Journal of Cystic Fibrosis最新文献

{"title":"Evidence for secondary ciliary dyskinesia in patients with cystic fibrosis","authors":"Romane Bonhiver ,&nbsp;Noemie Bricmont ,&nbsp;Maud Pirotte ,&nbsp;Marc-Antoine Wuidart ,&nbsp;Justine Monseur ,&nbsp;Lionel Benchimol ,&nbsp;Anne-Lise Poirrier ,&nbsp;Catherine Moermans ,&nbsp;Doriane Calmés ,&nbsp;Florence Schleich ,&nbsp;Renaud Louis ,&nbsp;Marie-Christine Seghaye ,&nbsp;Céline Kempeneers","doi":"10.1016/j.jcf.2024.10.003","DOIUrl":"10.1016/j.jcf.2024.10.003","url":null,"abstract":"<div><h3>Background</h3><div>Mucociliary clearance (MCC) impairment can be due to mucus abnormalities or to a ciliary dysfunction, which can be innate, or secondary to infection and/or inflammation. In cystic fibrosis (CF), it is well documented that MCC is impaired due to mucus abnormalities, but little is known concerning ciliary beating. This study aimed to confirm that ciliary dyskinesia is present in CF, and if this might be innate or secondary to the chronic infection and/or inflammation.</div></div><div><h3>Methods</h3><div>Ciliated epithelial samples were obtained by nasal brushing from 51 CF patients, and from 30 healthy subjects. Ciliary beating was evaluated using digital high-speed videomicroscopy at 37 °C, allowing to evaluate ciliary beat frequency (CBF) and the percentage of abnormal beat pattern (CBP); this was repeated after air-liquid interface (ALI) cell culture.</div></div><div><h3>Results</h3><div>Ciliary dyskinesia was higher in CF patients than in healthy subjects, with a lower CBF and a higher percentage of abnormal CBP. Ciliary dyskinesia, already present in childhood, normalized after ALI cell culture. A chronic airway colonization did not worsen ciliary dyskinesia.</div></div><div><h3>Conclusions</h3><div>We showed that, in CF, a ciliary dyskinesia, present from childhood, might contribute to the impaired MCC. Our results also found that the abnormal ciliary beating was not associated with a chronic infection, and resolved after ALI cell culture, suggesting that ciliary dyskinesia in CF is not innate, and might be secondary to chronic inflammation.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 193-200"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466566","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":"Aging with CF: Characteristics of people with CF aged 40 and older in the United States","authors":"Joshua S. Ostrenga ,&nbsp;Kristina Robinson ,&nbsp;A. Whitney Brown ,&nbsp;Christopher H. Goss ,&nbsp;Elizabeth A. Cromwell","doi":"10.1016/j.jcf.2024.10.009","DOIUrl":"10.1016/j.jcf.2024.10.009","url":null,"abstract":"<div><div>We conducted a descriptive analysis of people with CF 40 years of age and older using CF Foundation Patient Registry data from 2022 to provide a current estimate of the population size and characteristics. We summarized demographic details including biological sex, race, ethnicity, insurance and employment status. Clinical data including body mass index, lung function, respiratory infections, hospitalization rates, prevalence of CF-related complications and CF therapy prescriptions were collated. A total of 5,243 individuals aged 40 years or older contributed data to the CFFPR: 2,687 (51 %) people aged 40–49 years; 1,410 (27 %) people aged 50–59 years; and 1,146 (22 %) people aged 60 years or older. The ≥60 year old group have unique characteristics compared to younger individuals, with later diagnosis of CF and greater proportion of females (58 %). These results highlight heterogeneity in the older CF adult population and the need to develop and individualize CF care practices.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 183-186"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583199","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":"Lens-related ocular changes in fetal rats following in-utero exposure to elexacaftor-tezacaftor-ivacaftor","authors":"Yimin Zhu ,&nbsp;Mengliang Wu ,&nbsp;Danni Li ,&nbsp;Mark Habgood ,&nbsp;Holly R Chinnery ,&nbsp;Elena K. Schneider-Futschik","doi":"10.1016/j.jcf.2024.11.014","DOIUrl":"10.1016/j.jcf.2024.11.014","url":null,"abstract":"<div><h3>Background and Objective</h3><div>Elexacaftor-tezacaftor-ivacaftor (ETI) is a drug treatment for cystic fibrosis that is debatable for use in pregnant women. Fetal ocular changes following prenatal exposure and while breastfeeding to ETI have been reported. The aim of this study was to assess eye development in rat fetuses following in-utero exposure to ETI.