Journal of Cystic Fibrosis最新文献

{"title":"CyFidb: A Molecular Atlas for Cystic Fibrosis.","authors":"Catarina Pereira, Margarida D Amaral, Andre O Falcao","doi":"10.1016/j.jcf.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.011","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) is a disease triggered by more than 2,100 variants in a single gene encoding for the CF Transmembrane Conductance Regulator (CFTR) protein, which is expressed in epithelial cells, where it functions an anion channel. A new era of high-throughput technologies ('omics') enabled the production and exploration of large CF-related datasets with unprecedented detail. However, this knowledge is scattered among different resources thus requiring a significant amount of time and training to collect and exploit. The objective of this work is to build a resource (CyFidb) that concentrates CF-related information in a single repository.</p><p><strong>Methods: </strong>This tool results from the intense manual curation of 407 scientific articles, including studies with CFTR variants in distinct conditions, drug treatments and cells/tissues.</p><p><strong>Results: </strong>CyFidb is divided into three levels of information: protein-protein interactions, gene expression and functional studies, from which it is possible to search and extract information.</p><p><strong>Conclusions: </strong>CyFidb is an open-access resource (https://cyfidb.di.fc.ul.pt) designed to provide continuously updated, curated information on CFTR variants and their associated biological data.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730267","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":"First real-world study of fetal therapy with CFTR modulators in cystic fibrosis: Report from the MODUL-CF study.","authors":"Anne-Sophie Bonnel, Tiphaine Bihouée, Mélanie Ribault, Marine Driessen, David Grèvent, Frantz Foissac, Ngoc Hoa Truong, Myriam Benhamida, Baptiste Arnouat, Roxana Borghese, Frédérique Chedevergne, Laure Couderc-Kohen, Jennifer da Silva, Dominique Grenet, Véronique Houdouin, Anais Le, Sarah Marchal, Eric Deneuville, Delphine Pouradier, Véronique Rousseau, Jean-Marc Treluyer, Arnaud Francart, Julie Steffann, Philippe Reix, Sihem Benaboud, Marie France Mamzer, Yves Ville, Clémence Martin, Pierre-Régis Burgel, Isabelle Sermet-Gaudelus","doi":"10.1016/j.jcf.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.009","url":null,"abstract":"<p><strong>Background: </strong>We aimed to build a cohort of Maternal-Cystic Fibrosis (CF) fetal dyads treated in utero with Variant Specific Therapy (VST), to assess the efficacy on Meconium Ileus (MI) and potential adverse effects of treatment.</p><p><strong>Methods: </strong>Dyads were included if the foetus had a genetic diagnosis of CF and carried at least one variant responsive to VST. Standardized assessment included pre-VST Magnetic Resonance Imaging (MRI), repeated ultrasound (US), and VST drug concentrations in cord blood, maternal and infant plasma.</p><p><strong>Results: </strong>We enrolled 13 dyads. One withdrew from the study. VST therapies (Elexacaftor (ELX)/Tezacaftor (TEZ)/Ivacaftor(IVA) (ETI) n = 11, ivacaftor (IVA) n = 1) were administered to the pregnant women between 19 and 36 weeks' of gestation for a median[IQR] of 35[55] days, either as a curative indication of MI (n = 8) or as a tertiary prevention of fetal CF-related intestinal symptoms (n = 4). One foetus experienced increased bowel dilatation after ETI introduction. MRI revealed intestinal atresia. One dyad received only 2 doses. In the other 6 cases, resolution of MI was observed within 14[10] days of ETI. Fetal development and neonatal tolerance were excellent. Fecal elastase at birth was always below 200 ng/g even in the ETI breast-fed infant. Cord-to-maternal concentration yielded median ratios of 0.40 for ELX, 0.54 for IVA and 1.59 for TEZ.</p><p><strong>Conclusion: </strong>ETI administration from the third trimester of pregnancy enables MI resolution. Trans-placental transfer is high. Fetal tolerance at ETI initiation needs to be monitored by a standardized assessment.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710075","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":"Elexacaftor-tezacaftor-ivacaftor pharmacokinetics with concurrent tacrolimus administration after lung transplant.","authors":"J S Guimbellot, Ashritha Chalamalla, Elizabeth Baker, K J Ryan, A Dowell, Saly Abouelenein, L E Bartlett, J Bergeron, G Turner, E P Acosta, K J Ramos","doi":"10.1016/j.jcf.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.010","url":null,"abstract":"<p><strong>Background: </strong>CFTR modulators in post-transplant people with cystic fibrosis (pwCF) are less frequently used due to uncertainty regarding effectiveness and interactions with immunosuppressive agents. Elexacaftor/tezacaftor/ivacaftor (ETI) is a triple combination cystic fibrosis (CF) therapeutic with benefits in multiple organ systems where complications can impact lung transplant (LTx) outcomes, including malnutrition, diabetes, and sinus disease. ETI use in LTx recipients is variable.