reported by patients after a COPD exacerbation relate to daily steps. Assessing PA barriers and enablers could be useful to improve future PA interventions after these events.
慢性阻塞性肺病(COPD)病情加重会减少体力活动(PA)。在这些事件发生后进行体育锻炼干预是可取的,但效果不一。了解体育锻炼的障碍和促进因素可能有助于改善干预效果。我们的目的是评估慢性阻塞性肺病恶化后进行体育锻炼的障碍和促进因素,以及体育锻炼与每日步数的关系。在出院后的 7 天内,使用加速度计对患者的 PA 进行了测量。患者填写了一份6点李克特量表的临时问卷,内容涉及13项运动障碍和9项运动促进因素。我们分析了每个项目与患者每日步数之间的关联。46 名患者完成了评估,他们的 FEV1%pred 值(平均值(sd))为 48.6(15.9)。他们的年龄为 65(10)岁,住院 8(2)天,出院后每天步行 5633(3314)步。报告 "呼吸困难"(中位数(p25-p75))(3813(2664-5639)对 5549(3692-9984),p 0.034)和 "情绪低落"(3813(2456-5471)对 5426(3612-8942),p 0.而如果他们认为 "PA 是健康的 "是一种促进因素,那么他们的日行走步数就会增加(5085 (3538-8703)versus2760 (2271-5298),P 0.031)。对患者在慢性阻塞性肺病加重后进行自我锻炼的障碍和促进因素进行评估,将有助于改进未来对这些事件进行的自我锻炼干预。
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引用次数: 0
Extracellular vesicles in sputum of children with cystic fibrosis pulmonary exacerbations 囊性纤维化肺恶化儿童痰中的胞外囊泡
Pub Date : 2024-07-11 DOI: 10.1183/23120541.00547-2024
E. Ben-Meir, Lina Antounians, Shafinaz Eisha, F. Ratjen, Augusto Zani, Hartmut Grasemann
The aim of this study was to quantify mediators of neutrophilic inflammation within airway extracellular vesicles (EVs) of children treated for a cystic fibrosis (CF) pulmonary exacerbation (PEx).EVs were isolated from stored sputum samples collected before and after antibiotic therapy for PEx between 2011–2013, and characterised by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Western blot analysis of EV protein extracts was used for EV canonical protein markers CD63, CD9, and flotillin-1 (FLOT1), as well as neutrophil elastase (NE), myeloperoxidase (MPO) and interleukin-8. EV content of NE and MPO was expressed as ratios of NE/FLOT1 and MPO/FLOT1 protein band densities.Sputum samples from 21 children aged 13.3 (range 8.0–17.0) years were analysed. NTA showed high concentrations of particles at the size of small EVs (50–200 nm), and typical EV morphology was confirmed by TEM. CD63, CD9 and FLOT1 was detectable in all samples. Median (IQR) NE/FLOT1 increased from 2.46 (1.68–5.25) before to 6.83 (3.89–8.89, p<0.001) after PEx therapy and MPO/FLOT1 from 2.30 (1.38–4.44) to 5.76 (3.45–6.94, p<0.01), while EV size remained unchanged. Improvement in lung function (ppFEV1) with PEx therapy correlated with NE EV content (r=0.657, p=0.001).Airways of children with CF contain EVs that carry NE and MPO as cargo. The lower NE and MPO content at the time of PEx compared to after therapy and the correlation with pulmonary function suggest both a functional role of EVs in CF airway inflammation and potential as a biomarker to monitor CF lung disease.
