Children (Basel). 2025 Jun 23;12(7):831. doi: 10.3390/children12070831.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a chronic genetic disease marked by progressive lung function decline and increased respiratory infections. Emerging evidence supports the role of physical exercise in improving lung function, aerobic capacity, and quality of life in pediatric CF patients.

METHODS: We reviewed randomized clinical trials and observational studies from the last ten years, sourced from PubMed and Google Scholar. Included studies involved children and adolescents (0-18 years) with CF and assessed physical exercise as a primary intervention to improve lung function, aerobic fitness, quality of life, or hospitalization rates.

RESULTS: Aerobic training, particularly when combined with strength training, improves cardiorespiratory fitness and muscle strength without compromising nutritional status. High-Intensity Interval Training and Inspiratory Muscle Training show potential but need further validation. Supervised, personalized exercise programs are key to promoting adherence and optimizing outcomes.

CONCLUSIONS: Exercise-based interventions in pediatric CF should evolve toward personalized, technology-enhanced, and sustainable models. Integrating wearable devices, adapting programs to individual needs, and leveraging early parental involvement may enhance engagement and outcomes, especially in the era of CFTR modulator therapies.

PMID:40723024 | DOI:10.3390/children12070831

Drug Ther Bull. 2025 Jul 27:dtb.2025.261989rep. doi: 10.1136/dtb.2025.261989rep. Online ahead of print.

NO ABSTRACT

PMID:40721231 | DOI:10.1136/dtb.2025.261989rep

JMIR Res Protoc. 2025 Jul 28;14:e68582. doi: 10.2196/68582.

ABSTRACT

BACKGROUND: Bronchodilators (BDs) have been used therapeutically to improve exercise capacity in patients with other chronic respiratory diseases. However, the effect of BDs on the exercise capacity of individuals with non-cystic fibrosis bronchiectasis (NCFB) is poorly understood.

OBJECTIVE: The aim of this study was to evaluate the effects of BDs on exercise capacity and thoracoabdominal kinematics in patients with NCFB.

METHODS: This crossover randomized controlled trial will involve 45 outpatients with NCFB aged 18 to 59 years. They will be evaluated in 3 visits. On day 1, the maximal exercise capacity (cardiopulmonary exercise test; peak work rate [Wpeak]) will be assessed. On day 2, individuals will be randomized to receive either BD (ipratropium bromide 160 µg and fenoterol hydrobromide 400 µg) or a placebo and then undergo simultaneous endurance exercise capacity (constant work-rate exercise test) and thoracoabdominal kinematics (optoelectronic plethysmography) assessments. After at least 1-week washout (day 3), the individuals will repeat the same assessments as on day 2 in the reverse order. The time to the limit of tolerance will be obtained in both groups (BD and placebo groups) as the primary outcome. Thoracoabdominal kinematics will be assessed at 3 time points: at rest, during unloaded exercise, and at 75% Wpeak. The total chest wall and compartmental volumes as well as thoracoabdominal asynchrony will be assessed. The assessors and patients will be blinded to the interventions (BDs or placebo). Data will be compared using 1-sided t tests or Wilcoxon tests and repeated-measures analysis of variance or Friedman tests. Categorical data will be analyzed using the chi-square test or Fisher test. The associations among variables will be analyzed using Pearson or Spearman correlation. The significance level will be set at 5% (P<.05).

RESULTS: The ethics approval was granted in November 2018, and a pilot study was commenced in April 2019 but was interrupted due to the COVID-19 pandemic. The study restarted in April 2022, and data collection is anticipated to continue until November 2025. The publication of the results is anticipated to be in 2025 or 2026.

CONCLUSIONS: There is no evidence that BDs can improve the exercise capacity of patients with NCFB. This trial will compare the endurance exercise capacity of the same individual with and without dual bronchodilation. If successful, this study will demonstrate that exercise capacity can be improved with the use of BDs in adults with NCFB.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05183841; https://clinicaltrials.gov/study/NCT05183841.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/68582.

PMID:40720815 | DOI:10.2196/68582

Am J Respir Cell Mol Biol. 2025 Jul 28. doi: 10.1165/rcmb.2025-0173OC. Online ahead of print.

