Journal of Cystic Fibrosis最新文献

{"title":"LONGITUDE: An observational study of the long-term effectiveness of elexacaftor/tezacaftor/ivacaftor in people aged ≥12 years with cystic fibrosis using data from the United Kingdom Cystic Fibrosis Registry - 2-year analysis.","authors":"Gabriela Vega-Hernandez, Gordon MacGregor, Andrew Wilfin, Francis Adams, Ciarán Haugh, Carl A Baxter, Heike Wöhling, Sarah L Clarke, Susan C Charman, Siobhán B Carr","doi":"10.1016/j.jcf.2025.04.012","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.04.012","url":null,"abstract":"<p><strong>Background: </strong>The cystic fibrosis (CF) transmembrane conductance regulator modulator (CFTRm) elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has demonstrated efficacy and safety in clinical trials and emerging observational studies in people with CF. This study evaluated the real-world impact of ELX/TEZ/IVA in a large cohort of people with CF in the UK.</p><p><strong>Methods: </strong>LONGITUDE is an observational, registry-based cohort study using data from the UK CF Registry to evaluate outcomes of ELX/TEZ/IVA in people aged ≥6 years who initiated ELX/TEZ/IVA from August 2019. Key outcomes included percent predicted forced expiratory volume in 1 s (ppFEV₁), body mass index (BMI), pulmonary exacerbations (PEx), lung infections, transplants, deaths, and treatment discontinuation. We report results of people ≥12 years with data up to December 31, 2022.</p><p><strong>Results: </strong>A total of 5187 people were included (mean follow-up 19.1 months). ppFEV₁ improvements were observed at 2 years (10.2; 95 % CI: 9.6, 10.8; n = 1448). A clinically meaningful difference in the annual change of ppFEV₁ between ELX/TEZ/IVA-treated people and historical CFTRm-naïve controls was observed, with those treated with ELX/TEZ/IVA having less of a decline in lung function over time by 1.1 percentage points (95 % CI: 0.9, 1.4). A 64.7 % reduction in the rate of PEx, increase in BMI by 1.7 kg/m² (SD: 2.3), reduced lung infections, and low number of lung transplants and deaths were also observed.</p><p><strong>Conclusions: </strong>People with CF aged ≥12 years in the UK who initiated ELX/TEZ/IVA had sustained improvements in multiple CF-related health outcomes, consistent with results from clinical trials. These results support the positive impact of ELX/TEZ/IVA on the lives of people with CF.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086291","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":"Pulmonary arteriole narrowing in end-stage cystic fibrosis lungs occurs with and without small airway disease.","authors":"Astrid Vermaut, Gitte Aerts, Lynn Willems, Vincent Geudens, Charlotte Hooft, Pieterjan Kerckhof, Lise Vanvuchelen, Marta Zapata-Ortega, Hanne Beeckmans, Xin Jin, Yousry Mohamady, Jan Van Slambrouck, Lucia Aversa, Janne Verhaegen, Emanuela E Cortesi, Charlotte De Fays, Birgit Weynand, Dirk E Van Raemdonck, Laurens J Ceulemans, Wim A Wuyts, Marianne Carlon, Robin Vos, Natalie Lorent, Ghislaine Gayan-Ramirez, Laurent Godinas, Marijke Proesmans, François Vermeulen, Lieven J Dupont, Bart M Vanaudenaerde, Mieke Boon","doi":"10.1016/j.jcf.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.04.002","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is an important, life-limiting co-morbidity in cystic fibrosis (CF), where multiple mechanisms such as hypoxia, inflammation and primary CF-transmembrane regulator (CFTR) dysfunction may affect vascular integrity. We aimed to characterize the structural impact of vascular wall changes in the pulmonary microcirculation, to uncover the potential need for therapeutic strategies targeting vascular disease.</p><p><strong>Methods: </strong>End-stage inflated CF (n=6), and control (n=4) lungs were processed to lung cores (2.8cm³) and scanned with micro-computed tomography (resolution: 8.5µm). The diameter and number of distal pulmonary arteries (dPA), distal airways (DA) and open terminal bronchioles (TB) were measured on 3D models (n= 2 cores/lobe) and compared per generation and within pairs. Morphometric assessment was paired with histological analysis (n= 1/lobe) to assess tissue morphology, collagen and connective tissue components.