Journal of Cystic Fibrosis最新文献

{"title":"WS15.01Post-lung transplant survival for people with cystic fibrosis before and during the elexacaftor/tezacaftor/ivacaftor era","authors":"K.J. Ramos ,&nbsp;A. Anand ,&nbsp;M.C. Bradford ,&nbsp;D. Young ,&nbsp;T. Milinic ,&nbsp;O.J. McElvaney ,&nbsp;C.H. Goss ,&nbsp;S.G. Kapnadak","doi":"10.1016/j.jcf.2025.03.576","DOIUrl":"10.1016/j.jcf.2025.03.576","url":null,"abstract":"<div><h3>Objective</h3><div>Evaluate survival outcomes after lung-transplant (LTx) for people with cystic fibrosis (CF) in the United States (US) before and after the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). Published US CF Foundation Patient Registry (CFFPR) data showed that almost half of LTx recipients were prescribed ETI prior to LTx in 2020-2022. At the 2024 North American CF Conference, the Toronto Program presented reduced survival for LTx recipients with CF in the ETI era.</div></div><div><h3>Methods</h3><div>LTx recipients with CF between Oct 1, 2016 and Dec 31, 2022 were identified using the Scientific Registry of Transplant Recipients dataset (the US national transplant registry), with follow-up through Jan 2024. Prior to the European CF Society annual scientific meeting, data will be linked with the CFFPR to allow for determination of ETI status for recipients at the time of LTx. Pre-ETI era was defined as Oct 1, 2016 to Sept 30, 2019 (ETI FDA-approved in the US in Oct 2019). We summarized demographics in both eras using descriptive statistics and calculated Kaplan-Meier estimates of one-year survival after LTx by transplant year, starting in Jan 2017.</div></div><div><h3>Results</h3><div>There were 803 LTx recipients with CF, 637 in the pre-ETI era and 166 in the ETI era. Recipients were 47% male, 95% White, 4% Black, and 7% Hispanic compared to 54%, 92%, 7%, and 14% in the pre-ETI vs ETI era, respectively. The proportion with Medicaid insurance increased from 20% to 27% between eras. The median (IQR) age was 31 years (25-38) pre-ETI and 31 years (25-40) in the ETI era. Qualitative assessment of 1-year survival estimates showed a decline in survival in the ETI era, which was most pronounced in 2021 (Table).</div></div><div><h3>Conclusions</h3><div>Post-transplant survival for people with CF may have worsened in the ETI era. There are shifts in some patient characteristics but not significantly older age. Understanding whether survival estimates differ for people on ETI vs. not prescribed ETI at the time of LTx is a critical next step.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S29-S30"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WS16.01Elucidating the pathogenesis of cystic fibrosis-related diabetes with induced pluripotent stem cells","authors":"I. Khondaker,&nbsp;D. Prasca-Chamorro,&nbsp;S.H. Park,&nbsp;M. Cao,&nbsp;J. Rapalo-Guarrero,&nbsp;D. Betancourth,&nbsp;G. Bao","doi":"10.1016/j.jcf.2025.03.582","DOIUrl":"10.1016/j.jcf.2025.03.582","url":null,"abstract":"<div><h3>Objectives</h3><div>Diabetes is the most common comorbidity of Cystic Fibrosis (CF), affecting nearly 50% of adult CF patients and severely worsening CF related disease mortality. While the root cause of CF-related diabetes (CFRD) is a mutation in the <em>CFTR</em> gene, the molecular mechanisms leading to CFRD are unclear, largely due to a lack of models that faithfully recapitulate human disease. The overall objectives of this study are to establish induced pluripotent stem cell (iPSC) derived islets (SC-islets) as a novel model for CFRD disease study and determine the consequence of the <em>CFTR</em> mutation in islet endocrine cell types.</div></div><div><h3>Methods</h3><div>iPSCs with <em>G542X/G542X</em> or <em>F508del/F508del CFTR</em> mutations (CF-iPSCs) were differentiated to SC-islets alongside wild-type (WT) H1 stem cells. SC-islet differentiation efficiency and hormone secretion were quantified with intracellular flow cytometry and enzyme linked immunosorbent assays (ELISAs).