Journal of Cystic Fibrosis最新文献

{"title":"WS09.06Investigation of HE4 expression in relation to epithelial mesenchymal transition in cystic fibrosis epithelial cells","authors":"M. Pócsi ,&nbsp;G.J. Balla ,&nbsp;F. Fenyvesi ,&nbsp;Á. Rusznyák ,&nbsp;Z. Fejes ,&nbsp;I. Balogh ,&nbsp;M. Macek Jr. ,&nbsp;M.D. Amaral ,&nbsp;B. Nagy Jr.","doi":"10.1016/j.jcf.2025.03.545","DOIUrl":"10.1016/j.jcf.2025.03.545","url":null,"abstract":"<div><h3>Objective</h3><div>Elevated expression of human epididymis protein 4 (HE4) was described in cystic fibrosis (CF), which was directly influenced by impaired CFTR via NF-κB in p.Phe508del-CFTR CFBE 41o− cells <em>in vitro</em>. Dysfunctional CFTR was also associated with epithelial mesenchymal transition (EMT) in CF. However, no data is available if HE4 expression alters and is linked to CF-related EMT.</div></div><div><h3>Methods</h3><div>EMT characteristics were compared between CFBE 41o− cells expressing p.Phe508del-CFTR and wt-CFTR through the expression of epithelial and mesenchymal markers by RT-qPCR and fluorescence microscopy. EMT was further triggered in p.Phe508del-CFTR CFBE cells by TGF-β1 from 24-96h to investigate the relationship of EMT with HE4 and MMP9 expression. To restore CFTR dysfunction, VX-445/VX-661/VX-770 was applied to monitor EMT phenotype. The direct effect of abnormal HE4 expression on EMT and MMP9 was analyzed when: <em>i)</em> mutant CFBE cells were treated with recombinant HE4, and <em>ii)</em> HE4 expression was artificially reduced by transfection with HE4 specific siRNA.</div></div><div><h3>Results</h3><div>Untreated p.Phe508del-CFTR CFBE cells had a trend to be more mesenchymal than wt-CFTR CFBE cells and showed higher HE4 and MMP9 levels. However, in response to TGF-β1, E-cadherin levels were lower, while those of N-cadherin and MMP9 were higher in p.Phe508del-CFTR CFBE cells. In parallel, HE4 levels were decreased already after 48h and further reduced until 96h. The EMT phenotype could be reversed by CFTR modulators causing a decrease in both HE4 and MMP9 levels. Finally, both treatment with recombinant HE4 and downregulated HE4 levels promoted EMT with induced MMP9 in p.Phe508del-CFTR CFBE cells.</div></div><div><h3>Conclusion</h3><div>High baseline HE4 levels in CF may contribute to the development of EMT accompanied with decreasing intracellular HE4 and upregulated MMP9 expression in airway epithelial cells.</div><div><strong>Grants:</strong> This study is supported by FK-135327 grant (BN) and UID/04046/2025 centre grant in MDA lab (to BioISI) from FCT/MCTES Portugal.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S19"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203907","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":"WS02.05The effect of sleep on the quality of life of children with cystic fibrosis","authors":"F.F. Karkın Gürel ,&nbsp;D. Ademhan Tural ,&nbsp;H. Yetisgin ,&nbsp;S.S. Akyan Soydas ,&nbsp;S. Ozkan Tabakci ,&nbsp;S. Eryilmaz Polat ,&nbsp;G.D. Tugcu ,&nbsp;G. Cinel","doi":"10.1016/j.jcf.2025.03.502","DOIUrl":"10.1016/j.jcf.2025.03.502","url":null,"abstract":"<div><h3>Objectives</h3><div>We aimed to evaluate the effects of sleep-disordered breathing, sleep quality, and sleepiness on the quality of life (QoL) of children with cystic fibrosis (cwCF).</div></div><div><h3>Method</h3><div>This cross-sectional observational study was conducted on cwCF and healthy children (control) aged 6-18 from July to November 2024. Aged-appropriate QoL, Pediatric Sleep Questionnaire (PSQ), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) were applied to all participants. Demographics of all participants and clinical characteristics of cwCF were collected. Subgroup analyses were made between patients who used (n:17) modulators and those who did not (n:23).