Journal of Cystic Fibrosis最新文献

{"title":"Poster: 13Mesenchymal stem cell transduced delivery of cathelicidin (LL-37) for efficient Pseudomonas aeruginosa infection resolution","authors":"E. Rudo, V. Polster, D. Rodriguez-Fuentes, R. Somoza, D. Fletcher, T. Bonfield","doi":"10.1016/j.jcf.2026.07.045","DOIUrl":"10.1016/j.jcf.2026.07.045","url":null,"abstract":"<div><h3>Background</h3><div>During the development of our human mesenchymal stem cell (hMSC) product for our cystic fibrosis (CF) clinical trial (NCT02866721), which demonstrated safety, we established a direct correlation between hMSC secretion of cathelicidin (LL-37) and the capacity to significantly decrease the survival of <em>Pseudomonas aeruginosa</em> (<em>P. aeruginosa</em>) as well as increase sensitivity of the bacteria to current standard of care antibiotics (p=0.02, R<sup>2</sup>=0.081) [1]. Due to variability in hMSC products, FDA approvals for clinical trials have been delayed. However, in 2024, the FDA approved an hMSC-based therapy for graft versus host disease, demonstrating that such therapies can be approved with sufficient data and robust trial design [2]. To overcome the limitations that have been found in the potential of hMSC therapeutics, we are pursuing hMSC optimization strategies to improve their therapeutic potential. <em>We hypothesize that culture-optimized or targeted delivery of LL-37 by hMSCs will provide effective resolution of P. aeruginosa infection.</em></div></div><div>During the development of our human mesenchymal stem cell (hMSC) product for our cystic fibrosis (CF) clinical trial (NCT02866721), which demonstrated safety, we established a direct correlation between hMSC secretion of cathelicidin (LL-37) and the capacity to significantly decrease the survival of <em>Pseudomonas aeruginosa</em> (<em>P. aeruginosa</em>) as well as increase sensitivity of the bacteria to current standard of care antibiotics (p=0.02, R<sup>2</sup>=0.081) [1]. Due to variability in hMSC products, FDA approvals for clinical trials have been delayed. However, in 2024, the FDA approved an hMSC-based therapy for graft versus host disease, demonstrating that such therapies can be approved with sufficient data and robust trial design [2]. To overcome the limitations that have been found in the potential of hMSC therapeutics, we are pursuing hMSC optimization strategies to improve their therapeutic potential. <em>We hypothesize that culture-optimized or targeted delivery of LL-37 by hMSCs will provide effective resolution of P. aeruginosa infection.</em></div><div><h3>Methods</h3><div>hMSCs were treated with a proprietary set of effectors to induce an enhanced functional secretome and molecular response. Alternatively, hMSCs were transduced with the gene for LL-37 (L-CAMP) for a specific molecular response and delivery of LL-37. The parent hMSC (hMSC<sub>c</sub>), effector-treated hMSC (hMSC<sub>e</sub>), L-CAMP transduced hMSCs (hMSC<sub>L-CAMP</sub>) secretomes were analyzed for (A) LL-37 and (B) antimicrobial activity measured in colony-forming units (CFUs) as described previously [1].</div></div><div>hMSCs were treated with a proprietary set of effectors to induce an enhanced functional secretome and molecular response. Alternatively, hMSCs were transduced with the gene for LL-37 (L-CAMP) for a specific molecular response and deli","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 6-7"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964933","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(26)03725-2","DOIUrl":"10.1016/S1569-1993(26)03725-2","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page ii"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964936","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":"Poster: 62Neutrophil NETosis promotes antibiotic tolerance to Pseudomonas aeruginosa in a cystic fibrosis airway model","authors":"V. Potlapalli, M. Higgs, J. Gilbertie, M. Wolfgang","doi":"10.1016/j.jcf.2026.07.094","DOIUrl":"10.1016/j.jcf.2026.07.094","url":null,"abstract":"<div><h3>Background</h3><div><em>Pseudomonas aeruginosa</em> is a common bacterial pathogen in advanced cystic fibrosis (CF) lung disease and is frequently associated with antibiotic treatment failure. In the CF airway, mucus obstruction, extracellular DNA, and bacterial aggregation create an environment that impairs bacterial clearance and promotes chronic infection. Neutrophils are abundant in this setting and often respond to <em>P. aeruginosa</em> aggregates by undergoing NETosis, yet remain ineffective at eradicating infection. We hypothesized that CF-like airway conditions promote bacterial aggregation and neutrophil NETosis, which in turn enhances tolerance to antibiotic therapy.