Journal of Cystic Fibrosis最新文献

{"title":"Characterization of 223 infants with CFTR-related metabolic syndrome/Cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID) identified during the first three years of newborn screening via IRT-DNA-SEQ in New York State.","authors":"Hossein Sadeghi, Denise M Kay, Elinor Langfelder-Schwind, Joan K DeCelie-Germana, Maria Berdella, Zafer N Soultan, Danielle M Goetz, Michele Caggana, Christopher N Fortner, Robert Giusti, Robert Kaslovsky, Colleen Stevens, Norma Tavakoli, Karen Voter, John J Welter, Catherine Kier","doi":"10.1016/j.jcf.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.10.015","url":null,"abstract":"<p><strong>Background: </strong>New York State implemented CFTR gene sequencing into the Cystic Fibrosis newborn screening (CF NBS) algorithm on 12/1/2017 to reduce false positive screens. With addition of sequencing, infants with 2 CFTR variants but low or intermediate sweat chloride levels classified as CFTR-related metabolic syndrome/CF screen-positive, inconclusive diagnosis (CRMS/CFSPID) are identified at a higher frequency, posing challenges to clinicians and families.</p><p><strong>Methods: </strong>Data from 375 screen-positive newborns between 12/1/2017 and 11/30/2020 were analyzed. We summarized 1-3 years of clinical follow-up for babies with CRMS/CFSPID following implementation of the IRT-DNA-SEQ algorithm.</p><p><strong>Results: </strong>Among 375 newborns referred, 223 (59.5 %) were classified as CRMS/CFSPID. Overall, 195/223 (87.4 %) had a CF-causing/pathogenic/likely pathogenic CFTR variant and a variant of varying clinical consequence (VCC) or uncertain significance (VUS). The most common VCC or VUS was 5T-12TG [n = 90/223 (40 %)]. All initial and repeat sweat chloride test (SCT) values for this cohort were <60 mmol/L after 1-3 years follow-up. Ninety-nine infants had ≥1 repeat SCT. Forty-two (18.8 %) had ≥1 SCT in the intermediate range (30-59 mmol/L) and 181 (81.2 %) were <30 mmol/L. Twenty-nine infants had sweat chloride increasing ≥5 mmol/L per year (29.3 % of infants with repeat testing). Fecal elastase was reported for 114/223 infants; none were abnormal. There were no conversions to CF during the 3-year follow-up period, however 2 infants have subsequently converted with diagnostic SCTs.</p><p><strong>Conclusions: </strong>The New York experience may help inform updates to clinical guidelines, which are needed to optimize care, management, counseling, and long-term follow-up of infants and children with CRMS/CFSPID.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619668","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":"A W1282X cystic fibrosis mouse allows the study of pharmacological and gene-editing therapeutics to restore CFTR function.","authors":"Margaret Michicich, Zachary Traylor, Caitlan McCoy, Dana M Valerio, Alma Wilson, Molly Schneider, Sakeena Davis, Amanda Barabas, Rachel J Mann, David F LePage, Weihong Jiang, Mitchell L Drumm, Thomas J Kelley, Ronald A Conlon, Craig A Hodges","doi":"10.1016/j.jcf.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.10.008","url":null,"abstract":"<p><strong>Background: </strong>People with cystic fibrosis carrying two nonsense alleles lack CFTR-specific treatment. Growing evidence supports the hypothesis that nonsense mutation identity affects therapeutic response, calling for mutation-specific CF models. We describe a novel W1282X mouse model and compare it to an existing G542X mouse.</p><p><strong>Methods: </strong>The W1282X mouse was created using CRISPR/Cas9 to edit mouse Cftr. In this model, Cftr transcription was assessed using qRT-PCR and CFTR function was measured in the airway by nasal potential difference and in the intestine by short circuit current. Growth, survival, and intestinal motility were examined as well. Correction of W1282X CFTR was assessed pharmacologically and by gene-editing using a forskolin-induced swelling (FIS) assay in small intestine-derived organoids.</p><p><strong>Results: </strong>Homozygous W1282X mice demonstrate decreased Cftr mRNA, little to no CFTR function, and reduced survival, growth, and intestinal motility. W1282X organoids treated with various combinations of pharmacologic correctors display a significantly different amount of CFTR function than that of organoids from G542X mice. Successful gene editing of W1282X to wildtype sequence in intestinal organoids was achieved leading to restoration of CFTR function.</p><p><strong>Conclusions: </strong>The W1282X mouse model recapitulates common human manifestations of CF similar to other CFTR null mice. Despite the similarities between the congenic W1282X and G542X models, they differ meaningfully in their response to identical pharmacological treatments. This heterogeneity highlights the importance of studying therapeutics across genotypes.