Journal of Cystic Fibrosis最新文献

{"title":"Characteristics of individuals with cystic fibrosis in the United States ineligible for ivacaftor and elexacaftor/tezacaftor/ivacaftor","authors":"Don B. Sanders ,&nbsp;Nicole Mayer-Hamblett ,&nbsp;Margaret Rosenfeld ,&nbsp;Deepika Polinieni ,&nbsp;Elliott Dasenbrook ,&nbsp;Rhonda Szczesniak ,&nbsp;Elizabeth A. Cromwell","doi":"10.1016/j.jcf.2024.07.015","DOIUrl":"10.1016/j.jcf.2024.07.015","url":null,"abstract":"<div><h3>Background</h3><div>We characterized people with cystic fibrosis (CF) ineligible by genotype (not age) for currently approved CFTR modulator therapy using data from the US CF Foundation Patient Registry (CFFPR).</div></div><div><h3>Methods</h3><div>We summarized clinical characteristics using CFFPR data from 2017 to 2022. Annual rate of change in percent predicted of forced expiratory volume in one second (ppFEV₁) was estimated using generalized estimating equations.</div></div><div><h3>Results</h3><div>A total of 2,790 individuals with CF met inclusion criteria. In 2022, 12 % were less than 6 years old, 16 % were age 6–12 years, 18 % age 12–18 years and 54 % were ≥18 years. The proportion identified as White was 74 %, 17 % Black, and 26 % as Hispanic. The median (IQR) age at diagnosis was 1.2 (0.5, 9.1) months for children and 3.1 (0.3, 17.4) years for adults. Median (IQR) ppFEV₁ among children was 91.9 (80.3; 102.4) and among adults, 74.3 (52.4; 90.4). Pancreatic enzymes were prescribed for 77.8 %. Population-level average (95 % CI) rates of decline in ppFEV₁ among the pancreatic insufficient population was -1.5 per year (-1.8; -1.2) for ages 6 to &lt;11 years, -2.2 per year (-2.6; -1.8) for ages 12 to &lt;18 years, and -1.5 per year (-1.7; -1.3) for adults.</div></div><div><h3>Conclusions</h3><div>We describe the CFTR modulator ineligible population in the US in 2017–2022. With a growing pipeline of therapies aimed at improving CFTR function for those who cannot benefit from modulators due to ineligibility, characterization of both the size and outcomes of these populations are critical to inform optimal clinical development plans and future clinical trials.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 255-262"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855668","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}

{"title":"Using heart rate data from wrist worn activity trackers to define thresholds for moderate to vigorous physical activity in children and young people with cystic fibrosis","authors":"Gizem Tanriver ,&nbsp;Sanja Stanojevic ,&nbsp;Nicole Filipow ,&nbsp;Helen Douglas ,&nbsp;Emma Raywood ,&nbsp;Kunal Kapoor ,&nbsp;Gwyneth Davies ,&nbsp;Nicky Murray ,&nbsp;Rachel O'Connor ,&nbsp;Elisabeth Robinson ,&nbsp;Eleanor Main","doi":"10.1016/j.jcf.2024.10.014","DOIUrl":"10.1016/j.jcf.2024.10.014","url":null,"abstract":"<div><h3>Background</h3><div>Children and young people with cystic fibrosis (CYPwCF) are encouraged to do an average of 60 min of moderate-to-vigorous physical activity (MVPA) daily. However, there are no agreed heart rate (HR) thresholds for defining MVPA, so it is difficult to ascertain whether these targets are actually achieved. Wearable activity trackers enable continuous monitoring of fitness-related measures such as HR and could be used to measure duration and intensity of habitual MVPA. We aimed to define personalized and responsive MVPA thresholds from HR in CYPwCF, to determine habitual time spent in MVPA during childhood and adolescence.</div></div><div><h3>Methods</h3><div>Continuous daily HR data were collected from 142 CYPwCF wearing activity trackers over 16 months. Linear mixed-effects models were used to develop personalised estimates of resting heart rate (RHR), peak heart rate (PHR) and MVPA thresholds, which were defined using the American College of Sports Medicine heart rate reserve (HRR) method.</div></div><div><h3>Results</h3><div>309,926 days of physical activity data showed that both RHR and PHR declined with age in CYPwCF, with considerable variability within and between individuals. The HRR method produced personalised MVPA thresholds for each CYPwCF based on age, which inherently accounted for individual demographic variability and personal factors such as cardiovascular fitness or disease severity.</div></div><div><h3>Conclusions</h3><div>By accounting for within and between person variability in RHR and PHR, our novel method provides more accurate age-related personalised MVPA thresholds for CYPwCF than existing estimates. Our findings provide population-based estimates for RHR, PHR and MVPA thresholds at different ages in CYPwCF. This approach may help guide development of international standards for objective MVPA measurement in the era of remote HR and activity monitoring and facilitate accurate measurement of habitual physical activity in children and young people.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 412-417"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604825","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}

