Exacerbations

Exacerbations
  • 文章类型: Journal Article
    该研究旨在比较过敏性表现和鼻炎的合并症患病率,哮喘和COPD患者的过敏测试及其与患者相关结局的关系.
    随机选择医生诊断为哮喘(n=1291)或COPD(n=1329)的瑞典患者的横断面研究。2014年的自我完成问卷提供了人口统计数据,鼻炎,接触花粉或毛茸茸的宠物时的过敏症状,恶化,哮喘控制测试(ACT)和COPD评估测试(CAT)的自我评估疾病严重程度和评分,并审查了过敏试验的记录.
    与COPD(38%)相比,过敏性表现在哮喘(75%)中更常见。70%的哮喘患者和58%的COPD患者报告有鼻炎。在过去的十年中,有28%的哮喘患者和8%的COPD患者进行了过敏测试。在哮喘患者中;共病变态反应和鼻炎均与哮喘症状控制不良的风险增加独立相关(ACT<20)(OR[95%CI]1.41[1.05to1.87]和2.13[1.60to2.83]),恶化(1.58[1.15至2.17]和1.38[1.02至1.86]),和自我评估的中度/重度疾病(1.64[1.22to2.18]和1.75[1.33to2.30])。在COPD患者中,合并症过敏和鼻炎均与低健康状况(CAT≥10)的风险增加独立相关(OR[95%CI]分别为1.46[1.20to1.95]和2.59[1.97to3.41]),在过去六个月中恶化(1.91[1.49至2.45]和1.57[1.23至2.01]),和自我评估的中度/重度疾病(1.70[1.31to2.22]和2.13[1.66to2.74])。
    过敏性表现和鼻炎在哮喘中比在COPD中更常见,但在这两种疾病中都与较差的预后相关。这突出了检查和治疗过敏和鼻炎合并症的重要性,不仅在哮喘中,而且在COPD中。
    UNASSIGNED: The study aimed to compare prevalence of comorbid allergic manifestations and rhinitis, allergy testing and associations with patient-related outcomes in patients with asthma and COPD.
    UNASSIGNED: Cross-sectional study of randomly selected Swedish patients with a doctor\'s diagnosis of asthma (n = 1291) or COPD (n = 1329). Self-completion questionnaires from 2014 provided data on demographics, rhinitis, allergic symptoms at exposure to pollen or furry pets, exacerbations, self-assessed severity of disease and scores from the Asthma Control Test (ACT) and the COPD Assessment Test (CAT), and records were reviewed for allergy tests.
    UNASSIGNED: Allergic manifestations were more common in asthma (75%) compared with COPD (38%). Rhinitis was reported in 70% of asthma and 58% of COPD patients. Allergy tests had been performed during the previous decade in 28% of patients with asthma and in 8% of patients with COPD.In patients with asthma; comorbid allergy and rhinitis were both independently associated with increased risk for poor asthma symptom control (ACT < 20) (OR [95% CI] 1.41 [1.05 to 1.87] and 2.13 [1.60 to 2.83]), exacerbations (1.58 [1.15 to 2.17] and 1.38 [1.02 to 1.86]), and self-assessed moderate/severe disease (1.64 [1.22 to 2.18] and 1.75 [1.33 to 2.30]). In patients with COPD, comorbid allergy and rhinitis were both independently associated with increased risk for low health status (CAT ≥ 10) (OR [95% CI] 1.46 [1.20 to 1.95] and 2.59 [1.97 to 3.41]) respectively, with exacerbations during the previous six months (1.91 [1.49 to 2.45] and 1.57 [1.23 to 2.01]), and with self-assessed moderate/severe disease (1.70 [1.31 to 2.22] and 2.13 [1.66 to 2.74]).
    UNASSIGNED: Allergic manifestations and rhinitis are more common in asthma than COPD but associated with worse outcomes in both diseases. This highlights the importance of examining and treating comorbid allergy and rhinitis, not only in asthma but also in COPD.