</p><p><strong>Methods: </strong>We conducted a pharmacokinetics (PK) study of concentrations of ETI parent compounds and the four major metabolites (M23-ELX, M1-TEZ, M1-IVA, M6-IVA) in a prospective non-randomized observational study, with all transplant participants concomitantly taking tacrolimus for LTx immunosuppression and excluded if taking any other medication with known interactions (e.g., azole antifungals) and compared to a non-transplant group of pwCF. We completed non-compartmental analysis (NCA) for both groups and compared the transplant to non-transplant PK parameters, as well as to published data from the manufacturer for non-transplant pwCF. Area under the curve (AUC), average concentrations (C_avg), minimum and maximum concentrations, clearance, and other parameters were determined.</p><p><strong>Results: </strong>Twelve transplant and fourteen non-transplant participants with CF completed the study. There were no significant differences between the mean values for any PK parameters for the transplant and non-transplant groups and no substantial differences in frequency of concentrations outside the therapeutic ranges in the two groups.</p><p><strong>Conclusions: </strong>Our data suggest there are not significant differences in concentrations of ELX, TEZ, IVA, or their major human metabolites in LTx recipients compared to non-transplant pwCF.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692329","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":"CFTR modulator therapy via carrier mother to treat meconium ileus in a F508del homozygous fetus: Insights from an unsuccessful case.","authors":"M Destoop, C Brantner, E B Wilms, Shaj Tytgat, B Peels, R van der Graaf, T B Y Liem, K M de Winter-de Groot","doi":"10.1016/j.jcf.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.006","url":null,"abstract":"<p><p>We present a case of a carrier mother treated with elexacaftor/tezacaftor/ivacaftor (ETI) for in-utero management of meconium ileus in a fetus diagnosed with cystic fibrosis (CF), homozygous for the F508del variant. Following multidisciplinary discussion and shared decision-making involving the parents, ETI was initiated at 27 weeks of gestation. At 38+4 weeks, the infant was delivered. Despite the treatment, the newborn developed meconium ileus, necessitating emergency surgery after birth. We explore potential factors contributing to the lack of success in our case compared to previously reported successful cases in USA and Spain. Drug levels measured in neonatal blood and in maternal breast milk indicated minimal drug exposure, raising questions about whether variability in placental transfer and excretion in breast milk or suboptimal ETI dosing in the overweight mother impacted the outcome. Additionally, the natural variability in meconium ileus outcome, which can range from spontaneous resolution to severe complications must be considered. In our case, ETI may have mitigated the severity of the condition, preventing serious complications like bowel perforation or peritonitis. However, given that about 20 % of all fetal bowel dilation resolves spontaneously, it remains uncertain whether the positive outcomes in prior cases were attributable to ETI or the natural course of the disease. We emphasize the need for more evidence on in utero ETI exposure by advocating for the collection of cases involving ETI treatment for fetal meconium ileus, regardless of outcomes. Developing guidelines will be essential to optimize benefits for both mother and fetus while minimizing risks.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674098","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":"Immunogenic adverse events to CFTR modulators - An international survey.","authors":"Ruth M Urbantat, Laura Behan, Sebastian Wisniewski, Joshua Gardner, Mirjam Stahl, Marcus A Mall, Daniel Peckham, Dean J Naisbitt, Jobst F Roehmel","doi":"10.1016/j.jcf.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.003","url":null,"abstract":"<p><strong>Background: </strong>CFTR modulator therapy has unprecedented positive effects on people with CF (pwCF). However, immunogenic reactions to CFTR modulator therapy may lead to drug discontinuation. We aimed to identify pwCF, intolerant to CFTR modulator therapy due to suspected immunogenic adverse events (iAE).</p><p><strong>Methods: </strong>This survey assessed the types of reaction (e.g. rash, liver injury, drug fever) including reactions after re-exposure and was completed by ECFS CTN Centers.</p><p><strong>Results: </strong>Response rate to the survey was 74 %. 89 CF centers treating approximately 12000 to 17500 pwCF in 28 countries participated and 75 (84 %) CF centers reported discontinuation of CFTR modulator therapy. 37 (41.1 %) of CF centers reported iAE affecting 200 (1.1 - 1.7 %) pwCF. Detailed information about iAEs was provided for 41 of 200 (20.5 % of affected) pwCF. Of the iAEs reported in detail 33/41 (80.5 %) were associated with elexacaftor/tezacaftor/ivacaftor modulator therapy, 6 (14.6 %) with lumacaftor/ivacaftor and 2 (4.9 %) with tezacaftor/ivacaftor. 72 % of pwCF with iAE were re-exposed to CFTR modulator therapy. 32 % of re-exposed pwCF reported a second iAE. Rash and elevated liver enzymes were most frequently reported iAEs.