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Short-term modification of breathprint by Elexacaftor/Tezacaftor/Ivacaftor in a paediatric cohort.
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-21 DOI: 10.1016/j.jcf.2025.01.004
Emmanuelle Bardin, Nicolas Hunzinger, Elodie Lamy, Camille Roquencourt, Bingqing Zhou, Yasmine Tabache, Laurence Le Clainche, Natascha Remus, Charlotte Roy, Philippe Devillier, Thao Nguyen-Khoa, Frédérique Chedevergne, Clément Pontoizeau, Mairead Kelly, Stanislas Grassin Delyle, Isabelle Sermet-Gaudelus

Background: The triple combination Elexacaftor/Tezacaftor/Ivacaftor (ETI) translates into major respiratory improvements in adults; yet current clinical endpoints may prove insufficiently sensitive in young children. We hypothesised that ETI rapidly modifies the lungs' metabolism, resulting in changes in breath composition.

Methods: Eleven children with CF were enrolled in a longitudinal pilot study at the paediatric Necker hospital. Breath was collected on sorbent tubes using a ReCIVA® device before, after one week and one month of ETI. Samples were analysed by 2D-gas chromatography-mass spectrometry (2D-GC-MS). A linear mixed-effect model, corrected for clinical confounding factors, identified exhaled metabolites differentially expressed throughout the visits. Correlations were calculated between these and clinical indicators.

Results: Breath collection was successful in all children from six years old. They presented a decreased sweat chloride and improved lung function as early as within one week of ETI. Breath composition gradually evolved over the visits. ETI induced significant modifications in the level of 12 breath metabolites. Amongst those, dimethyl sulphide and tetradecene changes correlated with improvements in forced expiratory volume in one second (FEV1) and forced expiratory flow (FEF25-75), whilst 3-methyldecane and 3-(chloromethyl)-heptane were predictive of changes in lung clearance index (LCI2.5).

Conclusions: ETI impacts the breath profile from the first week of treatment. Not only could "breathomics" bring mechanistic insights into the metabolic impact of ETI, but it may also offer novel non-invasive options to monitor CF disease and predict therapeutic response.

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引用次数: 0
Racial disparities in lung transplantation for cystic fibrosis in the era of highly effective modulator therapy. 在高效调节治疗时代囊性纤维化肺移植的种族差异。
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-16 DOI: 10.1016/j.jcf.2025.01.006
Jessica M Ruck, Shi Nan Feng, Alexandra H Toporek, Pali D Shah, Erin Tallarico, Noah Lechtzin, Allan B Massie, Dorry L Segev, Errol L Bush, Christian A Merlo

Background: Highly effective modulator therapies (HEMT) including ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ETI) have transformed treatment for people with cystic fibrosis (pwCF). However, non-HEMT-responsive mutations are more common in pwCF of non-White race/ethnicity; introduction of HEMT might have exacerbated racial/ethnic disparities in CF care.

Methods: Using the Scientific Registry of Transplant Recipients, we identified all lung transplant candidates and recipients 05/2005-12/2022 and categorized them by diagnosis (CF/non-CF), race/ethnicity (non-Hispanic White/Black/Hispanic) and era [Pre-HEMT (2005-1/30/2012), IVA (1/31/2012-10/30/2019), ETI (10/31/2019-12/31/2022)]. We compared the percentage of patients listed, delisted/died, or transplanted by race/ethnicity and era.

Results: 34,659 lung transplants were performed: 10,521 pre-HEMT, 15,944 in IVA era, and 7,888 in ETI era. Over the three eras, the percentage of lung recipients with CF of White race decreased (94.5 % to 92.4 % to 78.4 %) and of Black race (1.7 % to 2.4 % to 5.7 %) or Hispanic ethnicity increased (3.5 % to 4.6 % to 14.2 %; p < 0.001). Similarly, among candidates listed for CF over the three eras, the percentage that were of White race decreased (82.0 % vs. 78.6 % vs. 71.0 %) and of Black race (9.2 % vs. 10.0 % vs. 10.3 %) or Hispanic ethnicity increased (6.4 % vs. 8.6 % vs. 13.6 %; p < 0.001).

