ERJ Open Research最新文献

{"title":"The preclinical and Phase 1 development of the novel oral cathepsin C inhibitor BI 1291583","authors":"James D. Chalmers, P. Badorrek, Claudia Diefenbach, Harald Kögler, Wiebke Sauter, Stefan Kreideweiss, Jens M Hohlfeld","doi":"10.1183/23120541.00725-2023","DOIUrl":"https://doi.org/10.1183/23120541.00725-2023","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139593261","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":"Use of CompEx in eosinophilic patients with severe, uncontrolled asthma on benralizumab","authors":"Clare Bolton, Tim Harrison, N. Lugogo, Anne Fuhlbrigge, Ian Hirsch, Thomas Bengtsson, Stefan Peterson, Martin Sidaway, Esther Garcia Gil, M. Fagerås, Carla A Da Silva","doi":"10.1183/23120541.01025-2023","DOIUrl":"https://doi.org/10.1183/23120541.01025-2023","url":null,"abstract":"CompEx Asthma, a composite endpoint for asthma exacerbations, captures clinically relevant, diary-based acute worsening events (AWEs, defined as deterioration in daily peak expiratory flow concurrent with deterioration in asthma symptoms and/or rescue therapy use) and severe exacerbation events (SevEx, defined by ATS/ERS guidelines). We hypothesised that CompEx and SevEx would show similar benralizumab treatment effects and correlations to blood eosinophil counts (BECs) in patients with severe asthma.Thispost-hocanalysis of pooled 12-month data from two Phase III studies included patients aged ≥16 years with severe, uncontrolled asthma who were randomised to benralizumab 30 mg or placebo. Annualised event rates (AERs) were analysed using a negative binomial model. The impact of BEC on treatment effect was assessed.Among patients with BEC ≥300 cells/µL (n=913), benralizumab reduced AERsversusplacebo for CompEx (1.57versus2.57; risk ratio [RR] 0.61; 95% confidence interval [CI] 0.53–0.70; p<0.001), SevEx (0.94versus1.55; RR 0.60; 95% CI 0.52–0.70; p<0.001) and AWE (0.92versus1.57; RR 0.59; 95% CI 0.48–0.72; p<0.001), with greater treatment effects observed for higher BECs. In patients with BEC ≥300 cells/µL, benralizumab was associated with shorter median event duration (CompEx: 10.5versus17.0 days; SevEx: 10.0versus15.0 days; AWE: 5.0versus6.0 days).Benralizumab reduced the risk of CompEx events with treatment effects similar to those for SevEx and AWEs across a range of BECs. Use of CompEx supports the evaluation of benralizumab and other novel drugs in clinical studies.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139593777","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":"Adjustments to maintenance therapy and the reasoning behind them among COPD outpatients in Austria: the STEP study","authors":"Florian Vafai-Tabrizi, Ulrich Schwab, Stephan Brecht, Georg-Christian Funk","doi":"10.1183/23120541.00615-2023","DOIUrl":"https://doi.org/10.1183/23120541.00615-2023","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139594004","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":"The rate of hypercapnic respiratory failure in a pulmonary function test lab database","authors":"S. Fortis, Becky Skinner, A. Comellas","doi":"10.1183/23120541.01016-2023","DOIUrl":"https://doi.org/10.1183/23120541.01016-2023","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139595428","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":"PAP telehealth models and long-term therapy termination: a healthcare database analysis","authors":"Holger Woehrle, C. Schoebel, Joachim H. Ficker, A. Graml, Jürgen Schnepf, Ingo Fietze, P. Young, Michael Arzt","doi":"10.1183/23120541.00424-2023","DOIUrl":"https://doi.org/10.1183/23120541.00424-2023","url":null,"abstract":"Telemonitoring-guided interventions can improve short-term positive airway pressure (PAP) therapy adherence, but long-term effects are unknown. This study investigated long-term PAP therapy termination in patients with sleep apnoea managed with standard care, telemonitoring-guided proactive care, or telemonitoring-guided proactive care+patient engagement tool. German healthcare provider data were analysed retrospectively. Individuals aged 18–100 years who started PAP from 2014–2019 and had device type/interface data were included. Time-to-termination periods were analysed using