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621569","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":"Elexacaftor/tezacaftor/ivacaftor efficacy in intestinal organoids with rare CFTR variants in comparison to CFTR-F508del and CFTR-wild type controls.","authors":"Suzanne Kroes, Marlou C Bierlaagh, Juliet W Lefferts, Alessandra Boni, Danya Muilwijk, Carla Viscomi, Natascha D A Keijzer-Nieuwenhuijze, Luca Cristiani, Paul J Niemöller, Tibo F Verburg, Renato Cutrera, Alessandro G Fiocchi, Vincenzina Lucidi, Cornelis K van der Ent, Jeffrey M Beekman, Federico Alghisi, Fabiana Ciciriello","doi":"10.1016/j.jcf.2024.09.019","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.09.019","url":null,"abstract":"<p><p>Cystic fibrosis is a life-shortening genetic disease caused by pathological variants of the cystic fibrosis transmembrane conductance regulator gene. The CFTR modulator therapy elexacaftor, tezacaftor and ivacaftor (ETI) rescues CFTR protein function and has made a significant impact on the lives of many people with CF. In Europe, ETI is currently available for people with CF who have at least one F508del mutation whilst the effect of ETI on rare CFTR variants remains unknown, albeit that many of such variants may be restored through ETI. Italy has a high prevalence of rare CFTR variants compared to the rest of Europe, potentially leading to significant undertreatment of people with rare CFTR variants. In this study, we used patient-derived intestinal organoids to identify individuals harboring rare CFTR variants who might benefit from ETI modulator therapy. Two CFTR-dependent readouts (steady-state lumen area and forskolin-induced swelling) in intestinal organoids were characterized to assess CFTR function rescue upon ETI incubation. Functional restoration by CFTR modulators was compared to wild type CFTR function, ETI-treated organoids harboring genotypes currently eligible for ETI therapy (F508del/class I) and organoids harboring non-responsive genotypes. Our data showed in vitro response to ETI within or beyond the range of CFTR function associated with F508del-ETI in 19 out of 28 organoids. This suggest that a large percentage of people with rare CFTR variants without access to ETI may benefit from this treatment.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620293","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":"Associations between income level and health outcomes in people with cystic fibrosis in Turkey.","authors":"Neval Metin Cakar, Seyda Karabulut, Mine Yuksel Kalyoncu, Merve Selcuk Balcı, Ceren Ayça Yıldız, Damla Kocaman, Burcu Uzunoglu, Gamze Tastan, Almala Pınar Ergenekon, Ela Erdem Eralp, Yasemin Gokdemir, Fazilet Karakoc, Bulent Karadag","doi":"10.1016/j.jcf.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.10.010","url":null,"abstract":"<p><strong>Background: </strong>Our study aimed to identify the social domains that pose the greatest barriers to managing and supporting pwCF, particularly in relation to income levels.</p><p><strong>Methods: </strong>To identify associations between income and health outcomes in pwCF in our center the shorter form of the survey \"Your Current Life Situation\" (YCLS) was used in face-to-face interviews. Participants were also asked to complete the validated Turkish versions of the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder scale (GAD-7) to assess depression and anxiety, respectively.</p><p><strong>Results: </strong>In total, 282 pwCF were included in this study. 51.1 % were female (n = 144), mean (±SD) age was 13.8 (±8.7) years and 75 % (n = 211) were <18 years old. The median (IQR) values of pwCF; FEV_1pp (percent predictive) 83 % (41-97), BMI (body mass index) 17 kg/m² (15∼20), BMI z-score -0.1 (-1∼0.3). Of the pwCF in the study 89 % (n = 251) had an income below the poverty threshold and 21 % (n = 60) of them had an income below the hunger threshold. The results of YCLS survey showed that the highest level of insecurity was in the social domain (68.5 %, n = 193); this was followed by health and clinical care (62.1 %, n = 173), financial (37.9 %, n = 106), and food insecurity (37.2 %, n = 103). All individuals experiencing housing insecurity stated that they had requested help from local organisations.</p><p><strong>Conclusion: </strong>The study highlights the substantial socioeconomic challenges faced by pwCF, a significant majority live below the poverty threshold and experience high levels of social and health insecurity, underscoring the need for comprehensive support systems to address these issues.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619666","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, Claudio Cobelli, K Sreekumaran Nair, Katherine Klaus, Gianna Toffolo, Lin Zhang, Antoinette Moran","doi":"10.1016/j.jcf.