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Brensocatib in non–cystic fibrosis bronchiectasis: ASPEN protocol/baseline characteristics 布仑索卡替(Brensocatib)治疗非囊性纤维化支气管扩张症:ASPEN 方案/基线特征
Pub Date : 2024-04-25 DOI: 10.1183/23120541.00151-2024
James D. Chalmers, Pierre-Régis Burgel, Charles L. Daley, A. De Soyza, C. Haworth, David Mauger, Kevin Mange, A. Teper, Carlos Fernandez, Dan Conroy, Mark Metersky
Brensocatib is an investigational, oral, reversible inhibitor of dipeptidyl peptidase-1 shown to prolong time to first exacerbation in adults with bronchiectasis. Outlined here are the clinical trial design, and baseline characteristics and treatment patterns of adult patients enrolled in the phase 3 ASPEN trial (NCT04594369).A global study enrolling patients with a clinical history consistent with bronchiectasis (cough, chronic sputum production, and/or recurrent respiratory infections), diagnosis confirmed radiologically, and ≥2 exacerbations in the prior 12 months, ASPEN was designed to evaluate the impact of two brensocatib doses (10 mg and 25 mg) on exacerbation rate over a 52-week treatment periodversusplacebo. Comprehensive clinical data, including demographics, disease severity, lung function,Pseudomonas(P.) aeruginosastatus, and quality of life, were collected at baseline.1682 adults from 35 countries were randomised from December 2020 to March 2023. Mean age was 61.3 years and 64.7% were female. Approximately 70% had moderate-to-severe Bronchiectasis Severity Index (BSI) scores, 29.3% had ≥3 exacerbations in the prior 12 months, and 35.7% were positive forP. aeruginosa. Mean BSI scores were highest in Australia/New Zealand (8.3) and lowest in Latin America (5.9). Overall, the most common aetiology was idiopathic (58.4%). InP. aeruginosa–positiveversus –negative patients, lung function was lower, with greater long-term macrolide (21.5%versus14.0%) and inhaled corticosteroid use (63.5%versus53.9%). There was wide regional variation in long-term antibiotic use in patients with bronchiectasis andP. aeruginosa.ASPEN baseline characteristics and treatment profiles were representative of a global bronchiectasis population.
布仑索卡替(Brensocatib)是一种正在研究的口服可逆性二肽基肽酶-1抑制剂,研究表明它能延长成人支气管扩张症患者首次病情加重的时间。本文概述了临床试验的设计以及参加 ASPEN 3 期试验(NCT04594369)的成年患者的基线特征和治疗模式。ASPEN 是一项全球性研究,招募临床病史与支气管扩张症相符(咳嗽、慢性痰液分泌和/或反复呼吸道感染)、经放射学确诊且在之前 12 个月内病情加重≥2 次的患者,旨在评估两种布仑索卡替剂量(10 毫克和 25 毫克)在 52 周治疗期内对病情加重率的影响。基线时收集了全面的临床数据,包括人口统计学、疾病严重程度、肺功能、铜绿假单胞菌状态和生活质量。平均年龄为 61.3 岁,64.7% 为女性。约 70% 的患者有中度至重度支气管扩张症严重程度指数 (BSI) 评分,29.3% 的患者在过去 12 个月中≥3 次病情加重,35.7% 的患者铜绿假单胞菌检测呈阳性。澳大利亚/新西兰的平均 BSI 评分最高(8.3),拉丁美洲最低(5.9)。总体而言,最常见的病因是特发性(58.4%)。在铜绿假单胞菌阳性与阴性患者中,肺功能较低,长期使用大环内酯类药物(21.5%对14.0%)和吸入皮质类固醇(63.5%对53.9%)的比例较高。支气管扩张和铜绿假单胞菌患者长期使用抗生素的情况存在很大的地区差异。
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引用次数: 0
Randomised, phase 1/2a trial of ION-827359, an antisense oligonucleotide inhibitor of ENaC ENaC反义寡核苷酸抑制剂ION-827359的1/2a期随机试验
Pub Date : 2024-04-25 DOI: 10.1183/23120541.00986-2023
Sivagurunathan Sutharsan, Rainald Fischer, Wolfgang Gleiber, Alexander Horsley, Jeff Crosby, Shuling Guo, Shuting Xia, Rosie Yu, Kenneth B Newman, J. S. Elborn
Hyperactivity of epithelial sodium channel (ENaC) with increased sodium absorption is a feature of cystic fibrosis (CF). ION-827359 is a 2.5-generation antisense oligonucleotide targeted to reduce ENaC protein. This study evaluated ION-827359 safety, pharmacokinetics, and pharmacodynamics.In this 3-part Phase 1/2a, double-blind, randomized study, healthy volunteers received single doses of placebo or ION-827359 (3, 10, 37.5, or 100 mg; Part 1) or multiple doses of placebo or ION-827359 (5×10 mg, 5×37.5 mg, 5×75 mg, or 10×37.5 mg; Part 2). People with CF(pwCF) received multiple doses of placebo or ION-827359 (5×10 mg, 