</div></div><div><h3>Results</h3><div>The study included 40 cwCF and 54 controls. There were no differences according to age and sex distribution between the groups. The QoL results are summarized in Table 1. PSQ, PSQI, and EUS scores were statistically significantly higher in cwCF than in the controls (p-values, respectively; &lt;0.001, &lt;0.001, 0.013). Table 2 summarizes the regression analysis results of sleep-disordered breathing, sleep quality, and sleepiness on QoL in cwCF aged 6-13. A statistically significant difference was found in the digestive subscale of QoL between patients receiving and not receiving modulators in cwCF aged 6-13 (p=0.036). The frequency of sleep-disordered breathing (p=0.047), poor sleep quality (p=0.030), and daytime sleepiness (p=0.248) was more common in patients who did not use modulators than those who did</div></div><div><h3>Conclusion</h3><div>Sleep-disordered breathing, daytime sleepiness, and sleep quality were found to have important roles in the quality of life of cwCF.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S4-S5"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204929","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":"WS06.04Cystic fibrosis and pregnancy: the impact of modulator therapy","authors":"H. Boyd ,&nbsp;D. Wat ,&nbsp;D. Nazareth ,&nbsp;F. Frost ,&nbsp;J. Daniels ,&nbsp;R. Ashworth ,&nbsp;D. Dickins","doi":"10.1016/j.jcf.2025.03.525","DOIUrl":"10.1016/j.jcf.2025.03.525","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;With the increased number of pregnacies seen in Patients With Cystic Fibrosis (pwCF) following the introduciton of Highly Effective Modulator Therapy (HEMT) the aim of our study was to look at outcomes at a single, large tertiary CF centre for women going through pregnancy with CF, to identify whether there were significant differences following the introduction of HEMT with a particular note looking at pregnancies defined as high risk (with an FEV1 &lt;60%).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Retrospective non-controlled study looking at pwCF who had a pregnancy between 2010 and 2023.&lt;/div&gt;&lt;div&gt;We reviewed electronic notes for patients at Liverpool Heart and Chest (LHCH) for miscarriage being recorded in notes. We reviewed notes from LHCH and Liverpool Women's Hospital (LWH) for demographic information and respiratory, obstetric and neonatal outcomes for pwCF who had a livebirth outcome.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We identified a total of 66 pregnancies over the period 2010 to 2023 for analysis; nineteen miscarriages and forty-seven livebirths.&lt;span&gt;&lt;div&gt;&lt;div&gt;&lt;table&gt;&lt;thead&gt;&lt;tr&gt;&lt;th&gt;Outcome&lt;/th&gt;&lt;th&gt;Non-HEMT (n= 27)&lt;/th&gt;&lt;th&gt;HEMT (n=39)&lt;/th&gt;&lt;/tr&gt;&lt;/thead&gt;&lt;tbody&gt;&lt;tr&gt;&lt;td&gt;Miscarriage Rate&lt;/td&gt;&lt;td&gt;33% (9/27)&lt;/td&gt;&lt;td&gt;25% (10/39)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;In Vitro Fertilisation&lt;/td&gt;&lt;td&gt;39% (7)&lt;/td&gt;&lt;td&gt;7% (2)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;Pre-Pregnancy FEV1&lt;/td&gt;&lt;td&gt;78% (range 45-97%)&lt;/td&gt;&lt;td&gt;73% (range 31-105%)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;Pregnancy FEV1&lt;/td&gt;&lt;td&gt;78% (range 36-97%)&lt;/td&gt;&lt;td&gt;72% (range 39-117%)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;Post Pregnancy FEV1&lt;/td&gt;&lt;td&gt;77% (range 36-99%)&lt;/td&gt;&lt;td&gt;74% (range 36-122%)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;Average change in FEV1 %&lt;/td&gt;&lt;td&gt;+0.4% (range –12% to +13%)&lt;/td&gt;&lt;td&gt;-0.9% (range –23 to +12)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;Change FEV1% post pregnancy&lt;/td&gt;&lt;td&gt;-1.5% (range –23 to +11%)&lt;/td&gt;&lt;td&gt;+0.8% (range –18 to +14)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;High Risk Pregnancies (FEV1 &lt;60%)&lt;/td&gt;&lt;td&gt;13% (2)&lt;/td&gt;&lt;td&gt;25% (8)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;Average