</p><p><strong>Results: </strong>dPA in CF were narrowed and disappeared in the last generations of dichotomous branching, resulting in a decreased total diameter per generation. While narrowing was already present where TB remained open, dPA disappearance was only present where no TB were left. dPA narrowing increased when DA collapsed. Histologically, fibrotic dPA changes were present in areas without distal airway disease.</p><p><strong>Conclusion: </strong>We showed for the first time the presence of dPA lumen narrowing and disappearance with fibrotic vascular wall changes in end-stage CF. Narrowing was present diffusely and fibrosis was also present in areas without airway disease. These findings suggest that vascular dysfunction in CF may not solely be secondary to hypoxic vasoconstriction and inflammation but may represent a distinct pathophysiological process related to CFTR dysfunction in the endothelium, warranting further study.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020373","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":"Trends in Medicare versus Medicaid spending on CFTR modulator therapy - an economic evaluation.","authors":"Wanjae Cho, Michael D Parkins, Christina S Thornton, Stephen E Congly","doi":"10.1016/j.jcf.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.04.008","url":null,"abstract":"<p><p>The introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has changed the landscape of therapy for persons with cystic fibrosis. However, the steep cost of targeted therapy poses significant financial burden for individuals and health systems. We aimed to determine the trends in Medicare and Medicaid spending on CFTR modulators between the years 2015 and 2022 through retrospective analysis of the Medicare and Medicaid claims data. The outcome measures included total dosage units prescribed, number of claims, spending per claim, and total spending on CFTR modulators for Medicare and Medicaid between 2015 to 2022. Average annual percentage changes (AAPC) were calculated for all outcome measures. Our results show that from 2015 to 2022, Medicaid consistently had higher total dosage units prescribed, number of claims, spending per claim, and overall spending on CFTR modulators compared to Medicare. Total spending for both Medicaid [AAPC 38.9, 95 % confidence interval [CI] 27.2-51.6, p < 0.01] and Medicare [AAPC 39.2, 95 % CI 30.2-55.1, p < 0.01] increased significantly during this period. Increases in CFTR spending was accelerated beginning in 2019, when the triple combination CFTR modulator therapy, elexacaftor/tezacaftor/ivacaftor, was introduced to the US market. This increase has been accompanied by a reduction in spending and use of other CFTR agents. This study evaluated the increases in spending for CFTR modulators over the years and the main drivers behind them, which may help inform future negotiations between healthcare systems and pharmaceutical companies, as well as policy makers and stakeholders.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023109","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":"Physical well-being and burden of care in adults on modulator therapy: A mixed methods study of patient-reported experiences from the Well-ME survey.","authors":"Cynthia D Brown, Carla Frederick, Elizabeth Yu, Emily Zagnit, Joel R King, Aricca D Van Citters","doi":"10.1016/j.jcf.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.04.010","url":null,"abstract":"<p><strong>Background: </strong>Despite widespread availability of modulator therapies and improved lung function in many people with cystic fibrosis (CF), physical symptoms may remain burdensome for some people with CF (PwCF). This study identifies the impact of ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ETI) on self-reported physical well-being and burden of care among adults with CF.</p><p><strong>Methods: </strong>We conducted a secondary analysis of data from the Well-ME Survey. Participants included adults with CF (age≥18) who reported taking IVA or ETI. We used a mixed methods approach to identify self-reported health status, physical well-being, and experience of CF care while taking IVA or ETI.</p><p><strong>Results: </strong>Among 414 eligible respondents, overall health status was reported very good/excellent by 59 % (n = 243), good by 26 % (n = 114), and poor/fair by 14 % (n = 57). While the majority of respondents experienced improvements in respiratory symptoms, PwCF reporting poor/fair health were less likely to report improvement in overall physical health, fatigue, and ability to exercise compared to those with good or very good/excellent health and less likely to report improvement in pain, sinus issues, and cough than those with very good/excellent health. PwCF reporting poor/fair health or good health were less likely to report improvements in gastrointestinal issues or experience reductions in CF medications or treatments, compared to those reporting very good/excellent health.