5×37.5 mg, 5×75 mg, and 5×100 mg; Part 3). Treatments were administeredviaPari eFlow©mesh nebulizer. The primary outcome was safety; pharmacokinetic and pharmacodynamic parameters were also assessed.Sixty-four healthy volunteers and 34 pwCF were enrolled. ION-827359 was well tolerated with an acceptable safety profile. There were no clinically relevant changes in laboratory values, ECG, or vital signs. Systemic drug exposure was low (plasma half-life approximately 2 weeks). Multiple doses of ION-827359 were associated with dose-dependent reductions in ENaC mRNA in bronchial epithelium. After multiple dosing, FEV1was slightly higher in pwCF receiving ION-827359 (+2.9% with ION-827359 100 mgversusplacebo; p=0.27).The tolerability and safety of ION-827359 appear favourable at this stage of investigation. Reduction in ENaC mRNA supports mechanistic efficacy at the doses and regimens tested, and supports further investigation of ION-827359 in pwCF.
上皮钠通道(ENaC)活性过高导致钠吸收增加是囊性纤维化(CF)的一个特征。ION-827359是一种旨在减少ENaC蛋白的2.5代反义寡核苷酸。这项研究评估了ION-827359的安全性、药代动力学和药效学。在这项由3个部分组成的1/2a期双盲随机研究中,健康志愿者接受单剂量安慰剂或ION-827359(3、10、37.5或100毫克;第1部分)或多剂量安慰剂或ION-827359(5×10毫克、5×37.5毫克、5×75毫克或10×37.5毫克;第2部分)。CF患者(pwCF)接受多种剂量的安慰剂或ION-827359(5×10毫克、5×37.5毫克、5×75毫克和5×100毫克;第3部分)。治疗在Pari eFlow©雾化器中进行。主要结果是安全性,同时还评估了药代动力学和药效学参数。ION-827359的耐受性良好,安全性可接受。实验室数值、心电图或生命体征均无临床相关变化。全身药物暴露量低(血浆半衰期约为 2 周)。多次服用 ION-827359 会导致支气管上皮细胞中 ENaC mRNA 的剂量依赖性降低。多次给药后,接受ION-827359治疗的pwCF的FEV1略高(ION-827359 100毫克与安慰剂相比+2.9%;p=0.27)。ENaC mRNA的减少支持在所测试的剂量和治疗方案下的机理疗效,并支持进一步研究ION-827359在pwCF中的疗效。
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引用次数: 0
A robust web-based tool to predict viral shedding in patients with Omicron SARS-CoV-2 variants 预测 Omicron SARS-CoV-2 变体患者病毒脱落情况的强大网络工具
Pub Date : 2024-04-19 DOI: 10.1183/23120541.00939-2023
Weilong Zhang, Xiaoyan Gai, Ben Wang, Zhonghui Duan, Qingtao Zhou, Lili Dai, Changjian Yan, Chaoling Wu, Jiarun Fan, Ping Wang, Ping Yang, Fang Bao, Hongmei Jing, Chao Cai, Chunli Song, Yingmin Ma, Yongchang Sun
Data on viral kinetics and variants affecting the duration of viral shedding (VS) were limited. Our objective was to determine VS in distinct SARS-CoV-2 variants, including Omicron BA.4/5 and BF.7, and to identify the relevant influencing factors.We carried out a longitudinal cohort study at Beijing Xiaotangshan Fangcang shelter hospital from May to June of 2022 (Omicron BA.4/5) and from November to December of 2022 (Omicron BF.7). Nucleocapsid protein (N) and open reading frame (ORF) genes were considered as the target genes of the reverse transcription-polymerase chain reaction. The daily results of cycle threshold (CT), including lowest ORF1ab-CT values for day1-day3 post of hospitalisation (CT3minORF) and lowest N-CT values for day1-day3 post of hospitalisation (CT3minN), and demographic and clinical characteristics were collected.A total of 1433 patients with COVID-19 were recruited from Fangcang shelter hospital, in which 278 patients were diagnosed with Omicron BA.4/5 and 1155 patients with Omicron BF.7. Patients with BF.7 infection showed a longer duration of VS. The duration of VS was associated with variants, age, alcohol use, the severity of COVID-19, and CT3minN. Moreover, the nomogram had excellent accuracy in predicting VS.Our results indicated that patients with Omicron BF.7 had a longer period of contagiousness than those with BA.4/5. The duration of VS was affected by a variety of factors and the nomogram may become an applicable clinical instrument to predict VS. Furthermore, we developed a new COVID-19 viral shedding predicting (CVSP) model that can accurately predict the duration of VS for COVID-19 and created a user-friendly website to easily apply this prediction model (https://puh3.shinyapps.io/CVSP_Model/).
