Journal of Cystic Fibrosis最新文献

{"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}

{"title":"Title Page","authors":"","doi":"10.1016/S1569-1993(25)01477-8","DOIUrl":"10.1016/S1569-1993(25)01477-8","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page ii"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204920","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":"WS02.01Provider perspectives related to the care of sexual and gender minority people living with cystic fibrosis in the United States and Canada","authors":"T. Kazmerski ,&nbsp;O. Stransky ,&nbsp;M. Lee ,&nbsp;A. Alpern ,&nbsp;J. Greenberg ,&nbsp;R. Jain ,&nbsp;M. Lunn ,&nbsp;J. Palla ,&nbsp;K. Prangley ,&nbsp;R. Salyer ,&nbsp;V. Tangpricha ,&nbsp;K. Kidd ,&nbsp;G. Sawicki ,&nbsp;PRIDE-CF Community Partner Group","doi":"10.1016/j.jcf.2025.03.498","DOIUrl":"10.1016/j.jcf.2025.03.498","url":null,"abstract":"<div><h3>Objectives</h3><div>LGBTQIA+ people face significant health inequities. We examined CF providers’ attitudes and practices toward the care of LGBTQIA+ people with CF via the PRIDE-CF Study.</div></div><div><h3>Methods</h3><div>We designed and administered a survey to United States (US) and Canadian (CA) CF providers in 2024. We compared response distributions with Chi-square tests.</div></div><div><h3>Results</h3><div>A total of 389 providers (330 US, 59 CA) completed the survey. Of all participants, 6% reported discomfort working with LGBTQIA+ people, and 15% felt that there are only two genders. Most (87%) agreed that asking about sexual orientation and gender identity is important to healthcare, and 63% agreed that gender-affirming hormone therapy is safe in CF. Most (86%) felt training on supporting LGBTQIA+ people would help them be better clinicians. US providers reported greater comfort in talking to patients about sexual orientation (US 73% <em>vs.</em> CA 53%, p&lt;0.01) and gender identity (US 74% <em>vs.</em> CA 54%, p&lt;0.01) as well as referring for gender-affirming mental health (US 83% <em>vs.</em> CA 56%, p&lt;0.01), medical (US 67% <em>vs.</em> CA 43%, p&lt;0.01), and surgical care (US 46% <em>vs.</em> CA 28%, p=0.02). US and CA providers had different beliefs on who has the primary role in LGBTQIA+ care for people with CF (US 51% CF team, 39% primary care <em>vs.</em> CA 25% CF team, 65% primary care, p&lt;0.01). US providers were more likely to ask CF patients about their sexual orientation (US 54% <em>vs.</em> CA 33%, p&lt;0.01), gender identity (59% US <em>vs.</em> 43% CA, p=0.04), and affirmed name and pronouns (75% US <em>vs.</em> 63% CA, p=0.07). US providers were more likely to have been trained to support LGBTQIA+ people (US 43% <em>vs.</em> CA 20%, p&lt;0.01).</div></div><div><h3>Conclusion</h3><div>CF providers valued addressing LGBTQIA+ health concerns but lacked expertise and resources to routinely provide this care. CA providers reported less comfort and practice differences compared to US providers. Future PRIDE-CF work will explore health experiences and outcomes of LGBTQIA+ people with CF.</div><div><strong>Funding:</strong> <em>CF Foundation(KAZMER23A0-HETS)</em></div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S3"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204925","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":"WS05.05SPL5AC, MUC5AC Lowering ASO for cystic fibrosis and other muco-obstructive diseases","authors":"E. Ozeri-Galai ,&nbsp;Y.S. Oren ,&nbsp;C.D. Stampfer ,&nbsp;R.M. Elgrabli ,&nbsp;T. Blinder ,&nbsp;T. Mordechai ,&nbsp;S.A. Jubeh ,&nbsp;B. Kerem ,&nbsp;G. Hart","doi":"10.1016/j.jcf.2025.03.520","DOIUrl":"10.1016/j.jcf.2025.03.520","url":null,"abstract":"<div><h3>Background</h3><div>Airway mucus functions as the first line of defense against pathogens and toxins. The major components of the airway mucus are the mucins, MUC5AC and MUC5B. In CF, defective CFTR channel activity leads to dehydrated mucus and increased mucin content. In muco-obstructive diseases, such as CF, asthma, COPD, and NCFB, mucins are overexpressed due to goblet cell hyperplasia and the ratio of MUC5AC to MUC5B is elevated, causing thick mucus, airway obstruction, and chronic infections and inflammation. Splisense is developing an antisense oligonucleotide (ASO) drug aiming to reduce MUC5AC levels in patients with CF and other muco-obstructive diseases (Asthma, COPD and NCFB), facilitating efficient mucus clearance and alleviating respiratory blockage and inflammation.