Gestation at Delivery&lt;/td&gt;&lt;td&gt;37.51 weeks&lt;/td&gt;&lt;td&gt;36.89 weeks&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;Number of Preterm Deliveries&lt;/td&gt;&lt;td&gt;28% (5)&lt;/td&gt;&lt;td&gt;40% (10)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;C-Sections&lt;/td&gt;&lt;td&gt;34% (6)&lt;/td&gt;&lt;td&gt;68% (17)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;-Elective&lt;/td&gt;&lt;td&gt;17% (3)&lt;/td&gt;&lt;td&gt;48% (12)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;-Emergency&lt;/td&gt;&lt;td&gt;17% (3)&lt;/td&gt;&lt;td&gt;20% (5)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;Vaginal Deliveries&lt;/td&gt;&lt;td&gt;67% (12)&lt;/td&gt;&lt;td&gt;32% (8)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;SCBU Admission&lt;/td&gt;&lt;td&gt;41% (7)&lt;/td&gt;&lt;td&gt;34% (8)&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td&gt;Birthweight&lt;/td&gt;&lt;td&gt;2966g (1620-3850g)&lt;/td&gt;&lt;td&gt;2851g (1155-3880g)&lt;/td&gt;&lt;/tr&gt;&lt;/tbody&gt;&lt;/table&gt;&lt;/div&gt;&lt;/div&gt;&lt;/span&gt;&lt;/div&gt;&lt;div&gt;While the number of women experiencing exacerbations in pregnancy was similar between groups, women in the HEMT group had fewer exacerbations and required fewer weeks of antibiotic treatment. The most common indications for C-section or induction was cystic fibrosis and respiratory decline/ chest infection.&lt;span&gt;&lt;div&gt;&lt;div&gt;&lt;table&gt;&lt;thead&gt;&lt;tr&gt;&lt;th&gt;Outcome&lt;/th&gt;&lt;th&gt;Non-high-risk Pregnancy on HEMT (FEV1% &gt;60%) (n=21)&lt;/th&gt;&lt;th&gt;High-risk Pregnancy on HEMT","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S12-S13"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204935","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":"WS01.02Use of medications for sleep, depression, and anxiety in people with cystic fibrosis before and after initiation of elexacaftor/tezacaftor/ivacaftor","authors":"J.N. Wang ,&nbsp;C. Bjørn Jensen ,&nbsp;H.K. Råket ,&nbsp;M. Frahm Olsen ,&nbsp;T. Qvist ,&nbsp;D. Faurholt-Jepsen ,&nbsp;J. Petersen ,&nbsp;E. Jimenez-Solem ,&nbsp;TransformCF Study Group","doi":"10.1016/j.jcf.2025.03.493","DOIUrl":"10.1016/j.jcf.2025.03.493","url":null,"abstract":"<div><h3>Objectives</h3><div>Investigate the association between initiation of elexacaftor/tezacaftor/ivacaftor (ETI) and the use of medications for sleep, depression, and anxiety in people with cystic fibrosis (pwCF).</div></div><div><h3>Methods</h3><div>All pwCF aged ≥12 years initiating ETI treatment 21.08.2020-31.12.2021 in Denmark were included in a pre-post study with two years of follow-up in both the pre- and post-intervention periods. A control group from the general population was matched 1:10 on age and sex. Outcomes were prevalent user status defined as at least one redeemed prescription in the preceding year of 1) sleep-promoting medicines (SPM) and 2) antidepressants and/or anxiolytics (AA). Prescriptions were obtained from the Danish National Prescription Registry, which records all redeemed prescriptions regardless of the prescribing physician. Odds ratios (ORs) for the outcome was derived from generalized linear mixed models adjusted for age and days of COVID lockdown.</div></div><div><h3>Results</h3><div>286 pwCF were included in the study. In the year prior to ETI initiation, 5.2% of pwCF were prevalent users of SPM, increasing to 9.0% at the second year after ETI initiation. Conversely, pwCF using AA increased from 4.9% to 8.1%.</div><div>The adjusted ORs for being a prevalent user of SPM at year 2 compared to the pre-ETI period was 10.9 (95% CI 2.1-55.2; p=0.004) for pwCF, and this increase in odds at year 2 was significantly higher (p=0.014) in pwCF than in controls.</div><div>The adjusted ORs for being a prevalent user of AA at year 2 compared to the pre-ETI period was 11.9 (95% CI 1.8-77.0; p=0.009) for pwCF. However, this effect was not significantly different in pwCF than in controls (p=0.090).