Journal of Cystic Fibrosis最新文献

{"title":"WS01.04Elexacaftor/tezacaftor/ivacaftor reduces the risk of lung transplantation or death among people with advanced CF lung disease in the United States","authors":"E. Cromwell ,&nbsp;J. Todd ,&nbsp;R.H. Keogh ,&nbsp;C. Lesko ,&nbsp;A.W. Brown ,&nbsp;E. Tallarico ,&nbsp;K.J. Ramos ,&nbsp;A. Faro","doi":"10.1016/j.jcf.2025.03.495","DOIUrl":"10.1016/j.jcf.2025.03.495","url":null,"abstract":"<div><h3>Objectives</h3><div>Individuals with advanced CF lung disease (ACFLD) are at increased risk of clinical deterioration, including death or lung transplant. This population was excluded from clinical trials but represent a group that could experience clinical benefit. We hypothesized that elexacaftor/tezacaftor/ivacaftor (ETI) would reduce the risk of death or first lung transplant among people with ACFLD.</div></div><div><h3>Methods</h3><div>We used the CF Foundation Patient Registry to identify individuals with ACFLD defined as those with lung function consistently below ppFEV₁ &lt;40, report of massive hemoptysis or pneumothorax, supplemental oxygen use or referral for transplantation. We emulated a target trial using sequential trials to include anyone with ACFLD prescribed ETI between July 2019 and December 2023 and those never prescribed ETI in that period, including those ineligible. Weighted Cox proportional hazards models for competing risks were used to estimate the effect of ETI on time to pre-transplant death and first lung transplant. Risk differences for death 4 years post-ETI were also estimated.</div></div><div><h3>Results</h3><div>Among 4,221 individuals, 3,302 (78.2%) were prescribed ETI at some point between July 2019-December 2023. There were 138 deaths and 51 transplants among those prescribed ETI and 168 deaths and 117 transplants among those never prescribed. ETI prescription had hazard ratios of 0.38 (95% CI: 0.27; 0.51) for death and 0.27 (95% CI: 0.18; 0.42) for lung transplantation. The risk difference for death was 5.6% lower with ETI use (95% CI: 4.0; 7.3) after 4 years.</div></div><div><h3>Conclusions</h3><div>ETI reduced the risk of death or first transplant among people with ACFLD, critical outcomes in a high-risk population not included in the original clinical trials. These findings can be used by providers and patients to understand the impact of ETI on disease trajectory in ACFLD. Additionally, these findings help quantify the potential impact of ETI in settings where it is not yet available.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S2"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204922","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":"WS02.04Perspectives on inhaled therapy in the post-CFTR modulator era: a survey of adults with cystic fibrosis","authors":"R.D. Sandler ,&nbsp;Z.H. Hoo ,&nbsp;S.M.B. Ariss","doi":"10.1016/j.jcf.2025.03.501","DOIUrl":"10.1016/j.jcf.2025.03.501","url":null,"abstract":"<div><h3>Objectives</h3><div>The transformative effects of CFTR modulators (CFTRm) have led adults with cystic fibrosis (awCF) and clinicians to re-evaluate the role of inhaled therapy. Our objective was to understand the perspectives of awCF.</div></div><div><h3>Methods</h3><div>A survey was shared via two CF-specific UK mailing lists and social media. Participants rated the importance of inhaled therapy from 0 (least) to 100 (most) and noted any changes since starting CFTRm. Free-text responses were categorised into insight-generating themes.</div></div><div><h3>Results</h3><div>Responses were received from 414 people with CF, of which 224 (54%) identified as female. Responders represented 17/26 UK adult CF centres (range 1-35 per centre). The majority were prescribed CFTRm (n=344, 83.1%) and/or inhaled therapy (n=321, 77.5%). Overall, the perceived importance of inhaled therapy was significantly lower among those on CFTRm, median of 72/100 (IQR: 48.0) compared to 88 (IQR: 45.3), p = 0.03. Among those prescribed CFTRm, 138 (40.1%) regarded inhaled therapy as less important than prior to CFTRm. This perspective was attributed to a reduction in symptoms, a lack of perceived benefit from inhaled therapy, and a desire to decrease treatment burden. Several considered inhaled therapy more appropriate for acute illness rather than routine maintenance. Conversely, 172 (50%) considered inhaled therapy equally or more important than before CFTRm. Their rationale included an awareness of cumulative lung damage, clinician recommendations, a discernible benefit from inhaled therapy, and the belief that it helps sustain the benefits of CFTRm into later life.