Journal of Cystic Fibrosis最新文献

{"title":"An update on cystic fibrosis Hepato-biliary involvement.","authors":"A Jay Freeman, Frank A J A Bodewes","doi":"10.1016/j.jcf.2026.03.022","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.03.022","url":null,"abstract":"<p><p>Liver involvement among people with cystic fibrosis (PwCF) has long been recognized as clinically important. However, a lack of consistent terminology, incomplete understanding of natural history, and poor clinical trial endpoints have historically hindered clinical and research advancements in this field. Recent efforts by the CF Foundation and international gastrointestinal societies have led to a phenotype-based classification for liver involvement, now referred to as Cystic Fibrosis Hepato-Biliary Involvement (CFHBI), with the most severe form of disease termed advanced CF liver disease (aCFLD). Longitudinal studies such as PUSH, combined with national patient registry data, has greatly improved our understanding of the natural history of CFHBI. Several studies have assessed the utility of conventional serological markers of liver disease, non-invasive liver fibrosis indices, and imaging with various elastography modalities to screen for CFHBI and monitor for progression to aCFLD. This has led to the first evidence-based consensus recommendations for the screening, evaluation and management of CFHBI in children. These recommendations provide a foundation from which future research can build from. Finally, while there is emerging population-level data suggesting that modulator therapies are decreasing the rates of aCFLD, the true impact of these medications on CFHBI remains unknown. In this review we provide an overview of the recent advancements leading to the recent consensus recommendations, summarize what is known about the impact of modulator therapies on CFHBI, and discuss the outstanding questions that need to be addressed to advance our understanding of CFHBI.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654314","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":"GI and liver updates in CF: The next frontier.","authors":"Steven D Freedman, Michael Wilschanski","doi":"10.1016/j.jcf.2026.03.025","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.03.025","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654306","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":"Investigation of HE4 expression concerning epithelial-mesenchymal transition (EMT) in cystic fibrosis epithelial cells.","authors":"Marianna Pócsi, György Jázon Balla, Ferenc Fenyvesi, Ágnes Rusznyák, Zsolt Fejes, István Balogh, Milan Macek, Margarida D Amaral, Béla Nagy","doi":"10.1016/j.jcf.2026.03.019","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.03.019","url":null,"abstract":"<p><strong>Background: </strong>Elevated levels of human epididymis protein 4 (HE4) have been observed in cystic fibrosis (CF), where its expression is directly affected by impaired CFTR through the NF-κB pathway in p.Phe508del-CFTR CFBE 41o- cells in vitro. Dysfunctional CFTR is also linked to epithelial-mesenchymal transition (EMT) in CF. However, no data is available whether HE4 expression changes and is associated with CF-related EMT.</p><p><strong>Methods: </strong>The level of EMT was compared between CFBE 41o- cells with the p.Phe508del-CFTR mutation and wt-CFTR by measuring epithelial and mesenchymal markers using fluorescence microscopy and RT-qPCR. EMT was also induced by TGFβ1 in p.Phe508del-CFTR CFBE cells from 24 to 120 h to explore relationship between EMT development and the expression of HE4 and MMP9. VX-445/VX-661/VX-770 treatment restored CFTR function to observe changes in EMT phenotype. The direct effects of HE4 on EMT and MMP9 levels were examined in CFBE cells where HE4 expression was reduced through transfection with HE4-specific siRNA. Cell proliferation was assessed by Ki67 positivity.</p><p><strong>Results: </strong>CFBE cells expressing p.Phe508del-CFTR were more prone to be mesenchymal than wt-CFTR CFBE cells and showed higher basal HE4 and MMP9 levels. In response to TGFβ1, even lower E-cadherin with higher N-cadherin and MMP9 levels were observed in p.Phe508del-CFTR CFBE cells compared to untreated cells. In contrast, HE4 expression decreased after 48 h and continued to decline up to 120 h. CFTR modulator treatment could reverse the EMT phenotype, normalizing HE4 and MMP9 levels. Finally, downregulated HE4 promoted EMT, resulting in higher MMP9 expression and reduced cell proliferation in p.Phe508del-CFTR CFBE cells.</p><p><strong>Conclusion: </strong>EMT is accompanied by decreasing HE4 expression and upregulated MMP9 level in the airway epithelial cells of CF.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623049","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":"Research updates in cystic fibrosis related diabetes: Understanding pathophysiology, expanding animal and human islet models, and advancing clinical and translational research.","authors":"Melissa S Putman, Rebecca L Hull-Meichle, Shafagh A Waters, Katherine Tuggle, Paula Sommer, Rebecca Conway, Lee A Borthwick, Jakob G Knudsen, E Danielle Dean, Sarah A Stanley, Xingshen Sun, John F Engelhardt, Shih-Hsing Leir, Lena Eliasson, Bibi Uhre Nielsen, Darko Stefanovski, Amanda Brennan, Charlotte K Boughton, Andrea Kelly, Amir Moheet, James A M Shaw","doi":"10.1016/j.jcf.2026.03.021","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.03.021","url":null,"abstract":"<p><p>In 2024-2025, the Cystic Fibrosis Foundation (US) and Cystic Fibrosis Trust (UK) hosted an International CFRD Consortium round-table webinar series for basic science, translational, and clinical researchers with the goal of sharpening mechanistic understanding of CFRD pathogenesis