Journal of Cystic Fibrosis最新文献

{"title":"47 Disruptions in mannitol metabolism lead to diagnostic evasive Staphylococcus aureus in cystic fibrosis patients","authors":"T. Zaputil, J. Zapata, A. Rozen, A. Fischer","doi":"10.1016/S1569-1993(25)01666-2","DOIUrl":"10.1016/S1569-1993(25)01666-2","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S23"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189935","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":"23 Mycobacteria acquisition from potable water across the drinking water system in Australia","authors":"K. Ramsay, K. Smith, C. Duplancic, S. Taylor, G. Rogers, C. Wainwright, R. Thomson, S. Bell","doi":"10.1016/S1569-1993(25)01643-1","DOIUrl":"10.1016/S1569-1993(25)01643-1","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S12a-S13"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190088","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":"Letter to the editor: Semaglutide-associated recurrent distal intestinal obstruction in cystic fibrosis.","authors":"Rita Kamoua, Kristen Paradine, Luke McCoy","doi":"10.1016/j.jcf.2025.09.007","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.09.007","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199468","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 pancreatic function recovery and fluctuation in young children with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor.","authors":"Laura Schembri, Delyth Jones, Siân Bentley, Siobhán Carr, Ian Balfour-Lynn","doi":"10.1016/j.jcf.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.09.004","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials showed improved faecal elastase (FE-1) levels in younger children with cystic fibrosis (cwCF) on elexacaftor/tezacaftor/ivacaftor (ETI). Lower sweat chloride has been linked to better clinical outcomes in people with CF. Our previous work showed increased vitamin A levels in cwCF aged 5-15 years. We aimed to evaluate changes in FE-1 and vitamin levels and explore associations between sweat chloride and FE-1, in 2-6-year-olds starting ETI in a real-world setting.</p><p><strong>Methods: </strong>In a large UK paediatric specialist CF centre, cwCF newly eligible for ETI when UK licensing age decreased to 2 years were included. Baseline vitamin A, D, E and FE-1 levels were collected retrospectively. Post ETI, FE-1, vitamin and sweat chloride levels were collected prospectively.</p><p><strong>Results: </strong>51/68 eligible patients were included. Median age on starting ETI was 4.1 (range 2.0-6.5) years. 12/43 (28 %) of pancreatic insufficient (PI) patients became pancreatic sufficient (PS) 6 months after ETI (p = 0.0005); 3 reverted to PI by 12 months, and 1 other patient became PS by 12 months. Enzymes were reduced or stopped for most children who became PS. Change in FE-1 negatively correlated with post ETI sweat chloride level (Spearman's ρ -0.49, p = 0.007). There was a significant increase in median vitamin D levels (p = 0.007) but no significant changes in vitamins A or E; particularly, high vitamin A levels were not seen.</p><p><strong>Conclusions: </strong>Reversal of PI appears possible in preschool cwCF, but may not be sustained. Enzyme adjustments should be made cautiously, and monitoring of symptoms and FE-1 continued.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080470","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 drug interaction between rifabutin and elexacaftor/tezacaftor/ivacaftor (ETI).","authors":"Madeline Sanders, Eunjin Hong, Peter S Chung, Adupa P Rao, Whitaker Cohn, Paul Beringer","doi":"10.1016/j.jcf.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.09.002","url":null,"abstract":"<p><strong>Background: </strong>Rifampin is a guideline-recommended treatment for nontuberculous mycobacteria infections; however, it is a strong inducer of CYP3A metabolism and therefore is contraindicated in patients receiving elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA; ETI). Rifabutin (RFB), a moderate CYP3A inducer, is a potential therapeutic alternative to rifampin. A prospective, single-arm study was conducted in healthy volunteers to evaluate the effect of RFB on ETI pharmacokinetics (PK) (NCT04840862, 2022-05-09).</p><p><strong>Methods: </strong>Six adults received a single dose of ETI (100 mg/50 mg/75 mg). After a washout, subjects received 2 weeks of RFB 300 mg daily followed by a second single ETI dose. The data were analyzed using noncompartmental PK.