Clin Transl Gastroenterol. 2025 Apr 18. doi: 10.14309/ctg.0000000000000846. Online ahead of print.

ABSTRACT

OBJECTIVE: Pathogenic variants (PVs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are commonly reported across the spectrum of pancreatitis, including acute (AP), recurrent acute (RAP), and chronic pancreatitis (CP). We aimed to define the pooled prevalence of CFTR PVs according to pancreatitis phenotype.

METHODS: A systematic search using synonyms for "CFTR" and "pancreatitis" was performed in Embase and Pubmed databases. The primary outcome was the frequency of subjects with at least one CFTR PV amongst those who underwent germline CFTR testing. Subgroup analyses included age, pancreatitis etiology, and genetic testing strategy. Confidence intervals (CIs) were obtained using the exact binomial method (Clopper-Pearson), and a Sidik-Jonkman random effects model was used to calculate pooled prevalence.

RESULTS: In total, 138 studies were included in the final analysis; 17 (n=1,873) reported populations with AP, 21 (n=1,172) with RAP, 86 (n=13,428) with CP, and 36 (n=4,521) with unspecified pancreatitis type. The pooled prevalence of at least one CFTR PV was 8.0% (95% CI: 4.3 - 14.4%) of AP, 16.4% (95% CI: 10.2 - 25.4%) of RAP, 15.3% (95% CI: 12.2 - 19.0%) of CP, and 25.0% (95% CI: 17.5 - 34.3%) of unspecified pancreatitis. Heterogeneity was high in each phenotype (I2 value range 88.3% to 96.7%).

CONCLUSIONS: These findings underscore the complex landscape of CFTR PVs in pancreatitis, emphasizing the importance of tailored approaches in addressing this genetic component across diverse patient groups and phenotypic presentations. Additionally, these data are useful for pre-test genetic counseling, and provide a justification for developing CFTR-directed interventions.

PMID:40249094 | DOI:10.14309/ctg.0000000000000846

Mhealth. 2025 Mar 21;11:20. doi: 10.21037/mhealth-24-66. eCollection 2025.

ABSTRACT

BACKGROUND AND OBJECTIVE: With the increased adoption of digital health solutions, such as telehealth, there is a need to consider current practices and considerations towards digital health Literacy. The objective of this review is to explore what digital health literacy considerations have been detailed in cystic fibrosis telehealth papers.

METHODS: The found papers published from a recent systematic review exploring telehealth within cystic fibrosis care were taken and analysed. These papers were obtained from PubMed, Web of Science, and Scopus databases and included any paper written in English up to May 2021. Data pertaining to Health Literacy, Digital Literacy/Competency, Digital Health Literacy, Training, Readiness Assessments, and Sustained Use were extrapolated using Elicit AI Research Assistant 2024.

KEY CONTENT AND FINDINGS: From the 26 papers, the data of interest was sparse and mostly unavailable for this review. This may be due to several reasons; however the implication of this mitigation is discussed with reference to the digital divide, health in-equalities, and safety.

CONCLUSIONS: This review highlights that a structured approach to assess digital health literacy of care teams and people with cystic fibrosis is critical to the future success of safe telehealth use, and other digital health solutions.

PMID:40248749 | PMC:PMC12004305 | DOI:10.21037/mhealth-24-66

J Clin Transl Endocrinol. 2025 Apr 2;40:100391. doi: 10.1016/j.jcte.2025.100391. eCollection 2025 Jun.

ABSTRACT

BACKGROUND/AIMS: People with CF (PwCF) have low total, high, and low density lipoprotein cholesterol (TC, HDL-C and LDL-C) and historically have had low prevalence of cardiovascular disease. More recently, cases of acute myocardial infarction are reported in PwCF. The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on cholesterol and triglyceride (TG) concentrations, traditional cardiometabolic risk factors, is unknown.