</div></div><div><em>Pseudomonas aeruginosa</em> is a common bacterial pathogen in advanced cystic fibrosis (CF) lung disease and is frequently associated with antibiotic treatment failure. In the CF airway, mucus obstruction, extracellular DNA, and bacterial aggregation create an environment that impairs bacterial clearance and promotes chronic infection. Neutrophils are abundant in this setting and often respond to <em>P. aeruginosa</em> aggregates by undergoing NETosis, yet remain ineffective at eradicating infection. We hypothesized that CF-like airway conditions promote bacterial aggregation and neutrophil NETosis, which in turn enhances tolerance to antibiotic therapy.</div><div><h3>Methods</h3><div>We developed an in vitro neutrophil-<em>P. aeruginosa</em> coculture model in SCFM2 with varying mucin and DNA concentrations to mimic healthy and diseased CF airway environments. Primary human neutrophils were cocultured with <em>P. aeruginosa</em>, and bacterial killing, phagocytosis, NETosis, and tobramycin tolerance were assessed. We further tested the contribution of NETs directly using isolated NETs and evaluated the effect of NETosis inhibition with GSK484.</div></div><div>We developed an in vitro neutrophil-<em>P. aeruginosa</em> coculture model in SCFM2 with varying mucin and DNA concentrations to mimic healthy and diseased CF airway environments. Primary human neutrophils were cocultured with <em>P. aeruginosa</em>, and bacterial killing, phagocytosis, NETosis, and tobramycin tolerance were assessed. We further tested the contribution of NETs directly using isolated NETs and evaluated the effect of NETosis inhibition with GSK484.</div><div><h3>Results</h3><div>Under conditions modeling a healthier airway, neutrophils reduced bacterial burden and did not increase tobramycin tolerance. In contrast, under CF-like conditions containing increased mucin and DNA, neutrophils significantly increased <em>P. aeruginosa</em> tolerance to tobramycin. These conditions were associated with reduced phagocytosis and increased NETosis. Purified NETs alone increased tobramycin tolerance, indicating that NET-associated components are sufficient to promote this phenotype. Consistent with this, inhibition of NETosis with GSK484 sensitized <em>P. aeruginosa</em> to tobramycin","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 30-31"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964940","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":"Poster: 92CFTR mutation drives airway epithelial inflammation via fumarate","authors":"Y. Chen, C. Knight, C. Britto-Leon, A. Prince, S. Riquelme","doi":"10.1016/j.jcf.2026.07.124","DOIUrl":"10.1016/j.jcf.2026.07.124","url":null,"abstract":"<div><h3>Background</h3><div>CFTR mutations drive pathological overproduction of IL-8, the dominant pro-neutrophilic cytokine in cystic fibrosis (CF) airways, particularly during <em>P. aeruginosa</em> infection — a leading cause of CF morbidity and mortality. This IL-8-driven milieu sustains a destructive neutrophil-dominated inflammatory cascade that progressively erodes lung function. Yet the mechanisms linking CFTR dysfunction to aberrant IL-8 signaling, and whether CFTR modulators can intercept this process, remain poorly understood. Here, we identify a metabolic circuit at the core of this pathology: CFTR dysfunction in airway epithelial cells impairs mitochondrial ATP synthesis, activating compensatory pathways — the malate-aspartate shuttle and argininosuccinate shunt — that converge on fumarate accumulation. Fumarate, in turn, directly drives IL-8 overproduction during <em>P. aeruginosa</em> infection. Critically, CFTR modulators suppress this inflammatory axis by restoring mitochondrial bioenergetics and normalizing fumarate levels, pinpointing a precise metabolic checkpoint governing neutrophil recruitment to the CF airway. These findings establish that CF airway neutrophilic inflammation is fundamentally a metabolic disease, and reposition CFTR modulators as bioenergetic correctors that restore tissue homeostasis beyond their canonical role as ion channel therapies.