</div></div><div><h3>Results</h3><div><em>G542X</em>-, <em>F508del</em>-, and H1-SCs differentiate to NKX6.1+/INS+ beta cells with 39±3%, 39±3%, and 42±2% efficiency, and GCG+/INS- alpha cells with 19±2%, 19±1%, and 35±4% efficiency respectively. <em>G542X</em>-, <em>F508del</em>-, and H1-beta cells are glucose responsive <em>in vitro</em> and secrete insulin at 1.8±0.4, 1.6±0.3, and 1.8±0.4 mIU/ml/10³ cells in high (20 mM) glucose conditions. <em>G542X</em>-, <em>F508del</em>-, and H1-alpha cells secrete 0.060±0.003, 0.84±0.24, and 0.70±0.12 pmol/L/10³ cells at low (2 mM) glucose conditions.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that CF-iPSCs differentiate to alpha and beta cells, and that there is no significant difference in insulin secretion for CF SC-islets and H1 SC-islets <em>in vitro</em>. Notably, our results show that <em>G542X</em>-islets secrete significantly lower glucagon at low glucose conditions compared to <em>F508del</em>- and H1-islets. Overall, these studies suggest a role for CFTR in alpha cell function and establish SC-islets as a novel and valuable model for studying CFRD.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S31"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205376","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":"WS07.02Investigating imaging biomarkers in cystic fibrosis preschoolers using manual and Artificial intelligence-based algorithms","authors":"P. Raut ,&nbsp;M. Bonte ,&nbsp;B. Manai ,&nbsp;P. Makani ,&nbsp;D. Caudri ,&nbsp;H.M. Janssens","doi":"10.1016/j.jcf.2025.03.529","DOIUrl":"10.1016/j.jcf.2025.03.529","url":null,"abstract":"<div><h3>Introduction</h3><div>Monitoring structural lung changes in preschoolers with cystic fibrosis (PrewCF) is challenging, but CT could be used to quantify structural lung changes. This study evaluates and compares manual vs automated image analysis tools as possible sensitive biomarkers in PrewCF.</div></div><div><h3>Methods</h3><div>76 Erasmus MC-Sophia PrewCF (1-5 yrs) were included, with 177 CT's. Manual PRAGMA-CF score include %Bronchiectasis (%BE), %Mucus plugging (%MP), %Airway wall thickening (%AWT), and overall %Disease (%DIS). With the AI-based LungQ^TM platform (Thirona) automated PRAGMA-AI was used to calculate %BE, %AWT and %DIS. Bronchial dimensions were assessed with the Bronchus-Artery (BA) method, and number of mucus plugs with the Mucus plugging (MP) algorithm. Manual and automated outcomes were compared using correlation, ICC and multivariable regression. Finally, progression over time was evaluated in 41 PrewCF with &gt;1 CT scans using both methods.</div></div><div><h3>Results</h3><div>All 177 CT's were scored manually, 126 (71%) also processed successfully with LungQ (free-breathing: 64%; inspiratory: 98%). AWT was the most prevalent abnormality. Correlations between manual and automatic PRAGMA analysis were strong for %DIS (0.67, CI:0.56-0.75, p&lt;0.001), moderate for %BE (0.53, CI:0.39-0.65, p&lt;0.001) and %AWT (0.59, CI:0.46-0.69, p&lt;0.001). ICC's showed good agreement for %DIS (0.77, CI:0.69-0.83), moderate for %AWT (0.58, CI:0.42-0.70) and weak for %BE (0.35, CI:0.18-0.50). In a backward stepwise multivariable model automated outer bronchial diameter (Bout/A ratio; β=2.54, p=0.01) and mucus plugs (β=0.18, p&lt;0.001) remained independent significant predictors of manual %DIS. Significant progression over time was detected using the manual %DIS and %AWT, as well as automated %DIS and bronchial wall thickness (Bwt/A ratio).</div></div><div><h3>Conclusion</h3><div>Both manual and automated CT analysis are feasible in PrewCF and methods show reasonable agreement. Both methods were able to detect significant disease progression over a 2-4 year period</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S14"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203903","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":"WS01.04Elexacaftor/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}