</p><p><strong>Conclusions: </strong>Despite improvements in respiratory symptoms, some adults with CF taking IVA or ETI report their health is poor/fair. A better understanding of physical well-being and burden of care may help identify underrecognized comorbidities to improve care.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009470","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":"Association between inhaled antibiotic use and treatment-emergent organisms among Canadian people with cystic fibrosis.","authors":"Jonathan D Cogen, Eric Zhang, Jane She, Michael R Kosorok, Stephanie Y Cheng, Marianne S Muhlebach","doi":"10.1016/j.jcf.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.04.007","url":null,"abstract":"<p><strong>Background: </strong>Inhaled antibiotics are frequently used as chronic Pseudomonas aeruginosa (Pa) suppressive therapy among people with cystic fibrosis (PwCF). However, their use might increase the risk of developing treatment-emergent respiratory organisms. This study aimed to describe the proportion of PwCF utilizing inhaled antibiotics, determine factors associated with inhaled antibiotic prescription, and determine if chronic inhaled antibiotic use is associated with an increased risk of Aspergillus fumigatus, Stenotrophomonas maltophilia, or Achromobacter spp.</p><p><strong>Methods: </strong>This retrospective cohort study utilized Canadian CF Registry data. Pa status (chronic, intermittent, and negative) was defined per calendar year. The risk of developing A. fumigatus, S. maltophilia, or Achromobacter spp was compared between PwCF prescribed versus not prescribed inhaled antibiotics, adjusting for confounding by indication using inverse probability of treatment weighting.</p><p><strong>Results: </strong>This analysis included data from 2800 PwCF. >75 % of PwCF with chronic Pa were prescribed inhaled antibiotics, while up to 13 % of PwCF negative for Pa received inhaled antibiotics during the study period. There was an increased risk of developing A. fumigatus among PwCF with intermittent Pa (HR 1.43, 95 %CI; 1.08-1.88; p = 0.01) and who were Pa negative (HR 2.44, 95 %CI; 1.65-3.61; p < 0.001), but not for PwCF with chronic Pa (HR 1.36, 95 %CI; 0.94-1.95; p = 0.10). No association was seen between inhaled antibiotics and developing either S. maltophilia or Achromobacter spp.</p><p><strong>Conclusions: </strong>Inhaled antibiotic use among Canadian PwCF was associated with an increased risk of A. fumigatus acquisition but not S. maltophilia or Achromobacter spp. Prospective studies are needed to better define this association.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020758","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":"Primary care physician involvement increases likelihood of cancer screening in people with cystic fibrosis: A population-based study from Ontario, Canada.","authors":"Anne L Stephenson, Isobel Sharpe, Jenna Sykes, Xiayi Ma, Ping Li, Sanja Stanojevic, Bradley S Quon, Stephanie Y Cheng, Paula A Rochon","doi":"10.1016/j.jcf.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.04.004","url":null,"abstract":"<p><strong>Background: </strong>People with cystic fibrosis (pwCF) are living longer and with an increased risk of malignancies, preventative cancer screening is crucial. The objectives of this study were to determine cancer screening rates for pwCF compared to the general population, and assess the impact of primary care provider (PCP) involvement on screening rates among those with CF.</p><p><strong>Methods: </strong>This population-based cohort study linked Canadian CF Registry data with health administrative databases. Four screening cohorts were identified: breast, cervical, colorectal pre-transplant, colorectal post-transplant. PCP involvement was defined using billing codes. Screening rates were calculated as the number screened divided by the number of person-years individuals were eligible for screening. Poisson regression was used to describe rates.