Journal of Cystic Fibrosis最新文献

{"title":"Changes in factors associated with inhaled antibiotic prescriptions for people with cystic fibrosis over time in the U.S.","authors":"Marianne S. Muhlebach ,&nbsp;Jane She ,&nbsp;Eric Y. Zhang ,&nbsp;Jonathan D. Cogen ,&nbsp;Michael R. Kosorok","doi":"10.1016/j.jcf.2024.09.017","DOIUrl":"10.1016/j.jcf.2024.09.017","url":null,"abstract":"<div><h3>Rationale</h3><div>CF care guidelines recommend chronic inhaled antibiotics for chronic <em>Pseudomonas aeruginosa</em> (Pa) lung infection. These medications are costly, time consuming and prescription needs may change with improved outcomes.</div></div><div><h3>Objectives</h3><div>We determined the proportion of pwCF with chronic, intermittent or negative Pa infection categories, their clinical and demographic characteristics, factors associated with inhaled antibiotic prescription and changes between 2011 and 2019.</div></div><div><h3>Methods</h3><div>This cohort study using the U.S. CF Foundation patient registry for pwCF &gt;2 years, no prior lung transplant, and with ≥3 respiratory cultures/year determined chronic inhaled antibiotics (≥3 months per calendar year) and Pa infection status from encounter level data. Outcomes and odds of prescription for relevant clinical factors were evaluated using generalized estimating equation models with additional interaction between the predictor and the calendar year to examine changes of predictors over time.</div></div><div><h3>Results</h3><div>Proportion of pwCF with chronic and intermittent Pa decreased and antibiotic prescription rates increased for these groups and decreased for Pa negative pwCF. Hispanic ethnicity, female sex, pancreatic insufficiency, CF diabetes, and ivacaftor/lumacaftor were associated with higher antibiotic prescriptions for each Pa status. Among Pa-negative pwCF prescriptions were higher with <em>Burkholderia spp</em>. (1.17, (CI₉₅ 1.03,1.34)) or MRSA (OR 1.45, (1.26,1.68)) but decreased between 2011 and 2019. For <em>Aspergillus</em> OR increased to 1.6,(1.3,1.8) in 2019. Prescriptions for pwCF on ivacaftor decreased, becoming lower in 2019 for chronic (OR 0.7, (0.5,0.8)) and Pa-negative pwCF (OR 0.7, (0.5,0.8)).</div></div><div><h3>Conclusions</h3><div>Factors predicting inhaled antibiotic prescription differed between 2011 and 2019 indicating changes in health and care for pwCF even prior to triple-modulators.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 98-104"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400430","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":"Glucagon-like-peptide-1 agonist therapy in adults with cystic fibrosis","authors":"Sanghoon Park ,&nbsp;Raksha Jain ,&nbsp;Sasan Mirfakhraee","doi":"10.1016/j.jcf.2024.08.005","DOIUrl":"10.1016/j.jcf.2024.08.005","url":null,"abstract":"<div><div>Glucagon-like-peptide-1 (GLP-1) agonists are commonly used to improve glycemic control and promote weight loss in individuals with type 2 diabetes mellitus (T2DM) and/or obesity. However, there is a paucity of evidence regarding GLP-1 agonist use in people with cystic fibrosis (pwCF). We present 11 people with CF (males: 3, females: 7; age range 24–47; BMI range 25.7–43.7) treated with GLP-1 agonists (semaglutide: 9,tirzepatide: 2) for variable duration (1–50 months). All experienced weight loss on GLP- 1 agonist therapy (median change in weight = -7.2 kg; change in BMI [kg/m2] = -0.9 to -8.1). Eight pwCF showed improvement in percent predicted forced expiratory volume in 1 second (ppFEV1) [change = -5 to + 18] and nine pwCF showed improvement in percent predicted forced vital capacity (ppFVC) [change= +1 to + 26]. Of the 7 pwCF with CFRD, all reduced their insulin quantity (mean, 31.5 % decrease in total daily insulin dose), and glucose time in range improved for most (mean, +11 % increase from baseline). Four pwCF stopped using GLP-1 agonists: 2 due to severe nausea/vomiting, 1 due to lack of perceived benefit, and 1 due to change in insurance coverage. This report is the largest published series to date of pwCF treated with GLP-1 agonist therapy. With the addition of GLP-1 agonists, all individuals experienced weight loss and a reduction in daily insulin dose, and most had improvement in pulmonary function. Future multi-center studies are needed to corroborate the efficacy and safety of these agents in the CF population.