Journal of Cystic Fibrosis最新文献

{"title":"Real-world association between ivacaftor initiation and lung function variability: A registry study.","authors":"Rhonda D Szczesniak, Eleni-Rosalina Andrinopoulou, Hancheng Li, Raksha Jain, Nicole Mayer-Hamblett, Josh Ostrenga, Anushka K Palipana, David J Pasta, Margaret Rosenfeld, Jonathan Todd, Elizabeth A Cromwell, Wayne J Morgan","doi":"10.1016/j.jcf.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.014","url":null,"abstract":"<p><strong>Background: </strong>Increased variability in forced expiratory volume in 1 s of % predicted (FEV₁pp) has been associated with accelerated lung function decline in individuals with cystic fibrosis (CF). Lung function variability is a leading predictor of decline, but the association between ivacaftor initiation and FEV₁pp variability has not been characterized.</p><p><strong>Methods: </strong>We utilized the Cystic Fibrosis Foundation Patient Registry (2008-2020) to quantify this association and identify risk factors of increased variability. Linear mixed effects models were used to compare pre- and post-ivacaftor initiation periods for established outcome measures of FEV₁pp variability: i) maximum and ii) median deviations from the best (highest) FEV₁pp during each period; iii) maximum, iv) median, and v) standard deviation about the trendline of the FEV₁pp trajectory in each period.</p><p><strong>Results: </strong>The analysis cohort included 527 individuals. Across outcomes, FEV₁pp variability was reduced after ivacaftor initiation (median reduction: 1.85 % predicted). Reductions were robust with highest magnitudes of effect identified using maximum deviation from the best FEV₁pp while most consistent findings were reached with trendline measures, particularly median deviation. Risk factors for increased FEV₁pp variability differed between children and adults but were consistent between G551D and R117H subgroups. F508del homozygous patients followed contemporaneously exhibited minimal change in variability (median change: 0.25 % predicted). Reduced variability weakly correlated with changes in FEV₁pp and slope, but higher levels of pre-ivacaftor variability were associated with greater reductions.</p><p><strong>Conclusions: </strong>There was evidence that ivacaftor initiation reduces FEV₁pp variability in people with CF. Quantifying FEV₁pp variability may have utility as a marker of therapeutic effectiveness.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391016","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":"Personalized therapy with CFTR modulators: Response of p.Ile148Asn variant.","authors":"Cláudia S Rodrigues, Violeta Railean, Sofia S Ramalho, Carlos M Farinha, Ines Pankonien, Margarida D Amaral","doi":"10.1016/j.jcf.2025.01.015","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.015","url":null,"abstract":"<p><strong>Background: </strong>Elucidating the molecular and cellular effects caused by CFTR variants is crucial to understand Cystic Fibrosis (CF) disease pathophysiology, but also to predict disease severity, to provide genetic counselling, and to determine the most adequate therapeutic strategy for people with CF (pwCF). While the current CFTR modulator drugs (CFTRm) are approved mainly for pwCF with the most prevalent variant, p.Phe508del, pwCF carrying rare and/or uncharacterized CFTR variants are not eligible. However, previous studies have shown that such rare variants can be rescued by the approved CFTRm, suggesting clinical benefit for those pwCF. Here, we characterized the rare and non-eligible p.Ile148Asn CFTR variant found in Portuguese pwCF, regarding CFTR processing, traffic and function, and response to existing CFTRm.</p><p><strong>Methods: </strong>We used the forskolin-induced swelling (FIS) assay in intestinal organoids (IOs) from 2 CF individuals carrying p.Ile148Asn in heterozygosity with p.Phe508del and p.Gly542Ter, respectively. Additionally, a Cystic Fibrosis Bronchial Epithelial (CFBE) cell line expressing p.Ile148Asn-CFTR was generated to study the molecular defect of this variant individually.</p><p><strong>Results: </strong>Our results show that p.Ile148Asn is a CF-causing variant, impairing both CFTR plasma membrane (PM) traffic and function, albeit partially. Moreover, p.Ile148Asn-CFTR can be rescued by approved CFTRm in CFBE cells and IOs, suggesting potential clinical benefit for these individuals.