and prioritizing therapeutic development. This review summarizes the research priorities identified in the International CFRD Consortium, including (i) further investigation into the role of pancreatic fibrosis, vascular abnormalities, and α-cell dysfunction in the development of CFRD; (ii) the creation and refinement of novel animal and human cell- and tissue-based models to understand the complex interplay of exocrine and endocrine cells in the CF pancreas; (iii) development and validation of circulating and imaging biomarkers, together with dynamic glucose testing to explore β-cell function and kinetics in people with CF across the dysglycemia spectrum; and (iv) prospective clinical studies to guide CFRD treatment options and investigate the changing landscape of aging, increasing prevalence of obesity and diabetes and their complications in the era of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Collectively, these priorities aim to accelerate transition from mechanism to intervention and expand evidence-based care for people with CF at risk of, or living with, CFRD.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622995","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":"Increased gastrointestinal cancer risk in cystic fibrosis: Screening, prevention, and future directions.","authors":"Linda C Cummings, Steven D Freedman","doi":"10.1016/j.jcf.2026.03.024","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.03.024","url":null,"abstract":"<p><p>The marked improvement in life expectancy from advances in treatment for cystic fibrosis has focused attention on diseases of aging. Cystic fibrosis (CF) is associated with increased risk for digestive system malignancies, including colorectal cancer and pancreaticobiliary cancers. Although risk factors for gastrointestinal malignancy include solid organ transplant and older age, people with CF may present with cancer at a younger age than the general population. Potential mechanisms for increased digestive cancer susceptibility include the underlying genetic defect, dietary patterns, or alterations in the gut microbiome. The impact of cystic fibrosis transmembrane regulator modulator therapies on gastrointestinal cancer risk remains unclear. Our review summarizes the previously published consensus screening recommendations for colorectal cancer, which endorsed starting colonoscopy at age 30 in patients with history of transplant and at age 40 in patients without a transplant. Recent work evaluating the use of non invasive testing for colorectal cancer is reviewed. We propose screening practices for non-colorectal cancers based on the limited evidence to date. We discuss potential preventative approaches and conclude with future directions to improve our ability to address this growing problem. Future work should focus on a greater understanding of the underlying mechanisms of pathogenesis at a molecular level, clinical risk factors for gastrointestinal malignancies at a population level, and preventative strategies.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609061","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":"Gastrointestinal-related aspiration in cystic fibrosis (GRASP-CF).","authors":"Isabelle Scheers, Jeffrey King","doi":"10.1016/j.jcf.2026.03.017","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.03.017","url":null,"abstract":"<p><p>The concept of gastroesophageal reflux (GER), aspiration, and swallowing dysfunction in cystic fibrosis (GRASP-CF) extends beyond GER to include esophageal dysmotility, impaired transit, and delayed gastric emptying as contributors to aspiration risk and pulmonary injury. Foregut dysfunction is common in people with cystic fibrosis and has been associated with accelerated lung function decline, increased pulmonary exacerbations, and worse post-lung transplant outcomes. Current diagnostic and therapeutic approaches remain centered on gastroesophageal reflux disease, relying on distal esophageal metrics that do not adequately capture proximal reflux or aspiration risk. The absence of validated diagnostic criteria and relevant physiological parameters limits accurate identification of GRASP-CF. In addition, standard treatments such as proton pump inhibitors may not reduce reflux burden and could have unintended adverse effects. Alternative strategies targeting reflux frequency, esophageal motility, and gastric emptying, as well as surgical interventions, show variable benefit. Future research priorities include establishing reliable biomarkers for GRASP-CF, establishment of physiologically relevant diagnostic thresholds, and evaluating targeted interventions in prospective studies. A structured, multidisciplinary approach incorporating objective assessment of both deglutitive and retrograde aspiration is essential to improve pulmonary outcomes and guide more effective, mechanism-based management strategies in people with cystic fibrosis.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609044","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":"Changes in nutritional priorities and management in people with CF.","authors":"Jessica A Alvarez, Sarah Jane Schwarzenberg, Nicole Green","doi":"10.1016/j.jcf.2026.03.026","DOIUrl":"10.1016/j.jcf.2026.03.026","url":null,"abstract":"<p><p>Nutritional priorities for people with cystic fibrosis (PwCF) are shifting rapidly with widespread use of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators. As undernutrition becomes less common with increasing longevity, adiposity- and age-driven metabolic risks have emerged as growing concerns for the CF population. Evidence now demonstrates that lean mass and muscle function, rather than body weight alone, are more closely aligned with pulmonary health, although these relationships may be altered based on CFTR modulator use. Modern nutrition care guidelines emphasize individualized assessment, body composition monitoring, optimization of diet quality, and lifestyle strategies that support muscle health and metabolic resilience. Additionally, growing understanding of gut dysbiosis and its potential modulation through diet, probiotics, and CFTR modulator therapy highlights new opportunities to improve gastrointestinal and systemic health. Together, these evolving insights underscore the need to modernize nutrition targets and develop evidence-based dietary and behavioral interventions suited to an aging CF population in the modulator era.