Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (299)

Search Parameters:
Keywords = CFTR (Cystic Fibrosis Transmembrane conductance Regulator)

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
19 pages, 4247 KiB  
Article
Assessing CFTR Function and Epithelial Morphology in Human Nasal Respiratory Cell Cultures: A Combined Immunofluorescence and Electrophysiological Study
by Roshani Narayan Singh, Vanessa Mete, Willy van Driessche, Heymut Omran, Wolf-Michael Weber and Jörg Grosse-Onnebrink
Int. J. Mol. Sci. 2025, 26(15), 7618; https://doi.org/10.3390/ijms26157618 - 6 Aug 2025
Abstract
Cystic fibrosis (CF), the most common hereditary lung disease in Caucasians, is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). We evaluated CFTR function using a newly developed Ussing chamber system, the Multi Trans Epithelial Current Clamp (MTECC), in an [...] Read more.
Cystic fibrosis (CF), the most common hereditary lung disease in Caucasians, is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). We evaluated CFTR function using a newly developed Ussing chamber system, the Multi Trans Epithelial Current Clamp (MTECC), in an in vitro model of human airway epithelia. Air–liquid interface (ALI) cultures were established from nasal brushings of healthy controls (HC) and CF patients with biallelic CFTR variants. ALI layer thickness was similar between groups (HC: 62 ± 13 µm; CF: 55 ± 9 µm). Immunofluorescence showed apical CFTR expression in HC, but reduced or absent signal in CF cultures. MTECC enabled continuous measurement of transepithelial resistance (Rt), potential difference (PD), and conductance (Gt). Gt was significantly reduced in CF cultures compared to HC (0.825 ± 0.024 vs. −0.054 ± 0.016 mS/cm2), indicating impaired cAMP-inducible ion transport by CFTR. Treatment of CF cultures with elexacaftor, tezacaftor, and ivacaftor (Trikafta®) increased Gt, reflecting partial restoration of CFTR function. These findings demonstrate the utility of MTECC in detecting functional differences in CFTR activity and support its use as a platform for evaluating CFTR-modulating therapies. Our model may contribute to the development of personalized treatment strategies for CF patients. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Cystic Fibrosis)
Show Figures

Figure 1

14 pages, 759 KiB  
Review
The State of Weight in Cystic Fibrosis: Understanding Nutritional Status and Individualizing Nutritional Care in the Modulator Era
by Sapna Khemka, Stacie Hunter, Jessica Jones, Keishla Valentín-Martínez, Christina B. Chadwick and Rosara Bass
Nutrients 2025, 17(15), 2533; https://doi.org/10.3390/nu17152533 - 31 Jul 2025
Viewed by 235
Abstract
There is a well-established association between cystic fibrosis (CF) and malnutrition. Several comorbid conditions have also been associated with undernutrition in people with cystic fibrosis (PwCF). Highly effective modulator therapy has allowed for a paradigm shift altering disease progression and management. Modulator use [...] Read more.
There is a well-established association between cystic fibrosis (CF) and malnutrition. Several comorbid conditions have also been associated with undernutrition in people with cystic fibrosis (PwCF). Highly effective modulator therapy has allowed for a paradigm shift altering disease progression and management. Modulator use has even been associated with acceleration of weight trajectory causing overnutrition, which can lead to cardiovascular and metabolic comorbid conditions. This review explores how nutritional status is evolving in the era of cystic fibrosis transmembrane conductance regulator (CFTR) modulators in people with CF, specifically in children. By synthesizing current research, we aim to support pediatric healthcare providers and nutritionists in delivering tailored, proactive nutritional care in this new therapeutic landscape. Full article
(This article belongs to the Special Issue Nutrition and Cystic Fibrosis in Children)
Show Figures

