ERJ Open Research最新文献

{"title":"Brensocatib in non–cystic fibrosis bronchiectasis: ASPEN protocol/baseline characteristics","authors":"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","doi":"10.1183/23120541.00151-2024","DOIUrl":"https://doi.org/10.1183/23120541.00151-2024","url":null,"abstract":"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.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656325","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}

{"title":"Randomised, phase 1/2a trial of ION-827359, an antisense oligonucleotide inhibitor of ENaC","authors":"Sivagurunathan Sutharsan, Rainald Fischer, Wolfgang Gleiber, Alexander Horsley, Jeff Crosby, Shuling Guo, Shuting Xia, Rosie Yu, Kenneth B Newman, J. S. Elborn","doi":"10.1183/23120541.00986-2023","DOIUrl":"https://doi.org/10.1183/23120541.00986-2023","url":null,"abstract":"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.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655633","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}

{"title":"A robust web-based tool to predict viral shedding in patients with Omicron SARS-CoV-2 variants","authors":"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","doi":"10.1183/23120541.00939-2023","DOIUrl":"https://doi.org/10.1183/23120541.00939-2023","url":null,"abstract":"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/).","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140684611","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}

{"title":"Epidemiology of patients with severe asthma in Japan: a nationwide descriptive study","authors":"Yuya Kimura, M. Suzukawa, T. Jo, Yohei Hashimoto, R. Kumazawa, M. Ishimaru, H. Matsui, A. Yokoyama, Goh Tanaka, Hideo Yasunaga","doi":"10.1183/23120541.00122-2024","DOIUrl":"https://doi.org/10.1183/23120541.00122-2024","url":null,"abstract":"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.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140685699","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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}