</div></div><div><h3>Conclusion</h3><div>We found an increase in use of SPM in pwCF after ETI initiation that was significantly higher than in the background population, strengthening the suspicion of a causal relationship between ETI and sleep disturbances. We also found an increase in use of AA in pwCF, but a similar increase was seen in the background population.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S1"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204942","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":"WS12.04Vitamin levels in children with cystic fibrosis – the effect of elexacaftor/tezacaftor/ivacaftor","authors":"C.R. Hansen,&nbsp;M. Nilsson,&nbsp;K. Björkman","doi":"10.1016/j.jcf.2025.03.561","DOIUrl":"10.1016/j.jcf.2025.03.561","url":null,"abstract":"<div><h3>Objectives</h3><div>In cystic fibrosis (CF), pancreatic insufficiency leads to malabsorption of fat-soluble vitamins A, D, E and K, and extra supplementation with these vitamins is recommended. The introduction of effective modulator treatment in CF have improved nutritional status of children with CF (cwCF). Although pancreatic destruction cannot be reversed, gut health is improved due to a decrease in inflammation, and studies have shown improvement in vitamin levels. We speculated that blood levels of vitamins A, D and E might have improved to a level that the daily vitamin dose had been decreased after up to 2 years of treatment with Elexacaftor-Tezacaftor-Ivacaftor (ETI) in a cohort of cwCF in Southern Sweden.</div></div><div><h3>Methods</h3><div>All cwCF followed in our centre were evaluated for inclusion in our study. Diagnosis was based on classical clinical symptoms and genotype. Only children treated with ETI for more than 1 year were included. Vitamin levels were measured before start of ETI, after 1 year and 2 years, and dose of daily vitamin supplementation (DEKAs) was recorded at the same time points.</div></div><div><h3>Results</h3><div>Forty cwCF (29 homozygous F508, 10 heterozygous, 1 with other mutations) were included. Mean age was 11.2 years (range 4.6 – 16.3 y) when ETI was introduced. Levels of vitamins A and E increased steadily after introducing ETI. Vitamin D level increased slightly during the first year, then went back to baseline. Dose of vitamin supplementation did not change. (Table 1). We speculate that compliance might have decreased due to the cwCF feeling better in general when treated with ETI.</div></div><div><h3>Conclusion</h3><div>Introduction of ETI may improve vitamin levels in cwCF, but studies should include compliance levels.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S24"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204948","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":"WS16.05Impact of elexacaftor/tezacaftor/ivacaftor on glucose tolerance in adolescents with cystic fibrosis. Data from the MODUL-CF study","authors":"A.-S. Bonnel ,&nbsp;A. Galderisi ,&nbsp;L. Weiss ,&nbsp;I. Sermet-Gaudelus ,&nbsp;A. Besancon ,&nbsp;A. Letierce ,&nbsp;D. Sahki ,&nbsp;Modul-CF Study Group","doi":"10.1016/j.jcf.2025.03.586","DOIUrl":"10.1016/j.jcf.2025.03.586","url":null,"abstract":"<div><h3>Objectives</h3><div>Highly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI), herald a new era in therapeutic strategy of cystic fibrosis (CF). ETI improves lung function and decreases recurrency of pulmonary infections. Its metabolic effects, including the impact on glucose tolerance and the risk for CF related diabetes (CFRD), remain controversial.