Journal of Cystic Fibrosis最新文献

{"title":"Detection of bacterial extracellular vesicles in patients with cystic fibrosis - a pilot study.","authors":"Celina von Mauch, Lisa-Maria Edrich, Julia Sobel, Annika Geppert, Jochen Mattner, Philipp Arnold, André Hoerning, Claudia Guenther, Alexander Schnell, Iris Stolzer","doi":"10.1016/j.jcf.2026.07.013","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.07.013","url":null,"abstract":"<p><strong>Background and aims: </strong>Pseudomonas (P.) aeruginosa is an opportunistic pathogen closely linked to Cystic Fibrosis (CF). Recent publications emphasize that an accumulation of bacterial derived extracellular vesicles within the circulation might be associated with the pathogenesis of various chronic inflammatory diseases and could potentially be used as diagnostic tool.</p><p><strong>Methods: </strong>Bacterial extracellular vesicles (bEVs) were isolated and characterized via Nanoparticle Tracking Analysis (NTA) and Transmission Electron Microscopy (TEM) from plasma samples of persons with CF (pwCF) without infection with P. aeruginosa (PsA-, n = 31), pwCF with confirmed P. aeruginosa infection (PsA+, n = 29), and control individuals (HC, n = 30). Size and concentration of bEVs were evaluated and correlated with clinical parameters. Western blot analyses were implemented to study the species-specific origin of bEVs, using lysates and reference vesicles.</p><p><strong>Results: </strong>bEVs could be detected in all samples from both, HC and pwCF. Relative NF‑κB induction, assessed via a TLR4 reporter assay, was significantly elevated in pwCF than in HC, with the strongest responses observed in PsA+ patients. emphasize bEV-associated activity. Surprisingly, CFTR modulator treatment (ETI) enhanced LPS concentration of bEVs in pwCF independent of P. aeruginosa colonization. Moreover, NF-kB induction correlated negatively with serum IgA levels in PsA+ patients. Direct detection of bEVs in plasma samples via Western blot was technically not possible.</p><p><strong>Conclusion: </strong>Our findings suggest a potential link between pulmonary P. aeruginosa colonization and increased systemic bEVs-associated activity as potential consequence of deficient mucosal barrier function. However, further research is required in order to validate our findings and to clarify the influence of ETI on bEV accumulation.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutrition and cardiometabolic health in cystic fibrosis: Emerging evidence and research gaps.","authors":"Veronica Lynch, Joanne Barrett, Sarah Collins, Paige Elliott, Darren Sills, Joanna Snowball, Pauline Douglas, Alan R Smyth, Audrey Tierney, Damian G Downey, Claire McEvoy","doi":"10.1016/j.jcf.2026.07.1983","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.07.1983","url":null,"abstract":"<p><p>Cardiometabolic risk is increasingly recognised as a significant and evolving health concern within the cystic fibrosis (CF) population. Although nutrition has long been central to CF management, its broader influence on cardiometabolic health, well established in the general population, is only beginning to be understood in the context of CF. This narrative review seeks to synthesise emerging evidence and highlight the key research gaps relating to the role of nutrition in moderating cardiometabolic risk among people with CF (pwCF). Substantial gaps remain across several domains, including overweight and obesity, dysglycaemia and diabetes, cardiovascular disease, gut microbiota alterations and overall diet quality. Addressing these gaps is essential as pwCF live longer and encounter new health challenges. Future nutrition research must generate the robust, clinically relevant evidence needed to support clinical teams as they transition away from traditional dietary paradigms, enabling the development of updated guidance and the advancement of clinical practice toward metabolically informed, contemporary models of care.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral defenses are diminished at birth in cystic fibrosis pig airways.","authors":"Jennifer A Bartlett, Miguel E Ortiz, Linda S Powers, Christine L Wohlford-Lenane, Camilla E Hippee, Laura Marquez Loza, Justin W Kaufman, Brajesh K Singh, Daniel I Sands, Eric D Huntemann, Ashley L Cooney, Mark P Rogan, Clifford C Taggart, David K Meyerholz, Paul B McCray","doi":"10.1016/j.jcf.2026.07.1985","DOIUrl":"10.1016/j.jcf.2026.07.1985","url":null,"abstract":"<p><strong>Background: </strong>There is evidence that antiviral defenses are impaired in airway epithelia derived from the lungs of people with cystic fibrosis (CF), however it is unclear whether this phenotype is an intrinsic feature of CF or an acquired trait that develops secondary to chronic airway infection and inflammation. To distinguish between these possibilities, we examined the antiviral responses of newborn CF pigs, prior to the onset of airway inflammation and chronic lung disease.