Journal of Cystic Fibrosis最新文献

{"title":"Elexacaftor/tezacaftor/ivacaftor and mental health: A workshop report from the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health working group.","authors":"C J Bathgate, D A Fedele, E M Tillman, J He, R S Everhart, L R Reznikov, F F Liu, K Kirby, K Raffensperger, K Traver, K A Riekert, S W Powers, A M Georgiopoulos","doi":"10.1016/j.jcf.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.11.006","url":null,"abstract":"<p><strong>Background: </strong>This report summarizes the 2023 inaugural annual meeting of the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health (PRIME) working group. This workshop focused on mental health and elexacaftor/tezacaftor/ivacaftor (ETI).</p><p><strong>Methods: </strong>We reviewed existing literature and identified key gaps and study design considerations in preclinical work, pharmacokinetics/pharmacodynamics, mood/anxiety, quality of life/self-perception, neuropsychological symptoms, sleep, and symptom management.</p><p><strong>Results: </strong>Limited studies have identified behavioral changes with modulator exposure in rodent models of depression, anxiety, and cognition. Longitudinal human studies reporting mean changes generally show no change or improvement. However, case reports and single-center studies identify subgroups reporting new or worsening symptoms.</p><p><strong>Conclusions: </strong>Future studies should focus on understanding the role of CFTR in the nervous system, defining ETI impacts in preclinical models, and mechanistic investigations. Innovative methods with larger samples and comprehensive assessments are needed to determine the incidence of new/worsening symptoms throughout the lifespan and effective management strategies.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729103","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":"Coping and learning to Manage Stress with cystic fibrosis (CALM): A multisite telehealth randomized controlled trial to reduce depression and anxiety symptoms in adults with cystic fibrosis.","authors":"Christina J Bathgate, Elizabeth D Smith, Nora H Murphy, Alexandra L Quittner, Kristin A Riekert, Jennifer L Goralski, Kristen E Holm","doi":"10.1016/j.jcf.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.11.002","url":null,"abstract":"<p><strong>Background: </strong>Adults with cystic fibrosis (AWCF) have higher rates of depression and anxiety than comparable community members. This multisite randomized waitlist-controlled trial tested the efficacy of \"Coping and Learning to Manage Stress with CF\" (CALM), a 6-session+booster telehealth intervention to improve depression and anxiety symptoms (primary outcomes) and perceived stress, coping self-efficacy, and key health-related quality of life domains (secondary outcomes).</p><p><strong>Methods: </strong>AWCF reporting mild to severe symptoms of depression and/or anxiety were randomized to receive CALM immediately (immediate, n = 66) or after a 13-week delay (waitlist, n = 66). Group differences post-intervention and at 1-month were examined via linear mixed models. Maintenance of treatment gains from baseline to 3-month follow-up was examined using combined data from both groups. Effect size calculations using Cohen's d assessed treatment effect magnitude.</p><p><strong>Results: </strong>Compared to the waitlist group, those that received CALM immediately reported lower depression and anxiety symptoms post-intervention and at 1-month follow-up (ps<0.001). For depression there was a large effect size post-intervention (d = 0.85) and a medium effect size at 1-month follow-up (d = 0.70); anxiety had a medium effect size post-intervention (d = 0.65) and at 1-month follow-up (d = 0.66). The immediate group also reported significantly higher coping self-efficacy, less stress, and increased vitality post-CALM and at 1-month follow-up (ps<0.01). Treatment gains were maintained at 3-month follow-up for all outcomes.</p><p><strong>Conclusions: </strong>CALM was efficacious for AWCF in reducing symptoms of depression, anxiety, and perceived stress while improving coping self-efficacy and vitality with evidence of treatment sustainability. Next steps are dissemination and implementation to CF psychosocial clinicians.