</div></div><div><h3>Methods</h3><div>We investigated the effect of ETI on glucose tolerance in adolescents with CF (awCF) enrolled in the national French registry MODUL-CF. All the participants underwent a baseline oral glucose tolerance test (OGTT) before ETI initiation (M0) and at 12 months (M12). The cohort was stratified in two subgroups based on the baseline OGTT: normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) defined by impaired fasting glucose or impaired glucose tolerance or diabetes not requiring insulin treatment.</div></div><div><h3>Results</h3><div>We included 106 awCF (age 14.1 ± 1.5 years), 75 with NGT, 31 with AGT. The baseline characteristics of the two groups were similar except for a higher glucose level at 1-h and 2-h OGTT in the AGT group. ETI induced an increase in BMI z-score and in Forced Expiratory Volume in one second (p&lt;0.001). After 12 months, awCF with NGT did not experience any change of 1-h and 2-h glucose. In contrast, awCF with AGT displayed a reduction of 2-h glucose at M12 (p=0.006). Fifteen awCF out of the 31 in the AGT group (48%) reversed to NGT whereas only 9/75 (17%) awCF in the NGT group progressed to AGT. The 3 participants with CFRD at baseline reversed to AGT. A 1-h glucose ≥ 8.7 mmol/L (157mg/dL) at baseline had 80% sensitivity to identify awCF with AGT at 12 months. A unitary increase of 1-h OGTT glucose at baseline increased by 1.51 [CI 1.20, 1.92] the risk of having AGT at 12-month ETI.</div></div><div><h3>Conclusion</h3><div>ETI improves glucose tolerance in awCF. One-hour glucose contributes to identify those at higher risk for AGT after 1 year of treatment.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S33"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205190","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":"WS04.05Faecal colorectal cancer-associated toxins in adults with cystic fibrosis: preliminary analysis","authors":"L.R. Caley ,&nbsp;A. Fuentes Balaguer ,&nbsp;D. Bottomley ,&nbsp;C. Young ,&nbsp;L. Wilkinson ,&nbsp;C. Sears ,&nbsp;P. Quirke ,&nbsp;D.G. Peckham","doi":"10.1016/j.jcf.2025.03.514","DOIUrl":"10.1016/j.jcf.2025.03.514","url":null,"abstract":"<div><h3>Objectives</h3><div>Cystic fibrosis is associated with an increased risk of colorectal cancer (CRC) owing to a complex interplay between CFTR dysfunction, inflammation, gut dysbiosis and diet. Toxigenic bacteria in the gut of non-CF individuals have been implicated in CRC pathogenesis. We explored the presence of CRC-associated toxins in a cohort of adults with CF (awCF).</div></div><div><h3>Methods</h3><div>Baseline faecal samples from 80 awCF were tested for the presence of the following CRC associated bacteria and toxins: <em>Fusobacterium nucleatum</em>, FadA, NusG, <em>Escherichia coli</em>, polyketide synthase (<em>pks</em>), <em>Bacteroides fragilis</em> (BF) and Enterotoxigenic BF (ETBF) by employing Taqman qPCR in triplicate. In a subgroup, changes pre and post elexacaftor/tezacaftor/ivacaftor (ETI) were analysed (n=25).</div></div><div><h3>Results</h3><div>At baseline, median age was 34 years (IQR 28, 40), ppFEV₁ 53 (IQR 39, 74) with 34% participants being female. Percentage of FadA, NusG, <em>pks</em>, ETBF positive samples are displayed in Table 1.</div><div>In the pre and post ETI group, median time between samples and duration of ETI were 15 (IQR 14, 18) and 6 months (IQR 3,10) respectively. Changes in CRC-associated bacteria/toxins are presented in Table 1. Descriptively, there was no change in CRC-associated bacteria and toxins post ETI.</div></div><div><h3>Conclusion</h3><div>CRC-associated bacteria and toxins are present in CF stool samples and do not appear to change with short-term ETI therapy. Analysis in ongoing, including comparing levels to controls and CRC samples, to elucidate clinical implications of these findings.