</p><p><strong>Methods: </strong>We performed an in vivo viral challenge experiment in newborn CF and non-CF pigs, using influenza A (IAV) as a model respiratory virus. To learn more about the contributions of epithelia in this setting, we carried out a parallel in vitro infection experiment using cultured airway epithelia derived from newborn CF and non-CF pig controls.</p><p><strong>Results: </strong>We found that viral growth kinetics and host antiviral responses were relatively similar in the cultured epithelia from CF and non-CF pigs. However, we observed divergent host responses in the animal experiment, with the newborn CF pigs exhibiting comparatively increased innate immune activation and increased viral loads after IAV challenge.</p><p><strong>Conclusions: </strong>Our findings indicate a reduced effectiveness of antiviral host defense at birth in the CF pig model and suggest that this phenotype is not driven solely by altered airway epithelial cell function. These results highlight a likely contribution of early life viral infections in initiating CF lung disease.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world population pharmacokinetic modeling of elexacaftor, tezacaftor, and ivacaftor.","authors":"A K Kunzelmann, S Naehrig, C Shad, M Breuling, M Goetschke, K Habler, O Sommerburg, J Behr, L M Schatz, J Starp, M Vogeser, M Paal, U Liebchen","doi":"10.1016/j.jcf.2026.07.1984","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.07.1984","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis transmembrane conductance regulator modulators have revolutionized therapy for people with cystic fibrosis, yet marked interindividual variability in drug exposure limits targeted individualized dosing. We aimed to characterize the pharmacokinetics of elexacaftor, tezacaftor, and ivacaftor and develop population pharmacokinetic models that enable model-informed precision dosing in adults with cystic fibrosis.</p><p><strong>Methods: </strong>In this retrospective analysis of real-world therapeutic drug monitoring data from 176 adults (62.5% male; median age 36 years; median body-mass index 22.5 kg/m²), nonlinear mixed-effects modeling was used to fit one-compartment models with first-order absorption and elimination for each substance. The developed model was employed to evaluate real-world target attainment and Monte Carlo simulations (n = 1000) were used to predict steady-state exposures.</p><p><strong>Results: </strong>Graphical and numerical diagnostics supported adequate model fit. In covariate analyses, concomitant antifungal therapy was associated with a significant reduction in clearance, whereas higher albumin exerted a modest effect on reduction in clearance. Higher bilirubin and higher levels of vitamins D and E were likewise associated with lower clearance. Simulations revealed substantial interindividual variability. Target-attainment analysis identified a subset of patients with inadequate exposure CONCLUSIONS: Our population pharmacokinetic analysis of a large real-world cohort identified clinically relevant covariates driving variability in elexacaftor, tezacaftor, and ivacaftor exposure. These models complement previous population PK studies by identifying clinically accessible covariates associated with ETI exposure in a real-world adult CF cohort and may inform future personalized dosing approaches, pending external validation and prospective exposure-response evaluation.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forced vital capacity in pulmonary exacerbations of cystic fibrosis.","authors":"Oliver J McElvaney, Sonya L Heltshe, Don B Sanders, Natalie E West, Kathleen J Ramos, Barbra Fogarty, Patrick A Flume, Christopher H Goss","doi":"10.1016/j.jcf.2026.07.010","DOIUrl":"10.1016/j.jcf.2026.07.010","url":null,"abstract":"<p><strong>Background: </strong>Forced expiratory volume in one second (FEV₁) is routinely used to assess pulmonary exacerbations (PEx) in cystic fibrosis (CF) but underrepresents air trapping and small airways dysfunction. Forced vital capacity (FVC) may better capture these processes, yet its behavior, clinical relevance, and utility as a trial endpoint remain uncertain.