</div></div><div><h3>Conclusions</h3><div>The impact of CFTRm on perspectives regarding inhaled therapy is variable amongst the awCF in the UK. Whilst population-level evidence regarding the clinical impact of changing inhaled therapy regimens for awCF taking CFTRm is awaited, clinicians should be aware of the variation in patient perspective during the process of shared decision-making and individualisation of care.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S4"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204928","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":"WS09.02Intestinal current measurement detects age-dependent differences in CFTR function in rectal epithelium","authors":"S.Y. Graeber ,&nbsp;O. Sommerburg ,&nbsp;Y. Yu ,&nbsp;J. Berges ,&nbsp;S. Hirtz ,&nbsp;H. Scheuermann ,&nbsp;J. Berger ,&nbsp;J. Duerr ,&nbsp;M.A. Mall","doi":"10.1016/j.jcf.2025.03.541","DOIUrl":"10.1016/j.jcf.2025.03.541","url":null,"abstract":"<div><h3>Objective</h3><div>Intestinal current measurement (ICM) provides a sensitive bioassay for assessment of CFTR function in rectal biopsies <em>ex vivo</em>. Results from clinical trials of CFTR modulators across age groups indicate that CFTR function in the sweat duct may be age-dependent with children reaching higher levels than adults. However, little is known about age dependency of CFTR function in the intestinal epithelium.</div></div><div><h3>Methods</h3><div>We investigated CFTR-mediated chloride secretion in rectal biopsies from 258 people without CF and 72 people with pancreatic-insufficient CF from 1 month to 68 years of age with ICM. Furthermore, morphometric analysis of epithelial cells lining the crypts and surface of the rectal mucosa were performed.</div></div><div><h3>Results</h3><div>We found that CFTR-mediated chloride secretion across rectal tissues, as determined from cAMP-mediated as well as cholinergic chloride-secretory responses was highest during infancy and early childhood and declined with age in people without CF. In people with CF, potassium-secretory responses induced by cholinergic stimulation were also reduced with increasing age. Morphometric analyses demonstrated that CFTR expressing colonocytes at the crypt base were decreased with age. A secondary analysis of the ICM data of our previous studies on the effects of lumacaftor/ivacaftor on CFTR function in <em>F508del</em> -homozygous people with CF aged 12 years and older and 2 to 11 year old children showed correlations of the change in cAMP-mediated and cholinergic chloride secretory response with the age of people with CF.</div></div><div><h3>Conclusion</h3><div>These results demonstrate that CFTR function in the rectal epithelium is reduced with increasing age and indicate that this change is likely due to a decline in the number of secretory colonocytes at the crypt base. These findings suggest that differences in CFTR expressing cells may explain increased functional responses to CFTR modulator therapies in children compared to adult people with CF.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S18"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205229","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":"WS03.03Capturing a cough. Results of a pilot study to assess the utility of cough plates for microbiological surveillance in CF","authors":"C. Fordyce ,&nbsp;P. Farrell ,&nbsp;A.M. Jones ,&nbsp;A. Horsley","doi":"10.1016/j.jcf.2025.03.506","DOIUrl":"10.1016/j.jcf.2025.03.506","url":null,"abstract":"<div><h3>Objectives</h3><div>Airway microbiology is increasingly hard to monitor in pwCF on HEMT. This pilot study aimed to evaluate the sensitivity of cough plates in detecting gram-negative bacteria compared to sputum samples.</div></div><div><h3>Methods</h3><div>Twenty-five adults (14 male, age range 21–55 yrs, FEV1 26–97%, 4/25 non-modulated) underwent airway clearance supervision to collect sputum samples, followed by directed coughs onto pseudomonas-selective and non-selective agar cough plates. If sputum collection failed, sputum induction was performed post-cough plate sampling (n=2). Bacterial infection status was determined by the presence of an infection on any sample in the previous 12months.