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  • 文章类型: Journal Article
    背景:支气管扩张(BE)传统上与中性粒细胞炎症有关,但嗜酸性粒细胞支气管扩张(EB)最近出现。有关患病率的数据,临床特征,缺乏疾病严重程度。本研究旨在评估EB的患病率,比较EB与非EB,评估BE(T2-highEB)中的2型(T2)高基因型与非T2-highEB,并确定EB预测因子。方法:我们进行了一项涉及153例BE患者的前瞻性研究。收集的数据包括临床,放射学,和微生物学发现。使用支气管扩张严重程度指数(BSI)评估BE严重程度,面对和电子面对得分,以及支气管扩张的病因和合并症指数(BACI)。EB被定义为血液嗜酸性粒细胞计数(BEC)≥300个细胞/μL,T2高EB为BEC≥300个细胞/μL,部分呼出气一氧化氮(FeNO)≥25ppb。结果:EB的患病率为27%,T2高EB的患病率为20%。EB患者表现出较差的肺功能和更严重的放射学特征,严重程度评分明显较高[BSI,面对,E-FACED,BACI(p<0.05)],和更高的中位数恶化率[4(2-5)与EB相比2(1-4)在非EB中,p=0.0002],与非EB患者相比。T2高EB患者表现出更高的严重程度评分[BSI,面对,E-FACED(p<0.05)],以及更差的肺功能参数[FEV1%,FVC%,FEF25-75%(p<0.05)]与非T2高EB患者相比。在我们的研究中,与非EB患者相比,EB患者的肺功能明显恶化,BE严重程度评分更高,恶化在这些差异中起着重要作用。我们发现BEC和疾病严重程度评分之间存在统计学上显著的正相关,比如BSI,面对,和mMRC,以及与肺功能的反比关系。EB存在的可能性与mMRC≥1相关(OR=2.53;95%CI,1.26-5.64),加重/年≥1(OR=1.27;95%CI,1.0-1.63),和慢性PA定植(OR=3.9;95%CI,1.08-15.8)。结论:EB是一种独特的内型。呼吸困难,恶化,PA定植可以预测EB,强调早期检测对改善结果的重要性。BEC可以作为诊断EB时考虑的疾病严重程度的有用生物标志物。
    Background: Bronchiectasis (BE) has been traditionally associated with neutrophilic inflammation, but eosinophilic bronchiectasis (EB) has recently emerged. Data about prevalence, clinical features, and disease severity are lacking. This study aimed to assess the EB prevalence, compare EB with non-EB, evaluate the Type-2 (T2) high endotype in BE (T2-high EB) versus non-T2-high EB, and identify EB predictors. Methods: We conducted a prospective study involving 153 BE patients. The data collected included clinical, radiological, and microbiological findings. BE severity was assessed using the bronchiectasis severity index (BSI), FACED and E-FACED scores, and the bronchiectasis etiology and comorbidity index (BACI). EB was defined as a blood eosinophil count (BEC) ≥ 300 cells/μL, and T2-high EB as BEC ≥ 300 cells/μL with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb. Results: Prevalence was 27% for EB and 20% for T2-high EB. EB patients exhibited poorer lung function and more severe radiologic features, with significantly higher severity scores [BSI, FACED, E-FACED, BACI (p < 0.05)], and a higher median exacerbation rate [4 (2-5) in EB vs. 2 (1-4) in non-EB, p = 0.0002], compared with non-EB patients. T2-high EB patients showed higher severity scores [BSI, FACED, E-FACED (p < 0.05)], as well as worse lung function parameters [FEV1%, FVC%, FEF 25-75% (p < 0.05)] compared with non-T2-high EB patients. In our study, patients with EB exhibited notably worsened lung function and higher BE severity scores compared with their non-EB counterparts, with exacerbations playing a major role in these differences. We found statistically significant positive correlations between BEC and disease severity scores, such as BSI, FACED, and mMRC, as well as an inverse relationship with pulmonary function. The likelihood of EB being present was significantly higher in association with mMRC ≥ 1 (OR = 2.53; 95% CI, 1.26-5.64), exacerbations/year ≥ 1 (OR = 1.27; 95% CI, 1.0-1.63), and chronic PA colonization (OR = 3.9; 95% CI, 1.08-15.8). Conclusions: EB is a distinct endotype. Dyspnea, exacerbations, and PA colonization may be predictive of EB, emphasizing the importance of early detection for improved outcomes. BEC could serve as a useful biomarker of disease severity to consider when diagnosing EB.