Cystic Fibrosis Pubmed Results

CONCLUSION: CEASE-CF positively impacted caregivers by increasing their awareness of the sources and harms of smoke exposure, equipping them with tools to change habits, and enhancing their self-reported confidence and self-efficacy for quitting. Consistent and multifaceted cessation support provided by a trained TTS is practice-changing and can be successfully integrated in CF care delivery.

CONCLUSIONS: P. aeruginosa EVs induced HBE cell inflammation, which was reduced in the presence of ETI.

CONCLUSIONS: This study showed that more frequent PEs in the first 2 years of age and chronic PA colonization were associated with poorer FEV1, FVC, and BMI values in CF patients.

CONCLUSION: This case shows that monitoring of etoposide plasma concentrations can be beneficial in complex clinical scenarios involving organ dysfunction and/or potential drug-drug interactions. This is especially important in curative treatment to avoid under dosing. This case report highlights the challenges of dosing etoposide in a patient with cystic fibrosis and liver cirrhosis who is taking multiple drugs that may interact with etoposide. The patient should be monitored closely on how the...

CONCLUSION: This study highlights ETI's efficacy in improving sinonasal involvement in children aged 6 to 12 with CF. This is in line with the observations of clinical improvement, and presents an alternative to sinus surgery, thus potentially leading to a reduction in surgical interventions.

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disorder, which manifests in many organ systems including the lungs. Chronic inflammation is a hallmark of CF lung disease leading to bronchiectasis and lung function decline. This is worsened by airway colonization and recurrent infections due to opportunistic pathogens such as Pseudomonas aeruginosa [PA], but the crosstalk between host-bronchial epithelium and immune system has been under characterized. Extracellular vesicles have...

Pseudomonas aeruginosa poses a significant therapeutic challenge in pediatric patients with cystic fibrosis (CF) due to increasing multidrug resistance (MDR) and carbapenem resistance, underscoring the need for surveillance to guide treatment strategies. In this study, sputum and throat swab samples were collected from inpatient and outpatient CF children with pulmonary infection at the Children's Medical Center in Tehran, Iran. Isolates were identified using standard culture and biochemical...

Prior studies in people with cystic fibrosis (CF) demonstrated a positive impact of ivacaftor on the stool microbiome. However, studies evaluating the impact of elexacaftor-tezacaftor-ivacaftor (ETI) on gut dysbiosis are limited. In this prospective, observational study, we evaluated the differences in stool microbiome in children (aged 2-17 years) with CF who were treated with ETI for at least two months and compared with children with CF who did not receive ETI. We also included healthy...

Background. Descriptions of genomic characters and dynamics related to Pseudomonas aeruginosa (PA) adaptation and survival in hospital water networks remain scarce but necessary for sustainable water management in hospitals.Methods. A new copper water network in an intensive care unit (ICU) was chronically colonized by a genotype sequence type (ST) 299 of PA and sporadically by a genotype ST2685. Sixty-eight ST299-PA and four ST2685-PA strains from ICU-water samples collected over 29 months and...

We report a paediatric case of acute recurrent pancreatitis (ARP) with persistently elevated salivary-type amylase levels, an uncommon biochemical pattern in ARP. Genetic analysis, focused on pancreatitis-related genes, identified heterozygous mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (p.Ala72Thr and p.Leu1156Phe). Although the patient showed no typical features or a family history of cystic fibrosis, partial CFTR dysfunction likely led to recurrent...

CONCLUSIONS: ETI therapy significantly improves glycemic control in CF, particularly when initiated at a young age. Further research is needed to confirm and detail these findings.

The population of adults with cystic fibrosis (CF) exceeds that of the pediatric CF population, and life expectancy for people with CF (PwCF) continues to improve, resulting in an adult CF population with chronic extrapulmonary comorbid conditions, including CF-related diabetes (CFRD), a common complication affecting roughly 50% of PwCF, as well as mental health disorders, including depression and generalized anxiety. These comorbidities have been strongly associated with increased risk of...

QUESTION: Cystic fibrosis (CF) affects > 11,300 people in the UK and is characterized by thick, sticky mucus in the lungs, leading to recurrent infections, inflammation, and progressive respiratory decline. Chest physiotherapy remains a cornerstone of airway clearance; however, many people with CF (pwCF) find it burdensome and time-consuming. Exercise has been proposed as a potentially effective and more acceptable alternative. The ExACT-CF feasibility trial evaluated the use of exercise as an...

