Journal of Cystic Fibrosis最新文献

{"title":"Impaired insulin secretion in response to mixed meal ingestion is associated with hypersomatostatinemia in individuals with cystic fibrosis.","authors":"Shana O Warner, Nat H Whitsett, Yufei Dai, Nicole Sheanon, Blair Hoeting, Veronica Indihar, Jason J Winnick","doi":"10.1016/j.jcf.2026.09.016","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.09.016","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a monogenic disease characterized by exocrine pancreas insufficiency, glucose intolerance, and a high prevalence of diabetes. Diminished insulin secretion is a key contributor to glucose intolerance and diabetes in people with CF, yet the pathophysiology of this deficiency is not fully understood. Somatostatin is a hormone secreted by several tissues in the body, including the delta cells of the pancreas, and is known to inhibit insulin secretion; however, its role in postprandial hypoinsulinemia in people with CF remains unclear. This cross-sectional study included 16 people with CF (CF group) and 8 healthy control subjects (HC), each of whom underwent a mixed meal tolerance test, during which their glucoregulatory responses were assessed. We hypothesized that impaired insulin secretion in CF would be associated with hypersomatostatinemia. Plasma glucose responses to the mixed meal were higher in CF compared to HC (AUC of 27,656±2,215 and 20,564±1,028 mg/dL*180 min, respectively, p<0.05), whereas the AUC for insulin (5866±730 and 11090±1628 µU/mL*180 min, respectively; p<0.05), and C-peptide (608±42 and 998±127 pg/mL*180 min, respectively; p<0.05), were both lower. Hypersomatostatinemia in CF (AUC of 4682±278 and 3353±277 pg/mL*180 min in CF and HC, respectively, p<0.01), was inversely associated with C-peptide (r=-0.54; p<0.01), and insulin (r=-0.60; p<0.01) responses to the mixed meal. These data suggest that hypersomatostatinemia is associated with diminished insulin secretion in people with CF, and that it could be a target for improving glucose tolerance in this population.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193934","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":"Distinct gastrointestinal symptom phenotypes in adults with cystic fibrosis are linked to complications and medication use: the GRAMPUS-CF study.","authors":"J Holaman, D Sills, H Saumtally, C Johnson, A Recto, R Marsh, A Prayle, K Gathercole, T Monaghan, L Marciani, R Spiller, H L Barr, D G Downey, C van der Gast, D Peckham, I Stewart, A Smyth","doi":"10.1016/j.jcf.2026.09.014","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.09.014","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal symptoms remain common in adults with cystic fibrosis (CF) despite cystic fibrosis transmembrane conductance regulator modulator use, suggesting persistent and heterogeneous gut dysfunction. This prospective observational study tests the hypothesis that distinct gut symptom phenotypes in CF can be observed and linked to underlying mechanisms.</p><p><strong>Methods: </strong>Adults from three UK CF centres completed the Gastrointestinal Symptom Rating Scale, Patient Assessment of Constipation Symptoms and a bowel-habit questionnaire. Latent class analysis using an ordinal logistic model was applied to 36 symptom indicators. Associations between phenotypes and demographic, clinical, and treatment variables were examined using generalised linear models.</p><p><strong>Results: </strong>Three hundred participants completed questionnaires (54% male; median 31 years). We identified four symptom phenotypes: mild; moderate-constipation predominant; moderate-diarrhoea predominant and severe. The severe phenotype was associated with gastroesophageal reflux (RRR 2.86; 95%CI: 1.30-6.31; p = 0.009), distal intestinal obstruction syndrome (RRR 2.46; 95%CI: 1.04-5.81; p = 0.04), proton pump inhibitor (RRR 3.29; 95%CI 1.39-7.74; p = 0.007), and laxative use (RRR 6.13; 95%CI 2.54-14.84; p < 0.001). CF-related liver disease was associated with both moderate-constipation and diarrhoea phenotypes, respectively (RRR 2.08; 95%CI 1.13-3.81; p = 0.018; RRR 2.11; 95%CI 1.03-4.29; p = 0.04). There was a lower likelihood of long-term oral antibiotic use in the moderate-constipation phenotype (RRR 0.53; 95%CI 0.3-0.92; p = 0.025) and moderate-diarrhoea phenotype (RRR 0.46; 95%CI 0.24-0.91; p = 0.025).