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景/目的:囊性纤维化是一种遗传决定的疾病,显著影响和缩短寿命。用CFTR调节剂(CFTR-T)治疗是患者的新希望。它可以改变不良预后的预测值(例如,恶化率和FEV1值)。该研究的目的是分析波兹南CF中心85名CF患者在CFTR-T治疗一年(+/-2周)前后的恶化发生率和肺活量测定数据。据我们所知,这是对中东欧人口CFTR-T效率的首次分析。方法:我们回顾性分析85例CF成年患者(男性和女性)的肺活量测定和恶化数据,2022年中期开始使用CFTR调节剂进行治疗。结果:严重加重导致的一年住院率从每年1.25降至0.21。我们还看到非卧床恶化率下降了66%。中位数FEV1%的绝对值增加了9.60%,增加了460mL。即使在严重梗阻组(FEV1<35%),中位FEV1%的绝对值增加5.9%.我们还证明了研究组中FVC%的增加(绝对值和600mL的中位数为17.10%)。结论:经过一年的治疗,在不良预后的两个重要预测值中观察到了令人印象深刻的改善:加重率和FEV1值.需要进一步观察以确定改善的时间及其对生活质量和预期寿命的影响。
    Background/Objectives: Cystic fibrosis is a genetically determined disease that significantly influences and shortens life. Treatment with CFTR modulators (CFTR-T) is a new hope for patients. It can change the predictive values of a poor prognosis (e.g., exacerbation rate and FEV1 value). The aim of the study was to analyse exacerbation incidence and spirometry data before and after one year (+/- 2 weeks) of CFTR-T in 85 CF patients at the CF Centre in Poznań. To our knowledge, this is the first analysis of CFTR-T efficiency in the Central-Eastern Europe population. Methods: We retrospectively analysed the spirometry and exacerbation data of 85 CF adult patients (both men and women), who in the middle of 2022 began treatment with CFTR modulators. Results: The one-year ratio of hospitalisation caused by severe exacerbations lowered from 1.25 to 0.21 per patient per year. We also saw a 66% decline in ambulatory exacerbations. The median FEV1% increased by 9.60% in absolute values and by 460 mL. Even in the group with very severe obstruction (FEV1 < 35%), there was an increase in median FEV1% of 5.9 in absolute values. We also proved the increase in FVC% (median 17.10% in absolute value and 600 mL) in the study group. Conclusions: After one year of treatment, an impressive improvement was observed in two important predictive values of poor prognosis: exacerbation rate and FEV1 values. Further observation is needed to determine how long the improvement will be present and its influence on quality of life and life expectancy.
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  • 文章类型: Journal Article
    背景:3期VOYAGE(NCT02948959)和开放标签延伸EXCURSION(NCT03560466)研究评估了dupilumab在儿童(6-11岁)未控制的中度至重度哮喘中的治疗。此事后分析评估了每2周(q2w)添加的dupilumab200mg的疗效和安全性,两项研究中最大的剂量队列,参加旅行的VOYAGE儿童。
    方法:重度哮喘急性发作(AERs)的年化发生率,1s内支气管扩张剂前预测用力呼气量百分比的变化(ppFEV1),在VOYAGE和EXCURSION(dupilumab/dupilumab组)中接受dupilumab200mgq2w治疗的中重度哮喘儿童,以及在VOYAGE中接受安慰剂和在EXCURSION中接受dupilumab200mgq2w治疗的儿童(安慰剂/dupilumab组),我们对因治疗引起的不良事件进行在患有中度至重度2型哮喘的儿童中也评估了这些终点(定义为在父母研究基线[PSBL]时血液嗜酸性粒细胞计数≥150个细胞/µL或FeNO≥20ppb)。
    结果:在总体人口中,dupilumab在dupilumab/dupilumab组(n=158)中降低了AER并改善了支气管扩张剂前ppFEV1,持续2年.接受安慰剂/dupilumab的儿童(n=85)在EXCURSION中开始使用dupilumab200mgq2w后显示出类似的减少。对于PSBL的2型哮喘儿童也观察到了类似的结果。安全性与dupilumab的已知安全性一致。
    结论:在未控制的中度至重度2型哮喘的儿童(6-11岁)中,dupilumab200mg可在长达2年的时间内降低加重率并改善肺功能,其安全性与已知的dupilumab安全性一致.
    BACKGROUND: The phase 3 VOYAGE (NCT02948959) and open-label extension EXCURSION (NCT03560466) studies evaluated dupilumab in children (6-11 years) with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed the efficacy and safety of add-on dupilumab 200 mg every 2 weeks (q2w), the largest dose cohort in both studies, in children from VOYAGE who participated in EXCURSION.