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709541","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":"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":"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":"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":"Wobbly moments: Trust considerations for evolving cystic fibrosis care models","authors":"Stacy Van Gorp ,&nbsp;Rachel Grob ,&nbsp;Cynthia George ,&nbsp;Kathryn A. Sabadosa","doi":"10.1016/j.jcf.2024.09.006","DOIUrl":"10.1016/j.jcf.2024.09.006","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"23 6","pages":"Pages 1035-1037"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347597","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":"Cystic fibrosis foundation position paper: Redefining the cystic fibrosis care team","authors":"Rebekah F. Brown ,&nbsp;Charlotte T. Close ,&nbsp;Molly G. Mailes ,&nbsp;Luis J. Gonzalez ,&nbsp;Danielle M. Goetz ,&nbsp;Stephanie S. Filigno ,&nbsp;Rebecca Preslar ,&nbsp;Quynh T. Tran ,&nbsp;Sarah E. Hempstead ,&nbsp;Paula Lomas ,&nbsp;A. Whitney Brown ,&nbsp;Patrick A. Flume ,&nbsp;CFF Care Model Committee","doi":"10.1016/j.jcf.2024.09.011","DOIUrl":"10.1016/j.jcf.2024.09.011","url":null,"abstract":"<div><div>Interdisciplinary teams care for people with cystic fibrosis (pwCF) at specialized treatment centers. These teams have laid the foundation for the cystic fibrosis (CF) care model responsible for gains in health outcomes and quality of life within the CF community. However, the landscape of CF care is transforming, invigorated by new technologies, accessibility of cystic fibrosis transmembrane conductance regulator (CFTR) therapies, and increased utilization of telemedicine. In light of these advances, it is appropriate to re-evaluate the CF care team structure. This position paper offers guidance for the structure of a CF care center designed to meet the evolving needs of the CF community. Fundamental to the proposed center structure is recognition of pwCF and their families as integral members of their care teams, underpinning the necessity for shared decision making, awareness of social determinants of health, and active partnership between all healthcare professionals involved in the care of pwCF.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"23 6","pages":"Pages 1045-1054"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347591","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":"Symptom phenotyping in people with cystic fibrosis during acute pulmonary exacerbations using machine-learning K-means clustering analysis","authors":"Eliana R. Gill ,&nbsp;Christopher Dill ,&nbsp;Christopher H. Goss ,&nbsp;Scott D. Sagel ,&nbsp;Michelle L. Wright ,&nbsp;Sharon D. Horner ,&nbsp;Julie A. Zuñiga","doi":"10.1016/j.jcf.2024.05.014","DOIUrl":"10.1016/j.jcf.2024.05.014","url":null,"abstract":"<div><h3>Introduction</h3><div>People with cystic fibrosis (PwCF) experience frequent symptoms associated with chronic lung disease. A complication of CF is a pulmonary exacerbation (PEx), which is often preceded by an increase in symptoms and a decline in lung function. A symptom cluster is when two or more symptoms co-occur and are related; symptom clusters have contributed meaningful knowledge in other diseases. The purpose of this study is to discover symptom clustering patterns in PwCF during a PEx to illuminate symptom phenotypes and assess differences in recovery from PExs.</div></div><div><h3>Methods</h3><div>This study was a secondary, longitudinal analysis (<em>N</em> = 72). Participants at least 10 years of age and being treated with intravenous antibiotics for a CF PEx were enrolled in the United States. Symptoms were collected on treatment days 1–21 using the CF Respiratory Symptom Diary (CFRSD)-Chronic Respiratory Symptom Score (CRISS). K-means clustering was computed on day 1 symptom data to detect clustering patterns. Linear regression and multi-level growth models were performed.</div></div><div><h3>Results</h3><div>Symptoms significantly clustered based on severity: low symptom (LS)-phenotype (<em>n</em> = 42), high symptom (HS)-phenotype (<em>n</em> = 30). HS-phenotype had worse symptoms and CRISS scores (<em>p</em> <em>&lt;</em> 0.01) than LS-phenotype. HS-phenotype was associated with spending 5 more nights in the hospital annually (<em>p</em> <em>&lt;</em> 0.01) than LS-phenotype. HS-phenotype had worse symptoms over 21 days than LS-phenotype (<em>p</em> <em>&lt;</em> 0.0001).</div></div><div><h3>Conclusion</h3><div>Symptoms significantly cluster on day 1 of a CF-PEx. PwCF with HS-phenotype spend more nights in the hospital and are less likely to experience the same resolution in symptoms by the end of PEx treatment than LS-phenotype.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"23 6","pages":"Pages 1106-1111"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293426","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":"Establishment of a conditionally reprogrammed primary eccrine sweat gland culture for evaluation of tissue-specific CFTR function","authors":"Alice C. Eastman ,&nbsp;Gedge Rosson ,&nbsp;Noori Kim ,&nbsp;Sewon Kang ,&nbsp;Karen Raraigh ,&nbsp;Loyal A. Goff ,&nbsp;Christian Merlo ,&nbsp;Noah Lechtzin ,&nbsp;Garry R. Cutting ,&nbsp;Neeraj Sharma","doi":"10.1016/j.jcf.2024.06.013","DOIUrl":"10.1016/j.jcf.2024.06.013","url":null,"abstract":"<div><h3>Background</h3><div>Sweat chloride concentration is used both for CF diagnosis and for tracking CFTR modulator efficacy over time, but the relationship between sweat chloride and lung health is heterogeneous and informed by <em>CFTR</em><span><span> genotype. Here, we endeavored to characterize ion transport in eccrine </span>sweat glands (ESGs).