METHODS/RESULTS: TC, LDL-C, HDL-C, and TG concentrations were analyzed from participants enrolled in the observational PROMISE study of clinically prescribed ETI prior to and 12-18 months after initiation. Pre-ETI and follow-up concentrations were compared, and relationships between TC, LDL-C, HDL-C and TG and clinical factors were tested using linear mixed-effect models.Fasting samples were available for 51 participants (25 M/26F, median age 17.4 y) with pancreatic exocrine insufficiency at baseline and 12-18 months after ETI initiation. TC and HDL-C were higher after 12-18 mo ETI in an unadjusted model, but with adjustment for BMI-Z, only HDL-C remained significantly higher at follow up (p < 0.05). Low HDL-C was the most common abnormality (>50 %), but prevalence of participants meeting criteria for low HDL-C did not differ between timepoints.

CONCLUSIONS: In a population of youth and young adults with CF, TC and HDL-C were higher after 12-18 months of ETI, but differences in TC were attenuated with adjustment for BMI-Z. Prevalence of low HDL-C was high at both timepoints.

PMID:40248170 | PMC:PMC12005328 | DOI:10.1016/j.jcte.2025.100391

Learn Health Syst. 2024 Sep 14;9(2):e10453. doi: 10.1002/lrh2.10453. eCollection 2025 Apr.

ABSTRACT

BACKGROUND: Medication adherence data are an important quality indicator in cystic fibrosis (CF) care, yet real-time objective data are not routinely available. An online application (CFHealthHub) has been designed to deliver these data to people with CF and their clinical team. Adoption of this innovation is the focus of an National Health Service England-funded learning health system and Quality Improvement Collaborative (QIC). This study applies the capability, opportunity, and motivation model of behavior change to assess whether the QIC had supported healthcare professionals' uptake of accessing patient adherence data.

METHOD: This was a mixed-method study, treating each multidisciplinary team as an individual case. Click analytic data from CFHealthHub were collected between January 1, 2018, and September 22, 2019. Thirteen healthcare practitioners participated in semi-structured interviews, before and after establishing the QIC. Qualitative data were analyzed using the behavior change model.

RESULTS: The cases showed varied improvement trajectories. While two cases reported reduced barriers, one faced persistent challenges. Participation in the QIC led to enhanced confidence in the platform's utility. Reduced capability, opportunity, and motivation barriers correlated with increased uptake, demonstrating value in integrating behavior change theory into QICs.

CONCLUSION: QICs can successfully reduce barriers and enable uptake of e-health innovations such as adherence monitoring technology. However, ongoing multi-level strategies are needed to embed changes. Further research should explore sustainability mechanisms and their impact on patient outcomes.

PMID:40247895 | PMC:PMC12000760 | DOI:10.1002/lrh2.10453

Biol Direct. 2025 Apr 17;20(1):55. doi: 10.1186/s13062-025-00644-9.

ABSTRACT

BACKGROUND: Celiac disease (CD) is an autoimmune disorder that primarily affects the gut of genetically predisposed individuals and is triggered by gliadin peptides (PT) produced by the digestion of gluten. Although inappropriate activation of the immune system is thought to be the main trigger of CD, the interaction between PT and intestinal epithelial cells (IECs) remains a key step. Recently, the possible involvement of ER stress in the pathogenesis of CD has been pointed out, although its role is still largely unclear. Therefore, discovering the molecular mechanism(s) activated in IECs exposed to PT represents a unique opportunity to better understand the disease and define new potential therapeutic targets.

METHODS: In this study we used three different experimental set-ups: intestinal biopsies from CD patients and non-CD control subjects, an in vitro model, based on human CaCo-2 cells, and an ex vivo model, based on our recently described mouse gut-ex-vivo system (GEVS), with the latter two systems were studied after stimulation with gliadin peptides (PT). To understand the signaling pathways involved we monitor the expression of a number of proteins by qPCR, Western blotting, IF, ELISA or a combination of tests. Specifically, we have analyzed the level of CD, ER stress, tissue permeability, and inflammation markers.