</p><p><strong>Methods: </strong>We performed a secondary analysis of STOP2, a multicenter randomized trial of antimicrobial duration in adults with CF pulmonary exacerbations (PEx). Changes in percent-predicted FVC (ppFVC) and FEV₁ (ppFEV₁) were assessed relative to pre-PEx baseline. Clinical characteristics associated with large ppFVC decline were evaluated using adjusted analyses. Propensity score matching was used to compare recovery, residual deficit, and symptom response between groups with large versus modest ppFVC decline. Associations with time-to-next-exacerbation (TTNE) were assessed using survival analyses. Variability, responsiveness, and projected clinical trial sample sizes were compared between ppFVC- and ppFEV₁-based endpoints.</p><p><strong>Results: </strong>Among 760 participants, ppFVC responses were heterogeneous. Larger absolute declines were associated with higher baseline FVC and elevated C-reactive protein (CRP), while larger relative declines were associated with CRP alone. Participants with large initial ppFVC deficits showed greater absolute recovery but larger residual deficits, shorter TTNE, and higher future exacerbation risk. A one-standard-deviation worse residual ppFEV₁ deficit was associated with increased re-exacerbation risk, whereas residual ppFVC deficit was weaker and not independently prognostic. Absolute recovery in either measure was not associated with TTNE. Compared with ppFEV₁, ppFVC demonstrated similar or greater variability, resulting in larger estimated sample sizes for clinical trials.</p><p><strong>Conclusions: </strong>Distinct FVC response patterns occur during CF PEx but do not provide independent prognostic information beyond FEV₁. Use of ppFVC as a primary endpoint would require larger sample sizes without clear advantage.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormalities of the distal terminal ileum in people with cystic fibrosis assessed using magnetic resonance imaging.","authors":"Faiz Alqarni, Soma Kumasaka, Madeleine Taylor, Arantxa Recto, Darren Sills, Hisham Saumtally, Charlotte Hamann, Grace Lim, Jan Paul, Alexander Yule, Caroline L Hoad, Daniel Peckham, Iain D Stewart, Tanya M Monaghan, Christopher van der Gast, Katie Gathercole, Penny A Gowland, Robin C Spiller, Alan R Smyth, Luca Marciani","doi":"10.1016/j.jcf.2026.07.009","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.07.009","url":null,"abstract":"<p><strong>Background: </strong>The terminal ileum (TI) is commonly affected in people with cystic fibrosis (pwCF), but limited quantitative information is available on its appearance and dimensions. This study aimed to use magnetic resonance imaging (MRI) to: 1) measure the diameter of the distal TI in healthy volunteers (HVs) and pwCF; 2) test the hypothesis that the diameter of the TI in pwCF is larger than in HVs.</p><p><strong>Methods: </strong>Twenty-six adult pwCF (23 on modulators) and 30 HVs participated. A commercial image analysis platform (Entrolytics, Motilent, UK) was used to measure the long and short axes diameters of the TI on cross-sectional images, along the most distal 5 cm before the ileo-caecal valve. The cross-sectional area of the TI was calculated assuming an elliptical shape.</p><p><strong>Results: </strong>(mean±SD) pwCF had a larger TI compared with HVs: the long axis TI diameter (1.6 ± 0.3 cm for HVs versus 2.7 ± 0.7 cm for pwCF, p < 0.0001), the short axis TI diameter (1.2 ± 0.3 cm versus 2.2 ± 0.6 cm respectively, p < 0.0001) and the TI cross-sectional area (1.6 ± 0.7cm² versus 4.9 ± 2.5cm² respectively, p < 0.0001). Sixty-five% of pwCF showed heterogeneous, faeces-like chyme presence in the TI.</p><p><strong>Conclusions: </strong>This study showed that the TI is enlarged and filled with heterogeneous, faeces-like chyme in pwCF compared with HVs. These findings are in keeping with earlier surgical reports. Increased chyme viscosity and/or impaired motility may lead to accumulation of chyme in the TI in pwCF. New treatments correcting these abnormalities such as secretagogues could be evaluated using the new MRI-derived TI diameter and area endpoints.