有关病毒动力学和影响病毒脱落(VS)持续时间的变异体的数据十分有限。我们于 2022 年 5 月至 6 月(Omicron BA.4/5)和 2022 年 11 月至 12 月(Omicron BF.7)在北京小汤山防空洞医院进行了一项纵向队列研究。核壳蛋白(N)和开放阅读框(ORF)基因被认为是反转录聚合酶链反应的目标基因。从芳烃保护区医院共招募了1433名COVID-19患者,其中278名患者被确诊为Omicron BA.4/5,1155名患者被确诊为Omicron BF.7。BF.7 感染患者的 VS 持续时间较长。VS 持续时间与变异体、年龄、饮酒、COVID-19 严重程度和 CT3minN 有关。我们的研究结果表明,与 BA.4/5 感染者相比,Omicron BF.7 感染者的传染期更长。VS 的持续时间受多种因素影响,提名图可能成为预测 VS 的适用临床工具。此外,我们还开发了一种新的COVID-19病毒脱落预测模型(CVSP),该模型可准确预测COVID-19的VS持续时间,并创建了一个用户友好型网站以方便应用该预测模型(https://puh3.shinyapps.io/CVSP_Model/)。
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引用次数: 0
Epidemiology of patients with severe asthma in Japan: a nationwide descriptive study 日本严重哮喘患者的流行病学:一项全国性描述性研究
Pub Date : 2024-04-19 DOI: 10.1183/23120541.00122-2024
Yuya Kimura, M. Suzukawa, T. Jo, Yohei Hashimoto, R. Kumazawa, M. Ishimaru, H. Matsui, A. Yokoyama, Goh Tanaka, Hideo Yasunaga
The European Respiratory Society and the American Thoracic Society guideline defined severe asthma based on treatment intensity and estimated the proportion of severe asthma among all asthma cases to be 5–10%. However, data supporting the estimate and comprehensive and sequential data on asthma cases are scarce. We aimed to estimate the national prevalence and proportion of severe asthma during the last decade.Using a Japanese national administrative database, which covers ≥99% of the population, we evaluated the prevalence and proportion of severe asthma in 2013, 2015, 2017, and 2019. Additionally, we elucidated the demographic characteristics, treatments, and outcomes of patients with asthma.The national prevalence of mild–moderate and severe asthma in 2019 was 800 and 36 per 100 000 persons, respectively. While the prevalence of mild–moderate asthma remained almost constant in the study years, the prevalence of severe asthma decreased, resulting in a reduction in the proportion of severe asthma from 5.6% to 4.3%. Although treatment modalities have evolved, such as the increased use of combination inhalers and asthma biologics, approximately 15% of mild–moderate and 45% of severe asthma cases were still considered “uncontrolled”. The number of deaths from asthma decreased in patients with both mild–moderate and severe asthma.This study revealed that the prevalence of severe asthma decreased during the study period and fell below 5% in the most recent data. Despite treatment evolution, a substantial proportion of patients with both mild–moderate and severe asthma still have poor asthma control.