RESULTS: Indeed, our study demonstrated a prompt induction of the transcription factors ATF4, ATF6 and XBP1 in IECs upon PT exposure. Thus, the upregulation of TG2 and downregulation of CFTR were prevented by ER stress inhibition/buffering by a pharmacological chaperone, also leading to restored physiological expression of OCL, CLD-2 and CLD-15, while preventing the expression of IFNγ, IL-15 and IL-17 A.

CONCLUSION: Overall, our analysis has highlighted the key role of ER stress in the pathogenesis of CD and identified the chemical chaperones as a new potential valuable therapeutic treatment for CD patients.

PMID:40247380 | DOI:10.1186/s13062-025-00644-9

J Appl Microbiol. 2025 Apr 17:lxaf093. doi: 10.1093/jambio/lxaf093. Online ahead of print.

ABSTRACT

AIMS: We aimed to investigate phenotypic and genomic traits of three Cupriavidus spp. isolates recovered from people with cystic fibrosis (PWCF). These bacteria are recognised as emerging pathogens in PWCF.

METHODS AND RESULTS: Using short and long sequencing reads, we assembled three hybrid complete genomes for the genus Cupriavidus, adding to the 45 published currently, describing multipartite genomes and plasmids. The isolates likely represent three different species, and they carry a cumulative total of 30 ARGs with high homology to well-characterised resistance determinants from other bacteria. Multidrug resistance to antibiotics used in CF management was observed in all three isolates. However, two treatments were active across all isolates: cefotaxime and piperacillin/tazobactam. Biofilm formation was only seen at physiological temperatures (37°C) and lost at 20°C and all isolates had low lethality in Galleria mellonella larvae. Isolates demonstrated variable motility, with one non-motile isolate carrying a disrupted flhD transcriptional regulator, abolishing flagella expression.

CONCLUSIONS: Our Cupriavidus spp. isolates showed considerable genomic and phenotypic variability that may impact their virulence and treatment in PWCF, where multidrug resistance will negate treatments and biofilm formation and motility play key roles in infection establishment, as seen in CF pathogens like P. aeruginosa. More detailed investigation of clinical Cupriavidus isolates is needed for full understanding of the risk they pose to PWCF.

PMID:40246707 | DOI:10.1093/jambio/lxaf093

J Cyst Fibros. 2025 Apr 16:S1569-1993(25)00764-7. doi: 10.1016/j.jcf.2025.03.668. Online ahead of print.

ABSTRACT

Portal hypertension (pH) secondary to cystic fibrosis liver disease (CFLD) is the fourth most common cause for mortality (after respiratory/cardiorespiratory, transplant-related, and cancer-related) in adults with cystic fibrosis (CF) and more often occurs in the absence of cirrhosis (i.e. non-cirrhotic pH, NCPH). Here, we describe a patient with NCPH secondary to CFLD, with resolution of pH after starting a cystic fibrosis transmembrane conductance regulator (CFTR) modulator. As demonstrated in this patient, CFTR modulators may provide extra-pulmonary benefits including reversal of NCPH. Long-term use of CFTR modulators could potentially result in reductions in mortality from pH and need for future liver or combined lung-liver transplantation in patients with CFLD.

PMID:40246668 | DOI:10.1016/j.jcf.2025.03.668

Respiration. 2025 Apr 17:1-18. doi: 10.1159/000545645. Online ahead of print.

ABSTRACT

Ensifentrine is a novel, low molecular weight molecule that is a selective, dual inhibitor of phosphodiesterase (PDE)3 and PDE4. Inhibition of PDE3 has been shown to relax airway smooth muscle and inhibition of PDE4 to inhibit inflammatory responses and to stimulate the cystic fibrosis transmembrane conductance regulator in human airway epithelial cells through accumulation of intracellular cyclic adenosine monophosphate. Additionally, the dual inhibition of PDE3 and PDE4 demonstrates enhanced or synergistic effects compared with inhibition of either PDE3 or PDE4 alone on contraction of airway smooth muscle and suppression of inflammatory responses. Ensifentrine inhalation suspension 3 mg was recently approved in the United States for the maintenance treatment of chronic obstructive pulmonary disease in adult patients and is marketed under the tradename OHTUVAYRE™. This manuscript describes further evidence that ensifentrine is a selective dual inhibitor of both human PDE3 and PDE4 enzymes and that this drug has significant anti-inflammatory activity in vivo in both allergic guinea pigs and non-human primates. This dual bronchodilator and anti-inflammatory activity of ensifentrine makes it a promising strategy as a novel inhaled "bifunctional" drug for the treatment of obstructive and inflammatory diseases of the respiratory tract.