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 40-46"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107829","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":"Self-reported chronic therapy use after 24-weeks of follow-up by participants who completed the simplify randomized, controlled trial","authors":"Alex H. Gifford ,&nbsp;Katherine Odem-Davis ,&nbsp;Margaret Kloster ,&nbsp;Brian P. O'Sullivan ,&nbsp;Gregory J. Omlor ,&nbsp;Susan L. Millard ,&nbsp;John P. Clancy ,&nbsp;Gregory S. Sawicki ,&nbsp;Kristin Riekert ,&nbsp;Nicole Mayer-Hamblett ,&nbsp;David P. Nichols ,&nbsp;SIMPLIFY Study Group","doi":"10.1016/j.jcf.2024.08.008","DOIUrl":"10.1016/j.jcf.2024.08.008","url":null,"abstract":"<div><h3>Background</h3><div>Highly effective CFTR modulator therapy (HEMT) has improved the health of many people with cystic fibrosis (pwCF), offering opportunities to discontinue burdensome therapies. SIMPLIFY included randomized, controlled trials that confirmed non-inferiority of discontinuing versus continuing dornase alfa (DA) or hypertonic saline (HS) for 6 weeks in pwCF on HEMT. In this study of post-trial treatment use by SIMPLIFY participants, we hypothesized that randomization to discontinue DA or HS during the trial would be associated with a higher likelihood of non-use of each medication during follow-up.</div></div><div><h3>Methods</h3><div>We electronically surveyed SIMPLIFY participants every 4 weeks for 24 weeks after trial completion but before the main trial results were publicly disclosed. We asked them how often they used medications during the previous week. We estimated covariate-adjusted odds ratios (ORs) of DA or HS non-use by logistic regression with generalized estimating equations.</div></div><div><h3>Results</h3><div>After exclusions mostly due to lack of any surveys, 472 participants were included in the analysis population, 181 from the HS trial and 291 from the DA trial. Approximately half of the analysis population completed all six surveys. At every month of follow-up in both trials, the percentage of individuals reporting non-use of DA or HS during the previous week was greater among those randomized to discontinue therapy. Among participants with responses at 24 weeks, 30/122 (24.6 %) in the HS trial and 79/222 (35.6 %) in the DA trial reported non-use of the respective study medication. After adjusting for covariates, participants randomized to discontinue DA were 8.7-times (95 % CI: 4.3–17.7) more likely to not use DA during follow-up than those randomized to continue DA, and participants randomized to discontinue HS were 5.2-times (95 % CI: 2.1–12.8) more likely to not use HS during follow-up compared to those randomized to continue.</div></div><div><h3>Conclusions</h3><div>In healthy pwCF on ETI, randomization to discontinue DA or HS during SIMPLIFY was associated with greater odds of not using each medication after the trial compared to randomization to continue. These findings suggest that participation in a treatment discontinuation trial can influence participants’ post-trial treatment decisions. This possibility may be relevant during discussions about research participation and clinical care.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 91-97"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288303","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":"Development of metabolic syndrome in people with Cystic Fibrosis one year after exposure to elexacaftor-tezacaftor-ivacaftor","authors":"Gregory A. Ratti ,&nbsp;Hannah Smith ,&nbsp;Sasan Mirfakhraee ,&nbsp;Joan Reisch ,&nbsp;Leah Cohen ,&nbsp;Raksha Jain ,&nbsp;James D. Finklea","doi":"10.1016/j.jcf.2024.09.022","DOIUrl":"10.1016/j.jcf.2024.09.022","url":null,"abstract":"<div><h3>Background</h3><div>The constellation of hypertension, truncal obesity, impaired fasting glucose, low high-density lipoprotein, and hypertriglyceridemia is known as metabolic syndrome (MetSyn) and is associated with cardiovascular and other diseases. Elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) is associated with weight gain but effects on cardiovascular risk are unknown. This study sought to investigate ETI exposure and risk for development of MetSyn in pwCF.</div></div><div><h3>Methods</h3><div>A prospective cohort study including pwCF ≥ 18 years old exposed to ETI was performed. All data for calculating MetSyn was collected from the electronic medical record at initiation and 1 year ± 3 months after starting ETI. A total of 152 pwCF exposed to ETI and 34 pwCF never exposed to CF transmembrane conductance regulator modulators were included in the analysis. Changes to hypertension classification was also examined over this period.</div></div><div><h3>Results</h3><div>After 1 year of ETI there was an increase in MetSyn from 13 to 30 pwCF, <em>p</em> &lt; 0.0001. No new cases of MetSyn were seen in the group not exposed to ETI. After 1 year of ETI, more people met criteria for class 1 (BP 130–139/90–99 mm Hg) or class 2 hypertension (BP ≥140/≥90 mm Hg) regardless of prior modulator exposure, <em>p</em> &lt; 0.0001.</div></div><div><h3>Conclusions</h3><div>Exposure to ETI for 1 year resulted in an increased number of cases of MetSyn. There was an increased incidence of hypertension associated with ETI exposure. Additional studies are needed to further examine this trend and to determine if these changes will translate to cardiovascular complications over time.