欧洲呼吸学会和美国胸科学会的指南根据治疗强度对重症哮喘进行了定义,并估计重症哮喘在所有哮喘病例中所占比例为 5-10%。然而,支持这一估计的数据以及有关哮喘病例的全面和连续数据却很少。我们利用覆盖率≥99%的日本全国行政数据库,评估了2013年、2015年、2017年和2019年重症哮喘的患病率和比例。此外,我们还阐明了哮喘患者的人口统计学特征、治疗方法和结果。2019年,全国轻度-中度和重度哮喘的患病率分别为每10万人中有800人和36人。在研究年份中,轻中度哮喘的发病率几乎保持不变,但重度哮喘的发病率有所下降,导致重度哮喘的比例从 5.6% 降至 4.3%。虽然治疗方式有所发展,如更多地使用联合吸入器和哮喘生物制剂,但仍有约 15%的轻中度哮喘和 45%的重度哮喘病例被视为 "未受控制"。在轻度-中度和重度哮喘患者中,死于哮喘的人数都有所下降。这项研究显示,重度哮喘的发病率在研究期间有所下降,在最新数据中低于 5%。尽管治疗方法在不断改进,但仍有相当一部分轻中度和重度哮喘患者的哮喘控制情况不佳。
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引用次数: 0
Enhancing Quality of Life in Severe Post-COVID Survivors through Multidisciplinary Care 通过多学科护理提高严重宫颈糜烂后幸存者的生活质量
Pub Date : 2024-04-19 DOI: 10.1183/23120541.00214-2024
D. J. Cataneo-Piña, Armando Castorena-Maldonado, D. González-Islas, Susana Galicia-Amor, A. Orea-Tejeda, V. Peláez-Hernández, Alma Delia Gutiérrez-Álvarez, Jorge Rojas-Serrano, Eduardo Ortiz-Reyes, Aline Mendoza-Méndez, Ángel Mendoza-Escamilla, Sinuhe Fabre-Alonso, Ivette Buendía-Roldán, Laura Gochicoa-Rangel, C. López-García, Marian Radillo-Gil, Celia Gabriela Hernández Favela, S. Monraz-Pérez, J. Salas-Hernández, Patricio Santillán-Doherty
COVID-19 survivors who were hospitalized continue to experience long-term multi-systemic sequelae and symptoms, impacting their health-related quality of life (HRQo). The complexity of post-COVID-19 conditions underscores the importance of adopting a multidisciplinary, patient-centric approach to ensure ongoing care. This study aims to assess HRQoL and post-COVID symptoms in a cohort of severe COVID-19 survivors depending on their participation in a multidisciplinary program.This prospective study was conducted in a post-COVID clinic staffed by a multidisciplinary team (physical rehabilitator, nutritionist, psychologist, including experts in pulmonary rehabilitation, nutrition, psychology, and others). Subjects over 18 years old who were hospitalized by COVID-19 severe during acute phase and accept attend the post-COVID clinic within the first three months following discharge were included. Subjects who were unable or unwilling to provide informed consent to participate in the protocol were excluded. Linear mixed-effect models were employed to examine changes in SF-12 component scores. The resolution of post-COVID symptom clusters was compared using Cox Model.A total of 730 patients were included, with a mean age of 55.78±15.43 years, 60.55% were male, and 90.62% required mechanical ventilation during hospitalization. Program attendants demonstrated improved SF-12 physical and mental component scores at 3 and 12 months. A reduction in the prevalence of post-COVID symptoms was observed in both groups, with greater reductions in those attending the program.Our study showed that multidisciplinary programme experienced improvements in fatigue, musculoskeletal, gastrointestinal, neuropsychiatric, and respiratory symptoms, along with enhanced SF-12 mental and physical component scores.
住院治疗的 COVID-19 幸存者仍会出现多系统的长期后遗症和症状,影响他们与健康相关的生活质量 (HRQo)。COVID-19 后遗症的复杂性凸显了采用多学科、以患者为中心的方法来确保持续护理的重要性。这项前瞻性研究在一家由多学科团队(物理康复师、营养师、心理学家,包括肺康复、营养、心理等方面的专家)组成的 COVID 后诊所进行。受试者年龄在 18 周岁以上,在急性期因 COVID-19 重症住院,并在出院后的前三个月内接受 COVID 后门诊治疗。无法或不愿提供知情同意书参与方案的受试者被排除在外。采用线性混合效应模型来研究 SF-12 各部分得分的变化。共纳入 730 名患者,平均年龄(55.78±15.43)岁,60.55% 为男性,90.62% 在住院期间需要机械通气。项目参与者在 3 个月和 12 个月后的 SF-12 身心评分均有所改善。我们的研究表明,多学科计划改善了患者的疲劳、肌肉骨骼、胃肠道、神经精神和呼吸系统症状,同时提高了 SF-12 精神和身体部分的评分。