Figure 1

15 pages, 1371 KiB  
Systematic Review
Refining CFTR-Related Metabolic Syndrome (CRMS)/Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) Diagnosis: Impact of CFTR2 Variant Classifications
by MacKenzie Wyatt, Alexandra Quinn, Lincoln Shade and Meghan McGarry
Int. J. Neonatal Screen. 2025, 11(3), 60; https://doi.org/10.3390/ijns11030060 - 30 Jul 2025
Viewed by 339
Abstract
An unintended consequence of cystic fibrosis (CF) newborn screening (NBS) is the identification of infants with a positive NBS who do not meet the diagnostic criteria for CF (two CF-causing variants and/or sweat chloride > 60 mmol/L). This indeterminate diagnosis is called cystic [...] Read more.
An unintended consequence of cystic fibrosis (CF) newborn screening (NBS) is the identification of infants with a positive NBS who do not meet the diagnostic criteria for CF (two CF-causing variants and/or sweat chloride > 60 mmol/L). This indeterminate diagnosis is called cystic fibrosis transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive, inconclusive diagnosis (CFSPID). CRMS/CFSPID occurs when it is not clearly known whether CFTR variants are disease-causing. In 2024, the CFTR2 classification of many CFTR variants was changed from unknown significance to either CF-causing variants or variants of varying clinical consequences (VVCCs). We conducted a meta-analysis of CRMS/CFSPID cases from manuscripts to describe how the diagnoses would change using two different variant panels: (1) only CF-causing CFTR variants (PanelCF-causing) and (2) CF-causing variants and VVCCs (PanelCF-causing+VVCCs). Using the PanelCF-causing, 8.7% had two CF-causing variants (reclassified as CF), while 91.3% had less than two CF-causing variants (reclassified as Undetected). Using the PanelCF-causing+VVCCs, 51.4% had either two VVCCs or one VVCC with one CF-causing variant detected (reclassified as CRMS/CFSPD), 39.9% had less than two CF-causing variants detected (reclassified as Undetected), and 8.7% had two CF-causing variants (reclassified as CF). In conclusion, using the updated CFTR2 classification of CFTR variants significantly decreases the number of children with CRMS/CFSPID and gives a definitive diagnosis of CF to some children while not detecting as many children who are unlikely to develop CF. Full article
Show Figures

Figure 1

18 pages, 670 KiB  
Article
Genetic Heterogeneity Correlated with Phenotypic Variability in 48 Patients with Cystic Fibrosis
by Mădălina Andreea Donos, Lăcrămioara Ionela Butnariu, Dana Teodora Anton Păduraru, Alina Mariela Murgu, Cristina Rusu, Monica Cristina Pânzaru, Roxana Popescu, Elena Țarcă, Elena Cojocaru, Gabriela Ghiga and Laura Mihaela Trandafir
J. Clin. Med. 2025, 14(15), 5362; https://doi.org/10.3390/jcm14155362 - 29 Jul 2025
Viewed by 230
Abstract
Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in [...] Read more.
Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype–phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Clinical Manifestations and Treatment)
Show Figures

Figure 1

6 pages, 408 KiB  
Brief Report
Pulmonary Function Modulates Epigenetic Age in Subjects with Cystic Fibrosis
by Alice Castaldo, Mariella Cuomo, Paola Iacotucci, Vincenzo Carnovale, Lorenzo Chiariotti, Giuseppe Castaldo and Monica Gelzo
Int. J. Mol. Sci. 2025, 26(14), 6614; https://doi.org/10.3390/ijms26146614 - 10 Jul 2025
Viewed by 303
Abstract
Cystic fibrosis (CF) is the most common severe autosomal recessive disease among Caucasians. Modulators of cystic fibrosis transmembrane conductance regulator (CFTR) mutated protein significantly improved the outcome of subjects with CF. In the present study, we studied epigenetic age, applying the Horvath clock [...] Read more.
Cystic fibrosis (CF) is the most common severe autosomal recessive disease among Caucasians. Modulators of cystic fibrosis transmembrane conductance regulator (CFTR) mutated protein significantly improved the outcome of subjects with CF. In the present study, we studied epigenetic age, applying the Horvath clock model, in 52 adult subjects with CF, all treated with elexacaftor/tezacaftor/ivacaftor (ETI). At baseline (T0), we found that half of the subjects have a significantly accelerated epigenetic age and a worse lung function, evaluated by forced expiratory volume in one second (FEV1). One year of ETI therapy (T1) impacted both the parameters, indicating that therapy with modulators must be started early, particularly in CF subjects with impaired lung function. The second group of CF subjects had an epigenetic age lower than the chronological one at T0 and lung function was better maintained. In these subjects, ETI therapy further improved lung function and tended to increase the epigenetic age, possibly improving metabolic functions and the general state of well-being. This also translates into an increase in the physical activities of a group of subjects who, before the therapy, had grown up under a glass bell. The analysis of epigenetic age may represent a potential biomarker to assess the individual outcome of the therapy in subjects with CF, although long-term studies need to evaluate it. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Show Figures