PMID:40245851 | DOI:10.1159/000545645

J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Apr 14;1258:124604. doi: 10.1016/j.jchromb.2025.124604. Online ahead of print.

ABSTRACT

An ultra-high performance liquid chromatography-tandem mass spectrometry method was developed to quantify the cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor, tezacaftor, elexacaftor, and lumacaftor and their active metabolites hydroxymethyl ivacaftor, tezacaftor M1, and N-desmethylelexacaftor in human EDTA plasma. The analytical method utilized protein precipitation with stable isotope dilution for sample preparation, facilitating a simple and rapid assay, with a total runtime of only 2.1 min. Separation of the seven components and stable isotope-labeled internal standards was achieved on a C18 column, followed by detection using a tandem quadrupole mass spectrometer. Validation of the method was conducted in accordance with the "Bioanalytical Method Validation Guidance for Industry," of the Food and Drug Administration and with European Medicines Agency's "Guidance on bioanalytical method validation". The assay covers concentrations ranging from 0.010 to 10 mg/L for ivacaftor, hydroxymethyl ivacaftor and N-desmethylelexacaftor, from 0.025 to 25 mg/L for elexacaftor and tezacaftor, from 0.050 to 50 mg/L for tezacaftor M1 and from 0.100 to 100 mg/L for lumacaftor, using a sample volume of 10 μL. Matrix comparison confirmed the applicability of the assay to human serum and heparin plasma. Stability experiments indicated stability of the CFTR modulators in EDTA plasma over ten days under different conditions. At room temperature, all seven components remained stable for eight days and for ten days in the refrigerator in EDTA plasma and in EDTA whole blood. All seven components were stable in EDTA plasma for ten days in the autosampler after sample preparation and through four freeze-thaw cycles. The developed assay was applied in routine TDM analysis to investigate exposure to elexacaftor, tezacaftor, ivacaftor and their metabolites in people with CF undergoing treatment with Kaftrio®.

PMID:40245791 | DOI:10.1016/j.jchromb.2025.124604

Int J Mol Sci. 2025 Mar 31;26(7):3247. doi: 10.3390/ijms26073247.

ABSTRACT

Mycobacterium abscessus (Mab) is an opportunistic pathogen gaining increased importance due to its capacity to colonize the respiratory tract of patients with chronic lung diseases such as individuals with Cystic Fibrosis. The actual therapeutic regimen to treat Mab infections is based on repurposed drugs from therapies against Mycobacterium tuberculosis and avium. In addition to the need for new specific drugs against this bacterium, a possible strategy for shortening the therapeutic time and improving the success rate could be targeting Mab virulence factors. These drugs could become an important integration to the actual therapeutic regimen, helping the immune system to fight the infection. Moreover, this strategy applies a low selective pressure on the bacteria, since these elements are not essential for Mab survival but crucial for establishing the infection. This review aims to provide an overview of the Mab's virulence factors that are poorly studied and mostly unknown, suggesting some interesting alternatives to classical drug development.

PMID:40244091 | DOI:10.3390/ijms26073247

Pediatr Pulmonol. 2025 Apr;60(4):e71100. doi: 10.1002/ppul.71100.

ABSTRACT

OBJECTIVES: To characterize an observational cohort of ventilator-dependent infants and children with bronchopulmonary dysplasia (BPD) with or without tracheobronchomalacia (TBM) and determine the impact of TBM on the need for ventilator support, liberation from the ventilator and tracheostomy decannulation.