</div></div><div>CFTR mutations drive pathological overproduction of IL-8, the dominant pro-neutrophilic cytokine in cystic fibrosis (CF) airways, particularly during <em>P. aeruginosa</em> infection — a leading cause of CF morbidity and mortality. This IL-8-driven milieu sustains a destructive neutrophil-dominated inflammatory cascade that progressively erodes lung function. Yet the mechanisms linking CFTR dysfunction to aberrant IL-8 signaling, and whether CFTR modulators can intercept this process, remain poorly understood. Here, we identify a metabolic circuit at the core of this pathology: CFTR dysfunction in airway epithelial cells impairs mitochondrial ATP synthesis, activating compensatory pathways — the malate-aspartate shuttle and argininosuccinate shunt — that converge on fumarate accumulation. Fumarate, in turn, directly drives IL-8 overproduction during <em>P. aeruginosa</em> infection. Critically, CFTR modulators suppress this inflammatory axis by restoring mitochondrial bioenergetics and normalizing fumarate levels, pinpointing a precise metabolic checkpoint governing neutrophil recruitment to the CF airway. These findings establish that CF airway neutrophilic inflammation is fundamentally a metabolic disease, and reposition CFTR modulators as bioenergetic correctors that restore tissue homeostasis beyond their canonical role as ion channel therapies.</div><div><h3>Methods</h3><div>Primary human bronchial epithelial cells (ΔF508/ΔF508, WT/WT) and airway epithelial cell lines (ΔF508/W1282X, WT/WT) were studied, with CFTR correction using elexacaftor/tezacaftor","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 46"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964944","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":"Poster: 30Ferroptosis inhibition improves Pseudomonas aeruginosa lung infection outcomes in mice","authors":"E. Scandinari Manzolli, S. Fernandes, M. Vaillancourt, Y. Lee, H. Park, S. Kim, P. Jorth","doi":"10.1016/j.jcf.2026.07.062","DOIUrl":"10.1016/j.jcf.2026.07.062","url":null,"abstract":"<div><h3>Background</h3><div>Lung infections caused by <em>Pseudomonas aeruginosa</em> are a leading cause of morbidity and mortality in cystic fibrosis (CF) patients where persistent inflammation and oxidative stress contribute to progressive lung damage. Recently, we showed that <em>P. aeruginosa</em> can induce the iron-dependent cell death ferroptosis in infected macrophages in vitro.[1] Yet, it was unknown if <em>P. aeruginosa</em> induces ferroptosis during lung infections in either macrophages or other cell types. In this study we test the hypothesis that <em>P. aeruginosa</em> induces ferroptosis in vivo and whether pharmacologic ferroptosis inhibition can improve infection outcomes both in vitro and in vivo.</div></div><div>Lung infections caused by <em>Pseudomonas aeruginosa</em> are a leading cause of morbidity and mortality in cystic fibrosis (CF) patients where persistent inflammation and oxidative stress contribute to progressive lung damage. Recently, we showed that <em>P. aeruginosa</em> can induce the iron-dependent cell death ferroptosis in infected macrophages in vitro.[1] Yet, it was unknown if <em>P. aeruginosa</em> induces ferroptosis during lung infections in either macrophages or other cell types. In this study we test the hypothesis that <em>P. aeruginosa</em> induces ferroptosis in vivo and whether pharmacologic ferroptosis inhibition can improve infection outcomes both in vitro and in vivo.</div><div><h3>Methods</h3><div>Mouse bone marrow derived macrophages (BMDM) differentiated using L929-conditioned medium were infected in vitro with <em>P. aeruginosa</em> strains Wt-PAO1 and AzEvC10 for 6 hours with a multiplicity of infections of 100. BMDM were treated with either UAMC-3203, a second generation ferroptosis inhibitor, MIT-001, a next generation ferroptosis inhibitor, or DMSO vehicle control. Intracellular and total bacterial burden were quantified by colony forming unit assays. Lipid peroxidation was measured by detection of 4-hydroxynonenal (4-HNE), a marker of ferroptosis- associated oxidative damage, through immunofluorescence staining. For in vivo experiments, wild-type C57BL/6 mice were infected intratracheally with 5 × 10<sup>6</sup> CFUs AzEvC10 strain and treated with either UAMC-3203, MIT-001 or vehicle control. Lung bacterial burden was quantified, and pulmonary function was evaluated through the flexiVent system 48-hours post infection.</div></div><div>Mouse bone marrow derived macrophages (BMDM) differentiated using L929-conditioned medium were infected in vitro with <em>P. aeruginosa</em> strains Wt-PAO1 and AzEvC10 for 6 hours with a multiplicity of infections of 100. BMDM were treated with either UAMC-3203, a second generation ferroptosis inhibitor, MIT-001, a next generation ferroptosis inhibitor, or DMSO vehicle control. Intracellular and total bacterial burden were quantified by colony forming unit assays. Lipid peroxidation was measured by detection of 4-hydroxynonenal (4-HNE), a marker of ferropt","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 15"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965020","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":"Factors associated with adherence to inhaled medicines in