    METHODS: Annualized rate of severe asthma exacerbations (AERs), change in prebronchodilator percent predicted forced expiratory volume in 1 s (ppFEV1), and treatment-emergent adverse events were assessed in children with moderate-to-severe asthma who received dupilumab 200 mg q2w in VOYAGE and EXCURSION (dupilumab/dupilumab arm) and those who received placebo in VOYAGE and dupilumab 200 mg q2w in EXCURSION (placebo/dupilumab arm). These endpoints were also assessed in children with moderate-to-severe type 2 asthma (defined as blood eosinophil count ≥150 cells/µL or FeNO ≥20 ppb at the parent study baseline [PSBL]).
    RESULTS: In the overall population, dupilumab reduced AER and improved prebronchodilator ppFEV1 in the dupilumab/dupilumab arm (n = 158) for up to 2 years. Children receiving placebo/dupilumab (n = 85) showed similar reductions after initiation of dupilumab 200 mg q2w in EXCURSION. Similar results were observed for children with type 2 asthma at PSBL. The safety profile was consistent with the known safety profile of dupilumab.
    CONCLUSIONS: In children (6-11 years) with uncontrolled moderate-to-severe type 2 asthma, dupilumab 200 mg reduced exacerbation rates and improved lung function for up to 2 years and showed safety consistent with the known dupilumab safety profile.
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  • 文章类型: Journal Article
    目的:轻度/中度哮喘患者的未控制哮喘可能是由对哮喘控制产生负面影响的非肺部可治疗特征(TT)引起的。我们的目标是确定人口特征,行为(吸烟)和肺外(肥胖,合并症)根据全球哮喘倡议(GINA),未控制的哮喘患者的TTs和未来恶化的风险规定了第1-3步治疗。
    方法:纳入了2017年至2019年在瑞典国家气道登记册中登记的2万8000名哮喘患者(≥18岁)(索引日期)。该数据库已与其他国家登记册链接,以获取有关处方药物2年索引前和索引后1年恶化的信息。哮喘治疗分为步骤1-3或4-5,根据症状控制定义未控制的哮喘,恶化和肺功能。
    结果:GINA步骤1-3包括17,318名患者,其中9586(55%)不受控制(UCA1-3)。在调整后的分析中,UCA1-3与女性相关(OR1.34,95%CI1.27-1.41),年龄较大(1.00,1.00-1.00),初等教育(1.30,1.20-1.40)和中等教育(1.19,1.12-1.26),和TTs,如吸烟(1.25,1.15-1.36),肥胖(1.23,1.15-1.32),心血管疾病(1.12,1.06-1.20)和抑郁/焦虑(1.13,1.06-1.21)。此外,UCA1-3与未来急性加重有关;口服皮质类固醇(1.90,1.74-2.09)和哮喘住院(2.55,2.17-3.00),分别,当针对治疗步骤4-5进行调整时也是如此。
    结论:超过50%的轻度/中度哮喘患者患有未控制的疾病。评估和管理TT,如吸烟,肥胖和合并症应该以整体的方式进行,因为这些患者未来加重的风险增加。
    OBJECTIVE: Uncontrolled asthma in patients treated for mild/moderate disease could be caused by non-pulmonary treatable traits (TTs) that affect asthma control negatively. We aimed to identify demographic characteristics, behavioural (smoking) and extrapulmonary (obesity, comorbidities) TTs and the risk for future exacerbations among patients with uncontrolled asthma prescribed step 1-3 treatment according to the Global Initiative for Asthma (GINA).
    METHODS: Twenty-eight thousand five hundred eighty-four asthma patients (≥18 y) with a registration in the Swedish National Airway Register between 2017 and 2019 were included (index-date). The database was linked to other national registers to obtain information on prescribed drugs 2-years pre-index and exacerbations 1-year post-index. Asthma treatment was classified into step 1-3 or 4-5, and uncontrolled asthma was defined based on symptom control, exacerbations and lung function.