{"title":"Enhancing Quality of Life in Severe Post-COVID Survivors through Multidisciplinary Care","authors":"D. J. Cataneo-Piña, Armando Castorena-Maldonado, D. González-Islas, Susana Galicia-Amor, A. Orea-Tejeda, V. Peláez-Hernández, Alma Delia Gutiérrez-Álvarez, Jorge Rojas-Serrano, Eduardo Ortiz-Reyes, Aline Mendoza-Méndez, Ángel Mendoza-Escamilla, Sinuhe Fabre-Alonso, Ivette Buendía-Roldán, Laura Gochicoa-Rangel, C. López-García, Marian Radillo-Gil, Celia Gabriela Hernández Favela, S. Monraz-Pérez, J. Salas-Hernández, Patricio Santillán-Doherty","doi":"10.1183/23120541.00214-2024","DOIUrl":"https://doi.org/10.1183/23120541.00214-2024","url":null,"abstract":"COVID-19 survivors who were hospitalized continue to experience long-term multi-systemic sequelae and symptoms, impacting their health-related quality of life (HRQo). The complexity of post-COVID-19 conditions underscores the importance of adopting a multidisciplinary, patient-centric approach to ensure ongoing care. This study aims to assess HRQoL and post-COVID symptoms in a cohort of severe COVID-19 survivors depending on their participation in a multidisciplinary program.This prospective study was conducted in a post-COVID clinic staffed by a multidisciplinary team (physical rehabilitator, nutritionist, psychologist, including experts in pulmonary rehabilitation, nutrition, psychology, and others). Subjects over 18 years old who were hospitalized by COVID-19 severe during acute phase and accept attend the post-COVID clinic within the first three months following discharge were included. Subjects who were unable or unwilling to provide informed consent to participate in the protocol were excluded. Linear mixed-effect models were employed to examine changes in SF-12 component scores. The resolution of post-COVID symptom clusters was compared using Cox Model.A total of 730 patients were included, with a mean age of 55.78±15.43 years, 60.55% were male, and 90.62% required mechanical ventilation during hospitalization. Program attendants demonstrated improved SF-12 physical and mental component scores at 3 and 12 months. A reduction in the prevalence of post-COVID symptoms was observed in both groups, with greater reductions in those attending the program.Our study showed that multidisciplinary programme experienced improvements in fatigue, musculoskeletal, gastrointestinal, neuropsychiatric, and respiratory symptoms, along with enhanced SF-12 mental and physical component scores.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":" 48","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140684751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diagnostic value of the pepsin concentration in saliva and induced sputum for gastroesophageal reflux-induced chronic cough: a prospective clinical study 唾液和诱导痰中胃蛋白酶浓度对胃食管反流引起的慢性咳嗽的诊断价值:一项前瞻性临床研究
Pub Date : 2024-04-19 DOI: 10.1183/23120541.00046-2024
Wenhua Gu, Wei Chen, Tongyangzi Zhang, Yiqing Zhu, Wanzhen Li, Wenbo Shi, Na Li, Shengyuan Wang, Xianghuai Xu, Li Yu
To determine the diagnostic value of the pepsin concentration in saliva and induced sputum for gastroesophageal reflux-induced chronic cough (GERC).A total of 171 patients with chronic cough were enrolled. The diagnosis and treatment followed the chronic cough diagnosis and treatment protocol. Saliva and induced sputum were collected, and the pepsin concentration was determined using Peptest™. A gastroesophageal reflux diagnostic questionnaire (GerdQ) was completed. The diagnostic value of the pepsin concentration in saliva and induced sputum for GERC was analyzed and compared.The salivary pepsin concentration predicted GERC with an area under the receiver operating characteristic curve (AUC) of 0.845. The optimal cut-off value was 76.10 ng·mL−1, the sensitivity 83.58%, and the specificity 82.69%. The pepsin concentration in the induced sputum supernatant for GREC had an AUC of 0.523. When GerdQ was used for GERC diagnosis, the AUC was 0.670, and the diagnostic value of salivary pepsin was better compared to GerdQ (DeLong's test, p=0.0008). Salivary pepsin had a comparable diagnostic value to GerdQ (AUC=0.779versus0.826; p=0.4199) in acidic GERC. Salivary pepsin had superior diagnostic value compared to GerdQ (AUC=0.830versus0.533; p<0.0001) in non-acidic GERC.A salivary pepsin concentration >76.10 ng·mL−1is of good diagnostic value for GERC, especially in non-acidic GERC. The pepsin concentration in induced sputum has a low diagnostic value.
