ERJ Open Research最新文献

{"title":"Clinical improvements after endoscopic lung volume reduction with valves in patients with advanced emphysema and a 6-min walk test ≤140 m at baseline.","authors":"Jacopo Saccomanno, Lara Kilic, Thomas Sgarbossa, Konrad Neumann, Franz Stanzel, Angelique Holland, Christian Grah, Wolfgang Gesierich, Joanna Krist, Joachim H Ficker, Stephan Eggeling, Stefan Andreas, Bernd Schmidt, Stephan Eisenmann, Björn Schwick, Karl-Josef Franke, Andreas Fertl, Martin Witzenrath, Ralf-Harto Hübner","doi":"10.1183/23120541.00410-2024","DOIUrl":"10.1183/23120541.00410-2024","url":null,"abstract":"<p><strong>Background: </strong>Data regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with a very low 6-min walk test (6MWT) are limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutic benefits and increased complication risk.</p><p><strong>Study designs and methods: </strong>This study utilised data from the Lungenemphysemregister e.V., a large German national multi-centre prospective open-label clinical trial, and aimed to assess the outcomes of ELVR in patients with a baseline 6MWT ≤140 m and dyspnoea primarily attributed to hyperinflation.</p><p><strong>Results: </strong>54 patients with a baseline 6MWT ≤140 m and 365 patients with a baseline 6MWT between 140 and 450 m were included in the study. Baseline characteristics were representative for patients with advanced lung emphysema. Patients with a 6MWT ≤140 m at baseline had a lower forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide and higher symptom burden. In the 3-month follow-up, patients of both groups showed statistically significant improvements in lung function parameters, exercise capacity and quality of life parameters compared to baseline. Patients with a 6MWT ≤140 m at baseline showed significantly more 6MWT improvement compared to patients with baseline 6MWT between 140 and 450 m. Moreover, complication rates were similar in both groups.</p><p><strong>Interpretation: </strong>In summary, the data indicate that ELVR may be an effective and safe treatment for emphysema patients with a very low 6MWT of ≤140 m if very limited exercise capacity is predominately caused by lung emphysema. Therefore future studies should include emphysema patients with a very low 6MWT.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of follow-up algorithms for chronic thromboembolic pulmonary hypertension in pulmonary embolism survivors.","authors":"Dieuwke Luijten, Wilbert B van den Hout, Gudula J A M Boon, Stefano Barco, Harm Jan Bogaard, Marion Delcroix, Karl-Friedrich Kreitner, Matthias Held, Menno V Huisman, Luis Jara-Palomares, Stavros V Konstantinides, Lucia J M Kroft, Albert T A Mairuhu, Lilian J Meijboom, Thijs E van Mens, Maarten K Ninaber, Esther J Nossent, Piotr Pruszczyk, Luca Valerio, Anton Vonk Noordegraaf, Frederikus A Klok","doi":"10.1183/23120541.00575-2024","DOIUrl":"10.1183/23120541.00575-2024","url":null,"abstract":"<p><strong>Introduction: </strong>Achieving an early diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in pulmonary embolism (PE) survivors results in better quality of life and survival. Importantly, dedicated follow-up strategies to achieve an earlier CTEPH diagnosis involve costs that were not explicitly incorporated in the models assessing their cost-effectiveness. We performed an economic evaluation of 11 distinct PE follow-up algorithms to determine which should be preferred.</p><p><strong>Materials and methods: </strong>11 different PE follow-up algorithms and one hypothetical scenario without a dedicated CTEPH follow-up algorithm were included in a Markov model. Diagnostic accuracy of consecutive tests was estimated from patient-level data of the InShape II study (n=424). The lifelong costs per CTEPH patient were compared and related to quality-adjusted life-years (QALYs) for each scenario.</p><p><strong>Results: </strong>Compared to not performing dedicated follow-up, the integrated follow-up algorithms are associated with an estimated increase of 0.89-1.2 QALYs against an incremental cost-effectiveness ratio (ICER) of EUR 25 700-46 300 per QALY per CTEPH patient. When comparing different algorithms with each other, the maximum differences were 0.27 QALYs and EUR 27 600. The most cost-effective algorithm was the InShape IV algorithm, with an ICER of EUR 26 700 per QALY compared to the next best algorithm.