本研究旨在量化因囊性纤维化(CF)肺部恶化(PEx)而接受治疗的儿童气道细胞外囊泡(EV)中的中性粒细胞炎症介质。EV是从2011-2013年间因PEx而接受抗生素治疗前后收集的贮存痰液样本中分离出来的,并通过纳米颗粒追踪分析(NTA)和透射电子显微镜(TEM)对其进行了表征。对 EV 蛋白提取物进行了 Western 印迹分析,以检测 EV 的典型蛋白标记物 CD63、CD9、flotillin-1 (FLOT1),以及中性粒细胞弹性蛋白酶 (NE)、髓过氧化物酶 (MPO) 和白细胞介素-8。NE和MPO的EV含量以NE/FLOT1和MPO/FLOT1蛋白条带密度的比率表示。NTA显示出高浓度的小EV颗粒(50-200 nm),TEM证实了典型的EV形态。所有样本均可检测到 CD63、CD9 和 FLOT1。PEx治疗后,NE/FLOT1的中位数(IQR)从治疗前的2.46(1.68-5.25)增加到6.83(3.89-8.89,p<0.001),MPO/FLOT1从2.30(1.38-4.44)增加到5.76(3.45-6.94,p<0.01),而EV的大小保持不变。PEx疗法对肺功能(ppFEV1)的改善与NE EV含量相关(r=0.657,p=0.001)。与治疗后相比,PEx治疗时的NE和MPO含量较低,且与肺功能相关,这表明EVs在CF气道炎症中发挥着功能性作用,并有可能成为监测CF肺部疾病的生物标记物。
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引用次数: 0
Matrix metalloprotease-7 is associated with post-COVID persistent lung abnormalities. 基质金属蛋白酶-7 与 COVID 后持续性肺部异常有关。
Pub Date : 2024-07-11 DOI: 10.1183/23120541.00266-2024
I. Buendía-Roldán, L. Chávez-Galán, H. Aguilar-Duran, Andy Ruiz, R. Falfán-Valencia, G. Pérez-Rubio, A. Pardo, M. Selman
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引用次数: 0
Abnormal breathing pattern features in chronic refractory cough 慢性难治性咳嗽的异常呼吸模式特征
Pub Date : 2024-07-11 DOI: 10.1183/23120541.00416-2024
Jordan Jeffery, A. Vertigan, Sarah L. Bone, Peter G Gibson
Chronic refractory cough (CRC) is a challenging condition that responds to speech pathology intervention. Clinical observation suggests abnormal breathing patterns occur in CRC and may be indirectly addressed as part of behavioural treatment, yet breathing pattern changes in CRC are poorly understood. The aims of this study were to (1) describe breathing patterns in patients with CRC, (2) compare breathing pattern features between patients with CRC and inducible laryngeal obstruction (ILO), and (3) estimate the effect of breathing pattern features on clinical measures of laryngeal sensory and motor dysfunction.This retrospective cross sectional observational study included 634 patients with CRC or ILO. A file audit of speech pathology assessment data was undertaken. Analysis of self-reported laryngeal symptoms (viaquestionnaires) and clinical assessment of voice and breathing of those with CRC and ILO was conducted.Most participants with CRC (73%) demonstrated at least one abnormal breathing pattern feature. The most common feature was thoracic breathing (69%) followed by oral breathing (33%). The type and prevalence of abnormal breathing patterns were similar between CRC and ILO. Abnormal breathing patterns were associated with reduced maximum phonation time (MPT), however there was no association between these features and laryngeal hypersensitivity questionnaire scores.Abnormal breathing features are common in patients with CRC and are not significantly different from those occurring in ILO. There is some association between abnormal breathing features and MPT, suggesting impairment of laryngeal motor function. Conversely, there is no association between abnormal breathing features and laryngeal hypersensitivity.
慢性难治性咳嗽(CRC)是一种具有挑战性的病症,对语言病理学干预有反应。临床观察表明,CRC 会出现异常呼吸模式,可作为行为治疗的一部分间接解决,但人们对 CRC 的呼吸模式变化知之甚少。本研究的目的是:(1) 描述 CRC 患者的呼吸模式;(2) 比较 CRC 患者和诱发性喉阻塞 (ILO) 患者的呼吸模式特征;(3) 评估呼吸模式特征对喉感觉和运动功能障碍临床测量的影响。这项回顾性横断面观察研究纳入了 634 名 CRC 或 ILO 患者,并对语言病理学评估数据进行了档案审核。这项回顾性横断面观察研究共纳入了 634 名 CRC 或 ILO 患者,对他们的语言病理学评估数据进行了档案审核,并对 CRC 和 ILO 患者自我报告的喉部症状(通过问卷调查)以及语音和呼吸的临床评估进行了分析。最常见的特征是胸式呼吸(69%),其次是口腔呼吸(33%)。CRC 和 ILO 的异常呼吸模式类型和发生率相似。异常呼吸模式与最大发音时间(MPT)缩短有关,但这些特征与喉过敏性问卷评分之间没有关联。异常呼吸特征与 MPT 之间存在一定联系,这表明喉部运动功能受损。相反,异常呼吸特征与喉头过敏之间没有关联。
