Journal of Cystic Fibrosis最新文献

{"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}

{"title":"WS03.01Functional and clinical effect of intermittent intrapulmonary deflation versus autogenic drainage for airway clearance in cystic fibrosis: the MUCOSIM trial","authors":"T. Perez ,&nbsp;T. Ropars ,&nbsp;S. Leroy ,&nbsp;C. Poulet ,&nbsp;G. Beltramo ,&nbsp;I. Durieu ,&nbsp;M. Murris Espin ,&nbsp;S. Dominique ,&nbsp;L. Morin ,&nbsp;J. Delrieu","doi":"10.1016/j.jcf.2025.03.504","DOIUrl":"10.1016/j.jcf.2025.03.504","url":null,"abstract":"<div><h3>Objectives</h3><div>Improving mucus clearance remains an important aim in cystic fibrosis (CF), and was particularly critical before the widespread availability of high efficiency modulator therapy. Aim of MUCOSIM study was to evaluate the short term functional and clinical impact of instrumental airway clearance by intermittent intrapulmonary deflation (IID) with the Simeox® device (Physioassist), in comparison with the reference autogenic drainage (AD) technique in adult people with CF (pwCF), in stable condition.</div></div><div><h3>Methods</h3><div>IID with Simeox® and AD were compared in 31 adult pwCF with a crossover application of 4 sessions (3 training sessions and the 4^th one supervised) for each technique performed within 2 weeks, with a 7 days washout between sequences. Oscillometry (Tremoflo, Thorasys) was performed before and after each individual session. Primary endpoint was the comparison of R5 (resistance at 5 Hz) just before and 30 min after the 4th supervised session of each technique. Secondary oscillometric parameters were R20 (resistance at 20 Hz), R5-R20, reactance at 5 Hz (X5), area under the curve of reactance (AX). Spirometry was also performed before and after the 4^th session. Clinical impact of each session was assessed by a visual analog scale (VAS) for dyspnea (VAS dyspnea), perceived bronchial congestion (VAS congestion) and fatigue (VAS fatigue).</div></div><div><h3>Results</h3><div>No significant difference appeared between groups:</div></div><div><h3>Conclusion</h3><div>Despite the use of sensitive oscillometry parameters, no impact on lung function was found with both techniques after a single session of AD or IID. A subjective improvement of bronchial congestion post session was found with both techniques. Longer term studies could provide more significant results.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S6"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205321","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":"WS11.05Spatio-temporal association of Pseudomonas aeruginosa and Staphylococcus aureus in cystic fibrosis patients","authors":"V. Waters ,&nbsp;A. Morris ,&nbsp;S. Eisha ,&nbsp;Y. Yau ,&nbsp;W. DePas ,&nbsp;D. Nguyen ,&nbsp;M. Gaudet","doi":"10.1016/j.jcf.2025.03.556","DOIUrl":"10.1016/j.jcf.2025.03.556","url":null,"abstract":"<div><h3>Objectives</h3><div>Our aim was to visualize the interaction of <em>Pseudomonas aeruginosa</em> (PA), <em>Staphylococcus aureus</em> (SA) and staphylococcal protein A (SpA) in sputum of people with CF (pwCF) during pulmonary exacerbations.</div></div><div><h3>Methods</h3><div>This was a 3 year prospective, longitudinal observational study of pwCF with chronic PA infection from SickKids Hospital, St. Michael's Hospital and McGill University Health Centre. Sputum was collected from CF patients at baseline (B), day 0 of exacerbation (E), day 7 of antibiotic treatment (T) and recovery (R), fixed in paraformaldehyde then polymerized in a hydrogel followed by Microbial Identification after Passive CLARITY Technique (MiPACT). <em>Ex vivo</em> visualization of PA and SA in the sputum-hydrogels was performed by three-dimensional confocal laser scanning microscopy (CLSM) using fluorescence <em>in situ</em> hybridization (FISH); SpA was visualized using the protein A monoclonal antibody and concentrations measured by ELISA. PA, SA and SpA biovolume, spatial distance between microbes and number and maximum size of PA and SA aggregates were measured.