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.10.005","url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using heart rate data from wrist worn activity trackers to define thresholds for moderate to vigorous physical activity in children and young people with cystic fibrosis.","authors":"Gizem Tanriver, Sanja Stanojevic, Nicole Filipow, Helen Douglas, Emma Raywood, Kunal Kapoor, Gwyneth Davies, Nicky Murray, Rachel O'Connor, Elisabeth Robinson, Eleanor Main","doi":"10.1016/j.jcf.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.10.014","url":null,"abstract":"<p><strong>Background: </strong>Children and young people with cystic fibrosis (CYPwCF) are encouraged to do an average of 60 min of moderate-to-vigorous physical activity (MVPA) daily. However, there are no agreed heart rate (HR) thresholds for defining MVPA, so it is difficult to ascertain whether these targets are actually achieved. Wearable activity trackers enable continuous monitoring of fitness-related measures such as HR and could be used to measure duration and intensity of habitual MVPA. We aimed to define personalized and responsive MVPA thresholds from HR in CYPwCF, to determine habitual time spent in MVPA during childhood and adolescence.</p><p><strong>Methods: </strong>Continuous daily HR data were collected from 142 CYPwCF wearing activity trackers over 16 months. Linear mixed-effects models were used to develop personalised estimates of resting heart rate (RHR), peak heart rate (PHR) and MVPA thresholds, which were defined using the American College of Sports Medicine heart rate reserve (HRR) method.</p><p><strong>Results: </strong>309,926 days of physical activity data showed that both RHR and PHR declined with age in CYPwCF, with considerable variability within and between individuals. The HRR method produced personalised MVPA thresholds for each CYPwCF based on age, which inherently accounted for individual demographic variability and personal factors such as cardiovascular fitness or disease severity.</p><p><strong>Conclusions: </strong>By accounting for within and between person variability in RHR and PHR, our novel method provides more accurate age-related personalised MVPA thresholds for CYPwCF than existing estimates. Our findings provide population-based estimates for RHR, PHR and MVPA thresholds at different ages in CYPwCF. This approach may help guide development of international standards for objective MVPA measurement in the era of remote HR and activity monitoring and facilitate accurate measurement of habitual physical activity in children and young people.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase I study assessing the safety and tolerability of SPL84, an inhaled antisense oligonucleotide for treatment of cystic fibrosis patients with the 3849 +10kb C->T.","authors":"Yoseph Caraco, Maor Wanounou, Simcha Blotnick, Lital Friedman, Asaf Cohen, Gili Hart, Eitan Kerem","doi":"10.1016/j.jcf.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.10.004","url":null,"abstract":"<p><strong>Background: </strong>Antisense Oligonucleotides (ASOs) are small synthetic nucleic acid molecules able to bind specific sequences within target Ribonucleic Acid (RNA) molecules. SPL84 is an ASO drug developed for treatment of cystic fibrosis (CF) patients carrying the 3849 + 10 kb C->T Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) splicing mutation. The 3849 + 10 kb C->T variant leads to inclusion of cryptic exon harboring stop codon leading to the production of truncated non-functional CFTR proteins. in vitro, SPL84 treatment results in splicing modulation, which leads to an increase of correctly spliced CFTR RNA and higher levels of functional CFTR proteins.</p><p><strong>Methods: </strong>SPL84 was tested in a blinded, placebo-controlled phase 1 study in thirty two (32) healthy volunteers (HVs), each received a single dose of either SPL84 or placebo by inhalation. A total of 8 participants were randomized to each of the 4 escalating cohorts in a 3:1 ratio (active: placebo). Safety and tolerability were evaluated by monitoring adverse events (AEs), vital signs, physical exam findings, spirometry, electrocardiograms (ECG), and analyses of safety laboratories. Blood samples were obtained periodically over 24 h for measurement of systemic exposure.</p><p><strong>Results: </strong>There were no significant changes from baseline in vital signs, clinical laboratory values, ECG, physical examination, or pulmonary function. There were no Serious Adverse Events (SAEs) in the study, and there were no significant adverse events. The systemic exposure to SPL84 was low and tended to be dose dependent. The exposure, expressed in terms of area under the curve to infinity (AUC_inf), at the no observed adverse effect level (NOAEL) in 9-week toxicological mice study was 7.51 µg/ml*hrs, which is ∼20 times higher than the exposure at the 160 mg dose (444 ng/ml*hrs).