cystic fibrosis following the introduction of elexacaftor/tezacaftor/ivacaftor using electronically captured adherence data","authors":"Robert David Sandler,&nbsp;Lana Yin Hui Lai,&nbsp;Sarah Cameron,&nbsp;Sophie Dawson,&nbsp;Tracey Eileen Daniels,&nbsp;Martin James Wildman,&nbsp;Matthew Sperrin,&nbsp;Zhe Hui Hoo","doi":"10.1016/j.jcf.2026.05.012","DOIUrl":"10.1016/j.jcf.2026.05.012","url":null,"abstract":"<div><h3>Background</h3><div>Use of inhaled medicines by people with cystic fibrosis (pwCF) has declined since the introduction of CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI). Inhaled medicines may still benefit those with established lung disease. This study explored factors associated with adherence to inhaled medicines across a cohort of pwCF.</div></div><div><h3>Methods</h3><div>In this cross-sectional, observational study, all adults with CF (≥16 years) eligible for inhaled medicines at a single UK CF centre were included. Between July 2023 and August 2024, data were extracted from local medical records on 25 factors across four categories: demographic, socio-economic, health-related, and treatment-specific psychological factors (e.g. habit score, treatment necessity beliefs). Mean percent adherence, captured electronically via data-logging nebuliser devices, over the preceding 12 months was the outcome in a multivariable linear regression analysis.</div></div><div><h3>Results</h3><div>Of 240 pwCF on the centre’s caseload, 214 (88%) were eligible and 190 of these (89.2%) were prescribed a CFTR modulator. Mean adherence to inhaled medicines was 26.4% (95% CI 22.2–30.7%). In multivariable analysis, adherence was significantly associated with habit score, socio-economic status, treatment regimen complexity, neurodivergence, and age. Habit score explained the greatest variance (adjusted partial R² = 0.21). Those with the strongest habit for taking inhaled medicines had a mean adherence of 41.7% (34.7–47.3%), versus 11.7% (7.6–15.8%) in those with low/absent habit.</div></div><div><h3>Conclusion</h3><div>Habit continues to have an important association with adherence to inhaled medicines in the ETI era. Further studies are required to understand the role of habit-based interventions to support adherence among pwCF in the ETI era.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 844-850"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054798","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":"Vanzacaftor-Tezacaftor as an alternative therapeutic resource for the ETI-Resistant L467F-F508del Allele: Ex vivo prediction and exploratory clinical assessment","authors":"Valeria Capurro,&nbsp;Emanuela Pesce,&nbsp;Federico Cresta,&nbsp;Cristina Pastorino,&nbsp;Alice Mantero,&nbsp;Valeria Tomati,&nbsp;Valeria Daccò,&nbsp;Laura Claut,&nbsp;Benedetta Fabrizzi,&nbsp;Federico Zara,&nbsp;Carlo Castellani,&nbsp;Nicoletta Pedemonte","doi":"10.1016/j.jcf.2026.05.015","DOIUrl":"10.1016/j.jcf.2026.05.015","url":null,"abstract":"<div><h3>Background</h3><div>The triple combination of Elexacaftor/Tezacaftor/Ivacaftor (ETI) has revolutionized cystic fibrosis (CF) treatment; however, a subset of patients with eligible genotypes remains unresponsive. We previously identified the L467F-F508del complex allele as a cause of therapeutic failure, conferring a severe processing defect that renders the CFTR protein refractory to ETI.</div></div><div><h3>Methods</h3><div>To address this unmet need, we evaluated the efficacy of the next-generation combination comprising Vanzacaftor/Tezacaftor (Vnz/Tez). We utilized primary human nasal epithelial (HNE) cells derived from six patients carrying the L467F-F508del complex allele and a minimal function mutation and monitored the clinical response of a patient treated with Vanzacaftor/Tezacaftor/Deutivacaftor (VTD) via compassionate use. Mechanistic validation was performed in CFBE41o- cells.</div></div><div><h3>Results</h3><div>In patient-derived HNE models, treatment with Vnz/Tez resulted in a consistent and significant rescue of CFTR activity, overcoming the block previously observed with ETI. Of note, we report a patient treated with VTD who experienced a partial improvement in pulmonary function (FEV1 +220 mL) and exercise tolerance and a decrease of sweat Chloride concentration from 100 to 87 mmol/L. In heterologous expression systems, Vnz/Tez, but not Elx/Tez, successfully restored the processing of the L467F-F508del mutant, promoting the formation of the mature, complex-glycosylated CFTR form.