    RESULTS: GINA step 1-3 included 17,318 patients, of which 9586 (55%) were uncontrolled (UCA 1-3). In adjusted analyses, UCA 1-3 was associated with female sex (OR 1.34, 95% CI 1.27-1.41), older age (1.00, 1.00-1.00), primary education (1.30, 1.20-1.40) and secondary education (1.19, 1.12-1.26), and TTs such as smoking (1.25, 1.15-1.36), obesity (1.23, 1.15-1.32), cardiovascular disease (1.12, 1.06-1.20) and depression/anxiety (1.13, 1.06-1.21). Furthermore, UCA 1-3 was associated with future exacerbations; oral corticosteroids (1.90, 1.74-2.09) and asthma hospitalization (2.55, 2.17-3.00), respectively, also when adjusted for treatment step 4-5.
    CONCLUSIONS: Over 50% of patients treated for mild/moderate asthma had an uncontrolled disease. Assessing and managing of TTs such as smoking, obesity and comorbidities should be conducted in a holistic manner, as these patients have an increased risk for future exacerbations.
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  • 文章类型: Journal Article
    在COVID-19大流行期间,哮喘急性发作大幅减少,原因仍然知之甚少。我们调查了可改变的危险因素的变化,这可能有助于解释哮喘加重的减少。
    拟合了多级广义线性混合模型,以检查与大流行前(2019年)相比,2020-2022年期间哮喘加重的可改变风险因素的变化。使用观测,常规数据来自牛津-皇家全科医师研究和监测中心的一般实践。哮喘加重定义为任何GP记录:哮喘加重,泼尼松龙的处方,急症室就诊或因哮喘住院。可改变的危险因素是哮喘自我管理计划的所有权,哮喘年度回顾,吸入性皮质类固醇(ICS)处方,流感疫苗接种和呼吸道感染(RTI)。
    与2019年相比(n=550,995),2020年(n=565,956)和2022年(n=562,167)(p<0.05):哮喘恶化率从67.1%下降到51.9%和61.1%,哮喘发作的比例从20.4%降至15.1%和18.5%,哮喘自我管理计划从28.6%增加到37.7%和55.9%;ICS处方从69.9%增加到72.0%和71.1%;流感疫苗接种从14.2%增加到25.4%和55.3%;目前吸烟从15.0%下降到14.5%和14.7%;低RTI从10.5%下降到5.3%和8.1%;高RTI从10.7%下降到5.8%和7.6%.GP实践对哮喘加重有集群效应(p=0.001)。哮喘患者更有可能(p<0.05),如果他们有LRTI(7倍(x)),有URTI和ILI(均两次),是当前吸烟者(1.4倍),PPV疫苗接种(1.3倍),季节性流感疫苗接种(1.01倍),采用ICS(1.3倍),有哮喘评论(1.09倍)。如果哮喘患者有自我管理计划(7%),哮喘患者恶化的可能性较小。部分(4%)比完全接种COVID-19。
    我们已经确定了哮喘恶化的可改变的危险因素的变化,这些变化需要在大流行后时期保持。
    英国应用研究和健康数据研究中心。
    UNASSIGNED: There were substantial reductions in asthma exacerbations during the COVID-19 pandemic for reasons that remain poorly understood. We investigated changes in modifiable risk factors which might help explain the reductions in asthma exacerbations.
    UNASSIGNED: Multilevel generalised linear mixed models were fitted to examine changes in modifiable risk factors for asthma exacerbations during 2020-2022, compared to pre-pandemic year (2019), using observational, routine data from general practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre. Asthma exacerbations were defined as any of GP recorded: asthma exacerbations, prescriptions of prednisolone, accident and emergency department attendance or hospitalisation for asthma. Modifiable risk factors of interest were ownership of asthma self-management plan, asthma annual review, inhaled-corticosteroid (ICS) prescriptions, influenza vaccinations and respiratory-tract-infections (RTI).
    UNASSIGNED: Compared with 2019 (n = 550,995), in 2020 (n = 565,956) and 2022 (n = 562,167) (p < 0.05): asthma exacerbations declined from 67.1% to 51.9% and 61.1%, the proportion of people who had: asthma exacerbations reduced from 20.4% to 15.1% and 18.5%, asthma self-management plans increased from 28.6% to 37.7% and 55.9%; ICS prescriptions increased from 69.9% to 72.0% and 71.1%; influenza vaccinations increased from 14.2% to 25.4% and 55.3%; current smoking declined from 15.0% to 14.5% and 14.7%; lower-RTI declined from 10.5% to 5.3% and 8.1%; upper-RTI reduced from 10.7% to 5.8% and 7.6%. There was cluster effect of GP practices on asthma exacerbations (p = 0.001). People with asthma were more likely (p < 0.05) to have exacerbations if they had LRTI (seven times(x)), had URTI and ILI (both twice), were current smokers (1.4x), PPV vaccinated (1.3x), seasonal flu vaccinated (1.01x), took ICS (1.3x), had asthma reviews (1.09x). People with asthma were less likely to have exacerbations if they had self-management plan (7%), and were partially (4%) than fully COVID-19 vaccinated.