Kaplan-Meier plots and Cox proportional hazards regression, adjusted for age, sex, insurance type, and device and mask type. The per-protocol population (valid telemonitoring data) included 104 612 individuals (71% male; 95% aged >40 years). Mean follow-up was 3.3±2.0 years. The overall therapy termination rate was significantly lower in the telemonitoring-guided proactive care groupversusstandard care (20%versus27%; p<0.001), and even lower in the telemonitoring-guided care+patient engagement tool group (11%; p<0.001versusother treatment groups). Adjusted risk of therapy termination was lowerversusstandard care (hazard ratio [95% confidence interval]: 0.76 [0.74–0.78] and 0.41 [0.38–0.44] for telemonitoring-guided proactive care alone and+patient engagement). Age <50 or >59 years and use of a nasal pillows or full-face mask were significant predictors of therapy termination; male sex, use of telemonitoring-guided proactive care (± patient engagement), and private insurance were significantly associated with lower therapy termination rates. Use of telemonitoring-guided proactive care and a patient engagement tool was associated with lower rates of PAP therapy termination.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139593848","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":"Real-world walking cadence in people with COPD","authors":"Laura Delgado-Ortiz, Saverio Ranciati, A. Arbillaga-Etxarri, Eva Balcells, J. Buekers, H. Demeyer, Anja Frei, E. Gimeno-Santos, N. Hopkinson, Corina de Jong, Niklas Karlsson, Z. Louvaris, L. Palmerini, M. I. Polkey, M. Puhan, Roberto A. Rabinovich, Diego A. Rodríguez Chiaradia, Robert Rodriguez-Roisin, Pere Torán-Montserrat, Ioannis Vogiatzis, Henrik Watz, Thierry Troosters, J. Garcia-Aymerich","doi":"10.1183/23120541.00673-2023","DOIUrl":"https://doi.org/10.1183/23120541.00673-2023","url":null,"abstract":"The clinical validity of real-world walking cadence in people with chronic obstructive pulmonary disease (COPD) is unsettled. Objective: to assess the levels, variability and association with clinically relevant COPD characteristics and outcomes of real-world walking cadence.We assessed walking cadence (steps per minute during walking bouts >10 s) from 7-days accelerometer data in 593 individuals with COPD from five European countries, and clinical and functional characteristics from validated questionnaires and standardised tests. Severe exacerbations during 12-months follow-up were recorded from patient reports and medical registries.Participants were mostly male (80%) and had mean (sd) age 68 (8) years, post-bronchodilator FEV157 (19)%, and 6880 (3926) steps/day. Mean walking cadence was 88 steps/min, followed a normal distribution (sd=9), and was highly stable within-person (ICC 0.92 (95%CI 0.90–0.93)). After adjusting for age, sex, height and number of walking bouts in fractional polynomial or linear regressions, walking cadence was positively associated with FEV1,6-min walk distance, physical activity (steps/day, time in moderate-to-vigorous physical activity, vector magnitude units, walking time, intensity during locomotion), physical activity experience and health-related quality of life; and negatively associated with breathlessness and depression (all p<0.05). These associations remained after further adjustment for daily steps. In negative binomial regression adjusted for multiple confounders, walking cadence related to lower number of severe exacerbations during follow-up (IRR 0.94 per step/min, 95%CI 0.91–0.99, p=0.009).Higher real-world walking cadence is associated with better COPD status and lower severe exacerbations risk, which makes it attractive as future prognostic marker and clinical outcome.