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that the Vanzacaftor/Tezacaftor combination possesses superior corrective potency capable of rescuing the severe trafficking defect of the L467F-F508del complex allele. This study identifies a promising therapeutic solution for patients currently orphaned by standard-of-care modulators and highlights the utility of integrating <em>ex vivo</em> screening with clinical monitoring in defining precision medicine strategies.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 918-924"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163359","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":"Obesity in adults with cystic fibrosis following prescription of elexacaftor/tezacaftor/ivacaftor","authors":"Joshua S. Ostrenga,&nbsp;Christina M. Mingora,&nbsp;Sylvia Szentpetery,&nbsp;Raksha Jain,&nbsp;Michael S. Schechter,&nbsp;Elizabeth Cromwell,&nbsp;Patrick A. Flume","doi":"10.1016/j.jcf.2026.06.004","DOIUrl":"10.1016/j.jcf.2026.06.004","url":null,"abstract":"<div><div>We conducted a descriptive analysis of people with CF 20 years of age and older using CF Foundation Patient Registry data to provide (1) current estimate of the overweight and obese population and (2) the effect of elexacaftor-tezacaftor-ivacaftor (ETI) on weight gain. We summarized demographic details including biological sex, race, ethnicity, insurance, and variant status. Clinical data including body mass index, pulmonary function, prevalence of liver complications, and diabetes status were collated. A total of 8262 individuals age 20+ initiated ETI and met inclusion criteria for the weight gain analysis in the 1-year following ETI initiation: 1493 (18.1%) people lost weight, 4580 (55.4%) people gained &lt;5 kg; 1649 (20.0%) people gained 5-&lt;10 kg; and 540 (6.5%) people gained ≥10 kg. The numbers and proportion of adult pwCF who are overweight or obese have continued to increase, and at a rapid rate.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 827-831"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295098","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":"News article","authors":"","doi":"10.1016/j.jcf.2026.09.003","DOIUrl":"10.1016/j.jcf.2026.09.003","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 761-762"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014112","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":"Multi-omics identification of amino acid and redox dysregulation in cystic fibrosis-related diabetes","authors":"Su Yeon Oh,&nbsp;Susan O. Kim,&nbsp;James T. Lyles,&nbsp;Sonya Ajani,&nbsp;William R. Hunt,&nbsp;Nael A. McCarty,&nbsp;Tanicia Daley,&nbsp;Virginia A. Stallings,&nbsp;Arlene A. Stecenko,&nbsp;Vin Tangpricha,&nbsp;Thomas R. Ziegler,&nbsp;Jessica A. Alvarez,&nbsp;Joshua D. Chandler","doi":"10.1016/j.jcf.2026.04.012","DOIUrl":"10.1016/j.jcf.2026.04.012","url":null,"abstract":"<div><h3>Background</h3><div>Cystic fibrosis-related diabetes (CFRD) is one of the most common extrapulmonary complications of cystic fibrosis (CF), characterized by abnormal glucose tolerance due primarily to insulin insufficiency. CF-related prediabetes (CFRpD) represents an asymptomatic stage before CFRD onset, requiring routine screening for detection. We aimed to characterize the metabolic profiles underlying abnormal glucose tolerance in people living with CF (pwCF) and identify disrupted pathways associated with CFRD progression.</div></div><div><h3>Methods</h3><div>Fasting plasma samples from pwCF with normal glucose tolerance (CF-NGT), CFRpD, CFRD, and from healthy, normoglycemic controls without CF were analyzed using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and lipidomics. Annotated metabolites were used for their individual profiles and pathway analysis.</div></div><div><h3>Results</h3><div>Plasma BCAAs, choline, and methionine were lower in CFRD compared to CF-NGT, and leucine, isoleucine, and methionine were also lower in CFRpD after adjusting for sex and CFTR modulator use. In addition, LPCs and the percentage of methionine oxidation (%OxMet) were significantly higher in CFRD. Lean mass and LMI correlated positively with BCAAs and methionine, though only valine was significant after adjusting for sex in pwCF. In agreement with individual metabolites, pathway analysis indicated disruptions in BCAA biosynthesis and one-carbon metabolism in CFRD.</div></div><div><h3>Conclusion</h3><div>These findings suggest that impairments in branchedchain amino acid metabolism, redox balance, and one-carbon metabolism are associated with the pathogenesis of CFRD, including lower lean mass in the case of valine. These metabolites should be further tested as potential biomarkers of CF(p)RD and may provide mechanistic insights into CFRD pathogenesis and therapeutic avenues.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 900-908"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}