    UNASSIGNED: We have identified changes in modifiable risk factors for asthma exacerbation that need to be maintained in the post-pandemic era.
    UNASSIGNED: Asthma UK Centre for Applied Research and Health Data Research UK.
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  • 文章类型: Journal Article
    主要的随机临床试验表明,生物疗法可以降低重度嗜酸性粒细胞性哮喘患者的恶化率和口服皮质类固醇(OCS)剂量。然而,关于延续的数据,功效,老年哮喘患者生物治疗的安全性有限。因此,这项研究的目的是评估延续率的差异,功效,老年(≥65岁)和年轻(<65岁)哮喘患者之间的生物治疗安全性。
    在这项单中心回顾性观察研究中,我们收集了接受奥马珠单抗等生物药物治疗的哮喘患者的临床数据,美波利单抗,贝那利珠单抗,和dupilumab在2009年4月至2022年8月之间。我们比较分析了延续,功效,年龄较大(年龄≥65岁)和年龄较小(年龄<65岁)组之间的生物治疗安全性。还评估了停用或转换生物药物的原因。
    在观察期间,62名患者(31名年龄较大,31名年龄较小)接受了91种生物制剂治疗。老年患者的平均年龄为74.3±5.1岁,年轻患者的平均年龄为48.0±14.0岁。两组之间生物治疗的延续率没有显着差异。社会背景是两组停止生物治疗的最常见原因,效果不足是转换为生物药物的最常见原因。在生物治疗的前12个月内,两组的哮喘恶化率都有所下降。OCS的剂量在老年组中趋于减少,在年轻组中明显减少。
    可以继续对老年哮喘患者进行生物治疗,疗效和安全性与年轻哮喘患者相似。
    UNASSIGNED: Major randomized clinical trials have shown that biological therapy can reduce the exacerbation rate and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data on the continuation, efficacy, and safety of biological therapy in older patients with asthma are limited. Therefore, the aim of this study was to evaluate the differences in the continuation rate, efficacy, and safety of biological therapy between older (≥ 65 years) and younger (< 65 years) patients with asthma.
    UNASSIGNED: In this single-center retrospective observational study, we collected clinical data of patients with asthma who were administered biological drugs such as omalizumab, mepolizumab, benralizumab, and dupilumab between April 2009 and August 2022. We comparatively analyzed the continuation, efficacy, and safety of biological therapy between older (age ≥ 65 years) and younger patient (age < 65 years) groups. The reasons for discontinuation or switching of biological drugs were also evaluated.
    UNASSIGNED: Sixty-two (31 older and 31 younger) patients were treated with 91 biologics during the observational period. The mean age of older patients was 74.3 ± 5.1 years and that of younger patients was 48.0 ± 14.0 years. The continuation rate of biological therapy was not significantly different between the groups. Social background was the most common reason for discontinuation of biological therapy in both groups, and insufficient effect was the most common reason for switching to biological drugs. Asthma exacerbations decreased in both groups within the first 12 months of biologic therapy. The dosage of OCS tended to decrease in the older group and significantly decrease in the younger group.
    UNASSIGNED: Biologic therapy for older patients with asthma can be continued, with efficacy and safety similar to those in younger patients with asthma.
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  • 文章类型: Journal Article
    背景:建议在GOLDB患者中使用LABA/LAMA治疗。我们假设三联疗法(LABA/LAMA/ICS)在实现和维持临床控制(CC)方面优于LABA/LAMA。在GOLDB患者亚组(此处称为GOLDB+患者)中考虑影响和疾病稳定性的复合结局,其特征在于:(1)尽管接受常规LABA/LAMA治疗,但仍有症状(CAT≥10);(2)在过去一年中经历过一次中度加重;(3)血液嗜酸性粒细胞计数(BEC)≥150个细胞/μL.