{"title":"Letter to the Editor: Additional considerations for addressing pain in people living with cystic fibrosis","authors":"Anastasia Ward ,&nbsp;Ramil Mauleon ,&nbsp;Chee Y. Ooi ,&nbsp;Nedeljka Rosić","doi":"10.1016/j.jcf.2025.01.017","DOIUrl":"10.1016/j.jcf.2025.01.017","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 423-424"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414371","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":"The impact of pregnancy on mortality and lung function in cystic fibrosis patients.","authors":"Paul K Mohabir, Fatma Gunturkun, Jennifer Cannon, Yaowei Deng, Ariadna Garcia, Eahsan Shahriary, Alicia Mirza","doi":"10.1016/j.jcf.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.02.004","url":null,"abstract":"<p><strong>Background: </strong>As the lifespan of people with cystic fibrosis (pwCF) improves, more individuals are pursuing pregnancy. Historically, pregnancy was not recommended in this population; however, more recent evidence has revealed inconsistent survival and lung function outcomes. Our aim was to assess the differences in survival and lung function between pregnant and never-pregnant pwCF and to provide updated recommendations for contemporary clinical practice.</p><p><strong>Methods: </strong>In this retrospective matched parallel cohort study, data was collected from the American Cystic Fibrosis Foundation Patient Registry (CFFPR) from 1999 to 2019. 1743 adult pwCF with a reported pregnancy were matched with 1743 never-pregnant patients. Regression models were developed to estimate associations between patient characteristics, pregnancy, and outcomes. The primary endpoint was the probability of survival comparing pregnant and never-pregnant pwCF, while the secondary endpoint was lung function over time.</p><p><strong>Results: </strong>The study cohort (n = 3486) had a mean age of 24.96 years. There was no significant difference in survival probabilities between pregnant and never-pregnant pwCF (56.2 %, CI^{95 %}: 51.3 %-61.5 % vs. 55.8 %, CI^{95 %}: 52.1 %-59.7 %, p = 0.5). The multivariable time-dependent Cox regression analysis resulted in a significantly lower mortality hazard rate for pregnant cohorts (HR:0.78, p < 0.01). There was no significant association between pregnancy and lung function over time (0.99, p = 0.21).</p><p><strong>Conclusion: </strong>Pregnancy was associated with a reduced hazard of death compared to never-pregnant pwCF and did not demonstrate a significant impact on lung function. Therefore, pregnancy should not be generally discouraged in pwCF and clinicians should evaluate pregnancy risks and benefits on an individualized basis.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472532","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":"Evaluation of the response to elexacaftor-tezacaftor-ivacaftor of the rare CFTR variants L383S, I507del, L1065P and R1066H in intestinal organoid-derived epithelial monolayers.","authors":"Jessica Conti, Dora Angyal, Karina Kleinfelder, Roberta Valeria Latorre, Martina Calicchia, Alessia Farinazzo, Luca Rodella, Francesco Tomba, Arianna Massella, Luca Frulloni, Giovanni Taccetti, Vito Terlizzi, Anny Leung, Tessa A Groeneweg, Marcel J C Bijvelds, Paola Melotti, Claudio Sorio","doi":"10.1016/j.jcf.2025.02.008","DOIUrl":"10.1016/j.jcf.2025.02.008","url":null,"abstract":"<p><strong>Introduction: </strong>Cystic fibrosis (CF) is caused by mutation of the CFTR gene, encoding an epithelial anion channel. Here we evaluated the effect of the modulator combination elexacaftor-tezacaftor-ivacaftor (ETI) on the function of four rare, poorly characterized CFTR variants: L383S, I507del, L1065P and R1066H.</p><p><strong>Methods: </strong>Intestinal organoids were obtained from subjects carrying the CFTR variants L383S, I507del, L1065P or R1066H in trans of a minimal function allele (class I mutation). Organoids and epithelial monolayers were used to assess the effect of ETI on CFTR protein abundance and CFTR-mediated chloride, bicarbonate, and fluid transport.