Conclusion: The introduction of HEMT appears to have benefitted CF lung transplant candidates and recipients of Black race or Hispanic ethnicity less than those of White race. This is likely due to the higher prevalence of HEMT-ineligible CFTR mutations among Black and Hispanic patients and underscores the need for therapies aimed at non-HEMT-responsive mutations prevalent in these racial/ethnic populations.

背景:高效调节疗法(HEMT),包括ivacaftor (IVA)和elexaftor /tezacaftor/ivacaftor (ETI)已经改变了囊性纤维化(pwCF)患者的治疗方法。然而,非hemt反应性突变在非白种人/族裔的pwCF中更为常见;HEMT的引入可能加剧了CF治疗中的种族/民族差异。方法:使用移植受者科学登记处,我们确定了2005年5月至2022年12月所有肺移植候选人和受者,并根据诊断(CF/非CF),种族/民族(非西班牙裔白人/黑人/西班牙裔)和时代进行分类[Pre-HEMT (2005-1/30/2012), IVA (1/31/2012-10/30/2019), ETI(10/31/2019-12/31/2022)]。我们按种族/民族和时代比较了列入名单、未列入名单/死亡或移植的患者的百分比。结果:共进行肺移植34,659例:hemt前期10521例,IVA期15944例,ETI期7888例。在这三个时期,患有CF的肺受体白人的百分比下降(从94.5%到92.4%到78.4%),黑人(从1.7%到2.4%到5.7%)或西班牙裔增加(从3.5%到4.6%到14.2%;P < 0.001)。同样,在三个时代的CF候选人中,白人的比例下降(82.0%对78.6%对71.0%),黑人(9.2%对10.0%对10.3%)或西班牙裔增加(6.4%对8.6%对13.6%;P < 0.001)。结论:HEMT的引入似乎对CF肺移植候选人和黑人或西班牙裔受者的益处小于白人。这可能是由于黑人和西班牙裔患者中不符合hemt条件的CFTR突变的发生率较高,并强调了针对这些种族/民族人群中普遍存在的非hemt反应性突变的治疗需求。
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引用次数: 0
Longer term follow-up of abdominal symptoms (CFAbd-Score) after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis. 囊性纤维化成人患者开始使用Elexacaftor / Tezacaftor / Ivacaftor后腹部症状(CFAbd-Score)的长期随访
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-14 DOI: 10.1016/j.jcf.2025.01.010
L R Caley, L Gillgrass, C Zagoya, H Saumtally, F Duckstein, White H, J G Mainz, D G Peckham

Background: Whether improvements in gastrointestinal (GI) symptoms observed with Elexacaftor/Tezacaftor/Ivacaftor (ETI) treatment are sustained in the longer-term requires exploration. This study investigated how GI-symptoms change with longer-term ETI use in pancreatic insufficient adults with cystic fibrosis (awCF).

Methods: Participants completed up to three abdominal symptom questionnaires, employing the validated CFAbd-Score. Changes in total CFAbd-Score and its five domains, pain, gastroesophageal reflux-disease (GERD), disorders of bowel movement (DBM), disorders of appetite (DA) and quality of life (QOL), were analysed pre-ETI (T0) and at ≤1.5 years (T1) and 2-4 years of ETI-therapy (T2).

Results: A total of 165 CFAbd-Scores from 68 participants were analysed (median age: 34 years; IQR: 28-39). Total CFAbd-Score significantly (p < 0.05) and clinically meaningfully decreased from 20.4 ± 1.6 pre-ETI (median:40 weeks pre-treatment) to 15.3 ± 1.9 and 16.8 ± 1.6 at T1 (median: 25 weeks of ETI) and T2 (median: 148 weeks of ETI), respectively. The CFAbd-Score´s domains DA and QoL only significantly decreased between T0 and T1, whereas DBM only significantly decreased after 2-4 years of ETI therapy (T2). GERD scores were significantly lower at both T1 and T2.