</div></div><div><h3>Design and Methods</h3><div>Eyes from Sprague Dawley rats born to dams given clinically relevant ETI or sham treatment from embryonic day 12–19 (E12-E19) were investigated using histology and optical coherence tomography (OCT).</div></div><div><h3>Results</h3><div>Lens thickness was higher in the ETI-exposure group, as measured by OCT (<em>p</em> = 0.0003). Lens cavities were observed in both groups, but the median individual lens cavities area was higher in the ETI-exposed eyes (<em>p</em> &lt; 0.0001), as measured by histology.</div></div><div><h3>Conclusion</h3><div>In-utero exposure to ETI during E12-E19 was associated with subtle changes to lens anatomy, however the mechanism and clinical significance of this observation requires further investigation.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 21-25"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791740","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":"Next generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation","authors":"Anisha Gupta ,&nbsp;Christina Barone ,&nbsp;Elias Quijano ,&nbsp;Alexandra S. Piotrowski-Daspit ,&nbsp;J. Dinithi Perera ,&nbsp;Adele Riccardi ,&nbsp;Haya Jamali ,&nbsp;Audrey Turchick ,&nbsp;Weixi Zao ,&nbsp;W. Mark Saltzman ,&nbsp;Peter M. Glazer ,&nbsp;Marie E. Egan","doi":"10.1016/j.jcf.2024.07.009","DOIUrl":"10.1016/j.jcf.2024.07.009","url":null,"abstract":"<div><h3>Background</h3><div>Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein for which there is no cure. One approach to cure CF is to correct the underlying mutations in the CFTR gene. We have used triplex-forming peptide nucleic acids (PNAs) loaded into biodegradable nanoparticles (NPs) in combination with donor DNAs as reagents for correcting mutations associated with genetic diseases including CF. Previously, we demonstrated that PNAs induce recombination between a donor DNA and the <em>CFTR</em> gene, correcting the F508del CFTR mutation in human cystic fibrosis bronchial epithelial cells (CFBE cells) and in a CF murine model leading to improved CFTR function with low off-target effects, however the level of correction was still below the threshold for therapeutic cure.</div></div><div><h3>Methods</h3><div>Here, we report the use of next generation, chemically modified gamma PNAs (γPNAs) containing a diethylene glycol substitution at the gamma position for enhanced DNA binding. These modified γPNAs yield enhanced gene correction of F508del mutation in human bronchial epithelial cells (CFBE cells) and in primary nasal epithelial cells from CF mice (NECF cells).</div></div><div><h3>Results</h3><div>Treatment of CFBE cells and NECF cells grown at air-liquid interface (ALI) by NPs containing γtcPNAs and donor DNA resulted in increased CFTR function measured by short circuit current and improved gene editing (up to 32 %) on analysis of genomic DNA.</div></div><div><h3>Conclusions</h3><div>These findings provide the basis for further development of PNA and NP technology for editing of the CFTR gene.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 142-148"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897551","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 CFTR modulators on mental health: Moving the field forward","authors":"AM Georgiopoulos ,&nbsp;EM Tillman","doi":"10.1016/j.jcf.2024.12.002","DOIUrl":"10.1016/j.jcf.2024.12.002","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 5-7"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864392","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":"Regulatory adverse drug reaction analyses support a temporal increase in psychiatric reactions after initiation of cystic fibrosis combination modulator therapies","authors":"Jacob O'Connor ,&nbsp;Dilip Nazareth ,&nbsp;Dennis Wat ,&nbsp;Kevin W Southern ,&nbsp;Freddy Frost","doi":"10.1016/j.jcf.2024.09.010","DOIUrl":"10.1016/j.jcf.2024.09.010","url":null,"abstract":"<div><h3>Introduction</h3><div>Despite improved outcomes for many people with cystic fibrosis, there have been reports of adverse neuropsychiatric effects of modulator therapy. The aim of this research is to define temporal associations in adverse drug reaction (ADR) reports for available CFTR modulators.</div></div><div><h3>Methods</h3><div>Methods include an analysis of the UK Yellow Card Scheme data for ADRs through accessing interactive Drug Analysis Profiles (iDAPs) to define temporal trends in absolute and proportional counts.</div></div><div><h3>Results</h3><div>Since the introduction of ETI, there has been an increase in the absolute number of psychiatric ADRs reported as well as a statistically significant increase in the proportion of psychiatric ADRs in the pre-ETI and post-ETI periods.