</p><p><strong>Conclusion: </strong>The work emphasizes the importance of testing CFTRm for rare variants not included in the drug label. It also shows that the 'theranostic' approach using IOs from pwCF, which captures the genetic background of each individual, complements theratyping in cell lines that focuses only on CFTR variants.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370823","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":"Impact of CFTR modulator therapy on basic life needs and financial concerns in people with cystic fibrosis: Data from the Well-ME survey.","authors":"Heather Boas, Aricca D Van Citters, Elizabeth L Yu, Joel R King, Emily A Zagnit, Olivia Dieni, Clement L Ren","doi":"10.1016/j.jcf.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.001","url":null,"abstract":"<p><strong>Background: </strong>CFTR modulator (CFTR-M) therapy has led to improved clinical outcomes amongst people with cystic fibrosis (PwCF) eligible for these therapies. However, there is limited data on their impact on the basic life needs and financial concerns of PwCF.</p><p><strong>Methods: </strong>We used data from the Wellness in the Modulator Era (Well-ME) survey, which includes data from 900 PwCF both taking and not taking CFTR-M. We examined self-reported financial well-being over time and changes associated with school or work, financial planning, and costs of living. Descriptive statistics were used to analyze responses.</p><p><strong>Results: </strong>Most respondents reported no change in financial well-being, but 13 % identified a positive change and 16 % reported a negative change. Positive changes in basic life needs included fewer missed work and school days, while negative changes included medical out-of-pocket costs. Worries about financial problems were reported in 35 % of all respondents and were more common in PwCF who never took CFTR-M or had been taking one and then stopped, in PwCF with lower lung function, and in PwCF with Medicaid insurance.</p><p><strong>Conclusions: </strong>These results indicate that for most PwCF, CFTR-M have not affected their basic life needs, and a substantial proportion of PwCF continue to experience financial stress and concerns. Many respondents' financial concerns focused on medical costs and insurance. These data underscore the continued need for CF care teams to address PwCF's financial stress and ability to meet basic life needs, even in the era of improved physical health outcomes due to CFTR-M therapy.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073721","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":"Male sexual and reproductive health in cystic fibrosis: A concept mapping study.","authors":"Kelly A Prangley, Olivia M Stransky, Jessica G Burke, Sigrid L Ladores, Kara S Hughan, Gregory S Sawicki, Traci M Kazmerski","doi":"10.1016/j.jcf.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.011","url":null,"abstract":"<p><strong>Background: </strong>Males with cystic fibrosis (MwCF) face general and disease-specific sexual and reproductive health (SRH) concerns. Using concept mapping (CM), this study identified the SRH topics valued by members of the CF community.</p><p><strong>Methods: </strong>MwCF 18 years and older, parents and partners of MwCF, and healthcare providers participated in an online CM study. Participants individually brainstormed, sorted, and rated SRH topics important for MwCF. Using multidimensional scaling, hierarchical cluster analyses, and t tests to assess rating differences, participants interpreted results during an online meeting.</p><p><strong>Results: </strong>Eighty-nine participants (32 MwCF; 6 parents; 9 partners; and 42 providers) generated 125 statements on male SRH in CF. Seventy-eight percent completed sorting and 73% rated statements based on importance. During interpretation, 20 participants named six clusters of SRH topics: 1) Family building and fertility; 2) Psychosocial aspects of SRH; 3) Being a parent or partner as a MwCF; 4) Sexual development, function, and treatments; 5) SRH education, communication, and awareness; and 6) SRH risks, comorbidities, and aging. Participants rated family building and fertility as highest in importance (mean = 4.06±0.36 of 5). Providers issued higher importance ratings compared to MwCF and parent/partner participants. Participants identified patient-centered outcomes for each cluster and focused on enhancing SRH knowledge, decision-making, and patient-provider communication in CF care.