目的:确定唾液和诱导痰中胃蛋白酶浓度对胃食管反流性慢性咳嗽(GERC)的诊断价值。共有 171 名慢性咳嗽患者入选,诊断和治疗均按照慢性咳嗽诊断和治疗方案进行。收集唾液和诱导痰,用 Peptest™ 测定胃蛋白酶浓度。填写胃食管反流诊断问卷(GerdQ)。分析并比较了唾液和诱导痰中胃蛋白酶浓度对 GERC 的诊断价值。最佳临界值为 76.10 ng-mL-1,灵敏度为 83.58%,特异度为 82.69%。诱导痰上清液中的胃蛋白酶浓度对 GREC 的 AUC 为 0.523。当使用 GerdQ 诊断 GERC 时,AUC 为 0.670,与 GerdQ 相比,唾液胃蛋白酶的诊断价值更高(DeLong 检验,P=0.0008)。在酸性 GERC 中,唾液胃蛋白酶的诊断价值与 GerdQ 相当(AUC=0.779vs0.826;p=0.4199)。与 GerdQ 相比,唾液胃蛋白酶具有更高的诊断价值(AUC=0.830versus0.533;p76.10 ng-mL-1),对 GERC 具有良好的诊断价值,尤其是在非酸性 GERC 中。诱导痰中胃蛋白酶浓度的诊断价值较低。
{"title":"Diagnostic value of the pepsin concentration in saliva and induced sputum for gastroesophageal reflux-induced chronic cough: a prospective clinical study","authors":"Wenhua Gu, Wei Chen, Tongyangzi Zhang, Yiqing Zhu, Wanzhen Li, Wenbo Shi, Na Li, Shengyuan Wang, Xianghuai Xu, Li Yu","doi":"10.1183/23120541.00046-2024","DOIUrl":"https://doi.org/10.1183/23120541.00046-2024","url":null,"abstract":"To determine the diagnostic value of the pepsin concentration in saliva and induced sputum for gastroesophageal reflux-induced chronic cough (GERC).A total of 171 patients with chronic cough were enrolled. The diagnosis and treatment followed the chronic cough diagnosis and treatment protocol. Saliva and induced sputum were collected, and the pepsin concentration was determined using Peptest™. A gastroesophageal reflux diagnostic questionnaire (GerdQ) was completed. The diagnostic value of the pepsin concentration in saliva and induced sputum for GERC was analyzed and compared.The salivary pepsin concentration predicted GERC with an area under the receiver operating characteristic curve (AUC) of 0.845. The optimal cut-off value was 76.10 ng·mL−1, the sensitivity 83.58%, and the specificity 82.69%. The pepsin concentration in the induced sputum supernatant for GREC had an AUC of 0.523. When GerdQ was used for GERC diagnosis, the AUC was 0.670, and the diagnostic value of salivary pepsin was better compared to GerdQ (DeLong's test, p=0.0008). Salivary pepsin had a comparable diagnostic value to GerdQ (AUC=0.779versus0.826; p=0.4199) in acidic GERC. Salivary pepsin had superior diagnostic value compared to GerdQ (AUC=0.830versus0.533; p<0.0001) in non-acidic GERC.A salivary pepsin concentration >76.10 ng·mL−1is of good diagnostic value for GERC, especially in non-acidic GERC. The pepsin concentration in induced sputum has a low diagnostic value.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":" 37","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140685091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patients at risk of NTM-PD who need testing evaluated using a modified Delphi process by European experts 欧洲专家采用修改后的德尔菲程序,对需要检测的有 NTM-PD 风险的患者进行评估
Pub Date : 2024-04-19 DOI: 10.1183/23120541.00791-2023
Michael R. Loebinger, S. Aliberti, Charles Haworth, M. Janković Makek, Christoph Lange, N. Lorent, A. Papavasileiou, E. Polverino, Gernot Rohde, Nicolas Veziris, Dirk Wagner, J. van Ingen
Identifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality.European NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for NTM.Experts reached a consensus on the symptoms and comorbidities that should and should not prompt NTM testing. Requirements for testing were scored as high (mean ≥7), medium (mean 4–6), or low (mean ≤4). NTM testing should be undertaken when multiple suggestive symptoms are present simultaneously in all patients except those with cancer (7.3–8.8), or when radiology is indicative of NTM-PD (≥8.9). Symptoms of persistent sputum production, recurrent respiratory infection, and haemoptysis should prompt NTM testing, particularly in those with underlying respiratory diseases. Symptomatic patients with bronchiectasis or previous tuberculosis/NTM-PD or those being prescribed or undergoing long-term macrolide therapy for a respiratory condition should also be tested. Testing is not warranted in patients without an underlying respiratory disorder or in those without a history of respiratory disorders unless presenting with multiple symptoms.Assessing patients’ risk of NTM-PD is challenging. This Delphi consensus process provides insight into symptoms and clinical characteristics that should prompt NTM-PD assessment. Timely testing and diagnosis would enable initiation of appropriate management.