    方法:ANTESB+研究是一项前瞻性研究,多中心,开放标签,随机化,务实,旨在检验这一假设的对照试验。它将随机分配1028名B患者,以继续使用其主治医师开具的常规LABA/LAMA组合,或开始使用氟替卡松糠酸酯(FF)92μg/umecidinium(UMEC)55μg/维兰特罗(VI)22μg在单个吸入器q.d中进行12个月。主要疗效结果将是达到的CC水平。次要结果包括临床重要恶化指数(CID),年恶化率,和FEV1。探索目标包括BEC和吸烟状况的相互作用,全因死亡率和LABA/LAMA臂上切换治疗臂的患者比例。安全性分析包括不良事件和肺炎发生率。
    结果:首例患者于2024年2月29日招募;结果预计在2026年第一季度。
    结论:ANTESB+研究是第一个:(1)探索三联疗法在B+COPD患者人群中的疗效和安全性;(2)使用综合指数(CC)作为COPD试验的主要结果。
    BACKGROUND: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/μL.
    METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92μg/umeclidinium (UMEC) 55μg/vilanterol (VI) 22μg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia.
    RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026.
    CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.
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  • 文章类型: Journal Article
    背景:支气管扩张以急性加重为特征,但这些事件背后的生物学机制缺乏表征。目的探讨支气管扩张症急性加重的炎症和微生物特征。
    方法:纳入120例支气管扩张患者,并在12个月内出现急性加重。在临床稳定期间以及在接受抗生素治疗之前的恶化时再次获得自发痰样品。经过验证的细菌和病毒的快速PCR检测用于将恶化分类为细菌,病毒或两者。痰炎症评估包括无标记液体显色/质谱和痰细胞因子和中性粒细胞弹性蛋白酶活性的测量。16srRNA测序用于表征微生物组。
    结果:支气管扩张加重表现出明显的分子异质性。在103个样品(86%)中鉴定出至少一种细菌,并且在81个患者(68%)中观察到高细菌负荷(总细菌负荷>10(7)拷贝/g)。在55(46%)患者中发现了呼吸道病毒,鼻病毒是最常见的病毒(31%)。PCR比培养更敏感。在恶化时没有观察到微生物组的一致变化。急性加重与中性粒细胞弹性蛋白酶增加有关,蛋白酶-3、IL-1beta和CXCL8。这些标记与细菌和细菌+病毒恶化特别相关。在不同的恶化亚型之间观察到不同的炎症和微生物组概况,包括细菌,病毒和嗜酸性粒细胞事件在这两个假设导致,使用整合的微生物组和蛋白质组学进行无假设分析,显示恶化的4个亚型。
    结论:支气管扩张加重是由细菌引起的异质性事件,病毒和炎症失调。
    Rationale: Bronchiectasis is characterized by acute exacerbations, but the biological mechanisms underlying these events are poorly characterized. Objectives: To investigate the inflammatory and microbial characteristics of exacerbations of bronchiectasis. Methods: A total of 120 patients with bronchiectasis were enrolled and presented with acute exacerbations within 12 months. Spontaneous sputum samples were obtained during a period of clinical stability and again at exacerbation before receipt of antibiotic treatment. A validated rapid PCR assay for bacteria and viruses was used to classify exacerbations as bacterial, viral, or both. Sputum inflammatory assessments included label-free liquid chromatography-tandem mass spectrometry and measurement of sputum cytokines and neutrophil elastase activity. 16 s rRNA sequencing was used to characterize the microbiome. Measurements and Main Results: Bronchiectasis exacerbations showed profound molecular heterogeneity. At least one bacterium was identified in 103 samples (86%), and a high bacterial load (total bacterial load > 107 copies/g) was observed in 81 patients (68%). Respiratory viruses were identified in 55 (46%) patients, with rhinovirus being the most common virus (31%). PCR testing was more sensitive than culture. No consistent change in the microbiome was observed at exacerbation. Exacerbations were associated with increased neutrophil elastase, proteinase-3, IL-1β, and CXCL8. These markers were particularly associated with bacterial and bacterial plus viral exacerbations. Distinct inflammatory and microbiome profiles were seen between different exacerbation subtypes, including bacterial, viral, and eosinophilic events in both hypothesis-led and hypothesis-free analysis using integrated microbiome and proteomics, demonstrating four subtypes of exacerbation. Conclusions: Bronchiectasis exacerbations are heterogeneous events with contributions from bacteria, viruses, and inflammatory dysregulation.
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