CONCLUSION: This study highlights the emotional burden and caregiving responsibilities shouldered by family members of individuals with CF who have undergone lung transplantation. The findings emphasise the importance of person- and family-centred interventions, including support for palliative care discussions. A more structured and inclusive framework is essential to address the often-overlooked needs of families throughout the transplantation process.

Elexacaftor-tezacaftor-ivacaftor has transformed the treatment of people with cystic fibrosis (CF) and the predominant cystic fibrosis transmembrane conductance regulator (CFTR) variant F508del by delivering the faulty channel to the plasma membrane and potentiating its activity. However, the action of elexacaftor-tezacaftor-ivacaftor on the molecular behavior of F508del-CFTR is unknown. Here, we investigated the impact of elexacaftor-tezacaftor-ivacaftor on individual human F508del-CFTR Cl^(-)...

CONCLUSIONS: These findings indicate a reduction in insulin doses, particularly prandial insulin, as well as decreased glucose variability and hypoglycemia following ETI therapy in CFRD patients. Further long-term studies are needed to confirm these results.

P. aeruginosa and S. aureus are often co-isolated from biofilm-associated infections, such as those afflicting cystic fibrosis (CF) patients. Biofilms, along with the interspecies interactions, play a significant role in fostering antibiotic insusceptibility, contributing to infection chronicity. Previously, we showed that S. aureus adopts a viable but non-culturable (VBNC) state in biofilms with P. aeruginosa. Here, we aimed to gain insight into the impact of VBNC and phenomena such as...

CONCLUSIONS: The CF Foundation Mental Health Research Prioritization survey yielded a compelling roadmap for CF mental health research. These priorities are shaping initiatives to improve the mental health and well-being of PWCF and their families.

Cystic fibrosis-related diabetes (CFRD) is the most prevalent nonrespiratory complication of cystic fibrosis (CF), with its prominence growing as survival rates improve due to advances in CFTR modulator therapies. Its prevalence increases with age, affecting nearly 50% of patients with CF (PwCF) over 30 years old. CFRD primarily results from progressive pancreatic fibrosis leading to insulin deficiency, further compounded by intermittent insulin resistance during pulmonary exacerbations and...

CONCLUSIONS: Impaired glucose metabolism has a significant association with BMD in PwCF. Integrated monitoring of glucose and bone metabolism, along with a multidisciplinary approach is essential to optimize outcomes and reduce complications.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus, commonly found in patients with cystic fibrosis and severe asthma. It leads to bronchial inflammation, excessive mucus secretion, and progressive lung function decline. The diagnosis is challenging and is based on clinical, biological, and radiological criteria. Treatments include systemic corticosteroids, antifungals, and monoclonal antibodies such as omalizumab and mepolizumab. The triple...

Quantitative reverse transcription PCR (RT-qPCR) is a popular and reliable tool for monitoring fluctuations in functional bacterial gene expression. A necessary step of the qRT-qPCR process is the use of a reference gene, which acts to distinguish between technical bias and true biological variation. Many reference genes have been defined for bacterial species; however, few studies have validated their stability across strain types and environmental test conditions. In this study of Pseudomonas...

High mobility group box 1 (HMGB1), a highly conserved nuclear protein, is released into the extracellular milieu serving as a modulator of inflammatory responses. HMGB1 levels are elevated in the airspaces of CF patients and mice with cystic fibrosis (CF)--like lung disease. To reduce extracellular release of HMGB1 into the lung airspaces, we previously introduced airway epithelial cell-specific HMGB1 deficiency in Scnn1b-Tg+ (Tg+) mice, a model of human CF-like lung disease. While the deletion...

Clinical studies have shown that Elexacaftor-Tezacaftor-Ivacaftor (ETI) improves lung disease and body weight in individuals with cystic fibrosis (CF); however, gastrointestinal system effects remain unclear. The purpose of this study was to evaluate exocrine pancreatic function using fecal elastase-1 (FE-1) levels in CF patients receiving ETI therapy and to assess changes in fat-soluble vitamin levels specifically within the pancreatic-insufficient (PI) subgroup. We retrospectively evaluated...

CONCLUSION: In pwCF, HGS was associated with inspiratory muscle strength and FVCpp, underscoring its potential as a feasible adjunctive measure alongside lung function testing. These findings highlight resistance training as a modifiable target warranting further investigation to support both muscular and respiratory outcomes in this population.