Figure 1

14 pages, 469 KiB  
Systematic Review
Effects of CFTR Modulators on Pseudomonas aeruginosa Infections in Cystic Fibrosis
by Camelia Corina Pescaru, Alexandru Florian Crișan, Adelina Marițescu, Vlad Cărunta, Monica Marc, Ștefan Dumitrache-Rujinski, Sorina Laitin and Cristian Oancea
Infect. Dis. Rep. 2025, 17(4), 80; https://doi.org/10.3390/idr17040080 - 7 Jul 2025
Viewed by 431
Abstract
Background: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Modulator therapies have the ability to improve CFTR function in CF patients, but despite the clear evidence of benefits regarding CFTR [...] Read more.
Background: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Modulator therapies have the ability to improve CFTR function in CF patients, but despite the clear evidence of benefits regarding CFTR modulator therapy, including improved lung function, the reduced rate of exacerbations, and an overall improved quality of life, studies focusing on the reduction rates of P. aeruginosa infections during modulator therapy expressed the need for future research on this topic. Objective: This study aimed to evaluate the impact of CFTR modulator therapies on the prevalence, density, and persistence of P. aeruginosa infection in CF patients and to explore the mechanisms involved. Methods: A systematic literature review was performed by searching five major databases (PubMed, Cochrane Library, Scopus, Google Scholar, and Web of Science), and 21 relevant articles investigating the link between CFTR therapy and P. aeruginosa infections were selected following the PRISMA guidelines. Results: The data indicated that Ivacaftor and the combination Elexacaftor/Tezacaftor/Ivacaftor (ETI) can reduce total bacterial load and markers of systemic inflammation. However, clonal lines of P. aeruginosa persist in most cases, and complete eradication is rare, mainly due to biofilm formation and antimicrobial resistance. Conclusions: Although CFTR-modulating therapies help to improve clinical condition and reduce inflammation, they do not consistently lead to the elimination of P. aeruginosa. Full article
Show Figures

Figure 1

25 pages, 1270 KiB  
Review
Biofilm Formation of Pseudomonas aeruginosa in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and Pathogenesis
by Dayana Borisova, Tsvetelina Paunova-Krasteva, Tanya Strateva and Stoyanka Stoitsova
Microorganisms 2025, 13(7), 1527; https://doi.org/10.3390/microorganisms13071527 - 30 Jun 2025
Viewed by 838
Abstract
Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting a large number of individuals in Europe. The disease arises from mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator, a chloride ion channel crucial for maintaining epithelial ion and [...] Read more.
Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting a large number of individuals in Europe. The disease arises from mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator, a chloride ion channel crucial for maintaining epithelial ion and fluid homeostasis. Dysfunctional CFTR disrupts mucociliary clearance, particularly in the respiratory tract, resulting in persistent bacterial colonization, chronic inflammation, and progressive pulmonary damage—ultimately leading to respiratory failure, the principal cause of mortality in CF patients. Early diagnosis and advances in therapy have substantially improved both survival and quality of life. A hallmark of CF pathology is the establishment of polymicrobial infections within the thickened airway mucus. Pseudomonas aeruginosa is the dominant pathogen in chronic CF lung infections and demonstrates a remarkable capacity for adaptation via biofilm formation, metabolic reprogramming, and immune evasion. Biofilms confer increased tolerance to antimicrobial agents and facilitate long-term persistence in hypoxic, nutrient-limited microenvironments. P. aeruginosa exhibits a wide range of virulence factors, including exotoxins (e.g., ExoU, ExoS), pigments (pyoverdine, pyochelin), and motility structures (flagella and pili), which contribute to tissue invasion, immune modulation, and host damage. During chronic colonization, P. aeruginosa undergoes significant genotypic and phenotypic changes, such as mucoid conversion, downregulation of acute virulence pathways, and emergence of hypermutator phenotypes that facilitate rapid adaptation. Persistent cells, a specialized subpopulation characterized by metabolic dormancy and antibiotic tolerance, further complicate eradication efforts. The dynamic interplay between host environment and microbial evolution underlies the heterogeneity of CF lung infections and presents significant challenges for treatment. Elucidating the molecular mechanisms driving persistence, hypermutability, and biofilm resilience is critical for the development of effective therapeutic strategies targeting chronic P. aeruginosa infections in CF. Full article
(This article belongs to the Section Biofilm)
Show Figures