</div></div><div><h3>Results</h3><div>Gram-negative bacteria were detected in 18 sputum samples and on 8 cough plates. In 6 cases, the same organism was isolated from sputum and cough plate. In one case, <em>Pseudomonas aeruginosa</em> was cultured at low density solely on cough plate (not on sputum) and differing gram-negative organisms were isolated from the cough plate and sputum in one case. Four samples showed no growth on either sputum or plate.</div><div>Over the preceding 12 months, 21 participants (84%) cultured gram-negative bacteria in sputum samples. Based on this, sensitivity of sputum sampling was 72% and cough plates was 32%.</div><div>High gram-negative bacterial load in sputum samples (CFU&gt;100) were observed in 9 participants (50%). Cough plates demonstrated lower colony counts overall (range 2–100, median CFU 8.5), with only one plate showing CFU&gt;100. There was no association between high CFU on sputum and detection of the same organism on cough plates.</div></div><div><h3>Conclusions</h3><div>Although cough plates may serve as a supplemental tool for microbial surveillance in CF adults, their limited sensitivity compared to sputum samples make them insufficient as a stand-alone diagnostic method at the present time. Further refinement of cough plate techniques would be needed to improve the diagnostic utility, particularly if planning to use in adults who are non-productive.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S6-S7"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205323","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":"WS03.04Impaired oxygen pulse during exercise following lung transplant in cystic fibrosis: a case series","authors":"O. Tomlinson ,&nbsp;C. Pereira Chilima ,&nbsp;T. Kent ,&nbsp;L. Dobson ,&nbsp;P. Mitchelmore","doi":"10.1016/j.jcf.2025.03.507","DOIUrl":"10.1016/j.jcf.2025.03.507","url":null,"abstract":"<div><h3>Introduction</h3><div>Bilateral single sequential lung transplantation (BSSLT) technique has supplanted the en-bloc method, as the preferred mode of lung transplantation (LTx) in cystic fibrosis (CF). However, despite adoption of BSSLT, all forms of LTx carry inherent risk of mediastinal nerve damage, which can result in cardiac dysfunction. This dysfunction may be detected non-invasively via cardiopulmonary exercise testing (CPET), whereby all people with CF are recommended to undergo regular testing as part of routine disease monitoring. This case series characterises prevalence of cardiac dysfunction – represented by the oxygen pulse (O₂P)– in a cohort of post-LTx patients with CF (pwCF)</div></div><div><h3>Methods</h3><div>Retrospective analysis of routine CPET – Cycle ergometry performed to volitional exhaustion – by six post-LTx pwCF under the care of a regional CF service.</div></div><div><h3>Results</h3><div>Data from six post-LTx pwCF was available for review (5 male; mean age = 41 years [range 34 – 49 years]; mean FEV₁ = 80% [range = 59-110%]). All patients had undergone LTx via BSSLT, with mean duration post-surgery being 8.3 years (range 6.0 – 11.8 years). Two patients – with longest time post-LTx (10.9, and 11.8 years) – exhibited diminished, and non-linear O₂P, failing to augment ≥10 mL^.beat^-1, the recognised threshold for impaired function. The remaining four pwCF all increased O₂P sufficiently ≥10 mL^.beat^-1 during exercise. Both pwCF with diminished O₂P reached peak heart rate values ≥90%_predicted, inferring inadequate stroke volume during exercise.</div></div><div><h3>Discussion</h3><div>This cohort of post-LTx pwCF, one-third displayed impaired O₂P and non-linear heart rate response to incremental exercise, suggesting a degree of autonomic dysfunction that may reflect mediastinal nerve damage seen in en-bloc LTx, and cardiac transplantation. Given increasing recognition of cardiac disease risk in CF, clinical teams must be aware of subclinical cardiac dysfunction, particularly in those post-LTx, which may be detected via routine CPET.