</p><p><strong>Conclusions: </strong>Four distinct symptom phenotypes were identified, independent of demographics and pancreatic status, but associated with specific complications and medication profiles. These phenotypes provide a framework for mechanistic studies within the GRAMPUS-CF cohort and precision management of CF-related gut disease.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207156","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":"Model-informed dose reduction of elexacaftor/tezacaftor/ivacaftor therapy in adult people with cystic fibrosis: A simulation study.","authors":"Tom C Zwart, Syendon Bc Baromeo, Inez Bronsveld, Harry Gm Heijerman, Erik B Wilms, Renske van der Meer","doi":"10.1016/j.jcf.2026.10.003","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.10.003","url":null,"abstract":"<p><strong>Background: </strong>Most people with cystic fibrosis (pwCF) use elexacaftor/tezacaftor/ivacaftor (ETI) therapy. While generally efficacious, some pwCF experience adverse events. This is typically managed by empirical dose reduction, but the optimal regimen remains unknown. We performed a population pharmacokinetic (PK) study incorporating a simplified exposure effect approximation to evaluate ETI dose reduction strategies.</p><p><strong>Methods: </strong>ETI exposure under five dose reduction strategies was simulated using available population PK models. Standard dose ETI PK was simulated, from which individuals were selected for dose reduction based on elexacaftor predicted minimum concentrations (C_min). ETI exposure was translated to predicted relative effect using simplified PD models constructed from previously reported exposure-effect data.</p><p><strong>Results: </strong>Demographic data of 885 adults pwCF were available as virtual population. Dose reduction for pwCF showing simulated elexacaftor Cmin >75th percentile (8687 µg/L) yielded seemingly limited PK-PD impact compared to the standard dose. Reduction to a 100/50/75 mg ETI morning dose with a 75-150 mg ivacaftor evening dose (regimen A-B) resulted in limited median predicted effect shifts of 93.7%→92.7% and 89.9%→88.7% for elexacaftor and tezacaftor, and 96.2%→95.8 and 96.2%→95.5 for ivacaftor. This was accompanied by limited predicted EC_70-90 attainment reductions of ≤13.5% for elexacaftor, ≤30.1% for tezacaftor, and ≤4.6% and ≤7.8% for ivacaftor.</p><p><strong>Conclusions: </strong>In this simulation study, dose reduction to one morning ETI tablet (100/50/75 mg) with an evening 75-150 mg ivacaftor dose showed a seemingly limited simulated PK and predicted exposure-effect impact in pwCF displaying high elexacaftor exposure. This hypothetical regimen shows promise for clinical evaluation in a formal dose reduction study.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193906","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":"Basic science & translational research in cystic fibrosis - insights from the 20th ECFS basic science conference.","authors":"Patrick T Harrison, Batsheva Kerem, Dean A Madden","doi":"10.1016/j.jcf.2026.09.017","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.09.017","url":null,"abstract":"<p><p>The development of CFTR modulators revolutionized the approach to treating Cystic Fibrosis (CF) by targeting the ion channel that causes the disease rather than just the symptoms. For those people with CF who have access and good responses to modulators, their day-to-day health, quality and quantity of life continue to improve. But there are still many people with CF unable to tolerate these medicines, and/or without access, ineligible due to their CF genotype, cost, or lack of approval in their home country. There is a lot more basic science and translational research to be done until the mission of the CF community is complete. A leading platform to promote the process of propagating, peer-review, and ultimately progress work towards this goal is the annual ECFS Basic Science Conference. The aim of this special issue of JCF is to highlight the diverse yet interconnected nature of basic science research in CF and its progress to clinical evaluation. This work is reflected in nine review articles authored by faculty members who presented their findings at the twentieth iteration of the conference, held in Viareggio, Italy.