</p><p><strong>Results: </strong>In the CF cohort, 74/110 (67.3 %) were screened for breast cancer, and 321/541 (59.3 %) for cervical cancer. 186/402 (46.3 %) in the pre-transplant cohort were screened with colonoscopy and 75/148 (50.7 %) in the post-transplant cohort. Those with CF were significantly more likely to be screened for breast cancer (RR 3.39, 95 % CI 2.70-4.26) and colorectal cancer pre-transplant (RR 1.58, 95 % CI 1.37-1.82) compared to the non-CF cohort. Having a PCP increased the likelihood that pwCF received screening for breast cancer (RR 3.6, 95 % CI 1.13-11.44), cervical cancer (RR 1.71, 95 % CI 1.13-2.57), and colorectal cancer (pre-transplant population only) (RR 1.57, 95 % CI 1.06-2.32).</p><p><strong>Conclusions: </strong>Screening rates for cancers in CF remain suboptimal. These results highlight opportunities to improve screening uptake through better integration of PCP in CF care models and to increase awareness of cancer risk.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012919","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":"The role of islet CFTR in the development of cystic fibrosis-related diabetes: A semi-systematic review.","authors":"Matilda Engström, Efraim Westholm, Anna Wendt, Lena Eliasson","doi":"10.1016/j.jcf.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.04.006","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis related diabetes (CFRD) is the most common comorbidity of cystic fibrosis (CF) still, its pathogenesis is poorly understood. Recent studies have suggested that although pancreatic insufficiency is an important explanation for CFRD development, inherent pancreatic islet cell dysfunction may play a role. This study aimed to systematically compile current data regarding the impact of pancreatic islet cell dysfunction on the development of CFRD.</p><p><strong>Methods: </strong>A systematic search was conducted in PubMed and Embase. The resulting articles were screened for relevant experimental design and outcomes. Articles underwent data extraction and quality assessment before compilation and analysis of the results.</p><p><strong>Results: </strong>A total of 268 articles were initially screened and 19 studies conducted between 2006-2022 were finally included in this review. Half of the studies in human tissue and most of the studies in animal tissue could detect CFTR in the islets. Similarly, half of the publications in human islets and most studies in animal islets detect decreased insulin secretion with inhibition/mutation of CFTR.</p><p><strong>Conclusions: </strong>The literature on the role of islet CFTR is contradictory. However, a pattern emerges where CFTR loss-of-function mutations have the potential to negatively affect islet cell function in a way that, together with previously described exocrine damage occurring in CF, could play a part in the development of CFRD.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064130","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":"Remote monitoring of cystic fibrosis lung disease in children and young adults.","authors":"Marcus Svedberg, Jens Michelsen, Emma Roberts, Huda Abdulahi Ostrand, Christine Hansen, Christina Krantz, Petrea Ericsson, Ulrika Lindberg, Henrik Imberg","doi":"10.1016/j.jcf.2025.03.670","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.670","url":null,"abstract":"<p><strong>Aim: </strong>Cystic fibrosis (CF) care increasingly demands flexible and personalised approaches, particularly with the growing role of telemedicine in disease management. This study aimed to evaluate the use of home-based spirometry and antibiotic monitoring for assessing lung function trends and treatment patterns in individuals with CF.</p><p><strong>Method: </strong>Individuals aged 0-25 years from seven Swedish CF centres participated in 12 months of routine CF care, digitally recording antibiotic usage and performing home spirometry (aged ≥5 years). Home spirometry sessions were graded according to ATS/ERS criteria, with A-C representing high-quality sessions. Longitudinal FEV₁ trends from home and hospital spirometry were analysed using linear mixed effects models, adjusting for clinical stability.