</p><p><strong>Conclusion: </strong>Subjecting all PE survivors to any of the currently established dedicated follow-up algorithms to detect CTEPH is cost-effective and preferred above not performing a dedicated follow-up, evaluated against the Dutch acceptability threshold of EUR 50 000 per QALY. The model can be used to identify the locally preferred algorithm from an economical point-of-view within local logistical possibilities.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of environmental exposures on exhaled breath and lung function: NELA Birth Cohort.","authors":"Rosa A Sola-Martínez, Pedro Jiménez-Guerrero, Manuel Sánchez-Solís, Gema Lozano-Terol, Julia Gallego-Jara, Adrián Martínez-Vivancos, Eva Morales, Luis García-Marcos, Teresa de Diego Puente","doi":"10.1183/23120541.00597-2024","DOIUrl":"10.1183/23120541.00597-2024","url":null,"abstract":"<p><strong>Introduction: </strong>Exposure to environmental factors (<i>i.e.</i> air pollution and second-hand tobacco smoke) have been associated with impaired lung function. However, the impact of environmental factors on lung health is usually evaluated separately and not with an exposomic framework. In this regard, breath analysis could be a noninvasive tool for biomonitoring of global human environmental exposure.</p><p><strong>Methods: </strong>Data come from 337 mother-child pairs from the Nutrition in Early Childhood Asthma (NELA) birth cohort. Levels of BTEX (benzene, toluene, ethylbenzene and xylenes) in exhaled breath from mothers and children at 3 months after birth were estimated using gas chromatography-mass spectrometry. Short-term residential exposures (breath sampling day and 15 days before breath sampling) to nitrogen dioxide, particulate matter (PM_2.5) and ozone were determined by chemical dispersion/transport modelling. Forced vital capacity, forced expiratory volume in 0.5 s (FEV_0.5) and forced expiratory flow at 75% of FVC and at 25%-75% of FVC were measured in infants according to the raised-volume rapid thoracoabdominal compression technique.</p><p><strong>Results: </strong>The results showed significant associations between short-term exposure to external agents and levels of benzene and toluene in exhaled breath. It was observed that exhaled levels of benzene and toluene were influenced by smoking status and outdoor air pollution in mothers, and by air pollution in infants (3 months of age). No significant relationship was observed between exposure to maternal tobacco smoking and/or short-term air pollution and lung function in healthy infants. However, there was a significant relationship between FEV_0.5 and exhaled toluene in children.</p><p><strong>Discussion: </strong>These findings indicated a significant relationship between environmental exposures and exhaled levels of benzene and toluene, suggesting that breath analysis could be a helpful exposure biomonitoring tool.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote monitoring of patients with COPD disease using a tablet system: a randomised crossover study of quality-of-life measurements.","authors":"Malte Frerichs, Huiqi Li, Anders Andersson, Kristina Andelid, Monica Crona, Lowie E G W Vanfleteren","doi":"10.1183/23120541.00532-2024","DOIUrl":"10.1183/23120541.00532-2024","url":null,"abstract":"<p><strong>Background: </strong>Remote patient monitoring (RPM) has been evaluated in COPD, but with varying results. We aimed to evaluate whether a tablet system that monitors disease-related parameters in patients with COPD could influence physical and mental health-related quality of life, compared with usual care (UC).</p><p><strong>Methods: </strong>70 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D COPD (61% women, aged 71±8 years, forced expiratory volume in 1 s % predicted 41±13%, COPD Assessment Test (CAT) 19±7 points) were recruited at the COPD centre in Gothenburg, Sweden, and randomised to a tablet-based RPM system or UC for a 26-week period, after which they crossed over to the alternative management for another 26 weeks. The Short Form-12 (SF-12) (primary outcome), CAT, modified Medical Research Council (mMRC) Dyspnoea Scale, EuroQol-5 Dimensions (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) were evaluated at four visits. Exacerbations were continuously reported, as was adherence to RPM.