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182132","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":"Perspectives on inhaled medicines in the CFTR modulator era: A national survey of adults with cystic fibrosis.","authors":"R D Sandler, Z H Hoo, S M B Ariss","doi":"10.1016/j.jcf.2026.10.001","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.10.001","url":null,"abstract":"<p><strong>Introduction: </strong>The transformative effects of CFTR modulators (CFTRm) have led people with cystic fibrosis (PwCF) and clinicians to re-evaluate the role of inhaled medicines. Our objective was to understand the perspectives of pwCF.</p><p><strong>Methods: </strong>A survey was shared via two CF-specific UK email lists and social media. Participants rated the importance of inhaled medicines from 0 (least) to 100 (most) and noted any relative changes since commencing CFTRm. Free-text responses were categorised into insight-generating themes.</p><p><strong>Results: </strong>Responses were received from 414 pwCF, of whom 208 (50%) were female, representing 17 of the 26 UK adult CF centres. Most were prescribed CFTRm (n = 344, 83%) and/or inhaled medicines (n = 321, 78%). Perceived importance of inhaled medicines was significantly lower among those prescribed CFTRm (median 72/100, IQR 49-94) compared with those not prescribed CFTRm (88/100, 52-100, p = 0.03). Among those prescribed CFTRm, 138 (40%) considered inhaled medicines less important than before treatment, citing reduced symptoms, lack of perceived benefit, and a desire to decrease treatment burden. Conversely, 174 (51%) regarded inhaled medicines as equally or more important, referencing cumulative lung damage, clinician advice, perceived benefit, and sustaining long-term health.</p><p><strong>Conclusion: </strong>The impact of CFTRm on the perceived importance of inhaled medicines is variable amongst pwCF. Whilst population-level evidence regarding the clinical impact of reducing inhaled medicines regimens for PwCF taking CFTRm is awaited, clinicians should be aware of the variation in patient perspective during the process of shared decision-making and individualisation of care.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166916","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":"Comfort discussing financial challenges and accessing resources in cystic fibrosis care among people with cystic fibrosis and their care partners: A cross-sectional survey study.","authors":"Ryan C Perkins, Karen Carey, Joel R King, Laura Beidler, Joseph Moo-Young, Katelyn Broekema, Gregory S Sawicki, Debbie Benitez, A Whitney Brown, Christina Duncan, Isaac Groenendyk, Meghan E McGarry, Hanna Phan, Clement L Ren, Ashley Shaver, Anne Willis, Olivia Dieni, Aricca D Van Citters","doi":"10.1016/j.jcf.2026.10.002","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.10.002","url":null,"abstract":"<p><strong>Background: </strong>People with cystic fibrosis (PwCF) face considerable financial burdens. PwCF who are most likely to make financial and healthcare tradeoffs, had the lowest comfort discussing financial issues with their CF team. The association of comfort with financial discussions and accessing resources is unknown. Our study assessed the relationship between comfort discussing financial issues with the CF care team and PwCF accessing resources.</p><p><strong>Methods: </strong>We evaluated responses of adults with CF, parents/guardians of children with CF, and spouses/partners/guardians of PwCF from the 2024 COST-CF survey. We examined financial discussion frequency, resource usage, barriers, and perceptions of accessing resources as a function of comfort discussing financial issues with the care team.</p><p><strong>Results: </strong>875 respondents reported their comfort with financial discussions, with 51% feeling comfortable/very comfortable, 38% slightly/somewhat comfortable, and 11% not at all comfortable. Overall, 50% had cost discussions with their CF care team that cost of care presented a financial burden in the last 12 months. Most respondents (69%) experienced at least 1 barrier to accessing financial resources. Those reporting lower comfort with discussions generally endorsed higher need (e.g., understanding and planning for healthcare costs), lower confidence in getting support to prevent/reduce cost burden, and more barriers to accessing care (e.g., did not know where to find financial resources).