European Respiratory Journal最新文献

{"title":"Arousal threshold modifies the effect of CPAP on executive function among individuals with obstructive sleep apnea.","authors":"Andrey V Zinchuk, Clete A Kushida, Alexander Walker, Andrew Wellman, Ali Azarbarzin, Raichel M Alex, Andrew W Varga, Scott A Sands, H Klar Yaggi","doi":"10.1183/13993003.01183-2024","DOIUrl":"https://doi.org/10.1183/13993003.01183-2024","url":null,"abstract":"<p><p>Arousal Threshold Modifies the Effect of CPAP on Executive Function Among Individuals with Obstructive Sleep Apnea.</p><p><strong>Background: </strong>Obstructive Sleep Apnea (OSA) is associated with neurocognitive dysfunction. However, randomized trials evaluating the effects of continuous positive airway pressure (CPAP) on neurocognition in those without dementia do not show a benefit. We thus aimed to assess whether arousal threshold (ArTH) modifies the effect of CPAP on neurocognitive function.</p><p><strong>Methods: </strong>We performed a secondary analysis of a randomized, sham-controlled trial, Apnea Positive Pressure Long-term Efficacy Study. ArTH was estimated from polysomnography using a translatable method (Sands <i>et al</i>., SLEEP 2018). Neurocognitive outcomes included the Sustained Working Memory Test-Overall-Mid-Day score (SWMT-OMD, executive function, primary outcome), with the Pathfinder Number Test - total time (attention) and Buschke Selective Reminding Test - sum recall (learning and memory) as secondary outcomes. Generalized linear modeling assessed whether the effect of CPAP was modified by baseline ArTH (treatment-by-ArTH interaction). 833 participants with OSA, [apnea-hypopnea index (AHI) ≥10 events/h], available ArTH, and outcomes were analyzed (CPAP n=437, Sham n=396).</p><p><strong>Results: </strong>For executive function, the effect of CPAP treatment was modified by ArTH (p-interaction=0.042). Specifically, for every 1 sd increase in ArTH, the SWMT-OMD score improved by 0.10 95% CI (0.01, 0.18) in active compared to sham CPAP at 6 months; At ArTH 1 sd above the mean SWMT-OMD improvements were nearly three times that in those with average ArTH (0.139 [0.018, 0.261] <i>versus</i> 0.053 [-0.034, 0.140] respectively. No effect modification was observed for attention (p=0.311) or learning and memory (p=0.744).</p><p><strong>Conclusion: </strong>In OSA, a higher ArTH is associated with greater improvements in executive function following CPAP therapy.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting neutrophil serine proteases in bronchiectasis.","authors":"James D Chalmers, Marcus A Mall, Sanjay H Chotirmall, Anne E O'Donnell, Patrick A Flume, Naoki Hasegawa, Felix C Ringshausen, Henrik Watz, Jin-Fu Xu, Michal Shteinberg, Pamela J McShane","doi":"10.1183/13993003.01050-2024","DOIUrl":"10.1183/13993003.01050-2024","url":null,"abstract":"<p><p>Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis (BE). Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase, cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur. Despite the defined role of prolonged, high levels of NSPs in BE, no drug that controls neutrophilic inflammation is licensed for the treatment of BE. Previous methods of suppressing neutrophilic inflammation (such as direct inhibition of neutrophil elastase) have not been successful; however, an emerging therapy designed to address neutrophil-mediated pathology, inhibition of the cysteine protease cathepsin C (CatC, also known as dipeptidyl peptidase 1), is a promising approach to ameliorate neutrophilic inflammation, since this may reduce the activity of all NSPs implicated in BE pathogenesis, and not just neutrophil elastase. Current data suggest that CatC inhibition may effectively restore the protease-antiprotease balance in BE and improve disease outcomes as a result. Clinical trials for CatC inhibitors in BE have reported positive Phase III results. In this narrative review, we discuss the role of high NSP activity in BE, and how this feature drives the associated morbidity and mortality seen in BE. This review discusses therapeutic approaches aimed at treating neutrophilic inflammation in the BE lung, summarising clinical trial outcomes, and highlighting the need for more treatment strategies that effectively address chronic neutrophilic inflammation in BE.