Conclusion: While GI symptoms in awCF significantly improve within the first 1.5 years of ETI-therapy, they appear to somewhat wane with longer-term use, despite GI-symptom burden still being lower compared to pre-ETI. However, we cannot differentiate whether this results from reduced adherence, a decrease in ETI effects, or long-term changes in diet, gut microbiota or symptom perception. The longer-term impact of ETI and other potential modulator therapies on GI symptoms requires ongoing monitoring.

背景:Elexacaftor/Tezacaftor/Ivacaftor (ETI)治疗对胃肠道(GI)症状的改善是否能长期持续需要探索。本研究调查胰腺功能不全成人囊性纤维化(awCF)患者长期使用ETI后gi症状的变化。方法:参与者填写多达三份腹部症状问卷,采用经验证的CFAbd-Score。分析eti前(T0)、≤1.5年(T1)和eti治疗2-4年(T2)时cfabd -总分及其5个领域(疼痛、胃食管反流疾病(GERD)、肠蠕动障碍(DBM)、食欲障碍(DA)和生活质量(QOL)的变化。结果:共分析了68名参与者的165份cfabd评分(中位年龄:34岁;差:28-39)。总CFAbd-Score分别从治疗前20.4±1.6(中位数:治疗前40周)降至T1(中位数:治疗前25周)和T2(中位数:治疗前148周)时的15.3±1.9和16.8±1.6,显著(p < 0.05)且具有临床意义。CFAbd-Score的DA和QoL仅在T0和T1之间显著下降,而DBM仅在ETI治疗2-4年后(T2)显著下降。在T1和T2时,GERD评分均显著降低。结论:虽然awCF的胃肠道症状在eti治疗的前1.5年内显著改善,但随着长期使用,它们似乎有所减弱,尽管GI症状负担仍低于eti前。然而,我们无法区分这是由于依从性降低,ETI效果降低,还是饮食,肠道微生物群或症状感知的长期变化。ETI和其他潜在调节剂治疗对胃肠道症状的长期影响需要持续监测。
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引用次数: 0
Effect of elexacaftor-tezacaftor-ivacaftor on liver transient elastography, fibrosis indices and blood tests in children with cystic fibrosis. elexaftor - tezactor -ivacaftor对囊性纤维化儿童肝脏瞬时弹性图、纤维化指标及血液检查的影响。
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-12 DOI: 10.1016/j.jcf.2024.12.010
Vito Terlizzi, Cristina Fevola, Martina Cecchetti, Alberto Terminiello, Franco Curci, Elisa Bartolini, Chiara Rubino, Mariangela Stinco, Simona Carrera, Paolo Bonomi, Giovanni Taccetti, Zachary M Sellers, Giuseppe Indolfi

Background: Elexacaftor-tezacaftor-ivacaftor (ETI) has significantly improved the clinical course of people with cystic fibrosis (pwCF) and eligible CFTR variants. In this study, we prospectively evaluated liver elastography, liver fibrosis indices and liver tests in children with CF aged 6-12 years started on ETI therapy.

Methods: Body mass index, sweat test, percent predicted forced expiratory volume in one second, serum markers of liver injury or portal hypertension, liver fibrosis indices, controlled attenuation parameter and liver stiffness were assessed before starting ETI and three and twelve months post-ETI, according to new international guidelines.

Results: 27 children with CF were enrolled, 14 with liver involvement and 13 without liver involvement at baseline. A significant improvement in sweat chloride after ETI was observed in all subjects. In those with liver involvement, liver stiffness significantly decreased at 12 months of ETI, with all individuals achieving normalization or near-normalization of liver stiffness. The majority of individuals with abnormal AST, ALT, GGT, or liver fibrosis indices at baseline experienced normalization by 12 months of ETI (AST: 67%, ALT: 100%, GGT: 50%, APRI: 100%, GPR: 100%). In the no liver involvement group, the only significant change in liver health metrics at 12 months was a significant reduction in platelets (P<0.05) that remained within the normal range.