</p><p><strong>Conclusions: </strong>The SRH topics, importance, and patient-centered outcomes identified in this study can inform future interventions and research to optimize the comprehensive clinical care delivery for MwCF.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066134","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":"Monitoring ETI effects over 1.7 years in an infant treated in utero, via breast milk and granules by repeated faecal elastase measurements.","authors":"Dorothea Appelt, Teresa Fuchs, Johannes Eder, Katharina Niedermayr, Anja Siedl, Helmut Ellemunter","doi":"10.1016/j.jcf.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.012","url":null,"abstract":"<p><p>Pancreatic insufficiency is a major complication of cystic fibrosis (CF), which traditionally has been managed with pancreatic enzyme replacement therapy in the vast majority of CF patients, even in the era of highly effective cystic fibrosis transmembrane conductance regulator modulator (CFTRm) therapy. We report on a 1.7 year old male infant with CF who was exposed to ETI both in utero and postpartum, via breast milk and oral granules. Repeated faecal elastase analyses were carried out to monitor pancreatic function closely, with normal levels at birth. Although faecal elastase values fluctuated over time, it never dropped below 100 µg/g for several subsequent measurements, while the infant continued to receive breast milk. However, at the age of 8 months PERT was initiated. ETI was introduced at 9 months of age in the form of crushed tablets as an individualised treatment, following a sustained increase in faecal elastase to >200µg/g to date. 3 weeks after starting oral ETI therapy, PERT was discontinued. With this case report we would like to show that continuous pre- and postnatal ETI exposure can maintain pancreatic function in CF for at least 1.7 years.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066203","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":"Contraceptive use and pregnancy in cystic fibrosis: Survey findings from 10 cystic fibrosis centers.","authors":"Emily M Godfrey, Amalia Magaret, Andrea Roe, Jennifer L Taylor-Cousar, Patricia Walker, Elinor Langfelder-Schwind, Traci M Kazmerski, Raksha Jain, Sheila K Mody, Ahmet Uluer, Natalie E West, Leigh Ann Bray, Chialing Hsu, Anna Fiastro, Karen D Hinckley Stukovsky, Dennis Hadjiliadis, George M Solomon, Sigrid Ladores-Barrett","doi":"10.1016/j.jcf.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.007","url":null,"abstract":"<p><strong>Background: </strong>Reproductive life planning is key, now that people with cystic fibrosis (pwCF) may live into their 60s. This study explores contraceptive use, pregnancy trends, and whether concomitant cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy reduces contraceptive effectiveness.</p><p><strong>Methods: </strong>Females with CF aged 18-45 years from 10 U.S. CF centers completed a self-administered web-based questionnaire. Pregnancy rates were calculated by linear-mixed models with a logit link detected associations with contraception and modulator use.</p><p><strong>Results: </strong>A total of 561 pwCF (median age of 29 years [IQR 24.9-35.8] years) completed the survey. Most participants (n = 499, 89%) used modulators, and almost all (n = 555, 99%) used contraception. Condoms (n = 448, 80%) and oral contraceptive pills (n = 363, 65%) were the most prevalent methods used. One-third (n = 189, 34%) reported ever being pregnant. Of those reporting pregnancies (n = 319), about half (n = 151, 48%) were unintended. Pregnancy was significantly associated with age (20-29 years or 30-39 years), partner cohabitation (aOR 21.5, 95% CI 5.1 to 91.1), and non-hormonal contraceptive use (aOR 5.1, 95% CI 1.1 to23.0). Among pwCF cohabitating with a partner, modulator use was positively associated with pregnancy (OR 1.8, 95% CI 1.3 to 2.6) (p = 0.0008).</p><p><strong>Conclusions: </strong>Despite almost universal contraceptive use, unintended pregnancy among pwCF is common. Likelihood of pregnancy is increased among CFTR modulator users who are partnered, although CFTR modulators themselves do not appear to decrease hormonal contraceptive effectiveness. Patient education about contraception is an increasingly critical aspect of CF care.