METHODS: Demographics and clinical outcomes were obtained by retrospective review from 12 centers participating in the outpatient BPD Collaborative registry. The cohort consisted of infants born between 2016 and 2021 who were dependent on invasive mechanical ventilation at home. The respiratory outcomes of those infants with TBM were compared to those who did not have TBM.

RESULTS: There were 154 subjects included and about half (48.7%) had documented TBM. Both the TBM and non-TBM groups had similar demographic characteristics and respiratory outcomes. However, the non-TBM were found to have lower mean birth weight (673 vs. 832 grams; p = 0.006), higher likelihood of having Nissen fundoplication (34.2% vs. 12.2%; p = 0.006) and higher use of diuretics (59.2% vs. 37.3%; p = 0.007). Both groups were similar in terms of ventilator requirements, timing of liberation from the ventilator, and rate of decannulation.

CONCLUSIONS: The presence of TBM in ventilator-dependent infants with BPD did not affect ventilator support needs, liberation from the ventilator and the rate of tracheostomy decannulation. We speculate that the relative contributions of the other components of BPD disease may play critical roles in determining the need for tracheostomy and their ultimate respiratory outcomes. A prospective multicenter study to assess the impact of TBM in severe BPD is urgently needed.

PMID:40243389 | DOI:10.1002/ppul.71100

Pediatr Pulmonol. 2025 Apr;60(4):e71096. doi: 10.1002/ppul.71096.

ABSTRACT

The field of pediatric rare and diffuse lung diseases continues to advance, with ongoing research deepening our understanding of the diagnosis and treatment of conditions such as children's interstitial and diffuse lung disease (chILD), non-cystic fibrosis (CF) bronchiectasis, and pulmonary complications of childhood cancer. Recent publications in Pediatric Pulmonology and other journals in 2024 have highlighted new insights into the pathophysiology, disease progression, and emerging diagnostic tools for these rare lung conditions, as well as innovative therapeutic approaches. This review features these important advancements within the context of current diagnostic practices and clinical care for pediatric patients with rare and diffuse lung diseases.

PMID:40243387 | DOI:10.1002/ppul.71096

Pediatr Pulmonol. 2025 Apr;60(4):e71087. doi: 10.1002/ppul.71087.

ABSTRACT

BACKGROUND: Despite pain's high prevalence and impact on quality of life and health outcomes, no studies have examined psychosocial approaches for treating pain in CF. We interviewed adults with CF and pain about their experiences to inform development of a CF-specific psychosocial pain management intervention.

METHODS: We partnered with CF Community Voice to recruit 14 adults with CF and pain for 1.5 h individual qualitative interviews and conducted a hybrid inductive-deductive thematic analysis (NVivo 14).

RESULTS: Participants' age ranged from 23 to 64 years; Seven were taking a modulator, 4 eligible/not taking, 3 ineligible. Pain sources included lung/chest, head/sinus, joint, bone, back, neuropathic, GI; 100% reported multiple sources. Pain experience: A major theme was the close interrelationship of pain and CF. Subthemes included pain being part of life with CF, having CF leads to high pain tolerance and effects of aging with CF. Participants described CFTR modulators effect pain experiences with 3 noting improvement and 4 worsening pain. Pain centralization was common: fatigue, difficulties with cognition/sleep, increased sensitivity to nonpainful stimuli. Pain impact: Pain has a widespread negative impact on quality of life and especially mental health. Resiliency was a theme: the need for coping strategies, support and strong self-advocacy. Advice for CF Care Teams: Participants endorsed a need for increased acknowledgment of pain experiences and co-development of a treatment plan.

CONCLUSIONS: Pain remains a prominent, burdensome symptom in the modulator era, necessitating a multi-component management approach. Results informed the development and pilot of a mind-body pain intervention for adults with CF.

PMID:40243360 | DOI:10.1002/ppul.71087

Pediatr Pulmonol. 2025 Apr;60(4):e71094. doi: 10.1002/ppul.71094.

ABSTRACT

BACKGROUND: Severe lung disease such as chronic pulmonary disease (CPD), severe asthma and cystic fibrosis (CF) in children is associated with increased risk of severe COVID-19. Information regarding SARS-CoV-2 infection, disease severity and outcome of COVID-19 is limited in this pediatric population.