Conclusions: ETI is associated with improvement in liver stiffness, liver function tests and fibrosis indices in pwCF and liver involvement. ETI may reduce the development of advanced CF liver disease, but longer observations with larger cohorts are needed.

背景:elexacaftor - tezactor -ivacaftor (ETI)显著改善了囊性纤维化(pwCF)患者和符合条件的CFTR变体的临床病程。在这项研究中,我们前瞻性地评估了6-12岁开始接受ETI治疗的CF儿童的肝弹性图、肝纤维化指数和肝脏检查。方法:根据新的国际指南,在开始ETI前和ETI后3个月和12个月评估体重指数、汗液测试、一秒钟内预测用力呼气量的百分比、肝损伤或门脉高压的血清标志物、肝纤维化指数、控制衰减参数和肝脏硬度。结果:27例CF患儿入组,14例肝受累,13例基线时无肝受累。在所有受试者中观察到ETI后汗液氯化物的显著改善。在肝受累患者中,肝僵硬度在ETI治疗12个月时显著降低,所有患者的肝僵硬度均达到正常化或接近正常化。大多数基线时AST、ALT、GGT或肝纤维化指标异常的患者在12个月ETI恢复正常(AST: 67%, ALT: 100%, GGT: 50%, APRI: 100%, GPR: 100%)。在无肝脏受累组中,12个月时肝脏健康指标的唯一显著变化是血小板显著减少(p结论:ETI与pwCF和肝脏受累患者的肝脏硬度、肝功能检查和纤维化指标的改善有关。ETI可能会减少晚期CF肝病的发展,但需要更长的观察时间和更大的队列。
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引用次数: 0
CFTR mutation is associated with bone differentiation abnormalities in cystic fibrosis. CFTR突变与囊性纤维化的骨分化异常有关。
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-11 DOI: 10.1016/j.jcf.2025.01.005
Claire Dumortier, Andrew Frauenpreis, Antony Hoarau, Amy L Ryan, Sophie C Gangloff, Soula Danopoulos, Frédéric Velard, Denise Al Alam

Background: Cystic Fibrosis-related Bone Disease is an emerging challenge faced by 50 % of adult people with cystic fibrosis (CF). The multifactorial causes of this comorbidity remain elusive. However, congenital bone defects have been observed in animal models with CFTR mutations, suggesting its importance. The role of CFTR in bone cells development is unknown. Studies from human cells remain somewhat controversial depending on the cells used and the disease state of the patients from which the cells derived.

Methods: Therefore, we investigated the role of CFTR in osteoblast development using induced pluripotent stem cells generated from homozygous CF donors for F508del and non-CF controls. This approach allows for a clear understanding towards how the CFTR mutation may influence osteoblast differentiation independently from other confounding factors.

Results: We observed a lower capacity of differentiation in CF cells as compared to control, already from mesenchymal stem cells (MSC) stage, whereby they retained expression of the pluripotency marker OCT4. Furthermore, our results demonstrated a delayed osteoblast commitment and altered expression of specific markers, such as an increased RANKL/OPG ratio and decreased BMP2, suggesting a potentially perturbed bone homeostasis associated with CFTR mutation.

Conclusions: This is the first study of its kind, clearly demonstrating a role for CFTR mutation in delaying osteoblast differentiation and/or regeneration.