</p><p><strong>Results: </strong>In L383S-CFTR expressing cells, normal levels of fully glycosylated CFTR protein (C-band) were detected. In contrast, in I507del, L1065P or R1066H organoids, only partially glycosylated CFTR (B-band) was detected. Chloride/bicarbonate transport was severely impaired in epithelial monolayers prepared from these latter three variants, while anion transport of the L383S variant was affected to a moderate extent. ETI, but not ivacaftor alone, significantly enhanced CFTR-mediated chloride and bicarbonate transport in L1065P and R1066H monolayers, and stimulated fluid transport. A corresponding increase in the abundance of C-band protein was observed in both variants. ETI also modestly improved L383S-CFTR function, with a marginal effect on I507del-CFTR.</p><p><strong>Conclusions: </strong>The I507del, L1065P and R1066H variants display severely impaired function. ETI treatment markedly enhanced L1065P- and R1066HCFTR function, whereas its effect on L383S- CFTR was less pronounced. Consequently, ETI may ameliorate disease symptoms in individuals carrying the L1065P or R1066H variant. More tentative, it may also benefit those carrying the L383S variant.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468210","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":"Evaluation of clinical practice guidelines on treatment of cystic fibrosis: A systematic review.","authors":"Yuting Huang, Jingxuan Zhang, Mianquan Zhang, Xuetao Kong, Zhufeng Wang, Yuxiang Zhang, Zhili Zou, Zhuyinjun Zong, Jiaying Guo, Quanzhen Liu, Jing Ling, Wangji Zhou, Xueqi Liu, Jie Liu, Xinlun Tian, Mei Jiang","doi":"10.1016/j.jcf.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.02.005","url":null,"abstract":"<p><strong>Background: </strong>Despite the existence of numerous clinical practice guidelines (CPGs) for cystic fibrosis (CF), there is limited understanding of their credibility and consistency. This systematic review aims to comprehensively evaluate the quality of CPGs for CF and its pulmonary complications, focusing on treatment recommendations for pulmonary care.</p><p><strong>Methods: </strong>We conducted a comprehensive search across four databases and relevant websites to identify eligible guidelines providing treatment recommendations. The quality of these guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. Pulmonary treatment recommendations were analyzed and synthesized narratively.</p><p><strong>Results: </strong>A total of 35 guidelines were identified. Most guidelines were of moderate quality according to the AGREE II instrument, with overall scores ranging from 21·05 to 76·13. Only six guidelines were recommended for use. These guidelines provide 359 pulmonary treatment recommendations for seven primary therapies and others. There was inconsistency in the use of airway clearance therapy, anti-inflammatories, antibiotics, inhaled drugs, and cystic fibrosis transmembrane conductance regulator modulator therapy. Four guidelines conditionally advocated for oral corticosteroids, while six opposed routine inhaled corticosteroids. One guideline discouraged lumacaftor-ivacaftor in the general CF population, two recommended only for children under 12 years old, and another strongly advocated for children between 2 and 5 years of age. However, one guideline noted a lack of evidence to recommend it for children under 6.</p><p><strong>Conclusion: </strong>The quality of CPGs for CF and its pulmonary complications has improved over time, reaching a moderate level generally, but there is still room for further improvement. Future efforts should focus on standardizing methodological frameworks and generating robust clinical evidence to enhance the overall quality and applicability of CF guidelines.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433253","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":"CF airway epithelia display exaggerated host defense responses and prolonged cilia loss during RSV infection.","authors":"Jennifer A Bartlett, Eric D Huntemann, Sateesh Krishnamurthy, Stacey M Hartwig, Alvin Pewa, Andrew L Thurman, Michael S Chimenti, Eric B Taylor, Steven M Varga, Paul B McCray","doi":"10.1016/j.jcf.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.02.003","url":null,"abstract":"<p><strong>Background: </strong>In individuals with cystic fibrosis (CF), respiratory viral infections frequently result in hospitalization and have been linked to secondary bacterial infection and colonization, highlighting viral infections as possible contributors to CF lung disease progression. We hypothesized that expression of antiviral host defense genes is dysregulated in CF airway epithelia.