</div><div>Funded by the UK CF Trust (SRC 012)</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S8-S9"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205220","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":"WS09.01CFTR activity in nasal epithelia from subjects with different genotypes","authors":"V. Capurro ,&nbsp;E. Pesce ,&nbsp;V. Tomati ,&nbsp;C. Pastorino ,&nbsp;M. Lena ,&nbsp;A. Dighero ,&nbsp;L.J.V. Galietta ,&nbsp;F. Cresta ,&nbsp;C. Castellani ,&nbsp;N. Pedemonte","doi":"10.1016/j.jcf.2025.03.540","DOIUrl":"10.1016/j.jcf.2025.03.540","url":null,"abstract":"<div><h3>Objectives</h3><div>The human nasal epithelial (hNE) cells are an interesting <em>ex-vivo</em> model to perform molecular and functional studies on CFTR. Reference values for normal CFTR activity are important to assess CFTR dysfunction in people with cystic fibrosis (pwCF) and its rescue by modulators.</div></div><div><h3>Methods</h3><div>We collected hNE cells (by nasal brushing) from a cohort of about forty non-CF donors. We generated well-differentiated nasal epithelia in air-liquid interface, and then we performed short-circuit current measurements to evaluate CFTR-dependent Cl- secretion. We opted for two different experimental conditions: first, we performed the measurements using symmetrical Cl- solution (standard condition, <strong>SC</strong>) and then by imposing a Cl- gradient (gradient condition, <strong>GC</strong>). This latter condition allowed us to maximize the anion transport by CFTR.</div></div><div><h3>Results</h3><div>Our data showed that, under <strong>SC</strong>, CFTR activities measured in our cohort varied between 10 and 35 µA/cm². In the majority of the subjects, when we switched to the <strong>GC</strong>, we observed a two-fold increase in CFTR activity. However, two small groups of subjects had different behaviours. Interestingly, both groups were composed by cultures showing the lowest levels of CFTR activity (ranging from 10 to &lt; 20 µA/cm²) in <strong>SC</strong>. However, in <strong>GC</strong>, the first group showed a higher improvement, around 3-fold, in CFTR activity. The second group showed a limited increase, around 1.5-fold, with CFTR-mediated currents that were lower than 30 µA/cm². Interestingly we found that the second group was composed by obligate carriers together with subjects that were actually unidentified carriers present in the cohort.</div></div><div><h3>Conclusion</h3><div>These results support the thesis of the robustness of the nasal model as a predictive model, that allowed us to detect subclinical CFTR dysfunction.</div><div>Supported by Fondazione Ricerca Fibrosi Cistica grants FFC #9/2019 and FFC #10/2021, and Italian Ministry of Health grant PNRR-MR1-2023-12378412.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S17-S18"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205228","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":"WS15.06Comparison of the Leeds criteria and CFHealthHub criteria for classification of chronic Pseudomonas aeruginosa infection in people with cystic fibrosis in the post-modulator era","authors":"G. Bonsignore ,&nbsp;R.D. Sandler ,&nbsp;Z.H. Hoo","doi":"10.1016/j.jcf.2025.03.581","DOIUrl":"10.1016/j.jcf.2025.03.581","url":null,"abstract":"<div><h3>Objectives</h3><div>The 2023 UK CF Registry reported a prevalence of chronic <em>Pseudomonas aeruginosa</em> (Pa) in people with CF (PwCF) ≥16y of 14.6%, down from 40.7% in 2019. Since the availability of elexacaftor/tezacaftor/ivacaftor (ETI) in 2020, many PwCF have less sputum, making clinicians increasingly reliant on less-sensitive cough swabs to detect Pa. As a result, classification methods like the Leeds Criteria, which rely solely on sample positivity, may underestimate prevalence. We aimed to compare chronic Pa prevalence across an entire centre cohort using the Leeds criteria and CFHealthHub (CFHH) criteria, which also incorporates Pa serology, strain typing and clinical context.</div></div><div><h3>Methods</h3><div>All PwCF (≥16 years) at a UK adult CF centre were classified as either “chronic Pa” or “not chronic Pa” based on both Leeds and CFHH criteria. Data were cross-tabulated, and agreement measured using Cohen's kappa.