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S7"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205324","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":"WS08.05Multi-omics insights into Pseudomonas aeruginosa’s adaptation to elexacaftor/tezacaftor/ivacaftor therapy","authors":"L. Veschetti ,&nbsp;S. Piccolo ,&nbsp;G. Vingiani ,&nbsp;C. Paganin ,&nbsp;E.V. Fiscarelli ,&nbsp;A. Bragonzi ,&nbsp;C. Cigana","doi":"10.1016/j.jcf.2025.03.538","DOIUrl":"10.1016/j.jcf.2025.03.538","url":null,"abstract":"<div><h3>Objectives</h3><div>Elexacaftor/tezacaftor/ivacaftor (ETI) offers significant clinical benefits for eligible people with cystic fibrosis (pwCF), though treatment effectiveness varies, potentially due to factors like individual lung microbiological profiles. We aim to investigate Pa response to ETI by integrating phenotypic, transcriptomic, and genomic data to identify adaptive traits and understand variability in treatment outcomes.</div></div><div><h3>Methods</h3><div>Clonally-related Pa isolates were collected from 3 pwCF before and up to 18 months after starting ETI treatment. Phenotypic traits linked to acute/intermittent infection and chronic colonization were analyzed. Isolates underwent a 6-hour <em>in vitro</em> exposure to ETI or DMSO in artificial sputum medium, simulating the conditions in CF sputum. Bacterial RNA was sequenced, transcripts were quantified, and differential expression (DEA) and pathways enrichment analysis were carried out.</div></div><div><h3>Results</h3><div>Phenotypic analysis showed strain-dependent adaptation, mainly affecting pyocyanin production and biofilm formation. DEA of longitudinal isolates revealed a small overlap in modulated transcripts across clonal lineages (upregulated=0.3%, downregulated=0.07%), indicating a strain-specific transcriptional response to <em>in vivo</em> ETI exposure. Shared modulated transcripts were linked to secretion systems, beta-lactam resistance, ABC transporters, and metabolic pathways. <em>In vitro</em> ETI treatment caused no consistent transcript modulation across isolates, but 0.6–3.7% of transcripts modulated <em>in vitro</em> were also affected <em>in vivo</em>, suggesting a direct ETI impact. Eight additional pwCF have been recruited, and whole genome sequencing is ongoing to explore pathoadaptive mutations.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that exposure to ETI treatment can modify specific Pa phenotypic traits and transcriptomes in a pwCF-specific manner, providing insights into variability in treatment efficacy. This study was supported by the Italian CF Foundation (FFC#16/2021).</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S17"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205339","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":"WS10.04Programmed cell death 1 receptor axis blockade enhances antigen-specific T cell proliferation in paediatric cystic fibrosis","authors":"E. Cahani,&nbsp;A. Rybak,&nbsp;S. Blanchon,&nbsp;C. Fernandez,&nbsp;A. Noto,&nbsp;M. Perreau,&nbsp;I. Rochat","doi":"10.1016/j.jcf.2025.03.549","DOIUrl":"10.1016/j.jcf.2025.03.549","url":null,"abstract":"<div><h3>Objectives</h3><div>Cystic Fibrosis (CF) is associated with recurrent pulmonary infections and high morbidity. Chronic infections can produce CD4+ T lymphocyte (CD4 T cell) exhaustion, characterized by overexpression of the Programmed Cell Death 1 Receptor (PD-1). Rare studies have assessed the role of the PD-1/PD-L1 (ligand) pathway in CF-associated immune dysregulation. We investigated CD4 T cell exhaustion in a cohort of pediatric CF patients and evaluated CD4 T cell rescue after blockade of the PD-1/PD-L1 axis.</div></div><div><h3>Methods</h3><div>Cross-sectional monocentric study including pediatric CF patients and controls. PD-1 expression was measured on total and memory CD4 T cells by mass cytometry. Antigen-specific CD4 T cell proliferation capacity in response to CF-relevant antigens stimulation (<em>Staphylococcus aureus</em> (Sa), or <em>Pseudomonas aeruginosa</em> (Pa)), was assessed using a CFSE-based flow cytometry assay in absence/presence of anti-PD-L1 blockade antibody.