</div></div><div><h3>Methods</h3><div>Splisense ASOs designed and optimized using a proprietary algorithm were screened and the effect of highly potent lead candidate ASOs was further analyzed in IL-13 induced primary HBEs using RT-qPCR and Western Blot. The lead candidate was further analyzed in industry standard disease mouse models.</div></div><div><h3>Results</h3><div>The SPL5AC clinical candidate ASO was found to be highly potent and effectively delivered through the mucus layer to IL-13-induced HBEs, leading to a significant reduction in MUC5AC RNA and protein levels. In vivo studies in muco-obstructive disease mouse models demonstrated that SPL5AC reduced Muc5ac levels, resulting in improved clinical features typical of muco-obstructive diseases. These included a reduction in mucus plugs, goblet cell hyperplasia, and an attenuated immune response. Initial tox studies indicate the promising safety profile of SPL5AC.</div></div><div><h3>Conclusions</h3><div>Restoring proper mucus viscoelasticity and clearance in the lungs of patients with muco-obstructive diseases like CF, remains a major goal. Our results demonstrate that SPL5AC ASO has a potential therapeutic benefit for CF and other muco-obstructive patients with the objective to advance to first in Human in 2025.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S10-S11"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204930","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":"WS05.06Design of an adenine base editor for temporospatial control of editing","authors":"I. Zollo ,&nbsp;L. Santos ,&nbsp;J. Alves ,&nbsp;A.S. Coroadinha ,&nbsp;P.T. Harrison ,&nbsp;C.M. Farinha","doi":"10.1016/j.jcf.2025.03.521","DOIUrl":"10.1016/j.jcf.2025.03.521","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Despite advances with modulators, 10-15% of people with cystic fibrosis, particularly those with nonsense variants, still lack effective treatments. For these cases, gene-based therapies offer the most promising path to a cure. Among gene editing tools, Adenine Base Editor (ABE) is particularly suitable for correcting W1282X, the second most common CF-causing variant without a therapy. However, it remains unclear which cell types in the lung epithelium, and how many of them, need editing to restore CFTR function to therapeutic levels.</div></div><div><h3>Methods and Results</h3><div>We developed a basal cell line bearing W1282X (BCi W1282X-CFTR) able of differentiating into airway epithelial cell types (1). Additionally, we engineered a split version of ABE (SplitABE) that allows temporal control of editing. Preliminary data show SplitABE reverts the premature stop codon to WT while minimizing bystander edits.</div><div>Here, we present a strategy integrating temporal and spatial control of ABE by placing the SplitABE cassette under five cell-type-specific promoters, targeting basal, ciliated, secretory (type 1 and 2), and ionocyte cells (2). These plasmids were used to transfect 293T cells for large-scale lentiviral particle production. Infectious titers, determined via ddPCR after transducing BCi W1282X-CFTR cells, ranged between 7E+06 and 1.5E+07 IU/mL. These titers are now being used to transduce BCi W1282X-CFTR cells at varying MOIs to establish cell lines with cell-type-specific SplitABE expression.</div></div><div><h3>Conclusion</h3><div>This advanced gene-editing platform, combined with a robust cellular model, will help pinpoint critical cellular targets for CFTR correction and optimize strategies for potential clinical application.</div><div>1. Santos L et al (2023) J Cyst Fibr 22 (S2), S32.</div><div>2. Zollo I et al (2024) J Cyst Fibr 23 (S2), S162.