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory support and bronchopulmonary dysplasia in infants born at 22-26 weeks gestation in Sweden, 2004-2007 and 2014-2016.","authors":"Linn Löfberg, Thomas Abrahamsson, Lars J Björklund, Lena Hellström Westas, Aijaz Farooqi, Magnus Domellöf, Ulrika Ådén U, Christian Gadsbøll, Karin Källén, David Ley, Erik Normann, Karin Sävman, Anders Elfvin, Stellan Håkansson, Mikael Norman, Richard Sindelar, Fredrik Serenius, Petra Um-Bergström","doi":"10.1183/13993003.01203-2024","DOIUrl":"10.1183/13993003.01203-2024","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate if increased survival and new ventilation strategies were accompanied by a changed incidence of bronchopulmonary dysplasia (BPD) in Sweden over a decade.</p><p><strong>Methods: </strong>Data from two Swedish population-based studies of live-born infants with gestational ages (GA) 22-26 weeks, born during 2004-2007 (n=702) and 2014-2016 (n=885), were compared for survival, any BPD, moderate BPD, severe BPD, and BPD/severe BPD or death at 36 weeks postmenstrual age (PMA). Ventilation strategies and interventions were analysed. Any BPD was defined as the use of supplemental oxygen or any respiratory support at 36 weeks PMA, moderate BPD as nasal cannula with <30% oxygen, and severe BPD as ≥30% oxygen, CPAP, or mechanical ventilation.</p><p><strong>Results: </strong>Survival to 36 weeks PMA increased from 72% to 81%(<i>p</i><0.001). Total days on mechanical ventilation increased from a median of 9 to 16 days (<i>p</i><0.001). The high-flow nasal cannula (HFNC) was introduced between the cohorts, and days of CPAP and HFNC increased from 44 to 50 days (<i>p</i><0.001). Any BPD was unchanged, 65% <i>versus</i> 68%. Moderate BPD increased from 37% to 47%(p=0.003), while incidence of severe BPD decreased from 28% to 23%(<i>p</i><0.046). Severe BPD or death decreased from 48% to 37%(<i>p</i><0.001) while any BPD or death remained unchanged at 74 <i>versus</i> 75%.</p><p><strong>Conclusion: </strong>Even though an increased survival of infants born at 22-26 weeks GA was accompanied by an increased duration of invasive and non-invasive respiratory support, the incidence of any BPD remained unchanged while severe BPD decreased in infants alive at 36 weeks PMA.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood RNA signatures for 8-week sputum tuberculosis culture sterilisation: how close are we?","authors":"Win Pa Pa Thu, Fei Kean Loh, Catherine W M Ong","doi":"10.1183/13993003.01669-2024","DOIUrl":"https://doi.org/10.1183/13993003.01669-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 5","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The volume-outcome relation for pulmonary endarterectomy in chronic thrombo-embolic pulmonary hypertension.","authors":"Samuel Heuts, Michal J Kawczynski, Arthur Leus, Laurent Godinas, Catharina Belge, Vanessa van Empel, Bart Meyns, Jos G Maessen, Marion Delcroix, Tom Verbelen","doi":"10.1183/13993003.01865-2024","DOIUrl":"https://doi.org/10.1183/13993003.01865-2024","url":null,"abstract":"<p><strong>Background: </strong>We conducted a volume-outcome (V-O) meta-analysis of PEA procedures for chronic thromboembolic pulmonary hypertension (CTEPH), to objectively determine the minimum required annual case load that can define a high-volume centre.</p><p><strong>Methods: </strong>Three electronic databases were systematically queried until May 1st, 2024. Centres were divided in volume tertiles (Ts). The primary outcomes were early mortality and long-term survival. Restricted cubic splines were used to demonstrate the V-O relation, and the elbow-method was applied to define high-volume centres. Long-term survival was assessed using Cox-frailty models.</p><p><strong>Results: </strong>Fifty-one centres (52 consecutive cohorts) were included and divided in tertiles (T1: <6 cases/year, T2: 6-15 cases/year, T3: >15 cases/year), comprising a total of 11 345 patients (mean age 52.3 years). Overall early mortality was 6.0% (T1: 11.6%, T2: 7.2%, T3: 5.2%, p<0.001), for which a significant non-linear volume-outcome relation was observed (p=0.0437) with a statistically determined minimally required volume of 33 cases/year (95% confidence interval [CI] 29-35 cases), and a modelled volume of 40 cases/year corresponding to a 5.0% mortality rate. Nevertheless, early mortality still progressively declined in higher volume centres (from 6.7% to 5.4% to 2.9% in centres performing 16-50, 51-100, and >100 procedures annually). In addition, a significant effect of volume was observed for long-term survival (adjusted hazard ratio per tertile 0.75, 95%CI 0.63-0.89, p=0.001).</p><p><strong>Conclusion: </strong>There is a significant association between procedural volume and early mortality in PEA. An annual procedural volume of >33-40 cases/year may define a high-volume centre, although higher volumes still lead to progressively lower mortality rates.