</div></div><div><h3>Results</h3><div>We included 25 pediatric CF patients and 7 controls (56% and 86% females, median age 11 and 9 years, respectively). No significant differences were observed between the two groups in terms of 1) PD-1 expression on total and memory CD4 T cells and 2) antigen-specific CD4 T cell proliferation capacity. However, PD-1/PD-L1 blockade significantly increased bacteria-specific CD4 T cell proliferation only in CF patients for Pa (n=20, p&lt;0.001) and Sa (n=12, p=0.02). No correlation was found between PD-1 expression on CD4 T cells, nor with antigen-specific T cell proliferative capacity, with markers of disease severity (clinico-microbiological or radiological parameters) in CF patients.</div></div><div><h3>Conclusion</h3><div>To our knowledge, this is the first study in pediatric CF patients showing enhanced Sa- and Pa-specific CD4 T cell proliferation after PD-1/PD-L1 blockade, despite stable PD-1 levels. Further understanding of the precise mechanism is needed, as PD-1/PD-L1 immunotherapy may represent a future therapeutic option for selected CF patients.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S20-S21"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WS01.05Time to reimbursement for elexacaftor/tezacaftor/ivacaftor across countries in the ECFS patient registry","authors":"B. Young ,&nbsp;J. Guo ,&nbsp;G. Hennessy ,&nbsp;A. Hill","doi":"10.1016/j.jcf.2025.03.496","DOIUrl":"10.1016/j.jcf.2025.03.496","url":null,"abstract":"<div><h3>Objectives</h3><div>Due to its high price, elexacaftor/tezacaftor/ivacaftor (ETI) is inaccessible to patients unless reimbursed by national health bodies. Such reimbursement deals are typically negotiated with the manufacturer on an individual country basis, resulting in delays and disparities in treatment access. Accordingly, we analysed timing disparities in ETI reimbursement across countries participating in the European Cystic Fibrosis Society Patient Registry (ECFSPR), examining relationships with health outcomes and national economic indicators.</div></div><div><h3>Methods</h3><div>Time to reimbursement (TTR) from initial regulatory approval was determined for countries within the ECFSPR using manufacturer and patient organisation press releases, national drug registries and stakeholder correspondence. Initial authorisation dates were obtained from medicines regulators. Associations between TTR, CF health outcomes and gross national income (GNI) were appraised using Spearman's Rank correlation coefficient.</div></div><div><h3>Results</h3><div>Of 40 countries in the ECFSPR, 31 had agreed reimbursement for ETI. Median TTR was 343 days (IQR=183.5-572.5, range 0-1,502 days) and displayed a highly positively skewed distribution (skewness=1.167, mean=434 days). Significant negative associations were found between TTR and the number of registered patients (r_s=-0.419, p&lt;0.05) and GNI (r_s=-0.515, p&lt;0.05). No significant associations were found between TTR and ppFEV₁, <em>Pseudomonas aeruginosa</em> colonisation or %F508del homozygosity/heterozygosity.</div></div><div><h3>Conclusion</h3><div>Time to ETI reimbursement varied significantly across the ECFSPR, demonstrating a grouping of early reimbursement deals followed by prolonged negotiations in predominantly poorer countries. Lower GNI and smaller CF populations were both associated with a longer TTR. Following the recent US authorisation of vanzacaftor/tezacaftor/deutivacaftor, these findings highlight important considerations for equitable access to existing and emerging CFTR modulator therapies internationally.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S2"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204923","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":"WS12.02Dietary protein intake and overall diet quality in adults with cystic fibrosis following elexacaftor/tezacaftor/ivacaftor therapy","authors":"L.R. Caley ,&nbsp;P.T. Morgan ,&nbsp;T.-J. Ellis ,&nbsp;B. Smeuninx ,&nbsp;L. Breen ,&nbsp;L. Kinsey ,&nbsp;O.W. Tomlinson ,&nbsp;H. White ,&nbsp;D.G. Peckham","doi":"10.1016/j.jcf.2025.03.559","DOIUrl":"10.1016/j.jcf.2025.03.559","url":null,"abstract":"<div><h3>Objectives</h3><div>This study characterised protein intake and diet quality in adults with cystic fibrosis (awCF), before and after elexacaftor/tezacaftor/ivacaftor (ETI), and compared to healthy controls, UK recommended dietary allowance (RDA, 0.75g·kg^-1·day) and recommendations for those with elevated protein requirements and/or increased risk of sarcopenia (≥1.2g·kg⁻¹·day⁻¹).