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139594342","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":"Clinical, tomographic, and functional comparison of sporadic and associated tuberous sclerosis complex forms of LAM: a retrospective cohort study","authors":"Martina Rodrigues de Oliveira, Mark Wanderley, Carolina Salim, Gonçalves Freitas, R. Kairalla, R. Chate, A. F. Amaral, F. E. Arimura, L. P. Samorano, Elieser Hitoshi Watanabe, C. R. Carvalho, B. Baldi","doi":"10.1183/23120541.00759-2023","DOIUrl":"https://doi.org/10.1183/23120541.00759-2023","url":null,"abstract":"Lymphangioleiomyomatosis (LAM) is a rare disease that can occur sporadically (S-LAM) or associated with the tuberous sclerosis complex (TSC-LAM). The natural history of LAM is not completely understood, including whether there is a difference between the clinical courses of the two forms. This study aimed to compare the clinical, functional, and tomographic features between S-LAM and TSC-LAM, and evaluate the annual rates of change in lung function.This retrospective cohort study included patients with LAM followed up between 1994 and 2019. Clinical, functional and imaging variables were evaluated, and the lung cysts were automatically quantified. Quality of life and predictors of lung function impairment were accessed, and the annual rate of lung function decline was compared between S-LAM and TSC-LAM.Of the 107 patients included, 77 had S-LAM and 30 had TSC-LAM. Although patients with TSC-LAM had a higher prevalence of renal angiomyolipomas and neurological and dermatological manifestations, pulmonary function tests were similar. Patients with S-LAM had a greater rate of FEV1decline and a higher extent of cysts. Pneumothorax, desaturation in the six-minute walking test and a higher extent of lung cysts were predictors of functional impairment. A greater impact on vitality and emotional health was observed in the TSC-LAM.Greater functional decline and a higher cystic extension were found in patients with S-LAM. Our study provides a broad clinical, functional, and tomographic characterisation of patients with LAM, adding valuable information to the existing evidence to better understand the two forms of the disease.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139594486","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":"Mild obstructive sleep apnoea in females: post hoc analysis of the MERGE randomised controlled trial","authors":"A. Wimms, Julia L Kelly, Christopher D Turnbull, A. McMillan, Sonya E Craig, John F O'Reilly, A. Nickol, Meredith D Decker, L. Willes, Peter M A Calverley, Adam V Benjafield, J. R. Stradling, Mary J Morrell","doi":"10.1183/23120541.00574-2023","DOIUrl":"https://doi.org/10.1183/23120541.00574-2023","url":null,"abstract":"A post-hoc analysis of the MERGE trial was conducted, to investigate whether sex differences are evident at the mildest end of the disease spectrum, for symptoms associated with Obstructive Sleep Apnoea (OSA) and the response to continuous positive airway pressure (CPAP) treatment.MERGE participants with mild OSA (AHI 5–15 events/hour; AASM 2012 criteria) were randomised to either CPAP plus standard care (sleep hygiene counselling), or standard care alone for 3 months. Quality of life (QoL) was measured by questionnaires completed before and after the 3-months. This post-hoc analysis of participants of the MERGE trial compared the symptom presentation, and response to CPAP, between the sexes.233 patients were included; 71 (30%) were female. Females were more symptomatic at baseline in all QoL questionnaires. Specifically, females had lower SF-36 Vitality scores (mean(sd) 39.1(10.1)versus44.8(10.3)), and higher Epworth sleepiness scale (ESS) scores (11.0(4.2)versus9.5(4.4)). Both sexes experienced snoring, but more females reported fatigue and more males reported witnessed apnoeas. All symptoms improved with CPAP for both sexes; however, females had larger improvements in Vitality scores, which was the primary outcome of the MERGE trial (mean change(95%CI) +9.4(6.8, 12.0)versus+6.0(4.3, 7.7) p=0.034) and ESS (−4.1(−5.1, −3.0)versus−2.5(−3.1, −1.8) p=0.015), after adjustment for baseline scores and CPAP usage.Sex differences are apparent in patients with mild OSA. Females experience worse QoL symptoms than males at presentation to sleep clinic; however, these improve significantly with CPAP treatment.