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 47-52"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466564","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":"Exogenous insulin does not reduce protein catabolism in pre-diabetic cystic fibrosis patients: A randomized clinical trial","authors":"Michele Schiavon ,&nbsp;Claudio Cobelli ,&nbsp;K. Sreekumaran Nair ,&nbsp;Katherine Klaus ,&nbsp;Gianna Toffolo ,&nbsp;Lin Zhang ,&nbsp;Antoinette Moran","doi":"10.1016/j.jcf.2024.10.005","DOIUrl":"10.1016/j.jcf.2024.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Cystic Fibrosis (CF) patients historically suffered from undernutrition, infection and inflammation. Insulin insufficiency-related protein catabolism further compromised health. We aimed to determine whether insulin improves protein catabolism in CF youth with abnormal glucose tolerance (AGT).</div></div><div><h3>Methods</h3><div>This double-masked, placebo-controlled trial in CF youth age 10–25 with AGT who were in their usual state of health used triple-tracer stable-isotope methodology to measure protein turnover during a baseline test meal and after four weeks of insulin/placebo treatment. Healthy controls were assessed once. CF patients were randomized 1:1:1 to once-daily long-acting insulin (0.25 U/kg/d), three-times daily rapid-acting insulin (0.5 U/15gr carbohydrate), or injectable placebo.</div></div><div><h3>Results</h3><div>Thirty CF patients completed the study. There were no differences in any measure of protein turnover between insulin- and placebo-treated subjects, including endogenous protein breakdown (primary study endpoint). In contrast to earlier studies, protein turnover in the 37 CF patients who completed the baseline meal was normal compared to 20 healthy controls. Meal isotope appeared in plasma earlier in CF than controls, suggesting more rapid gut emptying. The study was interrupted by the pandemic; futility analysis led to study discontinuation before the planned remaining 15 CF patients were studied.</div></div><div><h3>Conclusions</h3><div>Recent advances in CF have led to remarkable clinical improvements. In this study, CF youth with AGT had normal protein catabolism at baseline. Pre-meal or daily basal insulin therapy, while safe and well tolerated, did not significantly enhance protein turnover and does not appear to be necessary in clinically stable patients prior to development of CFRD.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 57-65"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620390","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":"Learning from the CFTR modulator baby boom","authors":"Raksha Jain ,&nbsp;Jennifer L. Goralski","doi":"10.1016/j.jcf.2024.12.003","DOIUrl":"10.1016/j.jcf.2024.12.003","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 3-4"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965140","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":"Differential times of submission and approval of CFTR modulators for the treatment of Cystic Fibrosis in the United States and the European Union","authors":"Enrico Costa ,&nbsp;Silvia Girotti ,&nbsp;Clément Mathieu ,&nbsp;Carlo Castellani ,&nbsp;Joseph S. Ross ,&nbsp;Jennifer L. Taylor-Cousar ,&nbsp;Hubert G.M. Leufkens","doi":"10.1016/j.jcf.2024.08.002","DOIUrl":"10.1016/j.jcf.2024.08.002","url":null,"abstract":"<div><h3>Background</h3><div>The objective of this study was to assess the differential times of submission and approval of CFTR modulators in the United States (US) and the European Union (EU).</div></div><div><h3>Methods</h3><div>By collecting publicly available data from the websites of the Food and Drug Administration and the European Medicines Agency, we quantified differential times in submission, review duration, and approvals of initial marketing authorization and variation of indications of CFTR modulators in the US and the EU by December 31, 2023.</div></div><div><h3>Results</h3><div>Applications regarding marketing of 4 CFTR modulators were submitted 103 (SD ±143) days later in the EU than in the US: 31 (SD ±39) days later for initial approval, and 124 (SD ±155) days for supplemental indications. The regulatory review process was completed in 181 days [IQR, 179 - 182] in the US and 325 days [IQR, 276 - 382] in the EU: 167 days [IQR, 102 - 232] in the US and 346 days [IQR, 302 - 400] in the EU for first approvals, 181 days [IQR, 181 - 182] in the US and 324 days [IQR, 264 - 382] in the EU for supplemental indication approvals. CFTR modulators were approved 267 (SD 143) days later in the EU than in the US: 220 (SD ±76) days for initial approval and 280 (SD ±157) days for supplemental indications.