</div><div><strong>Acknowledgements:</strong> Work supported by grants HARRIS21G0 and FARINH24G0 from CFF and centre grants UIDP/04046/2020 and UIDB/04046/2020 from FCT, Portugal (to BioISI).</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S11"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204931","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":"WS06.01Prenatal CFTR Modulator Exposure: a Review of the European and U.S. Experience","authors":"S. Szentpetery ,&nbsp;J. Taylor-Cousar ,&nbsp;C. Luna Parades ,&nbsp;I. Sermet-Gaudelus ,&nbsp;P. Aleksander ,&nbsp;A. Kowalik ,&nbsp;A. Morales-Tirado ,&nbsp;S. Gartner-Tizzano ,&nbsp;C. de Manuel-Gómez ,&nbsp;B. Fabrizzi","doi":"10.1016/j.jcf.2025.03.522","DOIUrl":"10.1016/j.jcf.2025.03.522","url":null,"abstract":"<div><h3>Objectives</h3><div>Evaluate clinical outcomes, ethical considerations, and emerging data from U.S. and European cases of prenatal elexacaftor-tezacaftor-ivacaftor (ETI) exposure in cystic fibrosis (CF) pregnancies, focusing on treatment timing, postnatal management, and access disparities.</div></div><div><h3>Methods</h3><div>Case data were gathered via standardized tools, including REDCap, from published and ongoing reports. Clinical outcomes, prenatal, postnatal findings, and complications were analyzed.</div></div><div><h3>Results</h3><div>In U.S. cases, 78% of CF infants were diagnosed via amniocentesis (mean 18 6/7 weeks). Abnormal prenatal ultrasounds occurred in 89% of cases - echogenic or dilated bowel loops. These resolved in all cases after a mean ETI treatment of 5 5/7 weeks. Postnatal complications included NICU admission (55%), transient feeding or meconium passage issues. Sweat chloride averaged 69 mmol/L, and 71% of breastmilk-fed infants were found to be pancreatic sufficient.</div><div>In European cases, 83% were diagnosed via amniocentesis and 82% had abnormal ultrasounds. Resolution of findings occurred in 63% after a mean ETI treatment duration of 6 2/7 weeks. Postnatal complications included unresolved meconium ileus in three infants, requiring enemas or bowel resection. Sweat chloride averaged 83 mmol/L, and pancreatic sufficiency was transient, in contrast to the reported U.S. cases. Fourteen French dyads who received prenatal treatment will also be reviewed.</div><div>Adverse maternal events were rare, with occasional rash or mild transaminase elevation. Neonatal complications included one case of hyperbilirubinemia. Long-term follow-up showed improved pancreatic function in infants transitioning to oral CFTR modulators.</div></div><div><h3>Conclusion</h3><div>Prenatal ETI exposure shows promise in improving outcomes for CF infants, resolving prenatal abnormalities, and supporting early pancreatic function. Standardized protocols, equitable access, and further study are needed to address unresolved cases and ensure long-term safety.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S11"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204932","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":"WS04.06Observations on CFTR modulators and pancreatic function in a clinical trial of ANG003, a novel pancreatic enzyme replacement therapy in people with cystic fibrosis","authors":"S.D. Freedman ,&nbsp;M. Sathe ,&nbsp;M. Clarkin ,&nbsp;D. Gallotto ,&nbsp;D. Borowitz","doi":"10.1016/j.jcf.2025.03.515","DOIUrl":"10.1016/j.jcf.2025.03.515","url":null,"abstract":"<div><h3>Background</h3><div>Highly efficacious CFTR modulators have greatly improved the daily lives of people with CF. Some patients and providers have attributed improvements in gastrointestinal symptoms to improved pancreatic function. A clinical study in people with cystic fibrosis of ANG003, a novel, microbially-derived lipase, protease and amylase product, required proof of exocrine pancreatic insufficiency as an inclusion criterion but did not have exclusions for concomitant CFTR modulators. We report observations about pancreatic functional status at baseline in this cohort.