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028811","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":"Short-term modification of breathprint by Elexacaftor/Tezacaftor/Ivacaftor in a paediatric cohort.","authors":"Emmanuelle Bardin, Nicolas Hunzinger, Elodie Lamy, Camille Roquencourt, Bingqing Zhou, Yasmine Tabache, Laurence Le Clainche, Natascha Remus, Charlotte Roy, Philippe Devillier, Thao Nguyen-Khoa, Frédérique Chedevergne, Clément Pontoizeau, Mairead Kelly, Stanislas Grassin Delyle, Isabelle Sermet-Gaudelus","doi":"10.1016/j.jcf.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.004","url":null,"abstract":"<p><strong>Background: </strong>The triple combination Elexacaftor/Tezacaftor/Ivacaftor (ETI) translates into major respiratory improvements in adults; yet current clinical endpoints may prove insufficiently sensitive in young children. We hypothesised that ETI rapidly modifies the lungs' metabolism, resulting in changes in breath composition.</p><p><strong>Methods: </strong>Eleven children with CF were enrolled in a longitudinal pilot study at the paediatric Necker hospital. Breath was collected on sorbent tubes using a ReCIVA® device before, after one week and one month of ETI. Samples were analysed by 2D-gas chromatography-mass spectrometry (2D-GC-MS). A linear mixed-effect model, corrected for clinical confounding factors, identified exhaled metabolites differentially expressed throughout the visits. Correlations were calculated between these and clinical indicators.</p><p><strong>Results: </strong>Breath collection was successful in all children from six years old. They presented a decreased sweat chloride and improved lung function as early as within one week of ETI. Breath composition gradually evolved over the visits. ETI induced significant modifications in the level of 12 breath metabolites. Amongst those, dimethyl sulphide and tetradecene changes correlated with improvements in forced expiratory volume in one second (FEV₁) and forced expiratory flow (FEF_25-75), whilst 3-methyldecane and 3-(chloromethyl)-heptane were predictive of changes in lung clearance index (LCI_2.5).</p><p><strong>Conclusions: </strong>ETI impacts the breath profile from the first week of treatment. Not only could \"breathomics\" bring mechanistic insights into the metabolic impact of ETI, but it may also offer novel non-invasive options to monitor CF disease and predict therapeutic response.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023720","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":"Longer term follow-up of abdominal symptoms (CFAbd-Score) after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis.","authors":"L R Caley, L Gillgrass, C Zagoya, H Saumtally, F Duckstein, White H, J G Mainz, D G Peckham","doi":"10.1016/j.jcf.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.010","url":null,"abstract":"<p><strong>Background: </strong>Whether improvements in gastrointestinal (GI) symptoms observed with Elexacaftor/Tezacaftor/Ivacaftor (ETI) treatment are sustained in the longer-term requires exploration. This study investigated how GI-symptoms change with longer-term ETI use in pancreatic insufficient adults with cystic fibrosis (awCF).</p><p><strong>Methods: </strong>Participants completed up to three abdominal symptom questionnaires, employing the validated CFAbd-Score. Changes in total CFAbd-Score and its five domains, pain, gastroesophageal reflux-disease (GERD), disorders of bowel movement (DBM), disorders of appetite (DA) and quality of life (QOL), were analysed pre-ETI (T0) and at ≤1.5 years (T1) and 2-4 years of ETI-therapy (T2).</p><p><strong>Results: </strong>A total of 165 CFAbd-Scores from 68 participants were analysed (median age: 34 years; IQR: 28-39). Total CFAbd-Score significantly (p < 0.05) and clinically meaningfully decreased from 20.4 ± 1.6 pre-ETI (median:40 weeks pre-treatment) to 15.3 ± 1.9 and 16.8 ± 1.6 at T1 (median: 25 weeks of ETI) and T2 (median: 148 weeks of ETI), respectively. The CFAbd-Score´s domains DA and QoL only significantly decreased between T0 and T1, whereas DBM only significantly decreased after 2-4 years of ETI therapy (T2). GERD scores were significantly lower at both T1 and T2.</p><p><strong>Conclusion: </strong>While GI symptoms in awCF significantly improve within the first 1.5 years of ETI-therapy, they appear to somewhat wane with longer-term use, despite GI-symptom burden still being lower compared to pre-ETI. However, we cannot differentiate whether this results from reduced adherence, a decrease in ETI effects, or long-term changes in diet, gut microbiota or symptom perception. The longer-term impact of ETI and other potential modulator therapies on GI symptoms requires ongoing monitoring.