</p><p><strong>Results: </strong>Of 126 invited participants, 110 were enrolled and followed for a median (range) duration of 12 months (9-17). A total of 779 usable home spirometry sessions were conducted, with 388 sessions (50 %) from 80 out of 95 (84 %) participants aged ≥5 years graded as high-quality. Mean (95 % CI) FEV₁ was (86-92 %) for home spirometry and 88 % (85-90 %) for hospital spirometry. After adjusting for clinical stability and including only high-quality home spirometry data, the mean difference was 0.6 % (-3.8 %-5.0 %, p=0.78). The mean annual rate of FEV₁ decline was -0.48 % (-1.29-0.32 %) for home spirometry and -0.18 % (-0.77-0.41 %) for hospital spirometry, with no statistically significant difference.</p><p><strong>Conclusion: </strong>High-quality home spirometry measurements, adjusted for clinical stability and antibiotic usage, may provide lung function levels and trends closely comparable to hospital spirometry.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020418","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":"Resolution of portal hypertension in a patient with cystic fibrosis after treatment with CFTR modulator: A case report.","authors":"Erica Loon, Joanne Billings, Nicholas Lim","doi":"10.1016/j.jcf.2025.03.668","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.668","url":null,"abstract":"<p><p>Portal hypertension (pH) secondary to cystic fibrosis liver disease (CFLD) is the fourth most common cause for mortality (after respiratory/cardiorespiratory, transplant-related, and cancer-related) in adults with cystic fibrosis (CF) and more often occurs in the absence of cirrhosis (i.e. non-cirrhotic pH, NCPH). Here, we describe a patient with NCPH secondary to CFLD, with resolution of pH after starting a cystic fibrosis transmembrane conductance regulator (CFTR) modulator. As demonstrated in this patient, CFTR modulators may provide extra-pulmonary benefits including reversal of NCPH. Long-term use of CFTR modulators could potentially result in reductions in mortality from pH and need for future liver or combined lung-liver transplantation in patients with CFLD.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010031","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":"Cystic Fibrosis-related neurodegenerative disease associated with tauopathy and cognitive decline in aged CF mice.","authors":"Danica F Patton-Parfyonov, Xinming Wang, Sarah Barker, Deborah A Corey, Edwin Vázquez-Rosa, Nichele Abeyesundere, Whitney M Ward, Rebecca Darrah, Jung-A A Woo, David E Kang, Andrew A Pieper, Thomas J Kelley","doi":"10.1016/j.jcf.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.04.003","url":null,"abstract":"<p><strong>Background: </strong>Highly effective modulator therapies (HEMT) are increasing the lifespan for many people with cystic fibrosis (pwCF), making it necessary to identify and understand CF specific age-related consequences. In this study, we examine the impact of aging on cognitive function and age-related brain pathology in a CF mouse model focusing on phospho-Tau (pTau) pathology.</p><p><strong>Methods: </strong>Cognitive function was measured by novel object recognition and spontaneous alternation behavior tests. Hippocampal neuronal function was assessed by measuring long-term potentiation (LTP) electrophysiology, the synaptic correlate of learning and memory. Tau pathology was assessed by immunohistochemical analyses and western blot assessment of pTau levels in CF mouse brain, as well as human nasal epithelial cells isolated from pwCF.</p><p><strong>Results: </strong>Cognitive function declined progressively with age in Cftr (G542X/G542X) (G542X) mice, a model of CF, compared to wild-type (WT) littermate controls. LTP was also deficient in older G542X mice. Increased pTau was observed by staining and western blot analysis in the hippocampus of aged CF mice. Secondary impacts of tauopathy, including increased microglial uptake of cholesterol and reduced neuronal density were also observed. Lastly, human nasal epithelial cells from pwCF were found to display elevated pTau levels compared to non-CF controls.</p><p><strong>Conclusions: </strong>Aging CF mice develop tauopathy, cognitive decline, LTP impairment, microglial activation, and neurodegeneration that is not experienced by age-matched WT littermates, a condition herein termed cystic fibrosis-related neurodegeneration (CFND). These findings suggest that pwCF may be at risk for tauopathy-related neurodegeneration and cognitive impairment with aging.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994483","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}