</div></div><div><h3>Results</h3><div>Over 150 sputum samples have been collected and processed from 40 pwCF. From B to E, there was a significant increase in the number of PA aggregates in pediatric patients, while SA remained relatively constant. In addition, from B to E, a geospatial shift in PA distance to the nearest SA was observed, where PA and SA were further apart and formed discretely large aggregates at E (Day 0) compared to baseline. Patients with PA-SA co-infection had greater maximum PA aggregate size compared to those with PA mono-infection and there was a positive correlation between PA biovolume and SpA concentration measured by ELISA (p ≤ 0.0001).</div></div><div><h3>Conclusion</h3><div>PwCF with chronic PA infection had greater PA aggregation in their sputum that was further apart from SA aggregates during exacerbation compared to baseline. In addition, greater PA biovolume was associated with increasing concentrations of SpA.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S22-S23"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205590","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":"WS10.03Shifts in systemic inflammatory profiles on elexacaftor/tezacaftor/ivacaftor predict clinical outcomes in cystic fibrosis","authors":"L. Jonckheere ,&nbsp;L. Vande Sande ,&nbsp;I. Janssens ,&nbsp;Y. Vande Weygaerde ,&nbsp;S. Van Biervliet ,&nbsp;H. Schaballie ,&nbsp;P. Schelstraete ,&nbsp;T. Maes ,&nbsp;C. Bosteels ,&nbsp;E. Van Braeckel","doi":"10.1016/j.jcf.2025.03.548","DOIUrl":"10.1016/j.jcf.2025.03.548","url":null,"abstract":"<div><h3>Objectives</h3><div>Cystic fibrosis (CF) is characterised by systemic inflammation, and CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) may influence immune responses in addition to clinical outcomes. This study investigated how ETI alters systemic cytokine levels and whether these changes independently predict clinical outcomes in people living with CF (pwCF).</div></div><div><h3>Methods</h3><div>Serum levels of eight cytokines (TNF-α, IL-6, IL-13, IFN-γ, IL-8, IL-17A, IL-10, and IL-1β) were measured in 90 pwCF before and after six months on ETI. Cytokines were reported using medians, and clinical outcomes (ppFEV₁, exacerbation frequency) using means. Paired t-tests were used to analyse log-transformed cytokine levels, and multivariate regression models to assess cytokine changes as independent predictors of clinical outcomes.</div></div><div><h3>Results</h3><div>ETI led to reductions in TNF-α, IL-6, IL-13, IL-8, IL-17A and IL-1β (from 0.54 to 0.45; 1.52 to 0.61; 0.98 to 0.69; 23.78 to 13.35. 8.74 to 3.18 and 0.11 to 0.03 pg/mL respectively; all p&lt;0.0001). IFN-γ increased (4.77 to 6.03 pg/mL, p&lt;0.05), while IL-10 remained unchanged (0.42 to 0.41 pg/mL, p=0.214). Clinical outcomes improved, with ppFEV₁ increasing from 80.49% to 89.79% and exacerbation frequency dropping from 1.78 to 0.50 episodes/year (both p&lt;0.0001). Multivariate regression analysis demonstrated that increase in IFNy and decrease in IL-6 predicted ppFEV1 increase, whereas increase in IL-10 and decrease in IL-1b predicted reductions in exacerbation frequency. Adjusted R² values were 0.406 for ppFEV₁ and 0.799 for exacerbation frequency.</div></div><div><h3>Conclusion</h3><div>In pwCF on ETI, greater reductions in pro-inflammatory cytokines (e.g. IL-6 and IL-1β) and larger increases in immunomodulatory cytokines (e.g. IL-10 and IFN-γ) independently predict better ppFEV₁ and fewer exacerbations. These findings highlight ETI's dual role as a therapeutic and immune-modulating agent, supporting use of cytokine profiling for personalised CF care.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S20"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203902","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}