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592406","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":"Effects of Elexacaftor/Tezacaftor/Ivacaftor on cough frequency, physical activity patterns, and sleep quality in adolescents and adults with cystic fibrosis.","authors":"Eva Van Braeckel, Andrew T Braun, Nicholas J Simmonds, Peter J Barry, Jane C Davies, Marie E Egan, Allen Lapey, Marcus A Mall, Edward F McKone, Daniel Peckham, Marijke Proesmans, Bonnie Ramsey, Saioa Vicente Santamaria, Daniel Smith, Jennifer L Taylor-Cousar, Elizabeth Tullis, Elke De Wachter, Nick Withers, Neil Ahluwalia, Sarah Conner, Mark Jennings, Yiyue Lou, Tanya G Weinstock, Dominic Keating","doi":"10.1016/j.jcf.2026.03.016","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.03.016","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) transmembrane conductance regulator modulators improve lung function, however, effects on cough frequency, physical activity, and sleep have not been assessed in clinical studies.</p><p><strong>Methods: </strong>After a 12-week, phase 4 pilot feasibility study, we conducted a 13-week, phase 3b, open-label study in participants with CF aged ≥12 years previously naïve to elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) to assess the effects of ELX/TEZ/IVA on cough frequency, physical activity, and sleep using wearable cough monitors and actigraphy sensors (VX-445-126).</p><p><strong>Results: </strong>In study VX-445-126 (N = 81), participants treated with ELX/TEZ/IVA experienced a 91.7% reduction in cough frequency (cough events per day) (95% CI, 89.2% to 93.6%; 241.3 coughs per day at baseline to 20.3 coughs per day) from baseline at the average of week 8 through week 12 (primary endpoint). Total steps per day (secondary endpoint) increased by 638 (95% CI, 298 to 977) at the average of week 8 through week 12. Time spent above sedentary physical activity per day, time spent on moderate-to-vigorous physical activity per day, and total mean activity count per day all increased from baseline at the average of week 8 through week 12 (other efficacy endpoints). While no changes in sleep activity patterns were observed in actigraphy data, patient-reported measures of sleep quality improved (other efficacy endpoints). ELX/TEZ/IVA was generally safe and well-tolerated.</p><p><strong>Conclusions: </strong>ELX/TEZ/IVA treatment led to a > 90% reduction in daily cough frequency, with sustained improvements in physical activity and better perceptions of sleep quality.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592443","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":"Altered responsiveness to photic stimuli contribute to circadian disruption in cystic fibrosis.","authors":"Danica F Patton-Parfyonov, Eden N Kenner, Deborah A Corey, Thomas J Kelley, Rebecca Darrah","doi":"10.1016/j.jcf.2026.03.020","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.03.020","url":null,"abstract":"<p><strong>Background: </strong>People with cystic fibrosis (pwCF) and animal models show evidence of disrupted circadian rhythms (CR). CRs are controlled by light sensitive neurons of the suprachiasmatic nucleus (SCN). Characterizing how the CF SCN responds to light will inform mechanisms behind CR disruption and help to inform CR based treatments to mitigate CF symptoms exacerbated by circadian disruption.</p><p><strong>Methods: </strong>Mice were entrained and subsequently exposed to a 30 min light pulse one hour after usual lights out. The magnitude of the resulting phase delay in subsequent activity onset and molecular correlates of photic input at the SCN were then compared between CF and WT mice.</p><p><strong>Results: </strong>Light induced phase delays of activity onset in CF mice were reduced compared to WT controls. Reduced behavioral responses were also associated with altered molecular responses in the SCN, including attenuated cFOS levels in CF vs WT SCN. Data show that phosphorylation of ribosomal protein 6 (pS6) is reduced in CF, while targets down stream of 4E-BP1 such as vasoactive intestinal polypeptide levels (VIP) appear the same between genotypes.</p><p><strong>Conclusions: </strong>Behavioral and molecular responses to a light pulse differ between CF and WT mice. Together these data suggest that similar photic input from the retina is being received by the SCN of CF and WT mice, but the mounted intracellular response to that photic input differs in CF. Investigation into these differences will be integral to understanding circadian disruption in CF and informing future intervention for CF symptoms known to be exacerbated by circadian disruption.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592478","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":"Redefining treatment complexity: Ready to reduce chronic respiratory therapies?","authors":"Jaclyn Davis, Thida Ong","doi":"10.1016/j.jcf.2026.03.008","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.03.008","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592434","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}