OBJECTIVES: We captured the number of SARS-CoV-2 infected children and evaluated COVID-19 disease severity in non-immunized children with CPD, asthma, and CF in a cohort at a Danish tertiary center.

METHODS: The number of children with PCR-verified SARS-CoV-2 infection in the cohort and in the age-related background population was identified through the Danish Microbiology Database. Clinical data were retrieved from the electronic medical health records and from the Danish Health Authority.

RESULTS: In a cohort of 664 children with severe lung disease 594 were either PCR-tested or had an antibody test for SARS-CoV-2 infection due to symptoms or exposure and 18 (3%) had verified SARS-CoV-2 infection. The total number of verified SARS-CoV-2 infection was at that time 34.575(4.342%) thus, not significantly different from the reference population (p = 0.152). The symptoms ranged from asymptomatic to mild symptoms, and none of the children with severe lung disease required hospitalization due to COVID-19. None of the children were treated with antiviral treatment during the acute infection.

CONCLUSION: Of the 664 children in the Danish cohort with severe lung disease, none were hospitalized with COVID-19. Our findings imply that this particular group of patients do not experience increased risk of severe COVID-19.

PMID:40243356 | DOI:10.1002/ppul.71094

Respirol Case Rep. 2025 Apr 15;13(4):e70185. doi: 10.1002/rcr2.70185. eCollection 2025 Apr.

ABSTRACT

The coexistence of trisomy 21 and cystic fibrosis (CF) is extremely rare, with fewer than 10 reported cases, all involving homozygous CFTR mutations. However, the impact of a heterozygous CFTR mutation in a patient with trisomy 21 remains unexplored. We present a male infant with trisomy 21 who experienced recurrent respiratory distress and was later found to carry a heterozygous pathogenic CFTR mutation (p.Phe508del). His respiratory complications were severe, requiring tracheostomy and long-term respiratory support. This case highlights the potential interplay between trisomy 21-associated anatomical features and CFTR-related airway abnormalities, possibly exacerbating respiratory morbidity. Given the high burden of respiratory complications in both conditions, clinicians should consider CFTR-related disorders in patients with trisomy 21 presenting with severe respiratory issues. Further research is warranted to determine the clinical significance of CFTR heterozygosity in trisomy 21 and its implications for disease severity and management.

PMID:40241998 | PMC:PMC12000535 | DOI:10.1002/rcr2.70185

Arch Virol. 2025 Apr 16;170(5):106. doi: 10.1007/s00705-025-06282-w.

ABSTRACT

The escalating challenges of antibiotic resistance in bacterial pathogens have necessitated the exploration of alternative therapeutic strategies. Among these, bacteriophage therapy has regained attention as a promising approach to combat multidrug-resistant bacteria. Bacteriophages are viruses that infect and lyse specific bacterial strains, making them attractive candidates for targeted antimicrobial treatment. Burkholderia multivorans, a Gram-negative bacterium, is known to cause opportunistic infections, particularly in individuals with a compromised immune system or with cystic fibrosis. The prevalence of antibiotic-resistant Burkholderia strains has raised concerns about treatment options. In this study, we characterized the Burkholderia phage Bm1, a virulent bacteriophage isolated from an environmental source. Electron microscopy revealed that Bm1 phage particles have myovirus morphology, with an icosahedral head of 72 nm in diameter and a contractile tail of 100 nm in length and 18 nm in width. The genome of phage Bm1 consists of a double-stranded DNA of 67,539 bp with a terminal repeat region at each end. Comparative analysis indicated that the closest relative of phage Bm1 is Burkholderia phage BCSR129, with a calculated VIRIDIC identity of 57.7%. The apparent absence of an integrase gene suggests that the Burkholderia phage Bm1 has a strictly lytic life cycle.

PMID:40240564 | DOI:10.1007/s00705-025-06282-w

Eur Radiol. 2025 Apr 16. doi: 10.1007/s00330-025-11589-y. Online ahead of print.