背景:囊性纤维化相关骨病是50%囊性纤维化(CF)成年患者面临的新挑战。这种合并症的多因素原因仍然难以捉摸。然而,在CFTR突变的动物模型中观察到先天性骨缺陷,表明其重要性。CFTR在骨细胞发育中的作用尚不清楚。基于人类细胞的研究仍然存在一些争议,这取决于所使用的细胞和细胞来源的患者的疾病状态。方法:因此,我们利用CF纯合供体F508del和非CF对照产生的诱导多能干细胞,研究CFTR在成骨细胞发育中的作用。这种方法可以清楚地了解CFTR突变如何独立于其他混杂因素影响成骨细胞分化。结果:我们观察到CF细胞的分化能力较低,与对照组相比,已经从间充质干细胞(MSC)阶段,他们保留了多能性标记物OCT4的表达。此外,我们的研究结果表明,成骨细胞承诺延迟和特定标记物的表达改变,如RANKL/OPG比率增加和BMP2降低,表明CFTR突变可能扰乱骨稳态。结论:这是同类研究中首次明确证明CFTR突变在延缓成骨细胞分化和/或再生中的作用。
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引用次数: 0
Does using the Lung Clearance Index (LCI) inform clinical decisions in children with cystic fibrosis? 使用肺清除率指数(LCI)对囊性纤维化儿童的临床决策有帮助吗?
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-11 DOI: 10.1016/j.jcf.2024.12.001
Lucy Perrem, Stephanie Jeanneret-Manning, Stephanie D Davis, Margaret Rosenfeld, Todd Edwards, Sanja Stanojevic, Felix Ratjen

Introduction: The Lung Clearance Index (LCI) is an established research test, but its role in clinical decision-making is not well defined. This study estimated the proportion of treatment decisions that are changed or supported by the added information provided by LCI.

Methods: A mixed methods prospective observational study was conducted in North America. Providers were invited to participate in a clinical vignette survey consisting of 10 hypothetical scenarios involving pediatric cystic fibrosis (CF) management. First, they made a clinical decision based on information captured in routine clinical visits. Then, the LCI value was made available, and providers were asked whether the LCI changed or supported their decision. A prospective study was also conducted at three CF centres to determine how often physicians make pulmonary treatment decisions at CF clinic visits and how often they perceive additional lung function data would be helpful for these decisions.

Results: We received 522 vignette responses from 62 participants. LCI changed the decision in 18.4 % of cases, supported the decision in 57.1 % and did not impact the decision in 24.5 %. Data from patient encounters in the prospective study demonstrated that changes to pulmonary treatments were considered in 98/322 (30.4 %) visits; additional lung function information could potentially have helped in 64.3 % of the treatment decisions.

Conclusion: LCI changes or supports a significant proportion of treatment decisions. Providers perceive that additional information about lung function could be helpful at the majority of encounters where changes in treatment are considered.

简介:肺清除率指数(LCI)是一项成熟的研究测试,但其在临床决策中的作用尚未明确。本研究估计了由LCI提供的附加信息改变或支持治疗决策的比例。方法:在北美进行了一项混合方法的前瞻性观察研究。提供者被邀请参加一项临床小插曲调查,包括10个涉及儿科囊性纤维化(CF)管理的假设场景。首先,他们根据在常规临床访问中获得的信息做出临床决策。然后,提供LCI值,并询问提供者LCI是否改变或支持他们的决定。在三个CF中心进行了一项前瞻性研究,以确定医生在CF门诊就诊时做出肺部治疗决定的频率,以及他们认为额外的肺功能数据对这些决定有帮助的频率。结果:我们收到了来自62名参与者的522份小问卷。LCI在18.4%的病例中改变了决定,在57.1%的病例中支持决定,在24.5%的病例中不影响决定。前瞻性研究中患者就诊的数据显示,98/322(30.4%)的患者考虑改变肺部治疗;额外的肺功能信息可能有助于64.3%的治疗决策。结论:LCI改变或支持很大比例的治疗决策。提供者认为,在大多数考虑改变治疗方案的情况下,关于肺功能的额外信息可能会有所帮助。
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引用次数: 0
Pain is a constant in our lives with CF: Please believe us. CF患者的痛苦是我们生活中的常态:请相信我们。
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-09 DOI: 10.1016/j.jcf.2024.12.004
Noor Elshaar, Cade Hovater, Kasey Raffensperger
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引用次数: 0
Clinical features associated with self-reported food insecurity in people with cystic fibrosis. 囊性纤维化患者自我报告食物不安全的临床特征
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-09 DOI: 10.1016/j.jcf.2024.12.005
Heather Boas, Jesse Y Hsu, Allen Koshy, Semret Seyoum, Marsha Regenstein, Gina Hong, Olivia Dieni, Anne Willis, Clement L Ren

Background: Food insecurity (FI) is more prevalent in people with cystic fibrosis (PwCF) than the reported national prevalence, but there are limited data on the relationship between FI and health outcomes in PwCF. The objective of this study was to analyze the relationship between FI in PwCF and pulmonary and nutritional status.