</p><p><strong>Results: </strong>The maximum plasma concentration (C_max) and area under the curve (AUC_0-∞) values following ETI alone were consistent with published data. Both C_max and AUC_0-∞ values were significantly reduced with concomitant RFB as expected. The AUC_0-∞ geometric mean ratios (GMR, 90% CI) with RFB vs. alone were: ELX (0.45, 0.35-0.58), TEZ (0.68, 0.56-0.82), and IVA (0.60, 0.45-0.78). Importantly, the AUC_0-∞ GMR for IVA with RFB is significantly higher than published data with rifampin. While these data suggest ETI dose adjustment may be needed, population compartmental modeling using standard ETI dosing indicates plasma concentrations remain above half-maximal effective concentration (EC₅₀) values, supporting maintained efficacy. RFB significantly altered IVA metabolite-to-parent ratios, but the reduced activity of M1-IVA suggests limited clinical significance.</p><p><strong>Conclusions: </strong>RFB alters ETI PK, but to a lesser extent than rifampin. These data indicate that a clinical trial evaluating the efficacy and safety of ETI with concomitant rifabutin treatment is warranted.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075328","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":"Elafin expression is regulated by CFTR-mutation and TGFβ₁ in human bronchial epithelial cells.","authors":"Jan Christoph Thomassen, Christina Vohlen, Ernst Rietschel, Miguel A Alejandre Alcazar, Silke van Koningsbruggen-Rietschel","doi":"10.1016/j.jcf.2025.08.016","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.08.016","url":null,"abstract":"<p><strong>Background: </strong>Cystic Fibrosis (CF) lung disease is characterized by inflammation and progressive matrix remodeling. These processes are influenced by genetic modifiers such as Transforming Growth Factor β₁, (TGFβ₁₎ which is enhanced by an imbalance of proteases, e.g. neutrophile elastase (NE) and its inhibitor elafin. Elevated TGFβ₁ concentrations in sputum are linked to impaired lung function in people with CF (pwCF); and decreased elafin levels in sputum are associated with P. aeruginosa infection. The direct influence of CFTR-mutations and the impact of TGFβ₁ on the expression of elafin has not yet been examined. Therefore, we investigated (1) the direct impact of the CFTR-mutation itself on elafin expression, (2) the interaction of TGFβ₁ and CFTR-mutation on elafin expression, and (3) the effect of inhibiting TGFβ₁ on the expression of elafin in human bronchial epithelial cells (HBE).</p><p><strong>Methods: </strong>(1) Gene expression of elafin was measured by qRT-PCR and ELISA in CFTR-diseased (delF508 homozygous; CF-DHBE) and wildtype HBE cells (NHBE). (2) CF-DHBE and NHBE were stimulated with TGFβ₁ or vehicle and finally (3) TGFβ₁ was inhibited by Pirfenidone/SB43. Gene expression of elafin and inflammatory mediators, as well as inhibitors of proteases were analyzed by qRT-PCR or immunoblot.</p><p><strong>Results: </strong>(1) mRNA and protein expression of elafin is significantly reduced in CFTR-mutated HBE when compared to NHBE cells. (2) Furthermore, the expression of elafin is inhibited by the genetic modifier TGFβ₁. (3) Inhibition of TGFβ₁ induced elafin expression in CF-DHBE cells and abrogated the CFTR- TGFβ₁ mediated inhibitory effect in HBE.</p><p><strong>Conclusions: </strong>Our study shows that CFTR-mutation itself mediates effects on the homeostasis of proteases by reducing the expression of elafin. Furthermore, the exposure to high TGFβ₁ concentrations increases the CFTR-mutation mediated reduction of elafin expression. Restoring elafin levels and/or inhibiting TGFβ₁ might be possible therapeutic options to reduce pulmonary inflammation and remodelling in CF.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064806","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":"Prevalence and production of superantigen exotoxins by cystic fibrosis Staphylococcus aureus isolates.","authors":"Ying Sun, Buqu Hu, Sahil Chhabra, Jade Tolentino, Nina Suzuki, Jesse Natarajan, Colleen Bianco, Paul Planet, Shardulendra P Sherchand, Rajan Adhikari, Javad Aman, Jon Koff, Govindarajan Rajagopalan","doi":"10.1016/j.jcf.2025.08.020","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.08.020","url":null,"abstract":"<p><p>Staphylococcus aureus (SA) is the most common cystic fibrosis (CF) lung pathogen that is uniquely capable of producing superantigen (SAg) exotoxins, which are recognized as the most potent