ABSTRACT

OBJECTIVES: MRI detects abnormal lung perfusion in patients with cystic fibrosis (CF). However, little is known about the contribution of bronchial arteries to lung perfusion in CF. We hypothesized that delayed perfusion can be detected by dynamic contrast-enhanced (DCE-)MRI and that bronchial artery dilatation (BAD) is associated with changes in lung perfusion.

MATERIALS AND METHODS: Morpho-functional MRI was prospectively acquired in 75 patients with CF (18.7 ± 7.6 years, range 6-39 years). Lungs and perfusion defects were segmented automatically to quantify perfusion defects in percent (QDP). Pulmonary blood flow (PBF), mean transit time (MTT), and perfusion delay were calculated for the whole lung, inside normally perfused and perfusion defect areas. Chest MRI score and BAD were assessed visually.

RESULTS: QDP and PBF correlated with MRI global score (r = 0.58 and -0.53, p < 0.001). In normally perfused lung, PBF was higher (161.2 ± 77.9 mL/100 mL/min vs. 57.5 ± 26.4 mL/100 mL/min, p < 0.001), and MTT (5.4 ± 1.7 s vs. 6.9 ± 2.3 s, p < 0.001) and perfusion delay were shorter than in perfusion defect areas (4.6 ± 5.3 s vs. 13.4 ± 16.2 s, p < 0.001). 48 (64.0%) patients showed BAD, had higher QDP (44.6 ± 20.8% vs. 17.3 ± 11.0%, p < 0.001) and lower PBF (91.9 ± 54.8 mL/100 mL/min vs. 178.3 ± 77.4 mL/100 mL/min, p < 0.001) than patients without BAD. MTT was shorter (6.3 ± 1.9 s vs. 8.0 ± 2.6 s, p < 0.001), and perfusion delay was longer (13.8 ± 10.1 s vs. 12.8 ± 23.7 s, p < 0.02) inside perfusion defects of patients with BAD compared to without BAD.

CONCLUSION: Perfusion parameters correlate with lung disease severity, and perfusion defects showed delayed perfusion in patients with CF. BAD was associated with more extensive perfusion defects and reduced PBF.

KEY POINTS: Question Dilated bronchial arteries are a common comorbidity in cystic fibrosis (CF), which can cause hemoptysis, but their quantitative contribution to lung perfusion is little researched. Findings Perfusion defects in percent (QDP) enabled objective assessment of perfusion abnormalities in CF patients, while perfusion delay and arterial correlation showed bronchial artery perfusion contribution. Clinical relevance The usage of quantitative perfusion metrics in CF may help tracking disease progression. By also including the proposed metrics perfusion delay and arterial correlation, bronchial artery inflow could be assessed and used to detect early onset of bronchial artery dilation.

PMID:40240556 | DOI:10.1007/s00330-025-11589-y

Eur J Hum Genet. 2025 Apr 16. doi: 10.1038/s41431-025-01835-8. Online ahead of print.

ABSTRACT

Using the Australian Census survey 2021 as base population, a microsimulation model, PreconMOD was developed to evaluate the cost-effectiveness of population-based expanded reproductive carrier screening (RCS) for 569 recessive conditions from the health service and societal perspectives. The model simulated the effect of expanded RCS including the downstream interventions for at-risk couples on cost and outcomes. The comparators were (i) no population screening (ii) limited screening for cystic fibrosis, spinal muscular atrophy, and fragile X syndrome and (iii) a 300 conditions screening panel. Averted affected births and health service cost with expanded RCS were projected to year 2061. At a 50% uptake, our model predicts that expanded RCS is cost saving (i.e., higher quality-adjusted life-years and lower costs) compared with other screening strategies in the model from the health service and societal perspectives. The number of affected births averted in a single cohort would increase from 84 [95% confidence interval (CI) 60-116] with limited screening to 2067 (95%CI 1808-2376) with expanded RCS. Expanded RCS was cost-saving compared to the 300-conditions screening panel. Indirect cost accounted for about one-third of the total costs associated with recessive disorders. Our model predicts that the direct treatment cost associated with current limited 3 genes screening would increase by 20% each year to A$73.4 billion to the health system by 2061. Our findings contribute insights on the cost burden of genetic diseases and the economic benefits of expanded RCS to better informed resource allocation decisions.