Methods: We leveraged an electronic cross-sectional survey that ascertained FI status and gave participants the option to link their survey data to their records in the Cystic Fibrosis Foundation Patient Registry (CFFPR). Linear regression and negative binomial models were used to estimate the associations in mean differences between FI and percent predicted FEV1 (ppFEV1), nutritional indices, and hospitalizations.

Results: There were 1,856 respondents, 1,234 (66.5 %) of whom granted permission to link to the CFFPR. FI was present in 352 (28 %) of the respondents. FI was associated with lower ppFEV1 (-6.5; 95 % CI -9.9, -3.1); however, this was no longer statistically significant after adjusting for confounders. FI was independently associated with increased hospitalizations. Higher weight for age was significantly associated with FI in the adjusted model, but there were no significant associations between height for age or absolute weight and body mass index (BMI) in adults.

Conclusions: FI in PwCF is associated with adverse health outcomes. These results support screening for FI during routine visits. Further studies are needed to investigate causal relationships between FI and adverse clinical outcomes.

背景:食物不安全(FI)在囊性纤维化(PwCF)患者中比报道的全国患病率更为普遍,但关于FI与PwCF患者健康结局之间关系的数据有限。本研究的目的是分析PwCF中FI与肺和营养状况的关系。方法:我们利用电子横断面调查来确定FI状态,并让参与者选择将他们的调查数据与他们在囊性纤维化基金会患者登记处(CFFPR)中的记录联系起来。使用线性回归和负二项模型来估计FI与预测FEV1百分比(ppFEV1),营养指数和住院率之间的平均差异的关联。结果:共有1856名受访者,其中1234人(66.5%)同意链接cfpr。352名(28%)受访者出现FI。FI与较低的ppFEV1相关(-6.5;95% ci -9.9, -3.1);然而,在调整混杂因素后,这不再具有统计学意义。FI与住院率增加独立相关。在调整后的模型中,较高的年龄体重与FI显著相关,但成人年龄身高或绝对体重与体重指数(BMI)之间没有显著关联。结论:PwCF患者FI与不良健康结局相关。这些结果支持在常规访问中筛查FI。需要进一步研究FI与不良临床结果之间的因果关系。
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引用次数: 0
Dry eye disease and morphological changes in the anterior chamber in people with cystic fibrosis. 囊性纤维化患者的干眼病和前房形态学改变
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-07 DOI: 10.1016/j.jcf.2024.12.009
Patricia Gutiérrez, Laura Jiménez, Jessica Martínez, Carmen Alba, María Victoria Girón, Gabriel Olveira, Pedro Ruiz-Esteban, Casilda Olveira

Background: Cystic fibrosis (CF) is caused by variants in a gene that encodes a protein essential for water and ion transport in the epithelial cells of exocrine organs. Given the possible relationship of this protein and conjunctival and corneal epithelium, the aim of this study was to evaluate ophthalmologic alterations in people with CF.

Methods: Forty-five people with CF underwent pulmonary evaluation including inflammatory score (IS). These people along with 98 sex-matched controls underwent ophthalmologic evaluation including dry eye disease (DED) testing, corneal topography using Pentacam™ and macular and peripapillary retinal nerve fiber layer (pRNFL) thickness with optical coherence tomography (OCT).

Results: The CF group presented a higher percentage of pathologic tear break-up time (T-BUT) (55.6 % vs 25 %, p = 0.001) and Schirmer's test 1 (40 % versus 19.4 %, p = 0.009) than the control group. In the CF group, an inverse correlation was observed between T-BUT and IS (r=- 0.373, p = 0.012), as well as T-BUT and peripheral eosinophilia (r=-0.338; p = 0.023). People with CF presented lower values of central corneal thickness (p = 0.009), thinnest point (p = 0.006), anterior chamber volume (p = 0.034), and anterior chamber angle (p = 0.011) than the control group and lower pRNLF thickness in the superior temporal sector (p = 0.002).