</div></div><div><h3>Conclusion</h3><div>In the post-ETI period, psychiatric ADRs are the most prevalent ADR reported via the Yellow Card scheme. Despite an unclear mechanism, there is significant clinical relevance in counselling and monitoring regarding psychiatric effects of CFTR modulator therapy.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 30-32"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288302","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":"Theranostics vs theratyping or theranostics plus theratyping?","authors":"Margarida D. Amaral,&nbsp;Ines Pankonien","doi":"10.1016/j.jcf.2024.09.013","DOIUrl":"10.1016/j.jcf.2024.09.013","url":null,"abstract":"<div><div>Treating all people with Cystic Fibrosis (pwCF) to the level of benefit achieved by highly efficient CFTR modulator therapies (HEMT) remains a significant challenge. Theratyping and theranostics are two distinct approaches to advance CF treatment. Both theratyping in cell lines and pwCF-derived biomaterials theranostics have unique strengths and limitations in the context of studying and treating CF. The challenges, advantages and disadvantages of both approaches are discussed here. While theratyping in cell lines offers ease of use, cost-effectiveness, and standardized platforms for experimentation, it misses physiological relevance and patient-specificity. Theranostics, on the other hand, provides a more human-relevant model for personalized medicine approaches but requires specialized expertise, resources, and access to patient samples. Integrating these two approaches in parallel and leveraging their respective strengths may enhance our understanding of CF and facilitate the development of more effective therapies for all pwCF.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 10-15"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347596","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":"Factors associated with prescription of elexacaftor/tezacaftor/ivacaftor among people with cystic fibrosis aged 12 years or older with at least one F508del allele","authors":"Georgene E Hergenroeder ,&nbsp;Jonathan V Todd ,&nbsp;Josh S. Ostrenga ,&nbsp;Christopher H Goss ,&nbsp;Raksha Jain ,&nbsp;Wayne Morgan ,&nbsp;Gregory S. Sawicki ,&nbsp;Michael S Schechter ,&nbsp;Elizabeth A Cromwell ,&nbsp;Clement L Ren","doi":"10.1016/j.jcf.2024.10.006","DOIUrl":"10.1016/j.jcf.2024.10.006","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to characterize the uptake of elexacaftor/tezacaftor/ivacaftor (ETI) following Food and Drug Administration (FDA) approval in October 2019.</div></div><div><h3>Methods</h3><div>People with cystic fibrosis (PwCF) ≥12 years enrolled in the CF Foundation Patient Registry (CFFPR) from 2019–2022 with at least one copy of F508del were included. We calculated summary statistics according to ETI prescription status. We used a Kaplan-Meier estimator to determine median days to ETI prescription to identify differences in prescription uptake by lung function, race, and ethnicity and a Cox proportional hazards model to identify risk factors associated with timing of first ETI prescription.</div></div><div><h3>Results</h3><div>A total of 17,183 people (91 %) were prescribed ETI. The median time to prescription was 121 days (95 % CI: 119, 122), with 75 % prescribed within 311 days (95 % CI: 301, 325). PwCF prescribed ETI were younger, had lower lung function, more pulmonary exacerbations in the prior year, earlier age of diagnosis, and were more likely to have been prescribed another <em>CFTR</em> modulator (if eligible). Public health insurance, ppFEV₁ &gt;90, Black race and Hispanic ethnicity were associated with lower hazards (e.g., later) of ETI prescription whereas prior modulator prescription, pancreatic insufficiency, increased exacerbation frequency and prior infections were associated with a higher hazard (earlier) of prescription.</div></div><div><h3>Conclusions</h3><div>While over 90 % of eligible individuals were prescribed ETI within three years, time of first prescription was associated with demographic factors and disease severity. Further research should investigate the reasons for this delay and approaches to reduce time to initiation for ETI and future therapies.