</p><p><strong>Results: </strong>59 patients completed the study: 28 patients randomised to start with UC and 31 randomised to start with RPM. The changes in the SF-12 Physical Component Summary (PCS) (UC: -1.17±6.90 <i>versus</i> RPM: -1.06±8.15) and Mental Component Summary (MCS) (UC: 0.63±11.14 <i>versus</i> RPM: -0.63±8.15), as well as in CAT, the mMRC scale, the EQ-5D, HADS anxiety, HADS depression and number of exacerbations, were similar in both intervention periods. Neither the 26-week UC period nor the intervention significantly affected the measured outcomes. There was a 95% adherence rate during RPM.</p><p><strong>Conclusions: </strong>A 26-week tablet-based RPM system that monitors CAT, oxygen saturation, blood pressure, pulse, weight and physical activity, connected to a case manager, is feasible and safe, but did not influence health-related quality of life in patients with COPD GOLD D.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update to: self-help cognitive behavioural therapy for anxiety in pulmonary hypertension.","authors":"Gregg H Rawlings, Grace Bowmer, Iain Armstrong, Andrew R Thompson","doi":"10.1183/23120541.00872-2024","DOIUrl":"10.1183/23120541.00872-2024","url":null,"abstract":"<p><p><b>Since being published in 2021 in <i>ERJ Open Research</i>, a self-help resource has been made widely available to adults with PH in the UK <i>via</i> PHA UK. This is an update on the continued impact of the intervention hearing from services users and PHA UK.</b> https://bit.ly/3YLHIHm.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeat expansions in <i>RFC1</i> gene in refractory chronic cough.","authors":"Barnaby Hirons, Peter S P Cho, Katie Rhatigan, Joe Shaw, Riccardo Curro, Bianca Rugginini, Natalia Dominik, Richard D Turner, Ewan Mackay, James H Hull, Hisham Abubakar-Waziri, Harini Kesavan, Caroline J Jolley, Robert D Hadden, Andrea Cortese, Surinder S Birring","doi":"10.1183/23120541.00584-2024","DOIUrl":"10.1183/23120541.00584-2024","url":null,"abstract":"<p><strong>Introduction: </strong>Refractory chronic cough (RCC), persisting despite addressing contributory diagnoses, is likely underpinned by neurally mediated cough hypersensitivity. <i>RFC1</i> disorders are genetic neurodegenerative conditions caused by biallelic <i>RFC1</i> repeat expansion sequences, commonly presenting with cough, followed by neurological features including cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). The prevalence and identifying clinical characteristics of <i>RFC1</i> repeat-expansion disorders in patients with RCC are unknown.</p><p><strong>Methods: </strong>Consecutive patients with RCC underwent <i>RFC1</i> genotyping, cough severity visual analogue scale (VAS) and cough-specific health status assessment (Leicester Cough Questionnaire (LCQ)). Participants with biallelic <i>RFC1</i> repeat expansions (RFC1⁺⁺) also underwent nerve conduction studies, brain imaging (MRI) and cough reflex sensitivity testing.</p><p><strong>Results: </strong>51 participants with RCC were recruited; 36 (71%) female, median (IQR) age 65 (56-70) years, duration of cough 12.8 (6.9-20.0) years. Four (8%) were RFC1⁺⁺, five (10%) monoallelic carriers (RFC1^+-) and 42 (82%) of wild-type genotype (RFC1^--). No difference was observed in age, sex, cough duration, spirometry, VAS or LCQ scores between RFC1⁺⁺ and RFC1^-- subjects (p>0.05). The symptom of pins and needles was more frequent in RFC1⁺⁺ (n=4, 100%) compared to RFC1^-- (n=12, 33%) (p=0.01). RFC1⁺⁺ participants had impaired sensory action potentials, and one had cerebellar atrophy. RFC1⁺⁺ participants had heightened cough reflex sensitivity to capsaicin, similar to previous CANVAS and RCC studies.</p><p><strong>Conclusion: </strong>Biallelic RFC1 repeat expansions (RFC1⁺⁺) were present in 8% of RCC patients. RFC1⁺⁺ participants demonstrated features of cough reflex hypersensitivity. RFC1⁺⁺ chronic cough had few identifying features, although symptoms of pins and needles were more common.