</div></div><div><h3>Results</h3><div>Among the 240 PwCF, the median age was 30 years (IQR: 23-38), 113 (47.1%) were female and 198 (82.5%) were on a CFTR modulator. Median %FEV1 was 86.7% (IQR 66.6-98.6) and BMI 25.1 (21.9-28.3). The Leeds criteria classified 32 people (13.3%) with chronic Pa infection compared to 107 (44.6%) using the CFHH criteria. Crude agreement was 68.8%, with a kappa coefficient of 0.32 (95% CI: 0.23–0.41).</div></div><div><h3>Conclusions</h3><div>In this single centre study, more than three times the number of PwCF were classified as having chronic Pa using the multi-component CFHH criteria compared to the Leeds criteria. The apparent reduction in chronic Pa prevalence since 2019 may partly reflect limitations in classification methods relying solely on microbiological samples. In PwCF with low or absent sputum production, additional investigations may be required to more accurately determine Pa status and guide treatment recommendations.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S31"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205247","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":"WS02.06Elexacaftor/tezacaftor/ivacaftor pharmacokinetics and occurrence of behavioural disorders in children aged 2 to 5 years old","authors":"N.H. Truong ,&nbsp;S. Benaboud ,&nbsp;L. Chouchana ,&nbsp;A.-S. Bonnel ,&nbsp;M. Barboura ,&nbsp;N. Bouazza ,&nbsp;S. Gautier ,&nbsp;S. Rouillon ,&nbsp;L. Froelicher-Bournaud ,&nbsp;T. Bihouee ,&nbsp;S. Bui ,&nbsp;J.-M. Treluyer ,&nbsp;I. Sermet- Gaudelus ,&nbsp;F. Foissac ,&nbsp;Modul-CF research group","doi":"10.1016/j.jcf.2025.03.503","DOIUrl":"10.1016/j.jcf.2025.03.503","url":null,"abstract":"<div><h3>Objectives</h3><div>Elexacaftor/tezacaftor/ivacaftor (ETI) was shown to improve CFTR function and clinical symptoms in people with cystic fibrosis (CF) with at least one <em>F508del</em> allele. In 2023, the FDA and the EMA approved ETI for children with CF (chCF) aged 2 to 5 who have at least one copy of the <em>F508del</em> mutation or other mutations that have demonstrated responsiveness to ETI in <em>in vitro</em> studies. In our experience, we observed a significant number of behavioral issues emerging after treatment initiation, including hyperactivity, mood disorders and sleep disturbances among these chCF. This study aimed to determine whether these behavioral issues may be associated with ETI pharmacokinetic (PK) parameters.</div></div><div><h3>Methods</h3><div>This study, part of the MODUL-CF cohort (NCT04301856), included chCF aged 2–5 years who adhered to current dosing recommendations, with therapeutic drug monitoring and documented behavioral data. Population PK models of ETI were performed using the Monolix software with area under the curve (AUC), maximal concentration (Cmax) and trough concentration (Ctrough) derived from individual Bayesian PK estimates.</div></div><div><h3>Results</h3><div>Sixty-three children (70% boys) were included: 20 (32%) weighed &lt;14 kg (median age 2.9±0.7 years), and 43 (68%) weighed &gt;14 kg (median age 4.6±0.9 years). Abnormal behavior was observed in 35 children (55.6%), with common issues including sleep disturbances, hyperactivity, irritability and mood disorders. No significant differences were observed in age, weight or sex distributions between the groups. Similarly, ETI AUCs, Cmax and Ctrough showed no statistical differences between children exhibiting abnormal behavior and those who did not.</div></div><div><h3>Conclusion</h3><div>To our knowledge, this is the first study assessing ETI plasma exposure in relation to behavioral issues in chCF aged 2–5 years. Overall, our findings do not indicate that these side effects are associated with increased exposure.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S5"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205320","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}