</div></div><div><h3>Methods</h3><div>This multicenter, randomized, parallel, active-treatment study evaluated the safety, tolerability and effect of a single dose of orally administered ANG003 in adult subjects with CF and documented EPI based on fecal elastase (NCT06052293).</div></div><div><h3>Results</h3><div>We enrolled 51 subjects (53% male; 94% white). Mean age was 30 years (range=18-58). On study entry, subjects were taking ∼5 capsules of porcine pancreatic enzyme replacement therapy per meal and 3 per snack (mean=20 capsules/day (range: 6-43 capsules); mean lipase units per day 548,000 (168,000-1,080,000); mean 8,000 lipase units/kg/day; 22% of subjects were taking &gt;10,000 units/kg/day). CFTR modulators were being taken by 47 subjects (92%). All were taking elexacaftor/ tezacaftor/ivacaftor with the exception of two subjects taking ivacaftor alone. Subjects had been taking these modulators for a median of 3.7 years (range 1 month-6.6 years). Fecal elastase values were all in the range consistent with severe pancreatic insufficiency. The median value was &lt;40 ug/g.</div></div><div><h3>Conclusion</h3><div>These data add to the body of information that adults taking highly efficacious CFTR modulators are not associated with objective improvement in pancreatic function. In addition, we observed lack of conformity with guidelines on limits of pancreatic enzyme dose per day.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S9"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205221","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":"WS03.02High-intensity interval training and moderate-intensity continuous training are equivalent in improving exercise capacity at submaximal intensity in adults with cystic fibrosis","authors":"W. Gruber ,&nbsp;J. Koop ,&nbsp;F.A. Haegele ,&nbsp;C. Falkenberg ,&nbsp;S. Dewey ,&nbsp;B. Weiser ,&nbsp;A. Bosy-Westphal","doi":"10.1016/j.jcf.2025.03.505","DOIUrl":"10.1016/j.jcf.2025.03.505","url":null,"abstract":"<div><h3>Objectives</h3><div>This randomised controlled trial investigates the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on exercise capacity at submaximal exercise intensity in adult people with Cystic Fibrosis (pwCF).</div></div><div><h3>Methods</h3><div>60 adult pwCF (34f/26m, mean age 38.9±10.4yrs, 19-58years, ppFEV₁ 67.9±19.3, 35.0-110.0%) agreed to participate. Cycle-ergometry was used to determine Oxygen Uptake (VO2) and Workload (W) at Ventilatory Threshold 2 (VT2). Participants were randomly assigned to either the HIIT or MICT group, with matching based on lung disease severity (ppFEV1 35-70% or &gt;70%). Both groups exercised 5 times per week, including three cycle ergometer sessions. The HIIT group performed 10 bouts of 1 minute at 90% VO2peak, followed by 2 minutes of active recovery at 40% VO2peak for a total of 30 minutes per session (10 minutes high-intensity, 20 minutes active recovery), while the MICT group completed 30 minutes at a constant load of 60% VO2peak. Data were collected during a 4-week inpatient rehabilitation program at two specialized CF institutions.</div></div><div><h3>Results</h3><div>VO2_VT2 and W_VT2 increased significantly (p&lt;0.001) in both groups (HIIT: VO2peak, D +9.4%, Wpeak +10.3%, MICT: VO2peak, D +14.0%, Wpeak +15.1%). The MICT group had slightly greater changes, but the time x training interaction revealed non-significant results (p&gt;0.05). No adverse events were reported, and the dropout rate was similar between groups</div></div><div><h3>Conclusion</h3><div>HIIT and MICT were equally effective in improving exercise capacity in adult pwCF during this 4-week rehabilitation course. The choice of training modalitiy should be individualized, considering aspects such as available time, initial exercise capacity, individual interests, preferences, and enjoyment. As this study represents a short-term exercise intervention, future studies should investigate the comparative effectiveness of these training modalities over longer time periods.</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":"144205322","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}