</span></div></div><div><h3>Methods</h3><div><span>First, ESGs were microdissected from a non-CF skin donor to analyze individual glands. We established primary cultures of ESG cells via conditional reprogramming for functional testing of ion transport by short circuit current measurement and examined cell composition by single-cell RNA-sequencing (scRNA-seq) comparing with whole dissociated ESGs. Secondly, we cultured nasal epithelial (NE) cells and ESGs from two people with CF (pwCF) to assess modulator efficacy. Finally, NEs and ESGs were grown from one person with the </span><em>CFTR</em> genotype F312del/F508del to explore genotype-phenotype heterogeneity.</div></div><div><h3>Results</h3><div>ESG primary cells from individuals without CF demonstrated robust ENaC and CFTR function. scRNA-seq demonstrated both secretory and ductal ESG markers in cultured ESG cells. In both NEs and ESGs from pwCF homozygous for F508del, minimal baseline CFTR function was observed, and treatment with CFTR modulators significantly enhanced function. Notably, NEs from an individual bearing F312del/F508del exhibited significant baseline CFTR function, whereas ESGs from the same person displayed minimal CFTR function, consistent with observed phenotype.</div></div><div><h3>Conclusions</h3><div>This study has established a novel primary culture technique for ESGs that allows for functional ion transport measurement to assess modulator efficacy and evaluate genotype-phenoytpe heterogeneity. To our knowledge, this is the first reported application of conditional reprogramming and scRNA-seq of microdissected ESGs.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"23 6","pages":"Pages 1173-1179"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537894","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":"Heterogeneity in response to Elexacaftor/Tezacaftor/Ivacaftor in people with cystic fibrosis","authors":"Gianfranco Alicandro ,&nbsp;Andrea Gramegna ,&nbsp;Federica Bellino ,&nbsp;Sathya Calogero Sciarrabba ,&nbsp;Chiara Lanfranchi ,&nbsp;Martina Contarini ,&nbsp;Mariangela Retucci ,&nbsp;Valeria Daccò ,&nbsp;Francesco Blasi","doi":"10.1016/j.jcf.2024.04.013","DOIUrl":"10.1016/j.jcf.2024.04.013","url":null,"abstract":"<div><h3>Background</h3><div>Highly effective modulators of the CFTR channel have been demonstrated to dramatically impact disease progression and outcome. However, real-world data indicates that the magnitude of the clinical benefit is not equal among all patients receiving the treatment. We aimed to assess the variability in treatment response (as defined by the 6-month change in sweat chloride concentration, forced expiratory volume in one second [ppFEV1], body mass index [BMI], and CF Questionnaire-Revised [CFQ-R] respiratory domain score) and identify potential predictors in a group of patients receiving Elexacaftor-Tezacaftor-Ivacaftor (ETI) triple combination therapy.</div></div><div><h3>Methods</h3><div>This was a single-center, prospective cohort study enrolling adults with CF at a major center in Italy. We used linear regression models to identify a set of potential predictors (including CFTR genotype, sex, age, and baseline clinical characteristics) and estimate the variability in treatment response.</div></div><div><h3>Results</h3><div>The study included 211 patients (median age: 29 years, range: 12–58). Median changes (10–90th percentile) from baseline were: - 56 mEq/L (–76; –27) for sweat chloride concentration, +14.5 points (2.5; 32.0) for ppFEV1, +0.33 standard deviation scores (–0.13; 1.05) for BMI and +17 points (0; 39) for the CFQ-R respiratory domain score. The selected predictors explained 23 % of the variability in sweat chloride concentration changes, 18 % of the variability in ppFEV1 changes, 39 % of the variability in BMI changes, and 65 % of the variability in CFQ-R changes.</div></div><div><h3>Conclusions</h3><div>This study highlights a high level of heterogeneity in treatment response to ETI, which can only be partially explained by the baseline characteristics of the disease.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"23 6","pages":"Pages 1072-1079"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904207","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}