ABSTRACT

RATIONALE: Viral lung infections are a major cause of morbidity and mortality worldwide. Despite significant advances in vaccines and antivirals, there remains a tremendous need for broadly applicable treatments that can be utilized across viral infections. Prior to infecting epithelial cells, viruses interact with the epithelial glycocalyx, which contains high molecular weight hyaluronan (HMWHA), a glycosaminoglycan that has beneficial effects in lung injury.

OBJECTIVE: To determine the role of HMWHA in viral pneumonia.

METHODS: We infected mice with Influenza or SARS-Cov2 and treated with prophylactic or therapeutic doses of HMWHA or saline control. We performed in vitro experiments of infection with viruses of respiratory and non-respiratory human and animal cells and evaluated the effect of HMWHA on infection. We analyzed existing databases for expression of hyaluronan and the transcription factor E2F1. Finally, we performed a clinical trial with HMWHA in patients with severe COVID-19 Measurements and Main Results: Exogenously applied HMWHA improved survival in SARS-CoV2 and influenza infection in mice, by ameliorating inflammation via the inhibition of E2F1. In a clinical study, inhaled HMWHA improved outcomes in patients with severe COVID-19. Furthermore, airway epithelia naturally express HMWHA, which is induced during viral infection and prevents infection via macromolecular crowding of viruses.

CONCLUSIONS: Our data provide a mechanistic justification for the use of HMWHA as a broadly effective prophylactic and therapeutic agent in viral airway infection. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMID:40720792 | DOI:10.1165/rcmb.2025-0173OC

Am J Respir Cell Mol Biol. 2025 Jul 28. doi: 10.1165/rcmb.2025-0141OC. Online ahead of print.

ABSTRACT

Secondary Streptococcus pneumoniae (Spn) infection to influenza A virus (IAV) frequently leads to an increase in morbidity and mortality of IAV. Our recent work establishes that IAV infection disrupts bacterial host defense in the lung epithelium through loss of cystic fibrosis transmembrane conductance regulator protein (CFTR) function, causing an acidification of the ASL and subsequently increasing susceptibility to Spn. Infection with IAV and other respiratory pathogens cause a robust endoplasmic reticulum (ER) stress response. However, the role of this acute ER stress response in predisposing the airway epithelium to susceptibility to bacterial infections remains unknown. Utilizing a primary differentiated human bronchial airway epithelial cell (HBEC) culture system, we find that both IAV-induced ER stress and ER stress alone increase susceptibility to Spn in the airway epithelium and lead to a loss of CFTR activity, subsequently causing a disruption in the rheostatic properties of the airway surface liquid. Importantly, in HBECs without functional CFTR, modulation of ER stress in the presence and absence IAV of has no effect on susceptibility to Spn. Restoration of ASL pH after ER stress in HBECs with functional CFTR reduces Spn, suggesting that ER stress increases susceptibility to bacterial infection by disrupting CFTR and causing an acidification of the ASL. Here, we demonstrate a clear role for ER stress in disruption of both the airway epithelium and bacterial host defense mechanisms during respiratory viral infection.

PMID:40720746 | DOI:10.1165/rcmb.2025-0141OC

PLoS One. 2025 Jul 28;20(7):e0328015. doi: 10.1371/journal.pone.0328015. eCollection 2025.

ABSTRACT

BACKGROUND: Gastrointestinal (GI) complications are the second most common disorders in persons with cystic fibrosis (PwCF). There is limited data on how having a dedicated CF-GI clinic and cystic fibrosis transmembrane conductance regulator (CFTR) modulators may affect rates of GI complications. Our aim was to assess the effect of the CF-GI clinic and CFTR modulators on GI complications with incidence of distal intestinal obstructive syndrome (DIOS).

METHODS: This was a retrospective study of adult PwCF who were seen in a CF-GI clinic from 2000-2023. Comparisons were made between the numbers of admissions and emergency department (ED) visits for DIOS at three years before and after CFTR modulator use and the first CF-GI clinic visit.

RESULTS: Of the 1,076 PwCF identified, 242 were seen in CF-GI clinic. Of this, 126 (52.1%) were female, with a median age of 40 (IQR: 30-47) years. There were 146 (60.3%) with regular use of laxatives. Of the 59 PwCF with CF-GI clinic visits for constipation, hospital admissions decreased in 16, were unchanged in 32, and increased in 11 (p = 0.402) while ED visits decreased in 9, remained the same in 40, and increased in 10 (p = 0.862). Of the 125 PwCF with CFTR modulator use, DIOS-related hospital admissions decreased in 15 patients, remained unchanged in 89, and increased in 21 (p = 0.021) while ED visits were fewer in 8, unchanged in 97, and increased in 20 (p = 0.587).