activators of the immune system and inducers of inflammation. Herein, we analyzed the distribution of SA-SAgs among pediatric and adult CF clinical isolates. We then investigated the production of biologically active SA-SAgs by some of these clinical isolates and tested the stability of SA-SAg in CF sputum. We demonstrate that 60-80 % of pediatric and adult CF SA isolates carried at least one SA-SAg gene, with the former harboring potent SA-SAgs (Staphylococcal enterotoxin A and B) more frequently (30-60 %) which may explain why the presence of SA associates with poorer respiratory outcomes in pediatric CF. Biofilms of clinical SA isolates readily produced biologically active SA-SAgs in artificial sputum medium and purified SA-SAgs retained their bioactivity in human CF sputum in vitro. Further, the immunostimulatory potential of the CF SA isolates depended on their SAg profile. Overall, our study confirms that SA-SAgs are widely prevalent in CF SA isolates. However, the immunostimulatory potential of these isolates varied depending on their SAg profile which may explain the heterogeneity in clinical presentation of CF lung disease.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053693","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":"Routine cell-free DNA prenatal screening identifies pregnancies at high risk for cystic fibrosis that may benefit from fetal therapy.","authors":"J Wynn, S Rego, D Chandler-Brown, R Carter, A Talati, M Zaretsky, A Trimble","doi":"10.1016/j.jcf.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.08.004","url":null,"abstract":"<p><p>Recent improvements in cell-free DNA technology have enabled non-invasive prenatal testing (NIPT) to screen for fetal single-gene autosomal recessive conditions from maternal blood as early as the first trimester. This technique can determine the fetal risk for cystic fibrosis (CF) with a single blood sample from a pregnant person without the need for a partner sample, which is required for traditional carrier screening. A retrospective review of 100,106 consecutive general-risk pregnant patients who underwent CF carrier screening was completed. All positive CF carriers underwent cell-free DNA testing, which reported a risk of the fetus being affected with CF. Pregnancies with at least a 1 in 4 risk were classified as high risk. Results of confirmatory testing were solicited from all high-risk cases, and a random sample of 50 % of low-risk cases were used to compute test performance analytics. The study cohort included 2,587 CF carriers and 20 cases with high-risk cell-free DNA results where the CF-affected status of the fetus/neonate was known, of which 13 were affected. All cases (n = 8) with a 9 in 10 cell-free DNA estimated risk were affected. The assay correctly identified all known affected fetuses as high risk (sensitivity of 100 %). Of the 13 affected, 12 cases had at least one CFTR variant eligible for CFTR modulator therapy. Additionally, 75 % of all cell-free DNA fetal risk results were returned before 18.5 weeks gestation, providing ample time for diagnostic testing and initiation of in utero treatment if indicated. Carrier screening with reflex to cell-free DNA analysis provides a personalized fetal risk assessment and efficient turnaround times at an early gestational age, without the need for a partner sample for a general risk population. This screening method can precisely guide prenatal diagnostic testing to identify CF-affected fetuses that may benefit from in utero therapy.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015438","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":"COVID-19 in people with Cystic Fibrosis beyond the pre-omicron era: a prospective study with a specific focus on long COVID.","authors":"Carla Colombo, Paola Medino, Marco Cipolli, Francesca Lucca, Giulia Cucchetto, Federico Alghisi, Fabiana Ciciriello, Angela Sepe, Camilla Romano, Giovanni Taccetti, Michela Francalanci, Maura Ambroni, Valentina Donati, Giovanna Pizzamiglio, Maura Spotti, Novella Rotolo, Maria Cristina Lucanto, Simona Cristadoro, Francesca Ficili, Giuseppina Leonetti, Paola Giordano, Elisabetta Bignamini, Elvira Rizza, Giovanna Pisi, Valentina Fainardi, Rosaria Casciaro, Clelia Formigoni, Mirco Ros, Isabella Comello, Piercarlo Poli, Pamela Vitullo, Barbara Messore, Luca Riberi, Nicola Palladino, Chiara Rosazza, Gianfranco Alicandro, Francesco Blasi","doi":"10.1016/j.jcf.2025.08.015","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.08.015","url":null,"abstract":"<p><strong>Background: </strong>The long-term clinical consequences of COVID-19 in cystic fibrosis (CF) remain largely unexplored. This study aimed to assess the incidence of long COVID in a large population of people with CF.