</p><p><strong>Conclusions: </strong>iAE were mostly transient. Drug allergy to CFTR modulator therapy was rare, but highly relevant for individual pwCF.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663449","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":"Genomic analysis of the liverpool epidemic strain of pseudomonas aeruginosa infecting persons with cystic fibrosis reveals likely Canadian origins.","authors":"Conrad Izydorczyk, Barbara J Waddell, Christina S Thornton, John M Conly, Shawn D Aaron, Paul D W Eckford, Deirdre L Church, Michael G Surette, Harvey R Rabin, Michael D Parkins","doi":"10.1016/j.jcf.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.02.009","url":null,"abstract":"<p><strong>Introduction: </strong>The Liverpool Epidemic Strain (LES) of Pseudomonas aeruginosa is one of several known strains to be transmissible between persons with cystic fibrosis (CF) (pwCF) and the only known strain to have infected large proportions of CF populations on two continents. Despite its prevalence, efforts to understand its spread have proven elusive.</p><p><strong>Methods: </strong>We leveraged a prospective collection of P. aeruginosa isolates from pwCF attending the Southern Alberta Adult CF clinic from 1986 to 2020 to identify all individuals with LES infection. LES isolates collected every 1-2 years from each pwCF were sequenced and compared with 171 published LES genomes by phylogenetic analysis.</p><p><strong>Results: </strong>Of 395 pwCF screened, ten pwCF infected with the LES were identified, from whom 46 LES isolates were sequenced. The earliest LES isolate was recovered in 1986, ∼2 years earlier than the previously oldest published LES isolate recovered in the UK. Phylogenetic analysis identified a diverse set of isolates at the root of the LES phylogeny that formed four clades, one of which gave rise to a \"classic LES\" clade. Canadian isolates formed a paraphyletic group that included the root of this clade and out of which the UK LES clade emerged. We estimated the date of the most recent common ancestor (MRCA) of the UK LES clade as 1977.</p><p><strong>Conclusions: </strong>Our study provides genomic evidence in support of a silent epidemic of LES infection occurring in the late 1970s among pwCF first originating in Canada and being spread to the UK, where transmission markedly accelerated.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663448","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":"Real-world pharmacokinetics of elexacaftor-tezacaftor-ivacaftor in children with cystic fibrosis: a prospective observational study.","authors":"Steffie E M Vonk, Suzanne W J Terheggen-Lagro, Eric G Haarman, S Hashimoto, Anke H Maitland-van der Zee, Ron A A Mathôt, E Marleen Kemper","doi":"10.1016/j.jcf.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.008","url":null,"abstract":"<p><strong>Background: </strong>The clinical efficacy of elexacaftor-tezacaftor-ivacaftor (ETI) in children with cystic fibrosis (cwCF) is variable; some respond, while others do not or have side effects. The pharmacokinetics (PK) of ETI are poorly described in published research, particularly when it comes to children. Knowledge of the PK in this population may provide more insight into the exposure-response relationship of the drugs and its corresponding inter-patient variability (IIV). The aim of this study was to evaluate the PK of ETI in cwCF in a real-world setting.</p><p><strong>Methods: </strong>A prospective, observational PK study was conducted in cwCF starting with ETI. PK samples were collected at home using dried blood spots (DBS), and during regular outpatient hospital visits. Clinical efficacy and safety data were gathered and evaluated. Population PK (popPK) models were developed using nonlinear mixed-effects modelling.</p><p><strong>Results: </strong>A total of 29 children were included in this study. Novel popPK models were developed for ETI and its main metabolites. There was significant variability in AUC of ETI within and between age groups, aligning with the references in the product information. All children had concentrations within or above the range needed for a clinical response. An exploratory exposure-response analysis found no direct linear relationship between AUC and sweat chloride, or ppFEV1.</p><p><strong>Conclusions: </strong>This study is the first analysis of ETI popPK in cwCF. The developed popPK models may be used to further study the exposure-response relationship and its variability within cwCF, as a basis for more personalized dosing.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634046","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":"Hemoglobin A1c in youth and adults with cystic fibrosis related diabetes decreases after elexacaftor-tezacaftor-ivacaftor.","authors":"Colleen Wood, Amir Moheet, Tim Vigers, Andrea Granados, Andrea Lorenz, Elinor Hanley, Edith Zemanick, Christine L Chan","doi":"10.1016/j.jcf.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.007","url":null,"abstract":"<p><strong>Background: </strong>Elexacaftor/tezacaftor/ivacaftor (ETI) has been highly effective for improving pulmonary disease and nutritional outcomes. However, the effect of this therapy on glycemic control in people with cystic fibrosis related diabetes (CFRD) is unclear. This study aimed to examine real-world effects of ETI on glycemia as captured by hemoglobin A1c (HbA1c) in people with pre-existing CFRD.