</p><p><strong>Conclusions: </strong>Our results show patient/family comfort level with financial discussions is related to levels of need, confidence in getting support, and barriers to accessing care. The CF care team should be proactive in assessing financial needs and connecting PwCF to resources.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167359","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":"Timeliness to diagnostic and early care milestones after newborn screening for Cystic Fibrosis in Texas: 14 years of experience at 2 centers.","authors":"Alexandra Pottorff, Savannah Knight, Carolyn L Cannon, MinJae Lee, Clement L Ren, Fadel Ruiz, Pamela Tuley, Donna Beth Willey-Courand, Christopher Wong, Meghana Sathe","doi":"10.1016/j.jcf.2026.09.013","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.09.013","url":null,"abstract":"<p><strong>Background: </strong>Texas implemented Newborn Screening (NBS) for Cystic Fibrosis (CF) in December 2009. This study aimed to determine the timeliness of key CF diagnostic milestones in Texas at two CF centers, NBS sensitivity for CF, and the impact of timeliness on anthropometric outcomes.</p><p><strong>Methods: </strong>This retrospective cohort study reviewed data from the electronic health record for people with CF (pwCF) born in Texas and cared for at two pediatric CF centers between 12/1/2009- 1/1/2024. Outcomes included time from birth to the NBS, first CF event, NBS results, number of variants identified, and long-term anthropometric outcomes.</p><p><strong>Results: </strong>Among 384 pwCF identified, 35 false negative cases yielded a sensitivity of 90.9%. Detection of two variants improved from 65.64% to 72.46% after expansion of the CFTR variant panel. Among 247 pwCF, median age of first CF event (AFE) was 29 days. Proportion of pwCF with AFE by 28 days of age improved from 35% to 54% after variant panel expansion (p = 0.011). PwCF with two variants identified had earlier median AFE (27 days) compared to those with one variant (33.5 days) or no variants (47.5 days; p < 0.0001). PwCF with very delayed AFE had lower weight-for-age and weight-for-length z-scores.</p><p><strong>Conclusion: </strong>Most pwCF experienced a delayed AFE, possibly related to timing of second NBS. PwCF with only one or no CF causing variants identified on NBS experienced greater delays, highlighting the concerns of utilizing a limited variant panel. These suggest a need to optimize Texas CF NBS practices and may inform screening methods in other states.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137027","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":"Long-term outcomes of adolescents/adults with CF screen positive, inconclusive diagnosis.","authors":"Vito Terlizzi, Angela Pepe, Chiara Cimbalo, Cristina Fevola, Silvia Gartner, Laura Claut, Andrea Gramegna, Angela Sepe, Marco Cipolli, Irene Esposito, Nicole Caporelli, Paolo Bonomi, Giulia Carreras, Donatello Salvatore, Rita Padoan, Carlo Castellani, Philip Farrell","doi":"10.1016/j.jcf.2026.09.012","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.09.012","url":null,"abstract":"<p><strong>Background: </strong>Long-term outcomes for infants labeled as Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) are poorly defined, especially into adolescence and adulthood. This study evaluates the clinical evolution and management of Italian patients initially classified as CFSPID or maintaining this label over time. The aim is to assess the progression toward cystic fibrosis (CF) or CFTR-related disorders (CFTR-RD) and to describe the long-term clinical status, lung function, and therapeutic management of this cohort.</p><p><strong>Methods: </strong>This retrospective, multicenter, observational study included subjects born before 2011 meeting CFSPID criteria at six Italian CF centers. Clinical data were analyzed from the first evaluation until June 30, 2025, focusing on diagnostic evolution, complications, and treatments.