CONCLUSION: PwCF had high burden of constipation with a majority of patients regularly using laxatives, and almost half had a history of DIOS. CFTR modulator use and CF-GI clinic were not associated with a decrease of DIOS incidence.

PMID:40720490 | DOI:10.1371/journal.pone.0328015

Ann Am Thorac Soc. 2025 Jul 28. doi: 10.1513/AnnalsATS.202502-170OC. Online ahead of print.

ABSTRACT

Introduction People with cystic fibrosis (pwCF) are living longer with increasing comorbidities. The objective of this study was to estimate the rate of emerging non-pulmonary comorbidities in adults with CF and to compare these rates with the non-CF population. Methods This is a population-based cohort study of adults using Canadian CF Registry data linked with health administrative databases in Ontario, Canada. Cardiovascular disease (CVD) and symptomatic kidney stone cases were identified using diagnostic and procedural codes. Chronic kidney disease (CKD) was defined as eGFR<60 mL/min/1.73m2. Cancer cases were obtained using the Ontario Cancer Registry. Poisson regression was used to estimate the rates per 1,000 person-years of follow-up. Results The age- and sex-adjusted rates of CVD, CKD, kidney stones, and cancer per 1,000 person years in the non-lung transplant cohort were 24.5 (95% CI 21.5-28.0), 3.7 (95% CI 2.7-5.2), 7.4 (95% CI 6.1-9.0), and 5.8 (95% CI 4.5-7.6) respectively. pwCF who received lung transplant had higher rates of all four conditions, and cancer and CKD occurred earlier compared to the non-transplant cohort. When comparing the CF to the non-CF population, pwCF without lung transplant had higher age- and sex-adjusted rates of CVD (RR 2.9, 95% CI 2.6-3.4), CKD (RR 2.1, 95% CI 1.5-2.9), kidney stones (RR 2.9, 95% CI 2.4-3.6) and cancer (RR 1.9, 95% CI 1.5-2.5). These events occurred at a median age of at least 20 years earlier in the CF cohort. In the post-transplant population, the rates of CVD, kidney stones, and cancers were similar between pwCF and the non-CF population, however events occurred earlier in pwCF. Conclusion Non-pulmonary complications occur at a high rate and at a younger age in pwCF compared to the non-CF population which highlights the importance of incorporating these issues in CF care models.

PMID:40720184 | DOI:10.1513/AnnalsATS.202502-170OC

COPD. 2025 Dec;22(1):2532076. doi: 10.1080/15412555.2025.2532076. Epub 2025 Jul 28.

ABSTRACT

PURPOSE: Chronic pulmonary conditions require complex treatment strategies involving long-term antibiotic treatment, which carries the highest risk of antimicrobial resistance and adverse drug events (ADE). Specific guidance on prescribing and deprescribing can help reduce these risks and improve therapy effectiveness. The aim of the study was to determine prescribing and deprescribing practices for long-term antibiotic treatment (≥30 days) in preventing exacerbations of stable chronic pulmonary conditions in adult patients across all healthcare settings.

PATIENTS AND METHODS: This umbrella review was part of a larger registered study (PROSPERO, CRD42022381268) including systematic reviews and meta-analyses retrieved from PubMed, Cochrane Library, and PsycInfo. Outcomes of interest included condition, antibiotic, dose, duration, (de-) prescribing advice. Standardized methodological tools were used to assess methodological quality of the selected publications (ROBIS), facilitate data extraction (EPOC), and guide narrative summary of findings (PRIOR).

RESULTS: In total, n = 14 publications were analyzed. (De-)prescribing advice is summarized for treatment (≥30 days) of chronic obstructive pulmonary disease, asthma, non-cystic fibrosis bronchiectasis, cystic fibrosis, and bronchiolitis obliterans syndrome. Macrolides are the most commonly recommended antibiotic for stable chronic pulmonary conditions. ADEs are the main reason for antibiotic discontinuation. Little consideration is given to emergence of antibiotic resistance.

CONCLUSION: There is a significant paucity of literature providing specific (de-)prescribing advice for clinical practice. More precise recommendations are required in view of patient safety.

PMID:40719419 | DOI:10.1080/15412555.2025.2532076

Cureus. 2025 Jun 25;17(6):e86774. doi: 10.7759/cureus.86774. eCollection 2025 Jun.