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006182","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":"Effect of elexacaftor-tezacaftor-ivacaftor on liver transient elastography, fibrosis indices and blood tests in children with cystic fibrosis.","authors":"Vito Terlizzi, Cristina Fevola, Martina Cecchetti, Alberto Terminiello, Franco Curci, Elisa Bartolini, Chiara Rubino, Mariangela Stinco, Simona Carrera, Paolo Bonomi, Giovanni Taccetti, Zachary M Sellers, Giuseppe Indolfi","doi":"10.1016/j.jcf.2024.12.010","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.12.010","url":null,"abstract":"<p><strong>Background: </strong>Elexacaftor-tezacaftor-ivacaftor (ETI) has significantly improved the clinical course of people with cystic fibrosis (pwCF) and eligible CFTR variants. In this study, we prospectively evaluated liver elastography, liver fibrosis indices and liver tests in children with CF aged 6-12 years started on ETI therapy.</p><p><strong>Methods: </strong>Body mass index, sweat test, percent predicted forced expiratory volume in one second, serum markers of liver injury or portal hypertension, liver fibrosis indices, controlled attenuation parameter and liver stiffness were assessed before starting ETI and three and twelve months post-ETI, according to new international guidelines.</p><p><strong>Results: </strong>27 children with CF were enrolled, 14 with liver involvement and 13 without liver involvement at baseline. A significant improvement in sweat chloride after ETI was observed in all subjects. In those with liver involvement, liver stiffness significantly decreased at 12 months of ETI, with all individuals achieving normalization or near-normalization of liver stiffness. The majority of individuals with abnormal AST, ALT, GGT, or liver fibrosis indices at baseline experienced normalization by 12 months of ETI (AST: 67%, ALT: 100%, GGT: 50%, APRI: 100%, GPR: 100%). In the no liver involvement group, the only significant change in liver health metrics at 12 months was a significant reduction in platelets (P<0.05) that remained within the normal range.</p><p><strong>Conclusions: </strong>ETI is associated with improvement in liver stiffness, liver function tests and fibrosis indices in pwCF and liver involvement. ETI may reduce the development of advanced CF liver disease, but longer observations with larger cohorts are needed.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971032","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":"CFTR mutation is associated with bone differentiation abnormalities in cystic fibrosis.","authors":"Claire Dumortier, Andrew Frauenpreis, Antony Hoarau, Amy L Ryan, Sophie C Gangloff, Soula Danopoulos, Frédéric Velard, Denise Al Alam","doi":"10.1016/j.jcf.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.005","url":null,"abstract":"<p><strong>Background: </strong>Cystic Fibrosis-related Bone Disease is an emerging challenge faced by 50 % of adult people with cystic fibrosis (CF). The multifactorial causes of this comorbidity remain elusive. However, congenital bone defects have been observed in animal models with CFTR mutations, suggesting its importance. The role of CFTR in bone cells development is unknown. Studies from human cells remain somewhat controversial depending on the cells used and the disease state of the patients from which the cells derived.</p><p><strong>Methods: </strong>Therefore, we investigated the role of CFTR in osteoblast development using induced pluripotent stem cells generated from homozygous CF donors for F508del and non-CF controls. This approach allows for a clear understanding towards how the CFTR mutation may influence osteoblast differentiation independently from other confounding factors.</p><p><strong>Results: </strong>We observed a lower capacity of differentiation in CF cells as compared to control, already from mesenchymal stem cells (MSC) stage, whereby they retained expression of the pluripotency marker OCT4. Furthermore, our results demonstrated a delayed osteoblast commitment and altered expression of specific markers, such as an increased RANKL/OPG ratio and decreased BMP2, suggesting a potentially perturbed bone homeostasis associated with CFTR mutation.</p><p><strong>Conclusions: </strong>This is the first study of its kind, clearly demonstrating a role for CFTR mutation in delaying osteoblast differentiation and/or regeneration.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970962","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}