Antibiotic-resistant infections remain a major challenge in cystic fibrosis (CF), where chronic Pseudomonas aeruginosa colonization drives lung infection. The overexpression of adhesion-related proteins and extracellular matrix components, including fibronectin (Fn), facilitates bacterial colonization. Recent evidence identifies the RNA-binding protein Human Antigen R (HuR) as a key regulator of this process, as it stabilizes Vav3 mRNA, promoting Fn deposition and the formation of bacterial...

CONCLUSION: "Do not call the global CF registry a dream, call it plan," and let's start with the first steps and get involved in the global CF community.

Drug-induced fever is a probably an under/misdiagnosed condition. The onset of drug-induced fever is highly variable among drugs and patients, usually occurring after 7-10 days of treatment, with rapid resolution after discontinuation. However, it sometimes appears at any time during treatment, even after stopping the drug. The estimated prevalence is 10%, and early diagnosis avoids hospitalizations, expensive treatments, and techniques, favoring the sustainability of the Health System. We...

Cystic fibrosis (CF) is caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, leading to abnormal anion transport and consequent airway dehydration and hyper-viscous mucus. Potential difference (PD) testing measures voltage across the epithelium and can be a sensitive marker for changes in ion transport reflective of CFTR activity. By the conventional method, agar gel salt-bridge-based probes in combination with calomel electrodes...

rhDNase I (recombinant human deoxyribonuclease I, known as Pulmozyme®) has mucolytic action, which is clinically exploited in cystic fibrosis (CF). In the lungs, its efficacy is hampered by both limited stability and presence of inhibitors such as G-actin. Here we synthesized three PEGylated rhDNase I conjugates differing in PEG length and conjugation chemistry, the latter affecting the overall charge of the conjugate. The aim was to preserve as much as possible the activity of the enzyme and to...

Trikafta modulators can correct the folding, thermal and gating defects of the most common cystic fibrosis mutant F508del of the human cystic fibrosis transmembrane conductance regulator. While folding correctors VX-445 and VX-809 are sufficient to rescue its folding and thermal defects by restoring Mg/ATP mediated dimerization between the two nucleotide binding domains (NBD1 and NBD2), the thermodynamic basis for the precise activity potentiation by VX-770 in Trikafta remains unknown. In this...

CONCLUSION: ETI therapy led to statistically significant improvements in lung function and a reduction in pulmonary exacerbations in CF patients with rare Middle Eastern variants. These findings, from the first report of its kind in this region, support the expansion of ETI access to individuals with rare CFTR variants, particularly in underserved populations, based on functional response. This underscores the benefit of ETI beyond the common F508del mutation.

CONCLUSIONS: SLC26A3 and CFTR perform distinct yet complementary functions. SLC26A3 dominates surface pH regulation and maintains bicarbonate efflux independently of CFTR, while CFTR drives agonist-stimulated fluid secretion. SLC26A3's ability to restore pH homeostasis and normalize mucin intracellular distribution in CF organoids demonstrates its critical importance for maintaining colonic mucosal health.

CONCLUSION: ETI treatment has a significant impact on children's QoL, particularly in physical health domains. Other QoL domains that are not improved by ETI need to be addressed, in particular, psycho-social components. Both children's and caregivers' perspectives must be considered for a holistic picture of children's QoL.

The SLC6A14 gene on chromosome X modifies disease presentation in individuals with cystic fibrosis (CF). Population studies have revealed distinct proximal and distal SNP clusters associated with gastrointestinal and lung phenotypes, respectively. Given the co-localization of cis-eQTLs within the corresponding associated chromosomal regions, where less SLC6A14 expression aligns with improved phenotypic outcomes, we sought to understand the SNP contributions to SLC6A14 expression regulation....

CONCLUSIONS: Nephrolithiasis events are common in PwCF. We observed an increased prevalence among PwCF with EPI, but did not observe a difference based on the degree of EPI control although this may be limited by reliance on clinician assessment of EPI control rather than a more objective measure. Prospective investigation with detailed assessment of risk factors including dietary habits and EPI control is warranted.

INTRODUCTION: Yoga is an emerging exercise choice for people with cystic fibrosis (CF), but evidence of its effect in this population is scarce, with a recent systematic review advocating for further research. Yoga Outcomes Get Assessed in CF (YOGA-CF) is a real-world multicentre randomised controlled trial (RCT) investigating a bespoke CF-specific online 12-week yoga intervention, vers usual care, to determine effectiveness for adults with CF.