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139595285","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":"Comparison of CMR, functional and haemodynamic variables in PAH: Insights from REPAIR","authors":"D. Kiely, Richard W. Channick, D. Flores, N. Galiè, Gwen MacDonald, Tim Marcus, Lada Mitchell, Andrew J. Peacock, Stephan Rosenkranz, Ahmed Tawakol, A. Torbicki, A. Noordegraaf, Andrew J Swift","doi":"10.1183/23120541.00547-2023","DOIUrl":"https://doi.org/10.1183/23120541.00547-2023","url":null,"abstract":"Measures that can detect large treatment effects are important for monitoring therapeutic effectiveness. The 2022 ESC/ERS Guidelines highlight the importance of imaging in monitoring disease status and treatment response in pulmonary arterial hypertension (PAH). Are the standardised treatment effect sizes (STES) of cardiac magnetic resonance imaging (CMR) comparable with functional and haemodynamic variables?REPAIR (NCT02310672) was a prospective, multicentre, single-arm, open-label, 52-week Phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition (PDE-5i), on right ventricular (RV) remodelling, cardiac function, and cardiopulmonary haemodynamics. Both CMR and functional assessments were performed at screening, and at Weeks 26 and 52; haemodynamic measurements were conducted at screening and Week 26. In thispost-hocanalysis, STES was estimated using the parametric Cohen's d and non-parametric Cliff's delta tests.At Week 26, large STES (Cohen's d) were observed for 10/20 CMR variables, including the prognostic measures of RV and left ventricular stroke volume and RV ejection fraction and the haemodynamic trial endpoint, pulmonary vascular resistance; medium STES were observed for 6-minute walk distance (6MWD). The STES were consistent in treatment-naïve patients and those escalating therapy and maintained at Week 52. Similar results were obtained using the non-parametric Cliff's delta method.The treatment effect of macitentan, alone or in combination with a PDE-5i, was comparable for several CMR and haemodynamic variables with prognostic value in PAH, and greater than that of 6MWD in patients with PAH, highlighting the emerging relevance of CMR in PAH.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139618024","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":"Next-generation sequencing reveals genetic heterogeneity and resistant mechanisms in patients withEGFR-mutated non-small cell lung cancer treated with afatinib","authors":"Sheng-Kai Liang, Pin-Fei Wei, Min-Shu Hsieh, Chia-Ling Wu, Jin-Yuan Shih","doi":"10.1183/23120541.00676-2023","DOIUrl":"https://doi.org/10.1183/23120541.00676-2023","url":null,"abstract":"Afatinib, an irreversible ErbB Family inhibitor, is widely used as first-line treatment for advanced lung adenocarcinoma patients harboring with mutant epidermal growth factor receptor (EGFR). With the advancements in next-generation sequencing (NGS), comprehensive research into the clinical impact of co-occurring genetic mutations and the molecular mechanisms of acquired resistance is required for afatinib users.From January 2010 to December 2019, we retrieved patients with advanced lung adenocarcinoma withEGFRmutations using afatinib as first-line treatment, and we retrospectively collected pre- and post-afatinib treatment specimens from these patients for NGS testing.Of the 362 enrolled patients, 73 samples (68.9%) from 56 patients successfully returned complete NGS reports. In pre-afatinib treatment specimens, the most frequent co-occurring alterations wereTP53,MUC16,USH2A,SNYE1,RECQL4, andFAT1; however, they were not related to progression-free survival. SCLC transformation,EGFRp.T790M, amplification ofMET,ERBB2,KRAS,EGFR, cell cycle-regulated genes, andMDM2,andPTENalterations were identified as acquired resistance mechanisms.EGFRp.T790M (p=0.0304) andAPCalterations (p=0.0311) in post-afatinib specimens were significantly associated with longer overall survival (OS), whileMETamplification was significantly associated with poor OS (p=0.0324). The co-existence ofTP53alterations was significantly associated with a shorter OS (p=0.0298).Our results show that the frequent co-occurring alterations in advancedEGFR-mutant lung adenocarcinoma did not influence the effectiveness of afatinib.EGFRp.T790M is not only the major resistance mechanism to afatinib but also related to favorable survival outcomes.METamplification andTP53mutations were poor factors for OS.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139618082","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}