识别非结核分枝杆菌肺病(NTM-PD)高危患者具有挑战性。欧洲非结核分枝杆菌肺病专家(n=12)参与了三轮改良德尔菲程序,对可能与非结核分枝杆菌肺病相关的症状和合并症进行评分,并将其作为检测非结核分枝杆菌的理由。检测要求分为高(平均值≥7)、中(平均值4-6)或低(平均值≤4)。除癌症患者(7.3-8.8 分)外,当所有患者同时出现多种提示症状时,或当放射学检查提示 NTM-PD(≥8.9 分)时,应进行 NTM 检测。出现持续痰量、反复呼吸道感染和咯血等症状时,应及时进行NTM检测,尤其是患有基础呼吸道疾病的患者。支气管扩张或曾患肺结核/NTM-PD 的无症状患者,或正在处方或因呼吸道疾病长期接受大环内酯类药物治疗的患者也应接受检测。对于没有潜在呼吸系统疾病或没有呼吸系统疾病史的患者,除非出现多种症状,否则不需要进行检测。本德尔菲共识程序提供了有关症状和临床特征的见解,这些症状和特征应促使对 NTM-PD 进行评估。及时检测和诊断将有助于启动适当的管理。
{"title":"Patients at risk of NTM-PD who need testing evaluated using a modified Delphi process by European experts","authors":"Michael R. Loebinger, S. Aliberti, Charles Haworth, M. Janković Makek, Christoph Lange, N. Lorent, A. Papavasileiou, E. Polverino, Gernot Rohde, Nicolas Veziris, Dirk Wagner, J. van Ingen","doi":"10.1183/23120541.00791-2023","DOIUrl":"https://doi.org/10.1183/23120541.00791-2023","url":null,"abstract":"Identifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality.European NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for NTM.Experts reached a consensus on the symptoms and comorbidities that should and should not prompt NTM testing. Requirements for testing were scored as high (mean ≥7), medium (mean 4–6), or low (mean ≤4). NTM testing should be undertaken when multiple suggestive symptoms are present simultaneously in all patients except those with cancer (7.3–8.8), or when radiology is indicative of NTM-PD (≥8.9). Symptoms of persistent sputum production, recurrent respiratory infection, and haemoptysis should prompt NTM testing, particularly in those with underlying respiratory diseases. Symptomatic patients with bronchiectasis or previous tuberculosis/NTM-PD or those being prescribed or undergoing long-term macrolide therapy for a respiratory condition should also be tested. Testing is not warranted in patients without an underlying respiratory disorder or in those without a history of respiratory disorders unless presenting with multiple symptoms.Assessing patients’ risk of NTM-PD is challenging. This Delphi consensus process provides insight into symptoms and clinical characteristics that should prompt NTM-PD assessment. Timely testing and diagnosis would enable initiation of appropriate management.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":" 32","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140682701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Altered circadian gene expression in primary human airway epithelial cells in asthma 哮喘患者原代气道上皮细胞中昼夜节律基因表达的改变
Pub Date : 2024-04-19 DOI: 10.1183/23120541.00005-2024
W.T. Powell, Lindsay V. Clark, L. M. Rich, E. Vanderwall, Camille Gates, M. White, J. Debley
{"title":"Altered circadian gene expression in primary human airway epithelial cells in asthma","authors":"W.T. Powell, Lindsay V. Clark, L. M. Rich, E. Vanderwall, Camille Gates, M. White, J. Debley","doi":"10.1183/23120541.00005-2024","DOIUrl":"https://doi.org/10.1183/23120541.00005-2024","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":" 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140684557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcriptomics using lung resection material to advance our understanding of COPD and IPF pathogenesis 利用肺切除材料进行转录组学研究,促进我们对慢性阻塞性肺病和 IPF 发病机制的了解
Pub Date : 2024-04-19 DOI: 10.1183/23120541.00061-2024
K. Rakkar, Dhruma Thakkar, M. Portelli, Ian Hall, Holger Schlüter, Ian Sayers
{"title":"Transcriptomics using lung resection material to advance our understanding of COPD and IPF pathogenesis","authors":"K. Rakkar, Dhruma Thakkar, M. Portelli, Ian Hall, Holger Schlüter, Ian Sayers","doi":"10.1183/23120541.00061-2024","DOIUrl":"https://doi.org/10.1183/23120541.00061-2024","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":" 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140684221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic role of haemodynamics at follow-up in patients with pulmonary arterial hypertension: a challenge to current ESC/ERS risk tools 肺动脉高压患者随访血流动力学的预后作用:对当前ESC/ERS风险工具的挑战
Pub Date : 2024-04-19 DOI: 10.1183/23120541.00225-2024
F. Dardi, D. Guarino, A. Ballerini, R. Bertozzi, F. Donato, Francesco Cennerazzo, Monica Salvi, Elena Nardi, I. Magnani, A. Manes, N. Galiè, M. Palazzini
Hemodynamic variables like right atrial pressure (RAP), cardiac index (CI), stroke volume index (SVI) and mixed venous oxygen saturation (SvO2) predict survival in patients with pulmonary arterial hypertension (PAH). However, there is the need to identify further prognostic haemodynamic parameters as well as to redefine their role in PAH risk stratification compared to current risk tools and non-invasive parameters.this cohort-study includes treatment-naïve patients assessed at baseline and after first line PAH therapy with clinical, functional, exercise, laboratory, and haemodynamic evaluations. Using a stepwise multivariate Cox regression analysis, independent prognostic haemodynamic parameters were identified and stratified according to cut-offs already defined in the ESC/ERS risk table or defined based on the highest chi2 of the log-rank test. Their discriminatory power was tested for all-cause death and a combined endpoint of death, hospitalization and need of treatment escalation.794 patients with PAH were enrolled. At first follow-up, RAP and pulmonary artery elastance were independently associated with death. Because of high correlations different multivariable analyses were done identifying other six variables (pulmonary arterial compliance, cardiac efficiency, pulmonary vascular resistance, SvO2, CI and SVI). Haemodynamic parameters were of no added prognostic value compared to ESC/ERS risk tools for the all-cause death endpoint, but, for the combined endpoint, are of added value to non-invasive parameters and, when taken alone, had a discriminatory capacity comparable to ESC/ERS risk tools.haemodynamics discriminative-ability for clinical worsening is comparable to current ESC/ERS risk tools and is of added value to non-invasive parameters.