</div></div><div><h3>Conclusion</h3><div>We found significant differences in times of submission and for approval of CFTR modulators between the US and EU, whereby initial approvals and subsequent indication approvals were always first granted in the US</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 125-132"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055691","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":"Insights into epithelial-mesenchymal transition from cystic fibrosis rat models","authors":"Nathan Rout-Pitt ,&nbsp;Bernadette Boog ,&nbsp;Alexandra McCarron ,&nbsp;Nicole Reyne ,&nbsp;David Parsons ,&nbsp;Martin Donnelley","doi":"10.1016/j.jcf.2024.09.003","DOIUrl":"10.1016/j.jcf.2024.09.003","url":null,"abstract":"<div><h3>Background</h3><div>Molecular pathways contributing to Cystic Fibrosis pathogenesis remain poorly understood. Epithelial-mesenchymal transition (EMT) has been recently observed in CF lungs and certain CFTR mutation classes may be more susceptible than others. No investigations of EMT processes in CF animal models have been reported.</div></div><div><h3>Aim</h3><div>The aim of this study was to assess the expression of EMT-related markers in Phe508del and knockout (CFTR-KO) rat lung tissue and tracheal-derived basal epithelial stem cells, to determine whether CFTR dysfunction can produce an EMT state.</div></div><div><h3>Method</h3><div>The expression of EMT-related markers in lung tissue and cultured tracheal basal epithelial stem cells from wildtype (WT), Phe508del, and CFTR-KO rats were assessed using qPCR and Western blots. Cell responses were evaluated in the presence of Rho-associated protein kinase (ROCK) inhibitor Y27632, which blocks EMT-pathways, or after treatment with TGFβ1 to stimulate EMT.</div></div><div><h3>Results</h3><div>Different gene expression profiles were observed between Phe508del and CFTR-KO rat models compared to wild type. There was lower expression of type 1 collagen in KO lungs and primary cell cultures, while Phe508del lungs and cells had higher expression, particularly when treated with TGFβ1. The addition of Y27632 rescued changes in EMT related genes in Phe508del cells but not in KO cells.</div></div><div><h3>Conclusion</h3><div>Our findings show the first evidence of upregulated EMT pathways in the lungs and airway cells of any CF animal model. Differences in the regulation of the EMT genes and proteins in the Phe508del and CFTR-KO cells suggest that the signalling pathways underlying EMT are CFTR mutation dependent.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 149-156"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288301","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":"Linkage of the CF Foundation Patient Registry with the Scientific Registry of Transplant Recipients database","authors":"Elizabeth A. Cromwell ,&nbsp;Yoon Son Ahn ,&nbsp;Patrick J. Johnson ,&nbsp;Kathleen J. Ramos ,&nbsp;A. Jay Freeman ,&nbsp;Albert Faro ,&nbsp;Jon J. Snyder","doi":"10.1016/j.jcf.2024.09.015","DOIUrl":"10.1016/j.jcf.2024.09.015","url":null,"abstract":"<div><h3>Background</h3><div>The Cystic Fibrosis Foundation Patient Registry (CFFPR) maintains clinical data, including history of solid organ transplant, on people with cystic fibrosis (CF) who obtain care at CF Foundation-accredited care centers. The Scientific Registry of Transplant Recipients (SRTR) database is a collection of national data related to organ transplantation that supports research to evaluate solid organ transplant candidate and recipient outcomes.</div></div><div><h3>Methods</h3><div>Individuals in the CFFPR were matched to SRTR records using an algorithm that compared names, last four digits of social security numbers, date of birth and date of death. We evaluated match quality by summarizing the extent to which transplant status agreed between the two data sources by organ and year of listing or transplant. We summarized CFFPR-reported characteristics for lung and liver transplants in the year prior to transplant.</div></div><div><h3>Results</h3><div>A total of 7,594 individuals who participated in the CFFPR matched SRTR records with approximately 75% having at least one transplant record in SRTR. Over 97% of the matched population had a CF diagnosis reported to SRTR. In total, 5,253 people were identified as lung transplant recipients and 499 as liver transplant recipients in SRTR. Clinical characteristics for lung and liver transplants were consistent with the epidemiology of transplantation for people with CF.</div></div><div><h3>Conclusions</h3><div>Linkage of the two data sources was successful, with high agreement between them supporting the use of the matched population as a valid resource to study transplantation in CF, particularly leveraging pre-transplant characteristics (collected in CFFPR) with detailed transplant data (collected in SRTR).</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 1","pages":"Pages 112-117"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365413","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 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}