</p><p><strong>Methods: </strong>We infected primary CF and Non-CF airway epithelia with respiratory syncytial virus (RSV) and characterized their responses at 12 hr, 24 hr, 48 hr, 72 hr, and 120 hr post infection (hpi) by RNA sequencing (RNAseq).</p><p><strong>Results: </strong>Our analysis revealed strikingly different gene expression profiles for the CF and Non-CF epithelia over the course of the infection. While both CF and Non-CF cells exhibited an early signature for interferon signaling and antiviral defense pathways, this response was relatively exaggerated and sustained in CF epithelia. We also observed, in both genotypes, a transient downregulation of cilia-associated genes and loss of ciliary activity by 72 hpi. Interestingly, recovery of cilia activity was delayed in the CF epithelia.</p><p><strong>Conclusions: </strong>These findings further our understanding of innate immune dysfunction in the CF airway epithelium and suggest that virus-induced cilia injury may further compromise host defenses in CF airways.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433200","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":"Cardiovascular function in people with cystic fibrosis on Elexacaftor/Tezacaftor/Ivacaftor: A cross-sectional, observational, single-centre study.","authors":"Lauren J Clayton, Anthony I Shepherd, Jo Corbett, Maria Perissiou, Gary Connett, Julian Legg, Mark Allenby, Thomas Daniels, Don S Urquhart, Kelly A Mackintosh, Melitta A McNarry, Zoe L Saynor","doi":"10.1016/j.jcf.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.02.001","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) has been associated with impaired cardiovascular and endothelial function. CF transmembrane conductance regulator (CFTR) modulator therapy, most recently Elexacaftor/Tezacaftor/Ivacaftor (ETI), has led to improved CFTR function and life expectancy. However, the rising prevalence of obesity in adults is concerning. This study assessed the micro- and macrovascular endothelial function, cardiovascular disease (CVD) risk factors, and physical activity (PA) profiles in people with CF (pwCF) on ETI compared to healthy matched controls.</p><p><strong>Methods: </strong>In 15 pwCF and 15 age- and sex-matched controls, microvascular endothelial function (via transdermal delivery of insulin [INS] and acetylcholine [ACh] on the forearm), macrovascular endothelial function (via flow-mediated dilation [FMD] of the brachial artery), central haemodynamic parameters, including heart rate (HR), stroke volume index (SVi) and cardiac output index (Q̇I) (via thoracic impedance cardiography), body mass index (BMI), blood pressure (BP), and accelerometer-assessed PA were measured.</p><p><strong>Results: </strong>There were no differences in INS or FMD-mediated vasodilation between the groups (P > 0.05). However, a reduced vasodilatory response was evident in pwCF following ACh-mediated vasodilation (P = 0.01) and FMD normalised for shear rate (P = 0.03). No differences in resting HR, SVi, Q̇I, BP, BMI or PA were found (P > 0.05).</p><p><strong>Conclusion: </strong>This study demonstrated reduced micro- and macrovascular function in pwCF. This dysfunction may have potential health implications, particularly regarding long-term cardiovascular risk and further longitudinal assessments are warranted.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433186","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":"Non-invasive evaluation of steatosis and fibrosis in the liver in adults patients living with cystic fibrosis.","authors":"Ana Piñar-Gutiérrez, Esther Quintana-Gallego, Pablo J Remón-Ruiz, Ángeles Pizarro, Irene González-Navarro, Andrés Jiménez-Sánchez, Silvia García-Rey, María Del Carmen Roque-Cuéllar, Sheila Gato, Inmaculada Domínguez, Francisco Javier Castell, Manuel Romero-Gómez, Pedro Pablo García-Luna","doi":"10.1016/j.jcf.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.02.007","url":null,"abstract":"<p><strong>Background & aims: </strong>Cystic fibrosis hepatobiliary involvement is a heterogeneous and systemic entity. The primary objective was to determine the prevalence of steatosis, by magnetic resonance-proton density fat fraction (MR-PDFF), and liver fibrosis, by magnetic resonance elastography (MRE), in a cohort of adults with cystic fibrosis. The secondary objective was to determine the diagnostic yield of widely available non-invasive liver markers for steatosis and fibrosis, and vibration controlled transitional elastography (VCTE) releasing Control Attenuation Parameter (CAP) (dB/m) and stiffness (kPa), with the aim of proposing a diagnostic algorithm.