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of highly effective modulator therapy on sinusitis and dysosmia in young children with cystic fibrosis: a prospective study protocol.","authors":"Christine M Liu, Jakob L Fischer, Edith T Zemanick, Jason C Woods, Karolin K Markarian, Sean B Fain, Deborah Froh, Sonya L Heltshe, Lucas R Hoffman, Stephen M Humphries, Elizabeth L Kramer, Katie Larson Ode, Michael Lewis, Douglas A Li, Jaime Mata, Sarah S Milla, Peter J Niedbalski, Benjamin D Sawatzky, Myung-Shin Sim, Jillian S Sullivan, Andrew T Trout, Christopher H Goss, Jennifer L Taylor-Cousar, Daniel M Beswick","doi":"10.1183/23120541.00137-2024","DOIUrl":"10.1183/23120541.00137-2024","url":null,"abstract":"<p><strong>Background: </strong>Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown. This proposed study aims to characterise CRS and OD in YCwCF and assess the efficacy of HEMT in improving sinus and olfactory health in this young age group.</p><p><strong>Methods: </strong>This six-centre, prospective, observational study will enrol 80 YCwCF aged 2-8 years. Patients are divided into two groups: those receiving HEMT and those not on HEMT based on clinical indication. Both groups undergo sinus magnetic resonance imaging, psychophysical olfactory tests, and complete patient- or parent-reported quality of life surveys over 2 years. Outcomes will be compared before and after initiation of HEMT and between groups. Ethical approval has been obtained for all sites, and this study has been registered on ClinicalTrials.gov (NCT06191640).</p><p><strong>Results: </strong>Enrolment began in April 2023. 21 participants have been enrolled as of October 2023 with ongoing enrolment at all sites.</p><p><strong>Conclusion: </strong>This investigation is expected to provide critical insights into the potential benefits of early HEMT initiation in managing CRS and OD in YCwCF. It will assist in developing targeted interventions and contribute to the understanding of HEMT's role in altering the disease course in this demographic.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variability in disease severity among cystic fibrosis patients carrying residual-function variants: data from the European Cystic Fibrosis Society Patient Registry.","authors":"Meir Mei-Zahav, Annalisa Orenti, Andreas Jung, Eitan Kerem","doi":"10.1183/23120541.00587-2024","DOIUrl":"10.1183/23120541.00587-2024","url":null,"abstract":"<p><strong>Background: </strong>People with cystic fibrosis (CF) variants that exhibit residual function (RF) of the CF transmembrane conductance regulator are considered to have a milder disease; however, the spectrum of CF phenotype within the different RF variants has not been extensively investigated. The aim of the present study was to characterise the spectrum of CF disease severity in people with CF (pwCF) carrying different RF variants, using the European Cystic Fibrosis Society Patient Registry (ECFSPR) data.</p><p><strong>Methods: </strong>A retrospective cross-sectional and longitudinal cohort study included data from the ECFSPR during 2008-2016. Demographic and clinical characteristics of pwCF carrying different RF variants were compared with the characteristics of pwCF who are homozygous for F508del. Among those with RF, a distinction was made between pwCF carrying class IV or class V variants and pwCF carrying specific RF variants.</p><p><strong>Results: </strong>Out of 56 701 pwCF in the ECFSPR, 6192 carried RF variants and 22 766 were homozygous for F508del. Class IV/F508del variants were associated with a milder course than class V/F508del; both were milder than pwCF homozygous for F508del. Forced expiratory volume in 1 s % predicted (FEV₁pp) declined in childhood in all groups. For adults, the hazard ratio of death for class V/F508del <i>versus</i> class IV/F508del was 2.14 (95% confidence interval 0.99-4.63, p=0.052). PwCF carrying 3849+10 kb C→T/F508del and pwCF carrying R334W/F508del had age-specific FEV₁pp and chronic bacterial colonisation similar to those of pwCF homozygous for F508del.</p><p><strong>Conclusion: </strong>There is a wide spectrum of disease severity between the different RF variants. Some, such as those carrying 3849+10 kb C→T, have severe disease, similar to that of pwCF homozygous for F508del.