Conclusions: Our findings indicate a higher prevalence of dry eye disease (DED) among people with CF compared to controls. The severity of the condition increases with higher systemic inflammation. Additionally, CF may affect the anterior segment of the eye, leading to a reduction in the nerve fiber layer and early signs of glaucoma.

背景:囊性纤维化(CF)是由一个基因变异引起的,该基因编码一种在外分泌器官上皮细胞中对水和离子运输至关重要的蛋白质。考虑到这种蛋白与结膜和角膜上皮的可能关系,本研究的目的是评估CF患者的眼科改变。方法:45例CF患者进行了肺部评估,包括炎症评分(IS)。这些人与98名性别匹配的对照组一起接受了眼科评估,包括干眼病(DED)测试、Pentacam™角膜地形图测试以及光学相干断层扫描(OCT)黄斑和乳头周围视网膜神经纤维层(pRNFL)厚度。结果:CF组病理撕裂破裂时间(T-BUT)百分比(55.6%比25%,p = 0.001)和Schirmer检验1(40%比19.4%,p = 0.009)高于对照组。CF组T-BUT与IS呈负相关(r=- 0.373, p = 0.012), T-BUT与外周血嗜酸性粒细胞呈负相关(r=-0.338;P = 0.023)。CF组角膜中央厚度(p = 0.009)、最薄点(p = 0.006)、前房容积(p = 0.034)、前房角(p = 0.011)均低于对照组,颞上区pRNLF厚度较低(p = 0.002)。结论:我们的研究结果表明,与对照组相比,CF患者中干眼病(DED)的患病率更高。全身炎症程度越高,病情越严重。此外,CF可能影响眼睛的前段,导致神经纤维层减少和青光眼的早期症状。
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引用次数: 0
Sweat chloride reflects CFTR function and correlates with clinical outcomes following CFTR modulator treatment. 汗液氯化物反映CFTR功能,并与CFTR调节剂治疗后的临床结果相关。
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2025-01-03 DOI: 10.1016/j.jcf.2024.12.006
Edith T Zemanick, Bonnie Ramsey, Dorota Sands, Edward F McKone, Isabelle Fajac, Jennifer L Taylor-Cousar, Marcus A Mall, Michael W Konstan, Nitin Nair, Jiaqiang Zhu, Emilio Arteaga-Solis, Fredrick Van Goor, Lisa McGarry, Valentin Prieto-Centurion, Patrick R Sosnay, Carmen Bozic, David Waltz, Nicole Mayer-Hamblett

Background: Highly effective CFTR modulators improve CFTR function and lead to dramatic improvements in health outcomes in many people with cystic fibrosis (pwCF). The relationship between measures of CFTR function, such as sweat chloride concentration, and clinical outcomes in pwCF treated with CFTR modulators is poorly defined. We conducted analyses to better understand the relationships between sweat chloride and CFTR function in vitro, and between sweat chloride and clinical outcomes following CFTR modulator treatment.

Methods: Mean sweat chloride values in healthy people, CF carriers, and pwCF treated with CFTR modulators at different doses were compared to chloride transport in corresponding human bronchial epithelial (HBE) cells. A pooled analysis of phase 3 CFTR modulator studies was performed to evaluate the relationship between attained values of sweat chloride and improvements in lung function, body mass index (BMI), patient reported outcomes, pulmonary exacerbations, and lung function change over time.

Results: Sweat chloride concentrations in vivo correlated strongly with CFTR-dependent chloride current in HBE cells in vitro. Sweat chloride values of <30 mmol/L and ≥30 to <60 mmol/L in pwCF following CFTR modulator treatment were associated with better clinical outcomes than sweat chloride ≥60 to <80 mmol/L and ≥80 mmol/L.