Figure 1

21 pages, 2246 KiB  
Review
Potential Resistance Mechanisms Exhibited by Cystic Fibrosis Patients Against SARS-CoV-2
by Yasmin K. Elsharabassi, Nuha T. Swaidan and Mohamed M. Emara
Viruses 2025, 17(7), 919; https://doi.org/10.3390/v17070919 - 27 Jun 2025
Viewed by 394
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease pandemic. The virus primarily spreads through person-to-person contact via aerosols and droplets, contributing to high case numbers and related morbidities. SARS-CoV-2 targets the respiratory tract, causing acute [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease pandemic. The virus primarily spreads through person-to-person contact via aerosols and droplets, contributing to high case numbers and related morbidities. SARS-CoV-2 targets the respiratory tract, causing acute respiratory distress syndrome, particularly in immunocompromised individuals such as those with cystic fibrosis (CF). CF is a life-threatening genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to impaired respiratory function and recurrent severe respiratory symptoms. Despite their potential vulnerability, CF patients have shown a lower incidence of severe COVID-19, suggesting protective factors against SARS-CoV-2. Differential expression of the ACE2 receptor, crucial for viral entry, and other host factors, such as TMPRSS2, may play a role in this resistance to SARS-CoV-2. Analyzing the genomics and transcriptomics profiles of CF patients could provide insights into potential resistance mechanisms. The potential resistance mechanisms include blood and extracellular ATP levels, a deleted/dysfunctional CFTR gene, ACE and ACE2 regulation and expression, ACE and ACE2 polymorphism effects, host proteins and SARS-CoV-2 interactions, and SMN1 and ACE/ACE2 interactions. This review discusses the underlying factors and potential resistance mechanisms contributing to CF patients’ responses to SARS-CoV-2 infection. The review provides an opportunity to further investigate future therapy and research through understanding the underlying potential resistance mechanisms exhibited by CF patients against SARS-CoV-2, including ACE and ACE2 polymorphisms. Full article
(This article belongs to the Section Coronaviruses)
Show Figures

Figure 1

14 pages, 1494 KiB  
Article
Reported Adverse Events in Patients with CF Receiving Treatment with Elexacaftor/Tezacaftor/Ivacaftor: 5 Years Observational Study
by Francesca Lucca, Ilaria Meneghelli, Gloria Tridello, Francesca Buniotto, Giulia Cucchetto, Sonia Volpi, Emily Pintani, Valentino Bezzerri and Marco Cipolli
J. Clin. Med. 2025, 14(12), 4335; https://doi.org/10.3390/jcm14124335 - 18 Jun 2025
Viewed by 524
Abstract
Background: Elexacaftor/tezacaftor/ivacaftor (ETI) treatment is showing remarkable beneficial effects in people with Cystic Fibrosis (pwCF) harboring the F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Although this therapy is generally well tolerated in pwCF, some adverse events (AEs) [...] Read more.
Background: Elexacaftor/tezacaftor/ivacaftor (ETI) treatment is showing remarkable beneficial effects in people with Cystic Fibrosis (pwCF) harboring the F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Although this therapy is generally well tolerated in pwCF, some adverse events (AEs) have been recently described both in controlled studies and in post-marketing observations. Methods: We followed 414 pwCF carrying F508del CFTR that initiated ETI treatment, recording AEs for a period of 5 years. Results: A total of 142 AEs were reported. The most frequent AEs in the whole cohort were liver marker elevation, skin rush, epigastric pain, headache, and depression. Considering pediatric subjects, psychiatric and gastrointestinal disorders were the most frequent AEs. Only one patient reported a severe AE, leading to treatment discontinuation. In case of AEs, different decisions on ETI treatment were made, including temporary interruption and temporary or permanent dosage modification. Conclusions: Throughout the long-term observational period, almost 21% of pwCF experienced at least one AE. Psychiatric disorders, in particular attention deficit, were the most prevalent issue in our pediatric cohort, whereas adult patients mainly reported depression, anxiety and sleep disorders. This study therefore strengthen the recommendation of screening for changes in mental health during ETI treatment. AEs led to the permanent reduction of ETI dosage in 32% of cases, raising the issue of safety in relation to dosage reduction, efficacy, and minimum ETI levels. Eventually, this study highlights the need for a longitudinal monitoring of ETI safety since a significant number of AEs occurred after one year of treatment. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Novel Strategies of Diagnosis and Treatments)
Show Figures