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ECG-based risk factors for adverse cardiopulmonary events and treatment outcomes in COPD.","authors":"R Chad Wade, Fernando J Martinez, Gerard J Criner, Lee Tombs, David A Lipson, David M G Halpin, MeiLan K Han, Dave Singh, Robert A Wise, Ravi Kalhan, Mark T Dransfield","doi":"10.1183/13993003.00171-2024","DOIUrl":"10.1183/13993003.00171-2024","url":null,"abstract":"<p><strong>Background: </strong>COPD has high mortality, compounded by comorbid cardiovascular disease. We investigated two electrocardiogram (ECG) markers, Cardiac Infarction Injury Score (CIIS) and P pulmonale, as prognostic tools for adverse cardiopulmonary events in COPD.</p><p><strong>Methods: </strong>Post hoc analysis of the IMPACT trial. Outcomes included odds (odds ratio [95% confidence intervals]) of adverse cardiopulmonary events stratified by CIIS threshold (<20/≥20) and P pulmonale (baseline). Events included all-cause death, hospitalisation/death, cardiovascular adverse event of special interest (CVAESI), severe COPD exacerbations, and moderate/severe COPD exacerbations. Effects of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) <i>versus</i> FF/VI or UMEC/VI based on CIIS and P pulmonale were also assessed.</p><p><strong>Results: </strong>We included 9448 patients. Patients with CIIS ≥20 had greater odds of all-cause death (1.73[1.27-2.37]; <i>p</i><0.001), hospitalisation/death (1.33[1.17-1.50]; <i>p</i><0.001), CVAESI (1.27[1.08-1.48]; <i>p</i><0.005), severe COPD exacerbations (1.41[1.21-1.64]; <i>p</i><0.001) and moderate/severe COPD exacerbations (1.25[1.13-1.40]; <i>p</i><0.001) <i>versus</i> CIIS <20. Patients with P pulmonale (<i>versus</i> without) had greater odds of all-cause death (2.25[1.54-3.29]; <i>p</i><0.001), hospitalisation/death (1.51[1.28-1.79]; <i>p</i><0.001), severe COPD exacerbations (2.00[1.65-2.41]; <i>p</i><0.001) and moderate/severe COPD exacerbations (1.25[1.08-1.46]; <i>p</i><0.001). A combined model demonstrated patients with CIIS ≥20 and P pulmonale had increased risk of all-cause death (3.38[1.23-9.30]; p=0.019), hospitalisation/death (1.61[1.14-2.22]; p=0.004), and rate of severe COPD exacerbations (1.89[1.22-2.91]; p=0.004) and moderate/severe COPD exacerbations (1.25[1.00-1.56]; p=0.046). The risk of all-cause death and CVAESI was reduced with FF/UMEC/VI <i>versus</i> UMEC/VI in patients with CIIS ≥20, but not CIIS <20.</p><p><strong>Conclusions: </strong>These findings suggest potential clinical relevance of CIIS and P pulmonale as risk indicators for adverse cardiopulmonary events in COPD.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological and pre-clinical safety profile of rSIV.F/HN, a hybrid lentiviral vector for cystic fibrosis gene therapy.","authors":"Alena Moiseenko, Anthony Sinadinos, Ana Sergijenko, Kyriel Pineault, Aarash Saleh, Konradin Nekola, Nathalie Strang, Anastasia Eleftheraki, A Christopher Boyd, Jane C Davies, Deborah R Gill, Stephen C Hyde, Gerry McLachlan, Tim Rath, Michael Rothe, Axel Schambach, Silke Hobbie, Michael Schuler, Udo Maier, Matthew J Thomas, Detlev Mennerich, Manfred Schmidt, Uta Griesenbach, Eric W F W Alton, Sebastian Kreuz","doi":"10.1183/13993003.01683-2023","DOIUrl":"10.1183/13993003.01683-2023","url":null,"abstract":"<p><strong>Rationale and objective: </strong>Cystic fibrosis (CF) is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene. CFTR modulators offer significant improvements, but approximately 10% of patients remain nonresponsive or are intolerant. This study provides an analysis of rSIV.F/HN, a lentiviral vector optimized for lung delivery, including CFTR protein expression, functional correction of CFTR defects and genomic integration site analysis in preparation for a first-in-human clinical trial.</p><p><strong>Methods: </strong>Air-liquid interface cultures of primary human bronchial epithelial cells (HBEC) from CF patients (F508del/F508del), as well as a CFTR-deficient immortalized human lung epithelial cell line mimicking Class I (CFTR-null) homozygous mutations, were used to assess transduction efficiency. Quantification methods included a novel proximity ligation assay (PLA) for CFTR protein expression. For assessment of CFTR channel activity, Ussing chamber studies were conducted. The safety profile was assessed using integration site analysis and <i>in vitro</i> insertional mutagenesis studies.</p><p><strong>Results: </strong>rSIV.F/HN expressed CFTR and restored CFTR-mediated chloride currents to physiological levels in primary F508del/F508del HBECs as well as in a Class I cells. In contrast, the latter could not be achieved by small-molecule CFTR modulators, underscoring the potential of gene therapy for this mutation class. Combination of rSIV.F/HN-CFTR with the potentiator ivacaftor showed a greater than additive effect. The genomic integration pattern showed no site predominance (frequency of occurrence ≤10%), and a low risk of insertional mutagenesis was observed in an <i>in vitro</i> immortalization assay.