Conclusions: In pwCF treated with CFTR modulators, lower sweat chloride levels (reflecting greater CFTR function) are associated with better clinical outcomes. These results support the therapeutic strategy of further restoring CFTR function towards normal, as reflected in lowering sweat chloride to below the diagnostic threshold for CF (<60 mmol/L) and to normal (<30 mmol/L), with CFTR modulators.

背景:高效CFTR调节剂可改善许多囊性纤维化(pwCF)患者的CFTR功能并显著改善其健康状况。CFTR功能测量(如汗液氯化物浓度)与CFTR调节剂治疗pwCF的临床结果之间的关系尚不明确。我们进行了分析,以更好地了解汗液氯化物与体外CFTR功能之间的关系,以及CFTR调节剂治疗后汗液氯化物与临床结果之间的关系。方法:比较不同剂量CFTR调节剂处理的健康人、CF携带者和pwCF的平均汗液氯化物值与相应的人支气管上皮(HBE)细胞的氯化物转运。对3期CFTR调节剂研究进行了汇总分析,以评估汗液氯化物的获得值与肺功能、体重指数(BMI)、患者报告的结局、肺恶化和肺功能随时间变化的改善之间的关系。结果:体内汗液氯化物浓度与体外HBE细胞cftr依赖的氯电流密切相关。结论:在CFTR调节剂治疗的pwCF中,较低的汗液氯化物水平(反映更强的CFTR功能)与较好的临床结果相关。这些结果支持进一步恢复CFTR功能的治疗策略,如将汗液氯化物降低到CF的诊断阈值以下(
{"title":"Sweat chloride reflects CFTR function and correlates with clinical outcomes following CFTR modulator treatment.","authors":"Edith T Zemanick, Bonnie Ramsey, Dorota Sands, Edward F McKone, Isabelle Fajac, Jennifer L Taylor-Cousar, Marcus A Mall, Michael W Konstan, Nitin Nair, Jiaqiang Zhu, Emilio Arteaga-Solis, Fredrick Van Goor, Lisa McGarry, Valentin Prieto-Centurion, Patrick R Sosnay, Carmen Bozic, David Waltz, Nicole Mayer-Hamblett","doi":"10.1016/j.jcf.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.jcf.2024.12.006","url":null,"abstract":"<p><strong>Background: </strong>Highly effective CFTR modulators improve CFTR function and lead to dramatic improvements in health outcomes in many people with cystic fibrosis (pwCF). The relationship between measures of CFTR function, such as sweat chloride concentration, and clinical outcomes in pwCF treated with CFTR modulators is poorly defined. We conducted analyses to better understand the relationships between sweat chloride and CFTR function in vitro, and between sweat chloride and clinical outcomes following CFTR modulator treatment.</p><p><strong>Methods: </strong>Mean sweat chloride values in healthy people, CF carriers, and pwCF treated with CFTR modulators at different doses were compared to chloride transport in corresponding human bronchial epithelial (HBE) cells. A pooled analysis of phase 3 CFTR modulator studies was performed to evaluate the relationship between attained values of sweat chloride and improvements in lung function, body mass index (BMI), patient reported outcomes, pulmonary exacerbations, and lung function change over time.</p><p><strong>Results: </strong>Sweat chloride concentrations in vivo correlated strongly with CFTR-dependent chloride current in HBE cells in vitro. Sweat chloride values of <30 mmol/L and ≥30 to <60 mmol/L in pwCF following CFTR modulator treatment were associated with better clinical outcomes than sweat chloride ≥60 to <80 mmol/L and ≥80 mmol/L.</p><p><strong>Conclusions: </strong>In pwCF treated with CFTR modulators, lower sweat chloride levels (reflecting greater CFTR function) are associated with better clinical outcomes. These results support the therapeutic strategy of further restoring CFTR function towards normal, as reflected in lowering sweat chloride to below the diagnostic threshold for CF (<60 mmol/L) and to normal (<30 mmol/L), with CFTR modulators.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Journal of Cystic Fibrosis
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