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic doses of efzofitimod demonstrate efficacy in pulmonary sarcoidosis.","authors":"Ogugua Ndili Obi, Robert P Baughman, Elliott D Crouser, Mark W Julian, Landon W Locke, Abhijeeth Chandrasekaran, Pavithra Ramesh, Nelson Kinnersley, Vis Niranjan, Daniel A Culver, Peter H S Sporn","doi":"10.1183/23120541.00536-2024","DOIUrl":"10.1183/23120541.00536-2024","url":null,"abstract":"<p><strong>Background: </strong>In a phase 1b/2a clinical trial of efzofitimod in patients with corticosteroid-requiring pulmonary sarcoidosis, treatment resulted in dose-dependent improvement in key end-points. We undertook a <i>post hoc</i> analysis pooling dose arms that achieved therapeutic concentrations of efzofitimod (Therapeutic group) <i>versus</i> those that did not (Subtherapeutic group).</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells incubated with tuberculin-coated beads were exposed to varying concentrations of efzofitimod in an <i>in vitro</i> assay to determine concentrations that inhibited granuloma formation. In the <i>post hoc</i> analysis, we compared time-to-first-relapse and changes in pulmonary function after a protocolised corticosteroid taper in the Therapeutic and Subtherapeutic groups.</p><p><strong>Results: </strong>Efzofitimod at ≥300 nM (19 µg·mL^-1) inhibited granuloma formation <i>in vitro</i>. Based on mean efzofitimod serum concentrations achieved in the phase 1b/2a study, the 3 and 5 mg·kg^-1 dose arms were pooled as the Therapeutic group, while the 1 mg·kg^-1 arm was pooled with the placebo arm as the Subtherapeutic group. Relapse rates were 54.4% and 7.7% in the Subtherapeutic group and Therapeutic group, respectively. Median time-to-first-relapse in the Subtherapeutic group was 126 days, whereas in the Therapeutic group, only one of 17 patients relapsed by the end of the 24-week study (p=0.017). Slopes analysis showed that forced vital capacity increased in the Therapeutic group, but decreased in the Subtherapeutic group, over the course of the trial (p=0.035).</p><p><strong>Conclusion: </strong>Treatment with efzofitimod at therapeutic doses, as compared with a subtherapeutic dose or placebo, was associated with a lower rate of relapse as corticosteroids were tapered.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhaled alpha-1 antitrypsin (AAT) restores lower respiratory tract protease-antiprotease homoeostasis and reduces inflammation in AAT-deficient individuals: a randomised phase 2 study.","authors":"Mark Brantly, James Stocks, Jorge Lascano, Tammy Flagg, Ann M Jeffers, Shuzi Z Owens, Torry A Tucker, Megan Devine, Noga Alagem, Naveh Tov","doi":"10.1183/23120541.00537-2024","DOIUrl":"10.1183/23120541.00537-2024","url":null,"abstract":"<p><strong>Background: </strong>Alpha-1 antitrypsin (AAT)-deficient individuals have a greater risk for developing COPD than individuals with normal AAT levels.</p><p><strong>Methods: </strong>This was a double-blind, randomised, parallel group, placebo-controlled trial to examine the safety and tolerability of \"Kamada-AAT for Inhalation\" (inhaled AAT) in subjects with AAT deficiency, and to explore its effect on AAT and biomarkers in the lung epithelial lining fluid (ELF). 36 patients with severe AAT deficiency were randomised 2:1 to receive 80 mg or 160 mg inhaled AAT or placebo once daily for 12 weeks. The primary outcomes were AAT and antineutrophil elastase capacity (ANEC) in bronchoalveolar lavage and plasma after treatment. Secondary outcomes included safety, levels of normal M-type AAT in the plasma and concentrations of AAT, neutrophil elastase (NE), AAT-NE complexes and neutrophil count in the ELF.</p><p><strong>Results: </strong>12 weeks of active treatment significantly increased AAT, ANEC and AAT-NE complexes in the ELF. Mean antigenic AAT levels in the ELF were restored to 5.2±2.3 μM in the 80 mg arm and to 17.7±2 μM in the 160 mg arm. Both doses significantly restored AAT antiprotease activity within the lung and reduced NE levels. M-specific AAT levels in plasma increased in a dose-dependent manner. A clinically meaningful reduction in ELF neutrophil % was observed in the 80 mg arm. AAT for inhalation was well tolerated.</p><p><strong>Conclusions: </strong>Inhaled AAT restores protease-antiprotease homoeostasis and may represent a safe and effective therapy.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}