Journal of Cystic Fibrosis最新文献

{"title":"Vitality is associated with systemic inflammation in cystic fibrosis adults on elexacaftor/tezacaftor/ivacaftor.","authors":"Jacob Gravelle, Sameer Desai, Kang Dong, Bradley S Quon","doi":"10.1016/j.jcf.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.004","url":null,"abstract":"<p><p>Fatigue is common among adults with cystic fibrosis (awCF) and may be associated with systemic inflammation. This study examines systemic inflammation, measured by C-reactive protein (CRP), and fatigue, assessed using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) vitality domain, in individuals initiating elexacaftor/tezacaftor/ivacaftor (ETI) therapy. In a cohort of 61 awCF from St. Paul's Hospital, Vancouver, CRP and vitality were measured at baseline and at 1, 3, 6, and 12 months post-ETI initiation. We observed reductions in CRP and increases in vitality over the 12-month period. Linear mixed-effects models were used to examine the relationship between CRP and vitality adjusted for age, sex, BMI, and lung function. Our findings demonstrated a significant, independent inverse association between CRP and vitality. These results highlight the potential role of systemic inflammation in influencing vitality in awCF undergoing ETI therapy. Further research incorporating additional inflammatory markers and psychosocial variables is warranted to deepen our understanding of fatigue mechanisms in this population.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of the defect distribution index to functional lung MRI of pediatric cystic fibrosis lung disease and controls.","authors":"Elisabeth Kieninger, Samal Munidasa, Marion Curdy, Carmen Streibel, Brandon Zanette, Jason Woods, Philipp Latzin, Felix Ratjen, Giles Santyr","doi":"10.1016/j.jcf.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.02.015","url":null,"abstract":"<p><strong>Introduction: </strong>Functional magnetic resonance imaging (MRI) of the lung usually assesses lung impairment as ventilation defect percentage (VDP). However, VDP only reflects the overall burden of disease and does not characterize the regional distribution (i.e. pattern) of defects. The defect distribution index (DDI) is a metric which shows quantitatively how clustered versus scattered defects are with a higher DDI indicating more clustered defects.</p><p><strong>Aim: </strong>To assess the applicability and validity of the DDI to ¹²⁹Xe-MRI and PREFUL-MRI of CF lung disease.</p><p><strong>Methods: </strong>The DDI algorithm was applied to fractional ventilation maps previously acquired with ¹²⁹Xe-MRI and PREFUL-MRI of 37 children with CF and 13 healthy controls.</p><p><strong>Results: </strong>The calculation of DDI was feasible for all MRI data. DDI was significantly higher in patients with CF compared to healthy controls (mean difference [95 % CI] ¹²⁹Xe-MRI DDI_{60 %mean} -1.94 [-2.86 - -1.02], p=0.0001), strongly correlated with other functional outcomes such as VDP and the lung clearance index, and decreased significantly in CF patients with pulmonary exacerbations after antibiotic treatment (e.g. ¹²⁹Xe-MRI DDI_{60 % mean} -1.03 [-0.44 - -1.63], p=0.002).</p><p><strong>Conclusion: </strong>The DDI is applicable to functional ¹²⁹Xe-MRI and PREFUL-MRI data providing complementary information to VDP by assessing defect distribution rather than defect size. It shows meaningful clinimetric properties and improves with treatment. The DDI shows potential as a parameter for comprehensive monitoring of CF lung disease and treatment.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse events to elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis due to elevated drug exposure?: A case series.","authors":"Syendon B C Baromeo, Renske van der Meer, Richard C J M van Rossen, Erik B Wilms","doi":"10.1016/j.jcf.2025.02.013","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.02.013","url":null,"abstract":"<p><strong>Background: </strong>Recent studies revealed that some people with cystic fibrosis (pwCF) receiving the full dose of Elexacaftor/Tezacaftor/Ivacaftor (ETI) experience adverse events (AEs), leading to discontinuation or dose adjustments of their modulator treatment. We aimed to investigate if pwCF who experienced AEs had high exposure to ETI, and to what extent dose reduction resulted in changes in exposure, side effects and efficacy.</p><p><strong>Method: </strong>This retrospective case series presents ETI exposure in pwCF who required ETI dose reduction due to AEs. ETI exposure was measured by minimal concentration (C_min) levels, while sweat chloride concentration (SCC) was used to assess efficacy. AEs were graded using the common terminology criteria for AEs. Ten pwCF who experienced AEs during ETI treatment were included in the study.</p><p><strong>Results: </strong>The mean C_min levels at the full ETI dose were 10.1 mg/L for elexacaftor, 4.2 mg/L for tezacaftor, and 1.2 mg/L for ivacaftor. These values exceed the mean C_min values from the registration studies, which are 5.5 mg/L for elexacaftor, 2.1 mg/L for tezacaftor, and 0.8 mg/L for ivacaftor. The most frequently reported AEs were psychiatric and nervous system disorders. In all ten pwCF, an improvement of AEs was noted after dose reduction. The mean SCC measured on the full ETI dose was 38 mmol/L. Post dose reduction, the mean SCC was 44 mmol/L.