Figure 1

20 pages, 285 KiB  
Review
Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis: A Review of Registry-Based Evidence
by Donatello Salvatore and Angela Pepe
J. Clin. Med. 2025, 14(11), 3978; https://doi.org/10.3390/jcm14113978 - 5 Jun 2025
Viewed by 1269
Abstract
Fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRms) have significantly improved outcomes in people with cystic fibrosis (CF). Real-world evidence, particularly from national and international CF registries, is essential to assess their long-term effectiveness and safety. We reviewed published studies using registry data to [...] Read more.
Fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRms) have significantly improved outcomes in people with cystic fibrosis (CF). Real-world evidence, particularly from national and international CF registries, is essential to assess their long-term effectiveness and safety. We reviewed published studies using registry data to evaluate the impact of CFTRms on clinical outcomes in individuals with CF. A narrative review of studies published between 2015 and 2025 was conducted, focusing on registry-based evaluations of ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor. Primary outcomes included lung function, pulmonary exacerbations, nutritional status, and survival. Fifty-seven registry-based studies confirmed the benefits of CFTRms across diverse CF populations. Ivacaftor has demonstrated sustained improvements in forced expiratory volume in one second (FEV1), reduced exacerbations, and improved nutritional outcomes. Lumacaftor/ivacaftor and tezacaftor/ivacaftor have shown modest benefits, especially in homozygous F508del patients. The introduction of elexacaftor/tezacaftor/ivacaftor has led to unprecedented improvements in lung function and quality of life, along with a reduced need for lung transplantation. Methodological heterogeneity and incomplete data remain challenges. Registry data provide essential, complementary evidence to clinical trials and support the effectiveness of CFTRms in routine care. Continued efforts are needed to harmonize registry methodologies and outcome measures. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Diagnosis and Treatment)
9 pages, 463 KiB  
Case Report
Elexacaftor/Tezacaftor/Ivacaftor Supports Treatment for CF with ΔI1023-V1024-CFTR
by Yunjie Huang, Jorge Moises Gonzales Cordova, Sarah Penrod, Lisa Lynn Bendy, Pi Chun Cheng, Don B. Sanders, Michael Denning Davis, Benjamin Gaston and James Francis Chmiel
Int. J. Mol. Sci. 2025, 26(11), 5306; https://doi.org/10.3390/ijms26115306 - 31 May 2025
Viewed by 514
Abstract
Cystic Fibrosis (CF) is a common genetic disease in the United States, resulting from mutations in the Cystic Fibrosis transmembrane conductance regulator (cftr) gene. CFTR modulators, particularly Elexacaftor/Tezacaftor/Ivacaftor (ETI), have significantly improved clinical outcomes for patients with CF. However, many CFTR mutations are [...] Read more.
Cystic Fibrosis (CF) is a common genetic disease in the United States, resulting from mutations in the Cystic Fibrosis transmembrane conductance regulator (cftr) gene. CFTR modulators, particularly Elexacaftor/Tezacaftor/Ivacaftor (ETI), have significantly improved clinical outcomes for patients with CF. However, many CFTR mutations are not eligible for CFTR modulator therapy due to their rarity. In this study, we report that a patient carrying rare complex CFTR mutations, c.1680-877G>T and c.3067_3072delATAGTG, showed positive clinical outcomes after ETI treatment. We demonstrate that ETI was able to increase the expression of CFTR harboring c.3067_3072delATAGTG in a heterologous system. Importantly, patient-derived nasal epithelial cells in an air–liquid interface (ALI) culture showed improved CFTR function following ETI treatment. These findings supported the initiation of ETI with the patient. Retrospective studies have suggested that the patient has shown small but steady improvement over the past two years in several clinical metrics, including lung function, body mass index (BMI), and sweat chloride levels. Our studies suggest that ETI could be beneficial for patients carrying c.3067_3072delATAGTG. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
Show Figures