ABSTRACT

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a chloride ion channel, and occurs frequently in the Caucasian population but rarely in Asia. Elevated sweat chloride using the sweat test is a gold standard for CF diagnosis, but it is not readily available in Japan. A 22-year-old man, who had past histories characteristic of CF, such as recurrent pneumonia, sinusitis, and pneumothorax, was referred to our hospital due to bronchiectasis and bronchial asthma. Examination revealed severely impaired lung dysfunction and abnormal chloride ion concentration in the sweat test corresponding to intermediate values, indicative of CFTR dysfunction. Analysis of his CFTR gene failed to detect any CF-causing variants, but showed the haplotype known to express a smaller amount of intact CFTR protein and associated with several pulmonary diseases. A diagnosis was made of bronchiectasis caused by CFTR dysfunction, and he was treated with inhalation solution of dornase alfa, hypertonic saline solution, and tobramycin at the age of 25; however, his lung deteriorated, and he died at the age of 32. As a result of retrospective reviewing of the lung images and functions from childhood, we found that pneumonia in childhood developed to cystic bronchiectasis in adulthood, and obstructive ventilator dysfunction already existed at the age of 13, progressing to the devastating decline of lung function as he grew. Pulmonary disease due to CFTR dysfunction in Japan has a poor prognosis because of challenges to access to the sweat test and a lack of recognition for CF.

PMID:40718166 | PMC:PMC12296961 | DOI:10.7759/cureus.86774

SAGE Open Med Case Rep. 2025 Jul 23;13:2050313X251359725. doi: 10.1177/2050313X251359725. eCollection 2025.

ABSTRACT

Congenital intra-abdominal masses can stem from various etiologies. However, the differential diagnoses in the presence of meconium peritonitis are primarily narrow to gastrointestinal disorders such as cystic fibrosis, Hirschsprung's disease, and colonic atresia. Additionally, literature has documented rare associations, including maternal hepatitis A infection. We present a case of a premature female infant born via cesarean section to a 25-year-old mother with adequate prenatal care. The mother had a history of flu-like symptoms and diarrhea during the first trimester and routine third-trimester pelvic sonogram findings raised concerns for fetal bowel obstruction or a pelvic mass accompanied by polyhydramnios. The infant presented with a rare occurrence of meconium peritonitis associated with maternal hepatitis A infection. This case is presented to engage and intrigue the medical community. In addition, it suggests that intrauterine exposure to the hepatitis A virus may contribute to fetal intra-abdominal vascular accidents, causing meconium peritonitis.

PMID:40717837 | PMC:PMC12290345 | DOI:10.1177/2050313X251359725

Respirology. 2025 Jul 27. doi: 10.1111/resp.70092. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: During exacerbations, when symptom and treatment burden are increased, individuals with cystic fibrosis (CF) are likely to prefer airway clearance techniques (ACTs) that require minimal effort. Therefore, in adults with CF who were hospitalised with an exacerbation, we sought to compare the effect of the MetaNeb with usual ACTs on respiratory function and expectorated sputum.

METHODS: This was a non-blinded randomised controlled trial where adults hospitalised with a CF exacerbation were allocated to an experimental intervention (EIx; MetaNeb) or a control intervention (CIx; their usual ACT). Both groups underwent twice-daily supervised airway clearance sessions, over an intervention period that ranged from 5 to 7 days during their hospitalisation. The primary outcome was ventilation inhomogeneity measured via lung clearance index (LCI) using the multiple breath washout technique. Secondary outcomes included adverse events, respiratory mechanics, forced expiratory volumes, sputum inflammatory markers, wellness, expectorated sputum, symptoms, participant satisfaction, and huff and cough counts.

RESULTS: Thirty participants were randomised (EIx group n = 14; CIx group n = 16). On completion of the intervention period, there was a greater improvement in LCI following the EIx than CIx (mean difference -0.84 units [-1.66 to -0.02], as well as some measures of respiratory mechanics. There were no between-group differences for the other secondary outcomes.

CONCLUSION: In adults with CF who were hospitalised with an exacerbation, twice daily MetaNeb produced greater improvements in ventilation inhomogeneity compared to twice daily usual ACTs. There were no between-group differences shown for the other outcomes, including respiratory symptoms.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12619001681145).