</p><p><strong>Methods: </strong>This prospective, multicentre study enrolled individuals with confirmed SARS-CoV-2 infection between July 2021 and October 2022. Data collected included clinical features prior to infection, symptoms during the acute phase, hospitalization and symptom persistence after 1 and 6 months. Long COVID was defined according to CDC criteria as persistence of at least one COVID-related symptom for one or more months after diagnosis. The mean variation of FEV₁ recorded 6 months after acute infection was also evaluated.</p><p><strong>Results: </strong>A total of 1102 people with CF were recruited (median age: 18 years, 520 younger than 18). The infection was symptomatic in 90.1 % of cases. During the acute phase, 8 subjects required oxygen support; 31 were hospitalized, one patient required intensive care. Complications included one thromboembolic event and two episodes of myocarditis, but no patient died. Mean variation of FEV₁ after 6 months from the infection was +1.8 % (95 % CI: 1.0-2.7). Long COVID was documented in 64 subjects (5.8 %, 95 % CI: 4.5-7.4) with a variety of symptoms which were still present in 12 cases 6 months after infection (1.1 %, 95 % CI: 0.6-1.9).</p><p><strong>Conclusions: </strong>In the omicron phase of the pandemic, COVID-19 was relatively mild and did not negatively impact pulmonary function after 6 months. Long COVID was observed at all ages, but extrapulmonary symptoms were more frequent and persistent in adults.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000625","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":"Association between inhaled antibiotic use and treatment-emergent organisms among Canadian people with cystic fibrosis","authors":"Jonathan D. Cogen ,&nbsp;Eric Zhang ,&nbsp;Jane She ,&nbsp;Michael R. Kosorok ,&nbsp;Stephanie Y. Cheng ,&nbsp;Marianne S. Muhlebach","doi":"10.1016/j.jcf.2025.04.007","DOIUrl":"10.1016/j.jcf.2025.04.007","url":null,"abstract":"<div><h3>Background</h3><div>Inhaled antibiotics are frequently used as chronic <em>Pseudomonas aeruginosa</em> (Pa) suppressive therapy among people with cystic fibrosis (PwCF). However, their use might increase the risk of developing treatment-emergent respiratory organisms. This study aimed to describe the proportion of PwCF utilizing inhaled antibiotics, determine factors associated with inhaled antibiotic prescription, and determine if chronic inhaled antibiotic use is associated with an increased risk of <em>Aspergillus fumigatus, Stenotrophomonas maltophilia,</em> or <em>Achromobacter</em> spp.</div></div><div><h3>Methods</h3><div>This retrospective cohort study utilized Canadian CF Registry data. Pa status (chronic, intermittent, and negative) was defined per calendar year. The risk of developing <em>A. fumigatus, S. maltophilia</em>, or <em>Achromobacter</em> spp was compared between PwCF prescribed versus not prescribed inhaled antibiotics, adjusting for confounding by indication using inverse probability of treatment weighting.</div></div><div><h3>Results</h3><div>This analysis included data from 2800 PwCF. &gt;75 % of PwCF with chronic Pa were prescribed inhaled antibiotics, while up to 13 % of PwCF negative for Pa received inhaled antibiotics during the study period. There was an increased risk of developing <em>A. fumigatus</em> among PwCF with intermittent Pa (HR 1.43, 95 %CI; 1.08–1.88; <em>p</em> = 0.01) and who were Pa negative (HR 2.44, 95 %CI; 1.65–3.61; <em>p</em> &lt; 0.001), but not for PwCF with chronic Pa (HR 1.36, 95 %CI; 0.94–1.95; <em>p</em> = 0.10). No association was seen between inhaled antibiotics and developing either <em>S. maltophilia</em> or <em>Achromobacter</em> spp.</div></div><div><h3>Conclusions</h3><div>Inhaled antibiotic use among Canadian PwCF was associated with an increased risk of <em>A. fumigatus</em> acquisition but not <em>S. maltophilia</em> or <em>Achromobacter</em> spp. Prospective studies are needed to better define this association.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 5","pages":"Pages 843-848"},"PeriodicalIF":6.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020758","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}