Figure 1

30 pages, 4822 KiB  
Review
Redox Imbalance in Cystic Fibrosis: The Multifaceted Role of Oxidative Stress
by Ilaria Artusi, Michela Rubin and Giorgio Cozza
Pharmaceuticals 2025, 18(6), 784; https://doi.org/10.3390/ph18060784 - 24 May 2025
Cited by 1 | Viewed by 727
Abstract
Cystic fibrosis (CF), a severe genetic disorder stemming from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, is characterized by a complex interplay of chronic inflammation and heightened oxidative stress, resulting in substantial patient morbidity. The diverse array of [...] Read more.
Cystic fibrosis (CF), a severe genetic disorder stemming from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, is characterized by a complex interplay of chronic inflammation and heightened oxidative stress, resulting in substantial patient morbidity. The diverse array of CFTR mutations, categorized into seven distinct classes based on their functional impact on the CFTR protein, presents a significant obstacle to effective therapeutic intervention. While CFTR modulator therapies offer clinical benefits, their applicability is restricted to specific mutation classes, leaving a considerable portion of the CF patient population with unmet therapeutic needs. This review provides a critical analysis of the intricate role of oxidative stress in CF, meticulously examining its origins, mechanistic pathways and downstream pathological consequences, with particular emphasis on lipid peroxidation (LPO). It elucidates the nuanced connection between LPO and inflammatory processes driven by cellular stressors such as endoplasmic reticulum dysfunction, mitochondrial impairment and persistent bacterial infections. Furthermore, it evaluates the current landscape of therapeutic proposals targeting oxidative stress, including antioxidant interventions, and explores the potential of microRNAs (miRNAs) as novel targets. This review aims to synthesize existing research to provide a comprehensive understanding of oxidative stress involvement in CF pathogenesis while critically appraising the advantages and limitations of current antioxidant therapeutic strategies. Full article
(This article belongs to the Section Pharmacology)
Show Figures

Graphical abstract

12 pages, 1959 KiB  
Article
Interactions of CFTR and Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) in Prostate Carcinoma
by Sumit Bhattacharyya and Joanne K. Tobacman
Int. J. Mol. Sci. 2025, 26(9), 4350; https://doi.org/10.3390/ijms26094350 - 3 May 2025
Viewed by 2346
Abstract
Defective CFTR (cystic fibrosis transmembrane conductance regulator) is pathognomonic for cystic fibrosis (CF), which is characterized by an accumulation of tenacious secretions in pulmonary airways, as well as by abnormal ductal secretions in other organs, including the pancreas and prostate. The advent of [...] Read more.
Defective CFTR (cystic fibrosis transmembrane conductance regulator) is pathognomonic for cystic fibrosis (CF), which is characterized by an accumulation of tenacious secretions in pulmonary airways, as well as by abnormal ductal secretions in other organs, including the pancreas and prostate. The advent of CFTR modulating therapies has markedly improved the clinical status and survival of CF patients, primarily attributable to improved lung function. Previous publications reported that a decline in CFTR function was associated with a decline in activity and expression of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB). ARSB removes 4-sulfate groups from N-acetylgalactosamine 4-sulfate residues and is required for the degradation of chondroitin 4-sulfate (chondroitin sulfate A) and dermatan sulfate, two sulfated glycosaminoglycans which accumulate in cystic fibrosis. Declines in both ARSB and in CFTR have been associated with the development of malignancies, including prostate malignancy. The experiments in this report show that similar effects on invasiveness are present when either CFTR or ARSB is inhibited in human prostate epithelial cells, and these effects resemble findings detected in malignant prostate tissue. The effects of CFTR inhibition are reversed by treatment with recombinant human ARSB in prostate cells. These results suggest that treatment by rhARSB may benefit patients with cystic fibrosis and prostate cancer. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Cystic Fibrosis)
Show Figures