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current diabetes therapy and use of diabetes technology in people living with cystic fibrosis-related diabetes (CFRD): Insights from the DPV network.","authors":"Thomas Hörtenhuber, Stefanie Schmid, Claudia Boettcher, Silke Herrlinger, Mareike Niemeyer, Martin Tauschmann, Reinhard W Holl, Nicole Prinz","doi":"10.1016/j.jcf.2026.07.002","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.07.002","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis-related diabetes (CFRD) is a common comorbidity in cystic fibrosis (CF), significantly impacting morbidity and mortality. Recent advancements in therapy and diabetes technology have transformed the management of CF and diabetes. This study aims to assess the evolution of CFRD and its treatment over the past few decades in a large cohort receiving routine care.</p><p><strong>Methods: </strong>Longitudinal data of 1039 persons with CFRD (median age at CFRD onset (Q1;Q3): 15.7 (13.2-19.9) years; 57.2% females) from the Diabetes Prospective Follow-up (DPV) database between 2000 and 2023 were analyzed. Changes in demographics, anthropometrics and diabetes therapy were studied using adjusted linear and logistic regression models.</p><p><strong>Results: </strong>BMI-SDS at CFRD diagnosis increased from -0.62 (-1.78;+0.12) in 2000 to -0.45 (-0.81; +0.36) in 2023 (p = 0.002), while age at CFRD diagnosis decreased from 14.8 (13.4;19.1) years in 2000 to 12.5 (11.3;14.7) years in 2023 (p = 0.033). Pharmacological CFRD treatment has changed over the past years. Insulin monotherapy increased from 65.1% to 78.7% (p = 0.044), while OAD/GLP-1 RA-only use decreased (16.9% to 0.7%, p < 0.001). Insulin pump therapy was documented in 26.2% of people with CFRD (PwCFRD) in 2023. The use of CGM increased continuously since 2015, with 76.7% of participants using CGM in 2023 (p < 0.001). Proportion with underweight dropped from 34.3% in 2000 to 14.2% in 2023 (p < 0.001), while overweight increased during this period from 1.5% to 6% (p = 0.011).</p><p><strong>Conclusions: </strong>Insulin monotherapy and in particular diabetes technology is used more frequently. Improvements in CF therapy are reflected in increasing BMI-SDS and a decrease in the proportion of underweight people with CFRD.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing and rate of reimbursement for cystic fibrosis modulator therapies in EU countries.","authors":"Enrico Costa, Silvia Girotti, Saif Elayan, Carlo Castellani, Maria Cavaller Bellaubi, Wim Goettsch, Momir Radulović, João Rocha, Pierluigi Russo, Steven Simoens, Christine Leopold","doi":"10.1016/j.jcf.2026.07.008","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.07.008","url":null,"abstract":"<p><strong>Background: </strong>In the EU, Cystic Fibrosis modulator therapies (CFTR modulators) are centrally licensed, but reimbursement is determined at the national level, resulting in variations in access. This study examined cross-country differences in timing and rate of reimbursement for CFTR modulators, exploring determinants of reimbursement timelines across Europe.</p><p><strong>Methods: </strong>Retrospective data on marketing authorisation, national reimbursement dossier submission, and reimbursement dates were collected for all CFTR modulators authorised in the EU across the 27 Member States. Kaplan-Meier methods were applied to analyse time to reimbursement from marketing authorisation (TTR) and from national reimbursement submissions (TTR2). A mixed-effects Cox proportional hazards model was used to identify determinants of reimbursement timelines.</p><p><strong>Results: </strong>As of 31 December 2024, the median TTR for CFTR modulators was 1479 days (95% CI: 1162-1691), with 62% of EU-approved indications reimbursed, while TTR2 decreased to 280 days (95% CI: 230-322). More recently authorised products were reimbursed faster, and extensions of indication for the same drug were associated with shorter TTRs. Higher Gross Domestic Product per capita and a larger pool of prevalent cystic fibrosis cases were associated with faster reimbursement. Random-effects estimates indicate substantial residual heterogeneity at the country level.</p><p><strong>Conclusions: </strong>There is considerable variability in the timing and rate of reimbursement for CFTR modulators across EU countries, primarily determined by the timing of manufacturer submissions to national authorities. While our findings point to a learning process in reimbursement practice over time, variations nonetheless arise from economic, epidemiological, and other structural factors, suggesting that smaller and less wealthy countries often face delays in reimbursement.