</p><p><strong>Methods: </strong>We conducted a cross-sectional study including 101 adult patients with cystic fibrosis seen in a multidisciplinary unit. The study encompassed a clinical evaluation, morpho-functional assessment, VCTE, non-invasive liver markers and MR-PDFF and MRE. Diagnostic accuracy was assessed using ROC curves and 2 × 2 tables.</p><p><strong>Results: </strong>MR-PDFF detected hepatic steatosis in 18 of 101 (17.8 %) patients, while MRE detected significant liver fibrosis in 15 of 101 (14.9 %). The VCTE cut-off with the best diagnostic yield, determined by the Youden index, was 222 dB/m for the presence of steatosis (AUC 0.864 (95 % CI 0.768-0.961; p < 0.001) and the VCTE cut-off was 6.65 kPa for liver fibrosis (AUC 0.951(95 % CI 0.81-1; p = 0.053). A screening algorithm for hepatic steatosis was developed using the fatty liver index (FLI) and CAP, with a negative predictive value of 83.3 %. For liver fibrosis, it was outperformed by the Hepamet Fibrosis Score (HFS) and VCTE, with a negative predictive value of 100 %.</p><p><strong>Conclusions: </strong>The prevalence of hepatic steatosis and liver fibrosis was 17.8 % and 14.9 %, respectively. VCTE alone or in combination with FLI for steatosis or HFS for fibrosis demonstrated high diagnostic accuracy. This approach effectively allows for the exclusion of steatosis and fibrosis, thereby reducing the need for MR-PDFF and MRE studies.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433255","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":"Evidence for altered immune-structural cell crosstalk in cystic fibrosis revealed by single cell transcriptomics.","authors":"Marijn Berg, Lisette Krabbendam, Esmee K van der Ploeg, Menno van Nimwegen, Tjeerd van der Veer, Martin Banchero, Orestes A Carpaij, Remco Hoogenboezem, Maarten van den Berge, Eric Bindels, Joachim G J V Aerts, Antoine Collin, Pascal Barbry, Lieke S Kamphuis, Rudi W Hendriks, Martijn C Nawijn, Ralph Stadhouders","doi":"10.1016/j.jcf.2025.01.016","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.01.016","url":null,"abstract":"<p><strong>Background: </strong>Chronic pulmonary inflammation strongly contributes to respiratory failure and mortality in patients with cystic fibrosis (pwCF). Effective anti-microbial immunity and maintaining lung homeostasis require continuous structural-immune cell communication. Whether and how this crosstalk is altered in CF remains poorly understood, obscuring potential new angles for therapy development to restore airway homeostasis in pwCF.</p><p><strong>Methods: </strong>We performed droplet-based single cell RNA-sequencing on bronchial biopsies from pwCF to investigate structural-immune cell crosstalk. Computational analyses were used to compare these data to samples obtained from healthy controls.</p><p><strong>Results: </strong>CF airway wall biopsies showed lower proportions and altered transcriptomes of basal cells, submucosal gland cells and endothelial cells, and a higher abundance of ciliated cells, monocytes, macrophages and T cells. Both B and T lymphocytes displayed aberrantly activated phenotypes with transcriptional changes linked to hypoxia and vascular endothelial growth factor signaling, indicative of crosstalk with endothelial cells. The CF lung displayed unique changes in intercellular communication potential involving ionocytes, macrophages, endothelial cells and lymphocytes. This included interactions between HLA-E on structural cells and the druggable CD94/NKG2A immune checkpoint on CD8⁺T cells.</p><p><strong>Conclusions: </strong>We report the first single cell transcriptome atlas of the CF lung containing the full spectrum of structural and immune cells, providing a valuable resource for investigating changes to cellular composition, phenotypes and crosstalk linked to CF. Our analyses highlight dysregulated basal cell function and adaptive immunity in pwCF - despite favorable responses to CFTR modulator therapy. We identify novel aspects of CF pathophysiology and potential entry points for therapeutic strategies.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414369","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}