</p><p><strong>Conclusions: </strong>SPL84 was safe and well-tolerated when administered as a single inhaled dose to HVs at doses up to 160 mg, with minimal systemic exposure. There were no safety issues observed, no SAEs, no significant related AEs, and, importantly, no significant effect on pulmonary function. The successful completion of the study enabled the initiation of multi-dosing of CF patients in a phase 2 clinical study.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583184","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":"Aging with CF: Characteristics of people with CF aged 40 and older in the United States.","authors":"Joshua S Ostrenga, Kristina Robinson, A Whitney Brown, Christopher H Goss, Elizabeth A Cromwell","doi":"10.1016/j.jcf.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.10.009","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","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":"Supporting adherence to the cystic fibrosis regimen: Development and validation of The Daily Care Check-In (DCC).","authors":"Kristin A Riekert, Christine Ford, Andrea Goodman, Thomas Eckmann, Angela Green, Alexandra L Quittner","doi":"10.1016/j.jcf.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.10.011","url":null,"abstract":"<p><strong>Background: </strong>The cystic fibrosis (CF) regimen is time-consuming and burdensome leading to barriers to self-management. This mixed-methods study developed the Daily Care Check-in (DCC) that is specific to the barriers faced by people with CF (PWCF) and evaluated its validity.</p><p><strong>Methods: </strong>Qualitative methods were used to identify barriers to self-management and develop items, with \"think aloud\" cognitive interviews conducted to refine the items. A multisite, cross-sectional study was conducted to test the internal consistency, test-retest reliability, and validity of the DCC scores, comparing them to objective medication adherence (composite medication possession ratio (cMPR)) and psychosocial measures (self-efficacy, medication beliefs, executive functioning, depressive and anxiety symptoms, treatment burden, and treatment complexity).</p><p><strong>Results: </strong>The DCC (18 items) includes two scales: Occurrence (score range 0-18) and Interference (score range 0-90). 405 participants completed the DCC, 344 (85 %) completed the survey, and 365 (90 %) had a cMPR calculated. On average, 6.8 barriers were reported (SD = 4.2 Occurrence Scale), and the Interference Scale had a mean score of 18.4 (SD = 14.0). Reliability was acceptable to good. cMPR was negatively correlated with the DCC (rho=-0.26, Occurrence and rho = -0.31, Interference, p-values<0.0001). A priori hypotheses between the DCC and the other measures were supported and demonstrated construct validity.</p><p><strong>Conclusions: </strong>This study provides evidence supporting the validity of the DCC for assessing the presence and impact of barriers to CF self-management, including medication adherence. Formal screening of self-management barriers (e.g., using the DCC) should be considered to facilitate conversations with the care team and identify tailored interventions to support CF self-management.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564561","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":"Pseudo-Bartter syndrome: A CFTR-related disorder?","authors":"Noelia Rodriguez Mier, Virginie Antoons, Senne Cuyx, Anabela Santo Ramalho, Mieke Boon, Marijke Proesmans, Djalila Mekahli, François Vermeulen","doi":"10.1016/j.jcf.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.10.007","url":null,"abstract":"<p><p>This case report presents a 14-month-old boy with a history of cystic fibrosis (CF) carrier status, diagnosed following a positive newborn screening for CF (CF-NBS), who developed symptoms suggestive of Pseudo-Bartter syndrome (PBS). Despite initial evaluations not meeting CF diagnostic criteria, subsequent investigations revealed an intermediate sweat chloride concentration, a second CFTR mutation, and CFTR dysfunction through rectal organoid morphology analysis (ROMA) consistent with CFTR-related disorder (CFTR-RD). This case raises important considerations regarding the diagnosis and management of CFTR-RD. PBS can be considered as a rare presentation of CFTR-RD and can occur in children with sweat chloride below the CF range. Functional testing of CFTR by ROMA enabled a more accurate diagnosis. Despite the negative work-up after CF-NBS, this infant developed CFTR-RD, but this should not be considered as a screen failure. Follow-up of children with CFTR-RD at a CF centre is preferred, because of the risk of developing CF.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557883","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}