</p><p><strong>Conclusion: </strong>This study suggest that AEs of ETI in most cases could be related to elevated exposure levels. Dose reduction decreases ETI exposure and AEs while maintaining efficacy as determined with sweat chloride levels.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CFTR modulators and pregnancy outcomes: Early findings from a nationwide cohort study.","authors":"Laurent Chouchana, Mathis Collier, Clémence Martin, Pierre-Régis Burgel, Jean-Marc Treluyer","doi":"10.1016/j.jcf.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.002","url":null,"abstract":"<p><strong>Objectives: </strong>Recent therapeutic advances, mainly with the advent of CFTR modulators, have been associated with an increasing number of pregnancies in females with cystic fibrosis (fwCF). This study aimed to evaluate the safety of the use of CFTR modulators, specifically elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) during pregnancy.</p><p><strong>Methods: </strong>A nationwide cohort study was conducted using the French health insurance data warehouse (SNDS), covering nearly all singleton pregnancies ending between January 2018 and December 2023. Exposure to CFTR modulators was defined as using prescriptions through pregnancy, including one month in the preconception period. The study compared pregnancy outcomes amongst fwCF between pregnancies exposed and unexposed to CFTR modulators.</p><p><strong>Results: </strong>Among 590 pregnancies in fwCF, 148 (24.7 %) were exposed to CFTR modulators, including 136 during first trimester. Of these, 147 (99.3 %) resulted in livebirths. The most common CFTR modulator used was ELX/TEZ/IVA, in 121 (81.8 %) pregnancies. The prevalence of major birth defects was similar between exposed and unexposed fwCF (3.38 % vs. 4.66 %; p = 0.72). The rate of small for gestational age (SGA, <10th percentile) was significantly lower in pregnancies exposed compared to unexposed (6.8 % vs. 16.1 %; p < 0.01).</p><p><strong>Discussion: </strong>The study provides early reassurance about the safety of CFTR modulators during pregnancy, particularly in terms of teratogenicity and adverse pregnancy outcomes. While findings suggest potential benefits, such as halved rate of SGA, further research is required to confirm these outcomes and investigate long-term effects on the development of children prenatally exposed to CFTR modulators.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585768","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":"Anti-inflammatory activity of Pseudomonas aeruginosa DEV phage in cystic fibrosis models.","authors":"Marco Cafora, Dorina Dobi, Jonahunnatha Nesson George William, Francesca Forti, Laura Belleri, Nicoletta Loberto, Rosaria Bassi, Sabrina Carbone, Massimo Locati, Massimo Aureli, Federica Briani, Anna Pistocchi","doi":"10.1016/j.jcf.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.jcf.2025.03.001","url":null,"abstract":"<p><p>Cystic fibrosis is caused by biallelic mutations in the gene encoding the CFTR conductor channel. The recent approval of the Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy has marked a milestone in the management of this disease, alleviating respiratory and digestive symptoms. However, this treatment has no impact on the increased susceptibility to bacterial infections. In this scenario, phage therapy, viruses capable of selectively targeting and killing bacteria, is an emerging option. In the exploration of phages as therapeutic agents, a crucial consideration is their interaction with host cells, especially the immune system. In a previous study, we established the anti-inflammatory effect of four selected phages using the cftr loss-of-function (LoF) zebrafish embryos. In this study, we dissected the interactions of one of them, i.e. the phage DEV, with two cell types crucial in the context of cystic fibrosis: bronchial epithelial cells carrying biallelic CFTR F508del mutation (CuFi-1) and macrophages chemically CFTR inhibited. DEV administration to both human cell types showed anti-inflammatory effects by decreasing the expression of pro-inflammatory cytokines. We further demonstrated that, when in contact with CuFi-1 cells, DEV is internalized and degraded through the lysosomal compartment. In zebrafish, we showed that DEV interacts with tissue-resident macrophages and, in turn, reduces neutrophil recruitment toward the inflammation site. This information sheds light on a previously undocumented aspect of phage therapy as a modulator of the immune response, inducing anti-inflammatory effects. This could be particularly noteworthy within the context of excessive inflammation observed in the airways of individuals with cystic fibrosis.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585754","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":"Sweat chloride reflects CFTR function and correlates with clinical outcomes following CFTR modulator treatment","authors":"Edith T. Zemanick ,&nbsp;Bonnie Ramsey ,&nbsp;Dorota Sands ,&nbsp;Edward F. McKone ,&nbsp;Isabelle Fajac ,&nbsp;Jennifer L. Taylor-Cousar ,&nbsp;Marcus A. Mall ,&nbsp;Michael W. Konstan ,&nbsp;Nitin Nair ,&nbsp;Jiaqiang Zhu ,&nbsp;Emilio Arteaga-Solis ,&nbsp;Fredrick Van Goor ,&nbsp;Lisa McGarry ,&nbsp;Valentin Prieto-Centurion ,&nbsp;Patrick R. Sosnay ,&nbsp;Carmen Bozic ,&nbsp;David Waltz ,&nbsp;Nicole Mayer-Hamblett","doi":"10.1016/j.jcf.2024.12.006","DOIUrl":"10.1016/j.jcf.2024.12.006","url":null,"abstract":"<div><h3>Background</h3><div>Highly effective CFTR modulators improve CFTR function and lead to dramatic improvements in health outcomes in many people with cystic fibrosis (pwCF). The relationship between measures of CFTR function, such as sweat chloride concentration, and clinical outcomes in pwCF treated with CFTR modulators is poorly defined. We conducted analyses to better understand the relationships between sweat chloride and CFTR function in vitro, and between sweat chloride and clinical outcomes following CFTR modulator treatment.