PMID:40240435 | DOI:10.1038/s41431-025-01835-8

J Cyst Fibros. 2025 Apr 16:S1569-1993(25)00769-6. doi: 10.1016/j.jcf.2025.04.003. Online ahead of print.

ABSTRACT

BACKGROUND: Highly effective modulator therapies (HEMT) are increasing the lifespan for many people with cystic fibrosis (pwCF), making it necessary to identify and understand CF specific age-related consequences. In this study, we examine the impact of aging on cognitive function and age-related brain pathology in a CF mouse model focusing on phospho-Tau (pTau) pathology.

METHODS: Cognitive function was measured by novel object recognition and spontaneous alternation behavior tests. Hippocampal neuronal function was assessed by measuring long-term potentiation (LTP) electrophysiology, the synaptic correlate of learning and memory. Tau pathology was assessed by immunohistochemical analyses and western blot assessment of pTau levels in CF mouse brain, as well as human nasal epithelial cells isolated from pwCF.

RESULTS: Cognitive function declined progressively with age in Cftr (G542X/G542X) (G542X) mice, a model of CF, compared to wild-type (WT) littermate controls. LTP was also deficient in older G542X mice. Increased pTau was observed by staining and western blot analysis in the hippocampus of aged CF mice. Secondary impacts of tauopathy, including increased microglial uptake of cholesterol and reduced neuronal density were also observed. Lastly, human nasal epithelial cells from pwCF were found to display elevated pTau levels compared to non-CF controls.

CONCLUSIONS: Aging CF mice develop tauopathy, cognitive decline, LTP impairment, microglial activation, and neurodegeneration that is not experienced by age-matched WT littermates, a condition herein termed cystic fibrosis-related neurodegeneration (CFND). These findings suggest that pwCF may be at risk for tauopathy-related neurodegeneration and cognitive impairment with aging.

PMID:40240239 | DOI:10.1016/j.jcf.2025.04.003

Eur Respir Rev. 2025 Apr 16;34(176):240227. doi: 10.1183/16000617.0227-2024. Print 2025 Apr.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) registries capture important information in high-burden health domains to support improvement in health outcomes, although a number of unanswered questions persist, as follows. 1) Do CF registries utilise implementation science strategies to improve patient outcomes? 2) Which implementation strategies have been engaged? 3) Has the engagement of these strategies been effective in improving clinical outcomes?

METHODS: We undertook a systematic review to exploring the use of implementation science strategies by CF registries for healthcare improvement. We searched MEDLINE, Embase, Scopus, Emcare and Web of Science databases for use of Expert Recommendations for Implementing Change (ERIC) implementations and use of the Knowledge to Action framework for improvement. We used the Risk of Bias in Non-randomised Studies - of Interventions tool for risk-of-bias assessment.

RESULTS: 1974 citations were identified and 12 studies included. Included studies described 45 ERIC implementation strategies from nine categories. Strategies included "use evaluative and iterative strategies" (n=9) and "develop stakeholder interrelationships" (n=10). Least-used strategies were "utilise financial strategies" (n=1), "support clinicians" category (n=3) and "provide interactive assistance" (n=2). All 12 studies utilised monitoring of knowledge use, and assessing barriers and facilitators of knowledge use. Only seven studies utilised mechanisms to sustain knowledge use.

DISCUSSION: Reported studies describe significant benefits in important CF outcomes for people with CF reported at site-specific and population levels. Studies highlighted the importance of governance, leadership, patient and family engagement, multidisciplinary engagement, quality improvement, data and analytics and research. The ready availability of clinical performance data feedback to clinicians and patients by CF registries is likely to strengthen the effectiveness of CF registries in driving healthcare improvement within a learning health system.

PMID:40240058 | DOI:10.1183/16000617.0227-2024