</p><p><strong>Results: </strong>Among 77 subjects (median age 20.9 years), 41.6% eventually received a CF diagnosis at a median age of 8.6 years, primarily due to sweat chloride levels, while 18.2% were reclassified as CFTR-RD. Most patients maintained preserved nutritional status and lung function with few complications. Notably, 40.2% remained asymptomatic with a persistent inconclusive diagnosis. Despite this, 80.6% and 64.5% of persistent CFSPID cases were prescribed airway clearance and salt supplementation, respectively. Two of ten eligible CF patients received triple-combination modulator therapy.</p><p><strong>Conclusions: </strong>Most adolescents and adults initially identified as CFSPID experience favorable clinical outcomes, regardless of progression to CF or CFTR-RD. However, the frequent prescription of treatments to asymptomatic individuals with inconclusive diagnoses suggests a potential for overtreatment, highlighting the need for more evidence-based management strategies.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127429","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":"Corrigendum to \"Personalized therapy with CFTR modulators: Response of p.Ile148Asn variant\" [J Cyst Fibros 24 (2025) 542-547].","authors":"Cláudia S Rodrigues, Violeta Railean, Sofia S Ramalho, Carlos M Farinha, Ines Pankonien, Margarida D Amaral","doi":"10.1016/j.jcf.2026.09.015","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.09.015","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110217","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":"Vanzacaftor/tezacaftor/deutivacaftor partially restores CFTR function of the L467F;F508del complex allele in primary nasal epithelial cells.","authors":"Jasmin Berger, Anita Balázs, Rebecca Dalferth, Katharina Schütz, Anna-Maria Dittrich, Valentina Cvejoska Cholakovska, Stojka Fushtik, Elena Krsteska, Stephanie Thee, Mirjam Stahl, Marcus A Mall, Simon Y Graeber","doi":"10.1016/j.jcf.2026.09.011","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.09.011","url":null,"abstract":"<p><p>Highly effective CFTR modulator therapies have transformed the treatment of cystic fibrosis (CF). Elexacaftor/tezacaftor/ivacaftor (ETI) leads to restoration of CFTR-mediated chloride transport of around 40% of normal CFTR activity and results in substantial clinical benefits in people with CF and at least one F508del allele. Interestingly, people carrying the complex allele L467F;F508del do not show clinical improvements following initiation of ETI. However, the effects of the novel triple combination vanzacaftor/tezacaftor/deutivacaftor (VTD) on this complex allele are unknown. In this study, we compared the effects of ETI and VTD on CFTR function in highly differentiated primary human nasal epithelial cultures (pHNECs) derived from 7 people with CF carrying at least one L467F;F508del complex allele and 9 healthy controls. CFTR-mediated chloride transport was quantified by transepithelial short-circuit current measurements in Ussing chambers following treatment with ETI, VTD, or vehicle control. Treatment with ETI showed a numerical but not statistically significant improvement in CFTR-mediated chloride currents in pHNECs carrying the L467F;F508del complex allele. In contrast, VTD significantly increased forskolin/IBMX-stimulated currents (p < 0.001), forskolin/IBMX plus deutivacaftor-stimulated currents (p < 0.01) and CFTRinhibitor-172-inhibited currents (p < 0.001) compared to vehicle control. The mean increase in forskolin/IBMX plus deutivacaftor-stimulated current corresponded to about 10% of CFTR-mediated currents in healthy cultures. In exploratory subgroup analyses, VTD-mediated CFTR rescue was more pronounced in L467F;F508del-homozygous than in compound heterozygous cultures. In conclusion, our results demonstrate that VTD partially restores CFTR function in epithelial cultures carrying the L467F;F508del complex allele. These findings provide a rationale for further clinical evaluation of VTD in people with CF carrying L467F;F508del and potentially other complex CFTR alleles that do not respond to ETI.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110251","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}