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 135-141"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545741","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":"Impact of elexacaftor/tezacaftor/ivacaftor on utilization of routine therapies in cystic fibrosis: Danish nationwide register study","authors":"Hans Kristian Råket ,&nbsp;Camilla Bjørn Jensen ,&nbsp;Joanna Nan Wang ,&nbsp;Tacjana Pressler ,&nbsp;Hanne Vebert Olesen ,&nbsp;Marianne Skov ,&nbsp;Søren Jensen-Fangel ,&nbsp;Janne Petersen ,&nbsp;Espen Jimenez-Solem ,&nbsp;for the TransformCF study group","doi":"10.1016/j.jcf.2024.11.004","DOIUrl":"10.1016/j.jcf.2024.11.004","url":null,"abstract":"<div><h3>Background</h3><div>Elexacaftor/tezacaftor/ivacaftor (ETI) has been effective in improving several outcomes in people living with cystic fibrosis (pwCF). Although clinical guidance regarding maintenance therapies has not changed, staff reports indicate that individuals reduce some therapies. This study aimed to evaluate ETI's effect on utilization of routine therapies among pwCF in Denmark.</div></div><div><h3>Methods</h3><div>We included all pwCF initiating ETI between 1 September 2020 and 31 October 2022. Utilization of routine therapies was analysed by drug class (e.g., gastrointestinal medications) and individual treatments (e.g., pancreatic enzymes) before and after ETI initiation using national registry data. Odds ratios (ORs) for prescription redemptions pre- and post-ETI were calculated to assess ETIs impact on the use of routine therapies.</div></div><div><h3>Results</h3><div>The study population consisted of 351 individuals. Median age was 23 years (IQR 14–32) and mean ppFEV₁ was 76 (SD 22) at index. Two-year follow-up was available for 205 individuals. Two years post ETI initiation, the one-year prevalence was reduced for airway medications, (89.5 % to 75.1 %) and inhaled antibiotics (59.5 % to 42.9 %.). OR for redeeming a prescription two years post-ETI initiation (95 % CI) was reduced for four out of five drug classes: airway medications (OR: 0.24 [0.19; 0.29]), inhaled antibiotics (OR: 0.28 [0.2; 0.39]), oral antibiotics (OR: 0.49 [0.41; 0.58]), gastrointestinal medications (OR: 0.66 [0.57; 0.77]).</div></div><div><h3>Conclusion</h3><div>Two years after ETI initiation, reductions in the use of several routine therapies were observed in a national cohort of pwCF, with the largest declines in airway medications and antibiotics. These findings highlight ETI's real-world impact beyond conventional clinical metrics.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 105-111"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709547","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":"Impact of UPLIFT, a group telehealth intervention, on symptoms of depression and anxiety in adults with CF.","authors":"Michael S Schechter, Andrea Molzhon, Robin S Everhart, Le Kang, Rachel Weiskittle, Brittany Castleberry, Nancy J Thompson","doi":"10.1016/j.jcf.2024.11.008","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.11.008","url":null,"abstract":"<p><strong>Background: </strong>Despite high rates of anxiety and depression, research regarding the effect of psychological interventions on people with CF (pwCF) is limited. We evaluated the impact of UPLIFT (Using Practice and Learning to Increase Favorable Thoughts), a group telehealth intervention using mindfulness-based cognitive behavioral therapy (MBCT), on symptoms of anxiety and depression in pwCF.</p><p><strong>Methods: </strong>This multicenter randomized trial compared changes in symptoms of anxiety and/or depression in adult pwCF who participated in the 8-week UPLIFT intervention to a treatment-as-usual (TAU) group. Follow up assessments occurred immediately after and 6- and 12-months post-intervention. Primary outcome measures were change in Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scores modeled in separate linear mixed-effects models.</p><p><strong>Results: </strong>Sixty-six pwCF participated. At baseline, 43 (65.15%) had some minimal symptoms of depression (PHQ-9≥5) and 44 (66.67%) had some minimal symptoms of anxiety (GAD-7≥5). During the 12 month follow up period, the overall change in PHQ-9 was greater in the UPLIFT group compared to TAU (p = .049). Analysis of individual time points showed a statistically significant difference between groups in change from baseline immediately post-treatment (-2.321, SD 0.684 vs 0.362, SD 0.656, p = .005); differences persisted but were not statistically significant at 6 and 12 months. Similar trends for changes in GAD-7 were non-significant.</p><p><strong>Conclusions: </strong>Participation in UPLIFT, a group telehealth intervention using MBCT, provides short-term improvement in symptoms of depression, as measured by changes in PHQ9. Improvement in symptoms of anxiety were suggested but could not be statistically confirmed.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818290","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}