</p><p><strong>Methods: </strong>Retrospective chart review was performed at 4 US CF centers. Individuals with CFRD included in the study started ETI before December 2020, and had an HbA1c within 1 year before and up to 2 years after ETI initiation. A sub-analysis comparing CGM data and insulin dosing within the year before and after ETI was performed. Summary statistics were calculated and within-subject results compared.</p><p><strong>Results: </strong>A total 175 individuals with CFRD had HbA1c data before and after ETI. Mean (±SD) age was 32.4 (±12.4) years, 49.1 % female. HbA1c were compared a median (IQR) of -40 (-93, 0) days before and 290 (107, 441) days after ETI initiation. Median (IQR) HbA1c decreased from 6.4 % (5.8, 7.2) to 6.0 % (5.5, 6.8), p<0.001. A subgroup of 13 individuals had CGM and basal insulin data for comparison. No changes were observed in CGM metrics, however, basal insulin dose in these patients decreased (p=0.03).</p><p><strong>Conclusion: </strong>Findings suggest clinical improvements in glycemia following ETI initiation in people with CFRD. Further studies are required to better understand the mechanisms by which ETI may modulate insulin and glucose dynamics in individuals with existing CFRD.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633969","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":"Vitality is associated with systemic inflammation in cystic fibrosis adults on elexacaftor/tezacaftor/ivacaftor.","authors":"Jacob Gravelle, Sameer Desai, Kang Dong, Bradley S Quon","doi":"10.1016/j.jcf.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.004","url":null,"abstract":"<p><p>Fatigue is common among adults with cystic fibrosis (awCF) and may be associated with systemic inflammation. This study examines systemic inflammation, measured by C-reactive protein (CRP), and fatigue, assessed using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) vitality domain, in individuals initiating elexacaftor/tezacaftor/ivacaftor (ETI) therapy. In a cohort of 61 awCF from St. Paul's Hospital, Vancouver, CRP and vitality were measured at baseline and at 1, 3, 6, and 12 months post-ETI initiation. We observed reductions in CRP and increases in vitality over the 12-month period. Linear mixed-effects models were used to examine the relationship between CRP and vitality adjusted for age, sex, BMI, and lung function. Our findings demonstrated a significant, independent inverse association between CRP and vitality. These results highlight the potential role of systemic inflammation in influencing vitality in awCF undergoing ETI therapy. Further research incorporating additional inflammatory markers and psychosocial variables is warranted to deepen our understanding of fatigue mechanisms in this population.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615659","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":"Application of the defect distribution index to functional lung MRI of pediatric cystic fibrosis lung disease and controls.","authors":"Elisabeth Kieninger, Samal Munidasa, Marion Curdy, Carmen Streibel, Brandon Zanette, Jason Woods, Philipp Latzin, Felix Ratjen, Giles Santyr","doi":"10.1016/j.jcf.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.02.015","url":null,"abstract":"<p><strong>Introduction: </strong>Functional magnetic resonance imaging (MRI) of the lung usually assesses lung impairment as ventilation defect percentage (VDP). However, VDP only reflects the overall burden of disease and does not characterize the regional distribution (i.e. pattern) of defects. The defect distribution index (DDI) is a metric which shows quantitatively how clustered versus scattered defects are with a higher DDI indicating more clustered defects.</p><p><strong>Aim: </strong>To assess the applicability and validity of the DDI to ¹²⁹Xe-MRI and PREFUL-MRI of CF lung disease.</p><p><strong>Methods: </strong>The DDI algorithm was applied to fractional ventilation maps previously acquired with ¹²⁹Xe-MRI and PREFUL-MRI of 37 children with CF and 13 healthy controls.</p><p><strong>Results: </strong>The calculation of DDI was feasible for all MRI data. DDI was significantly higher in patients with CF compared to healthy controls (mean difference [95 % CI] ¹²⁹Xe-MRI DDI_{60 %mean} -1.94 [-2.86 - -1.02], p=0.0001), strongly correlated with other functional outcomes such as VDP and the lung clearance index, and decreased significantly in CF patients with pulmonary exacerbations after antibiotic treatment (e.g. ¹²⁹Xe-MRI DDI_{60 % mean} -1.03 [-0.44 - -1.63], p=0.002).</p><p><strong>Conclusion: </strong>The DDI is applicable to functional ¹²⁹Xe-MRI and PREFUL-MRI data providing complementary information to VDP by assessing defect distribution rather than defect size. It shows meaningful clinimetric properties and improves with treatment. The DDI shows potential as a parameter for comprehensive monitoring of CF lung disease and treatment.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605148","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}