右心房压(RAP)、心脏指数(CI)、每搏量指数(SVI)和混合静脉血氧饱和度(SvO2)等血液动力学变量可预测肺动脉高压(PAH)患者的生存期。然而,与目前的风险工具和非侵入性参数相比,有必要确定更多预后血流动力学参数,并重新定义它们在 PAH 风险分层中的作用。这项队列研究包括在基线和一线 PAH 治疗后接受临床、功能、运动、实验室和血流动力学评估的治疗无效患者。通过逐步多变量 Cox 回归分析,确定了独立的预后血流动力学参数,并根据 ESC/ERS 风险表中已定义的临界值或根据对数秩检验的最高 chi2 进行了分层。对全因死亡以及死亡、住院和需要升级治疗等综合终点的判别能力进行了测试。首次随访时,RAP和肺动脉弹性与死亡有独立关联。由于存在高度相关性,因此对其他六个变量(肺动脉顺应性、心脏效率、肺血管阻力、SvO2、CI 和 SVI)进行了不同的多变量分析。就全因死亡终点而言,血流动力学参数与 ESC/ERS 风险工具相比没有额外的预后价值,但就综合终点而言,血流动力学参数与无创参数相比具有额外的价值,而且单独使用时,血流动力学参数对临床恶化的判别能力与当前的 ESC/ERS 风险工具相当,与无创参数相比具有额外的价值。
{"title":"Prognostic role of haemodynamics at follow-up in patients with pulmonary arterial hypertension: a challenge to current ESC/ERS risk tools","authors":"F. Dardi, D. Guarino, A. Ballerini, R. Bertozzi, F. Donato, Francesco Cennerazzo, Monica Salvi, Elena Nardi, I. Magnani, A. Manes, N. Galiè, M. Palazzini","doi":"10.1183/23120541.00225-2024","DOIUrl":"https://doi.org/10.1183/23120541.00225-2024","url":null,"abstract":"Hemodynamic variables like right atrial pressure (RAP), cardiac index (CI), stroke volume index (SVI) and mixed venous oxygen saturation (SvO2) predict survival in patients with pulmonary arterial hypertension (PAH). However, there is the need to identify further prognostic haemodynamic parameters as well as to redefine their role in PAH risk stratification compared to current risk tools and non-invasive parameters.this cohort-study includes treatment-naïve patients assessed at baseline and after first line PAH therapy with clinical, functional, exercise, laboratory, and haemodynamic evaluations. Using a stepwise multivariate Cox regression analysis, independent prognostic haemodynamic parameters were identified and stratified according to cut-offs already defined in the ESC/ERS risk table or defined based on the highest chi2 of the log-rank test. Their discriminatory power was tested for all-cause death and a combined endpoint of death, hospitalization and need of treatment escalation.794 patients with PAH were enrolled. At first follow-up, RAP and pulmonary artery elastance were independently associated with death. Because of high correlations different multivariable analyses were done identifying other six variables (pulmonary arterial compliance, cardiac efficiency, pulmonary vascular resistance, SvO2, CI and SVI). Haemodynamic parameters were of no added prognostic value compared to ESC/ERS risk tools for the all-cause death endpoint, but, for the combined endpoint, are of added value to non-invasive parameters and, when taken alone, had a discriminatory capacity comparable to ESC/ERS risk tools.haemodynamics discriminative-ability for clinical worsening is comparable to current ESC/ERS risk tools and is of added value to non-invasive parameters.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":" 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140683810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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