Figure 1

16 pages, 2833 KiB  
Article
Evolution of Lung Disease Studied by Computed Tomography in Adults with Cystic Fibrosis Treated with Elexacaftor/Tezacaftor/Ivacaftor
by Susana Hernández-Muñiz, Paloma Caballero, Adrián Peláez, Marta Solís-García, Carmen de Benavides, Javier Collada, Ignacio Díaz-Lorenzo, Cristina Zorzo, Rosa Mar Gómez-Punter and Rosa María Girón
J. Imaging 2025, 11(4), 124; https://doi.org/10.3390/jimaging11040124 - 21 Apr 2025
Viewed by 610
Abstract
Elexacaftor–tezacaftor–ivacaftor (ETI) has shown clinical and spirometric benefits in cystic fibrosis (CF). CT remains a vital tool for diagnosing and monitoring structural lung disease. This study aimed to assess the evolution of lung disease, as evaluated through CT, in adults with CF after [...] Read more.
Elexacaftor–tezacaftor–ivacaftor (ETI) has shown clinical and spirometric benefits in cystic fibrosis (CF). CT remains a vital tool for diagnosing and monitoring structural lung disease. This study aimed to assess the evolution of lung disease, as evaluated through CT, in adults with CF after at least one year of ETI treatment. This ambispective observational analysis assessed lung CT scans performed before initiating ETI and after at least one year of treatment, using the modified Bhalla scoring system. For those patients with an earlier CT scan, a pre-treatment phase analysis was performed. Epidemiological, clinical, and functional parameters were evaluated. Results: Sixty-two patients were included (35 males, median age 30.4 ± 7.87 years). After at least one year of ETI, significant improvements were observed in the global CT Bhalla score (12.2 ± 2.8 vs. 14.0 ± 2.8), peribronchial thickening (1.4 ± 0.6 vs. 1.0 ± 0.4), and mucus plugging (1.6 ± 0.7 vs. 0.8 ± 0.6) (p < 0.001). Spirometry parameters increased significantly: the percentage of the predicted forced expiratory volume in the first second (ppFEV1) increased from 66.5 ± 19.8 to 77.0 ± 20.4 (p = 0.005) and forced vital capacity (ppFVC) from 80.6 ± 16.4 to 91.6 ± 14.1 (p < 0.001). Additionally, body mass index showed a significant increase. A moderate correlation was found between the Bhalla score and spirometry results. In the pre-treatment phase (n = 52), mucus plugging demonstrated a significant worsening, whereas global CT score, other subscores, and spirometry did not change significantly. Conclusions: In adults with CF, after at least one year of ETI, a significant improvement in structural lung disease was achieved, as reflected by the CT Bhalla score. Full article
(This article belongs to the Special Issue Tools and Techniques for Improving Radiological Imaging Applications)
Show Figures

Graphical abstract

19 pages, 4065 KiB  
Article
Cis-Regulation of the CFTR Gene in Pancreatic Cells
by Clara Blotas, Anaïs Le Nabec, Mégane Collobert, Mattijs Bulcaen, Marianne S. Carlon, Claude Férec and Stéphanie Moisan
Int. J. Mol. Sci. 2025, 26(8), 3788; https://doi.org/10.3390/ijms26083788 - 17 Apr 2025
Viewed by 646
Abstract
Genome organization is essential for precise spatial and temporal gene expression and relies on interactions between promoters and distal cis-regulatory elements (CREs), which constitute ~8% of the human genome. For the cystic fibrosis transmembrane conductance regulator (CFTR) gene, tissue-specific expression, [...] Read more.
Genome organization is essential for precise spatial and temporal gene expression and relies on interactions between promoters and distal cis-regulatory elements (CREs), which constitute ~8% of the human genome. For the cystic fibrosis transmembrane conductance regulator (CFTR) gene, tissue-specific expression, especially in the pancreas, remains poorly understood. Unraveling its regulation could clarify the clinical heterogeneity observed in cystic fibrosis and CFTR-related disorders. To understand the role of 3D chromatin architecture in establishing tissue-specific expression of the CFTR gene, we mapped chromatin interactions and epigenomic regulation in Capan-1 pancreatic cells. Candidate CREs are validated by luciferase reporter assay and CRISPR knock-out. We identified active CREs not only around the CFTR gene but also outside the topologically associating domain (TAD). We demonstrate the involvement of multiple CREs upstream and downstream of the CFTR gene and reveal a cooperative effect of the −44 kb, −35 kb, +15.6 kb, and +37.7 kb regions, which share common predicted transcription factor (TF) motifs. We also extend our analysis to compare 3D chromatin conformation in intestinal and pancreatic cells, providing valuable insights into the tissue specificity of CREs in regulating CFTR gene expression. Full article
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
Show Figures

Figure 1

Back to TopTop