</div></div><div><h3>Methods</h3><div>As part of the Igloo-CF study, dietary intake was assessed in awCF at baseline (BL, n=40) and at &gt;3 months post-ETI therapy (FUP, n=40), and healthy controls (CON, n=80) at a single time point. Each participant's protein intake, dose and distribution throughout the day relative to bodyweight, and overall diet quality was calculated.</div></div><div><h3>Results</h3><div>Mean age and BMI of awCF (at BL) and CON were 35.6 ± 9.8 years, 23.3±2.8kg·m^-2 and 37.7±14.6 years, 25.0±5.0kg·m-2 respectively, across both cohorts 52% were male. In awCF, median ppFEV₁ was 46.8 (IQR 34.8, 65.8) at BL and 56.5 (IQR 43.5, 72.6) at FUP, with time points a median of 68 weeks (range 20-94 weeks) apart, median duration of ETI at FUP 23 weeks (range 7-72 weeks). Both CON (1.39±0.47g·kg^-1·day^-1) and CF cohorts (BL: 1.44±0.52 g·kg^-1·day^-1), FUP: 1.12±0.32g·kg^-1·day^-1) had a higher mean daily protein intake than the current RDA for healthy adults. Daily protein intake decreased in CF participants at FUP, with levels below (≥1.2g·kg⁻¹·day⁻¹) recommendations for those with elevated protein requirements and/or at risk of sarcopenia (<em>P</em>&lt;0.05). Only 72% of awCF at BL and 64% of CON group met the recommended RDA on all measurement days. In the CF cohort, overall diet quality fell at FUP when on ETI therapy.</div></div><div><h3>Conclusion</h3><div>Adequate protein quality and quantity is essential to maintain skeletal muscle mass and function, particularly in catabolic states such as CF. This is particularly pertinent for a rapidly ageing population. More research on optimal protein requirements is needed to promote healthy ageing in awCF.</div><div><strong>Funded by:</strong> UK CF Trust (SRC 012)</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S23-S24"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204946","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":"WS12.05Change in pancreatic status in children aged 2-5 years after initiation of elexacaftor/tezacaftor/ivacaftor","authors":"P. Roper ,&nbsp;E. Owen ,&nbsp;R. Brugha","doi":"10.1016/j.jcf.2025.03.562","DOIUrl":"10.1016/j.jcf.2025.03.562","url":null,"abstract":"<div><h3>Objectives</h3><div>CFTR modulators may improve or restore pancreatic function in young children(1). We sought to explore changes in Faecal Elastase (FE-1) and Pancreatic Enzyme Replacement Therapy (PERT) in a real-world population of children aged 2-5 years after initiation of Elexacaftor/Tezacaftor/Ivacaftor (ETI).</div></div><div><h3>Methods</h3><div>A prospective data collection was performed in Pancreatic Insufficient (PI) children at our centre, aged 2-5 years, at baseline and three months post initiation of ETI. We collected FE-1, PERT dose, genotype, prior modulator use, and anthropometry. PI was classified as (µg/g stool): &lt;100 severe, 100-200 moderate, &gt;200 Pancreatic Sufficient (PS). High PERT dose (units/lipase/kg/day) &gt;10,000 as per ECFS guideline(2). Moderate PERT dose classified as 3,000-9,999, &lt;3,000 low dose. Data were analysed using R 4.4.2, comparisons by Wilcoxon signed rank test and Chi-squared test.</div></div><div><h3>Results</h3><div>Twenty nine children were included, 18 homozygous dF508, 11 heterozygous dF508, 12 were Modulator-Naïve (MN). Mean (sd) age 4.1 (1.1)y at ETI initiation, BMI z-score 0.22(0.8). Paired FE-1 (median, IQR) was obtained in 28 children and increased from 15(0) µg/g to 15(4) µg/g, p=0.057. Categorical PERT doses were not significantly reduced (p=0.061), 5 children reduced from high to moderate, 4 children reduced from moderate to low, and 1 child became PS (not MN).</div></div><div><h3>Conclusions</h3><div>We demonstrate a small increase in FE-1 in the 2-5 year old children in our centre three months after starting ETI. PERT doses were not reduced. Our findings should be interpreted in the context of a small study size, risk of type I error, and the subjective nature of recording PERT administration. These data may add to the emerging evidence that early life administration of ETI has the potential to modify pancreatic function. Iterative data collection is ongoing in our centre.</div><div>1. Davies JC <em>et al.</em> Lancet Resp Med 2016</div><div>2. Wilschanski M <em>et al.</em> Clin Nutr 2024</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S24-S25"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204954","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}