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引用次数: 0
Questionnaire assessed genotypes and associations with symptoms in primary ciliary dyskinesia 调查问卷评估原发性睫状肌运动障碍的基因型及其与症状的关系
Pub Date : 2024-07-11 DOI: 10.1183/23120541.00288-2024
Esl Pedersen, M. Goutaki, L. Schreck, B. Rindlisbacher, L. Dixon, Jane S Lucas, C. Kuehni
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引用次数: 0
Effectiveness of ICS/LABA and LAMA/LABA in COPD due to Biomass ICS/LABA 和 LAMA/LABA 在慢性阻塞性肺病中的疗效,因生物量而异
Pub Date : 2024-07-04 DOI: 10.1183/23120541.00154-2024
A. Ramírez-Venegas, F. Montiel-Lopez, R. Robles-Hernández, Bartolome R Celli, R. Sansores, Maricruz Cassou-Martínez, J. L. P. Lara-Albisua, Claudia González-González, M. E. Mayar-Maya, Aloisa P. Hernández-Morales, R. Hernández-Zenteno, R. Falfán-Valencia, Ireri Thirión-Romero, Oliver Pérez-Bautista, Rogelio Pérez-Padilla
Chronic obstructive pulmonary disease due to biomass exposure (COPD-B) is highly prevalent in low-and middle-income countries, and there are no clinical trials designed to evaluate the effectiveness of the treatments currently recommended for patients with COPD due to cigarette smoking (COPD-C). The purpose of the study was to compare the efficacy of Fluticasone Furoate/Vilanterol (FF/V) 100/25 μg and Umeclidinium/Vilanterol (U/V) 62.5/25 μg on the rate of exacerbations, the time to first exacerbation, on dyspnea, health-related quality of life (HRQL) and forced expiratory volume during the first second (FEV1) and inspiratory capacity (IC) during six months in patients with COPD-B and COPD-C, at a third level referral center in Mexico City.A pilot, single-center, open-label, parallel-group study included 132 patients with a history of at least two exacerbations. They were randomised to receive one of four treatment groups: 33 COPD-B patients received FF/VI 100/25 μg, 31 COPD-B patients received UMEC/VI 62.5/25 μg, 34 COPD-C patients received FF/V, and 34 received UMEC/VI.There were no differences in exacerbation rates between patients receiving FF/VI or UMEC/VI in either the COPD-B [0.07 (CI 95%, 0.03–0.13), 0.06 (CI 95%, 0.03–0.12] or COPD-C group [0.06 (CI 95%, 0.04–0.11); 0.08 (CI 95%, 0.05–0.13)], nor in the time of first exacerbation, nor FEV1and IC. All groups showed improvement in dyspnea and HRQL, independently of medication used.Among patients with COPD-B and COPD-C with a history of exacerbation, FF/VI was equally effective as UMEC/VI in preventing exacerbations and improving dyspnea and HRQL.
生物质暴露引起的慢性阻塞性肺病(COPD-B)在中低收入国家发病率很高,目前还没有针对吸烟引起的慢性阻塞性肺病(COPD-C)患者推荐的治疗方法的有效性进行评估的临床试验。这项研究的目的是比较糠酸氟替卡松/维兰特罗(FF/V)100/25 μg和优甲乐/维兰特罗(U/V)62.在墨西哥城的一家三级转诊中心进行的一项试验性、单中心、开放标签、平行组研究纳入了 132 名至少有两次病情加重病史的患者。他们被随机分配到四个治疗组中的一组:33 名 COPD-B 患者接受 FF/VI 100/25 μg,31 名 COPD-B 患者接受 UMEC/VI 62.5/25 μg,34 名 COPD-C 患者接受 FF/V,34 名接受 UMEC/VI。无论是 COPD-B 组[0.07(CI 95%,0.03-0.13),0.06(CI 95%,0.03-0.12)]还是 COPD-C 组[0.06(CI 95%,0.04-0.11);0.08(CI 95%,0.05-0.13)],接受 FF/VI 或 UMEC/VI 治疗的患者在病情恶化率、首次病情恶化时间、FEV1 和 IC 方面均无差异。在有病情加重病史的 COPD-B 和 COPD-C 患者中,FF/VI 与 UMEC/VI 在预防病情加重、改善呼吸困难和 HRQL 方面效果相当。
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引用次数: 0
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