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement in functional exercise performance and quadriceps muscle strength after two years treatment with elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: A prospective observational study.","authors":"Anne-Sophie Aubriot, Catherine Song, Clémence Gonçalvès, Laura Santelé, Silvia Berardis, Christophe Goubau, Grégory Reychler, Morgane Penelle, Sophie Gohy","doi":"10.1016/j.jcf.2026.07.003","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.07.003","url":null,"abstract":"<p><strong>Background: </strong>As reduced exercise capacity and muscle weakness are common in people with cystic fibrosis (pwCF) and associated with worse life prognosis and quality of life, we aimed to evaluate the changes in functional exercise performance and peripheral muscle strength in pwCF after two years of elexacaftor/tezacaftor/ivacaftor (ETI).</p><p><strong>Methods: </strong>The 6-Minute Walk Test (6MWT), 1-Minute Sit-to-Stand Test (1STST) and measurement of Maximal isometric Voluntary Contraction of the Quadriceps (MVCQ) with a dynamometer were performed before initiating ETI and after one and two years of ETI.</p><p><strong>Results: </strong>82 pwCF (≥12y) were recruited. The 6MWT distance increased significantly after one and two years of ETI compared with baseline (608±73 m at baseline; 636±75 m after one year of ETI, p < 0.0001; 641±71 m after two years of ETI, p < 0.0001). The number of repetitions during the 1STST enhanced significantly after one and two years of ETI compared with baseline (51±15 at baseline; 55±14 after one year of ETI, p = 0.0022; 56±14 after two years of ETI, p = 0.0042). MVCQ also showed a significant improvement after one and two years of ETI compared with baseline (69±29Nm at baseline; 76±28Nm after one year of ETI, p = 0.0015; 82±29Nm after two years of ETI, p < 0.0001) as well as between one and two years (p = 0.0139). In contrast, no significant change was observed when comparing results in 6MWT and 1STST between one and two years of ETI.</p><p><strong>Conclusion: </strong>6MWT, 1STST and MVCQ improved after one year of ETI with improvements persisting at two years of treatment.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world experience with a generic formulation of elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis.","authors":"María Macarena Oneglia, Hilda Giugno, Ariela Agustinho, Paula Plubatsch, Claudio Castaños","doi":"10.1016/j.jcf.2026.07.004","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.07.004","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator protein. Since 2021, Argentina has provided a generic formulation of the triple modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI). The aim of this study is to evaluate clinical effects on pulmonary function, nutritional status, sputum microbiology, sweat test (ST), respiratory exacerbations, and quality of life in patients using this generic formulation.</p><p><strong>Methods: </strong>People with cystic fibrosis (PwCF), both sexes, aged ≥6 years, received the generic ETI formulation at Hospital de Pediatria Prof. Dr J.P. Garrahan.</p><p><strong>Primary endpoint: </strong>clinical variables were analyzed before and after one year of treatment. Secondary endpoint: pulmonary function was compared between groups with and without prior modulator therapy, both before and after treatment RESULTS: Fifty-five PwCF were included. The median age at ETI initiation was 11.6 years (IQR 8.9-14.5). Thirty-one (56.36%) had not previously received modulators. Baseline median ppFEV1 of the entire cohort was 80.7 (IQR 62.7-91), and after one year, ppFEV1 increased to101 (IQR 88.5-105.75). Median BMI z-score improved from -0.32 (IQR -0.77 to 0.35) to -0.09 (IQR -0.67 to 0.43) after one year. The median reduction in ST was 45 mEq/L. Pulmonary exacerbations showed significant decline. Pseudomonas aeruginosa decreased in sputum cultures, whereas the Burkholderia cepacia complex remained unchanged. Quality of life improved. No severe adverse effects were reported. After 12 months, lung function improved significantly in the group without previous modulator treatment.</p><p><strong>Conclusions: </strong>As previously reported for the original ETI formulation, the Argentine generic formulation showed similar results for clinical variables.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}