</div></div><div><h3>Methods</h3><div>Mean sweat chloride values in healthy people, CF carriers, and pwCF treated with CFTR modulators at different doses were compared to chloride transport in corresponding human bronchial epithelial (HBE) cells. A pooled analysis of phase 3 CFTR modulator studies was performed to evaluate the relationship between attained values of sweat chloride and improvements in lung function, body mass index (BMI), patient reported outcomes, pulmonary exacerbations, and lung function change over time.</div></div><div><h3>Results</h3><div>Sweat chloride concentrations in vivo correlated strongly with CFTR-dependent chloride current in HBE cells in vitro. Sweat chloride values of &lt;30 mmol/L and ≥30 to &lt;60 mmol/L in pwCF following CFTR modulator treatment were associated with better clinical outcomes than sweat chloride ≥60 to &lt;80 mmol/L and ≥80 mmol/L.</div></div><div><h3>Conclusions</h3><div>In pwCF treated with CFTR modulators, lower sweat chloride levels (reflecting greater CFTR function) are associated with better clinical outcomes. These results support the therapeutic strategy of further restoring CFTR function towards normal, as reflected in lowering sweat chloride to below the diagnostic threshold for CF (&lt;60 mmol/L) and to normal (&lt;30 mmol/L), with CFTR modulators.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 246-254"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927282","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":"The multiple tales on sweat chloride in cystic fibrosis","authors":"Burkhard Tümmler","doi":"10.1016/j.jcf.2025.02.014","DOIUrl":"10.1016/j.jcf.2025.02.014","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 212-214"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468214","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":"Race, genetic ancestry, and socioeconomic status – a tangled web","authors":"Michael S. Schechter","doi":"10.1016/j.jcf.2025.03.005","DOIUrl":"10.1016/j.jcf.2025.03.005","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 215-217"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663367","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":"Response to editorial","authors":"Amalia S. Magaret ,&nbsp;Maria S. Rayas ,&nbsp;Tanicia Daley","doi":"10.1016/j.jcf.2025.03.012","DOIUrl":"10.1016/j.jcf.2025.03.012","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 425-426"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674122","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":"Tolerability and effectiveness of face-masks in reducing cough aerosols for children with cystic fibrosis","authors":"George T.P. Tay ,&nbsp;Kim Smith ,&nbsp;Congrong He ,&nbsp;Emma L. Ballard ,&nbsp;Michelle E. Wood ,&nbsp;Rebecca E. Stockwell ,&nbsp;Lidia Morawska ,&nbsp;Claire E. Wainwright ,&nbsp;Scott C. Bell","doi":"10.1016/j.jcf.2025.01.008","DOIUrl":"10.1016/j.jcf.2025.01.008","url":null,"abstract":"<div><h3>Background</h3><div>People with cystic fibrosis (CF) are recommended to wear face-masks when in healthcare settings. We previously demonstrated that face-masks significantly reduce the release of <em>Pseudomonas aeruginosa</em> (<em>P. aeruginosa</em>) aerosols during coughing in adults with CF. There is a knowledge gap in relation to the impact of mask wear in children with CF. This study aimed to examine the tolerability and effectiveness in lowering emissions of hospital-grade surgical and one type of commercially available cotton face-mask in children with CF.</div></div><div><h3>Methods</h3><div>Twenty children with CF and <em>P. aeruginosa</em> infection were recruited. Participants performed three cough manoeuvres in a validated cough aerosol system both with and without face-masks of differing wear time. Cough aerosols were sampled at two meters using an Andersen Cascade Impactor. Quantitative sputum and aerosol bacterial cultures were performed. Participants also rated the comfort levels of the face-masks.</div></div><div><h3>Results</h3><div><em>P. aeruginosa</em> was cultured from the sputum in eight participants (40 %). During uncovered coughing (reference manoeuvre), seven of the 20 participants produced aerosols containing bacterial pathogens. There was a reduction in aerosolised bacterial load during coughing with both surgical and cotton face-masks. The mean percent reduction in CFU with both types of face-masks was 82 % (95 % CI 56 - 108) during the immediate face-mask wear test compared to the uncovered cough test. Face-masks were generally well tolerated.</div></div><div><h3>Conclusions</h3><div>Face-masks are well tolerated and effective in reducing cough-generated bacterial aerosols in children with CF.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 368-373"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066204","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}