</p><p><strong>Conclusions: </strong>The results underscore rSIV.F/HN as a promising gene therapy vector for CF, providing a mutation-agnostic treatment option.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The McMaster Cough Severity Questionnaire (MCSQ): a cough severity instrument for patients with refractory chronic cough.","authors":"Elena Kum, Gordon H Guyatt, Rayid Abdulqawi, Peter Dicpinigaitis, Lieven Dupont, Stephen K Field, Cynthia L French, Peter G Gibson, Richard S Irwin, Faye Johnston, Lorcan McGarvey, Robert Newman, Nada Popovic, Jaclyn A Smith, Woo-Jung Song, Paul M O'Byrne, Imran Satia","doi":"10.1183/13993003.01565-2024","DOIUrl":"10.1183/13993003.01565-2024","url":null,"abstract":"<p><strong>Background: </strong>Cough severity represents an important endpoint to assess the impact of therapies for patients with refractory chronic cough (RCC).</p><p><strong>Objective: </strong>To develop a new patient-reported outcome measure addressing cough severity in patients with RCC.</p><p><strong>Methods: </strong>Phase 1 (item generation): A systematic survey, focus groups, and expert consultation generated 51 items. Phase 2 (item reduction): From a list of 51 items, 100 patients identified those they had experienced in the previous year and rated their importance on a 5-point scale. The MCSQ included items reported to occur most frequently and that had the highest importance scores. Patient feedback on the MCSQ led to elimination of redundant items. Another 100 patients completed the MCSQ, from which we performed an exploratory factor analysis and a Rasch analysis to further refine items on the MCSQ.</p><p><strong>Results: </strong>Phase 2 led to selection of 15 items from the initial 51. Patient feedback on the 15 items led to elimination of 5 redundant items. An exploratory factor analysis of the 10-item MCSQ led to selection of two domains, elimination of one item that demonstrated cross-loading, and another that had high inter-item correlations. A Rasch analysis of the 8-item MCSQ confirmed that the response options functioned in a logically progressive manner and that no items exhibited differential item functioning. The final 8-item MCSQ has a one-week recall period and includes two domains (intensity and frequency). The 8-item MCSQ had high internal consistency (Cronbach's alpha, 0.89), proved able to distinguish different levels of cough severity (Pearson separation index, 0.89), and demonstrated high cross-sectional convergent validity (Pearson's correlation, 0.76 [95% CI 0.66 to 0.83]) with the 100-mm cough severity visual analogue scale.</p><p><strong>Conclusion: </strong>Initial evidence supports the validity of the MCSQ, an 8-item instrument measuring cough severity in patients with RCC. Future studies should evaluate its properties in measuring change over time.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the expanded label for elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with no F508del variant in the USA.","authors":"Elizabeth A Cromwell, Josh S Ostrenga, Don B Sanders, Wayne Morgan, Carlo Castellani, Rhonda Szczesniak, Pierre-Regis Burgel","doi":"10.1183/13993003.01146-2024","DOIUrl":"10.1183/13993003.01146-2024","url":null,"abstract":"<p><strong>Background: </strong>Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on <i>in vitro</i> data in the USA for those carrying at least one of 177 rare <i>CFTR</i> (cystic fibrosis transmembrane conductance regulator) variants.</p><p><strong>Methods: </strong>PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV₁) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively.</p><p><strong>Results: </strong>A total of 1791 individuals aged ≥6 years with rare <i>CFTR</i> variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV₁ % pred by +3.39 (95% CI 2.14-4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38-0.79). These effects were greater in individuals naïve of previous CFTR modulators.</p><p><strong>Conclusions: </strong>Extension of the ETI label to rare <i>CFTR</i> variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Until it's done for everyone: the role of CFTR modulator label expansion.","authors":"Clemente J Britto, Jennifer L Taylor-Cousar","doi":"10.1183/13993003.01898-2024","DOIUrl":"10.1183/13993003.01898-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 5","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}