CONCLUSIONS: Fungal colonization is common in children with CF and is associated with older age, impaired lung function, lower zBMI, and P. aeruginosa co-colonization. These findings support the need for routine fungal surveillance and further prospective studies to clarify clinical implications. Further research is needed to determine whether these relationships are causal.

IntroductionEffective management of pulmonary exacerbations (PEx) in cystic fibrosis (CF) is essential to minimise lung damage and reduce morbidity and mortality. Spirometry, the standard tool for lung function assessment in adult people with CF (pwCF), has limitations. Forced Oscillometry Technique (FOT) is an effort-independent method that assesses small airways disease and has been validated in other respiratory conditions. This study evaluated the feasibility and acceptability of...

CONCLUSION: In patients with CF and PEx, factors that suggest the possibility of concurrent PH include older age, infiltration or bronchiectasis on chest X-ray, NIV requirements, and elevated inflammatory markers.

CONCLUSION: Treatment with ETI in this unique cohort of pwCF was safe. Whereas ETI affected BMI in a subtle way, initiation of ETI was associated with stabilization of lung disease with a significant but moderate increase in lung function and a decline in the number of exacerbations in the follow-up period. Longer and larger studies will be needed to analyze the effect of ETI on an aging CF population.

Rare lung diseases are a group of diseases characterized by significant clinical heterogeneity, challenging diagnosis and treatment processes, and diverse underlying causes. Due to their uncommon symptoms and limited awareness among healthcare providers, these diseases are frequently misdiagnosed or diagnosed too late, resulting in poor patient outcomes and placing a significant healthcare burden on the healthcare system. However, in recent years, the rapid advancements in artificial...

Abstract.

CONCLUSION: The modified bronchoscopy score demonstrated moderate to excellent inter-rater reliability and added clinically relevant features specific to CF. It may serve as a standardized method to assess bronchoscopy for pediatric CF lung disease, although further validation is needed for features with lower inter-rater reliability.

The triple combinations of CFTR modulators, elexacaftor-tezacaftor-ivacaftor and more recently vanzacaftor-tezacaftor-deutivacaftor, have transformed the clinical course of cystic fibrosis (CF). These drug combinations were identified for their ability to restore CFTR function in F508del epithelial cells, and their efficacy has been shown in large randomized clinical trials involving people with CF with at least one F508del variant. Approximately 20 % of pwCF worldwide have no F508del variant...

CONCLUSIONS: The short- and long-term outcomes from our program are consistent with published registry data. These outcomes may reflect the benefits of a centralized pediatric lung transplant program, supported by a multidisciplinary team trained in high-capacity international centers.

PURPOSE OF REVIEW: Cystic fibrosis liver disease (CFLD) is a significant nonpulmonary complication of cystic fibrosis, affecting approximately 5-10% of patients. It encompasses a spectrum of hepatic abnormalities ranging from mild, transient elevations in liver enzymes to advanced CFLD (aCFLD), which is marked by clinically relevant portal hypertension due to cirrhotic or noncirrhotic liver pathology. This review focuses on aCFLD as the clinically meaningful form of the disease and summarizes...

Variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which causes cystic fibrosis, have become increasingly well-characterized in recent decades. However, clinicians remain challenged by CFTR variants that result in variable expressivity and reduced penetrance, including the variant R117H (c.350G>A) and the intron 9 poly-thymidine (poly-T) and poly-thymidine-guanosine (TG) tracts, highlighting a knowledge gap that impacts the delivery of accurate information to...

This non-interventional study was conducted at three cystic fibrosis (CF) treatment centers in Poland from August 2022 to July 2023. The aim was to assess the etiology of bacterial infection and evaluate antimicrobial susceptibility in CF patients. Prevalent pathogens were identified and their in vitro susceptibility to commonly prescribed antibiotics was assessed, highlighting potential needs in CF antibiotic therapy. Results indicated that Staphylococcus aureus was the most frequently isolated...

CONCLUSIONS: Our new and practical CXR score shows annual changes in CXR in adults with CF are insufficiently sensitive to detect disease progression and show no relationship to changes in other clinical parameters. These data suggest limited value in routine annual CXR for stable adults with CF.