PMID:40716955 | DOI:10.1111/resp.70092

NPJ Vaccines. 2025 Jul 25;10(1):169. doi: 10.1038/s41541-025-01220-y.

ABSTRACT

Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) are members of the ESKAPE pathogens, a group of bacteria that are a threat to human health due to their ability to resist antibiotics. They are known to cause severe infections, often as co-morbidities, in individuals with conditions such as people with cystic fibrosis, diabetes, wounds, pneumonia, and critically ill patients requiring intubation leading to ventilator-associated pneumonia. Emergence of multi-drug resistance in SA and PA is making traditional antibiotic treatment ineffective and unfortunately there are no licensed vaccines to prevent MRSA or PA infections. We have demonstrated that when delivered intranasally (IN) L-PaF, a genetic fusion of the PA type III secretion system (T3SS) proteins PcrV and PopB (PaF) with LTA1, the active moiety of heat-labile enterotoxin from enterotoxigenic E. coli, protects against PA. L-PaF was formulated as a nanoemulsion (ME) to increase the protective immune response against clinically relevant PA strains in a mouse lung colonization model. With the addition NEAT2, the heme capturing domain of the SA protein IsdB, a bivalent vaccine was generated. IN administration of the bivalent formulation protected MRSA pre-exposed mice from both MRSA and PA infection. Sera from mice vaccinated with our formulation contained strong IgG titers with high levels of opsonophagocytic killing of homologous and heterologous PA and SA strains. Additionally, the bivalent L-PaF/NEAT2 formulation elicited stimulation of IL-17A and IL-2 cytokines. Because established PA and SA lung infection models with rabbits better reproduce the clinical hallmarks of severe human acute pneumonia, rabbits were immunized with the bivalent L-PaF/NEAT2 formulation. All of the vaccinated rabbits survived the challenges while the controls did not. These findings demonstrate that our L-PaF/ME/NEAT2 formulation has potential as a broad-spectrum vaccine against both SA and PA infection.

PMID:40715169 | DOI:10.1038/s41541-025-01220-y

J Cyst Fibros. 2025 Jul 24:S1569-1993(25)01536-X. doi: 10.1016/j.jcf.2025.07.012. Online ahead of print.

ABSTRACT

BACKGROUND: Maintaining optimal nutrition is often an important concern for persons with cystic fibrosis (PWCF). With the introduction of effective modulators, the focus has now shifted from preventing malnourishment to instead stabilizing weight and preventing further weight gain. Research on how PWCF experience and manage their nutrition in this new era remains limited.

METHODS: The Exploring Attitudes Toward Nutrition (EATN) study employed a qualitative, multi-site approach to conduct semi-structured interviews with 44 adults living with CF. These interviews explored participants' definitions of "good" nutrition, the facilitators that help support their diet and lifestyle, and the barriers they face. Thematic analysis was used to identify key barriers and facilitators across personal, social, and healthcare-related domains.

RESULTS: Interviews revealed PWCF defined nutrition in a multitude of ways, from 'a means to achieve optimal health,' to categorizing foods as "good" or "bad." Key facilitators for maintaining good nutrition included support from registered dietitian/CF care teams, convenience, physical activity, social support, and observations of weight stabilization after elexacaftor/tezacaftor /ivacaftor (ETI). Conversely, barriers included lack of convenience or time, gastrointestinal symptoms, sick days/ hospitalization, negative dietitian/care team member experiences, finances, and the impact of medications or enzymes.

CONCLUSIONS: Understanding these supports and challenges is essential for developing effective and personalized nutritional strategies for PWCF. Enhancing access to knowledgeable dietitians, simplifying nutritional recommendations, and addressing cost barriers can significantly improve nutritional outcomes. Future research should focus on applicable solutions that utilize existing successful strategies while addressing common barriers many with CF face.

PMID:40713200 | DOI:10.1016/j.jcf.2025.07.012

J Cyst Fibros. 2025 Jul 25:S1569-1993(25)01531-0. doi: 10.1016/j.jcf.2025.07.006. Online ahead of print.

NO ABSTRACT

PMID:40713242 | DOI:10.1016/j.jcf.2025.07.006

J Cyst Fibros. 2025 Jul 24:S1569-1993(25)01535-8. doi: 10.1016/j.jcf.2025.07.013. Online ahead of print.

ABSTRACT

Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction leads to progressive exocrine pancreatic insufficiency, resulting in difficulty in the secretion of digestive enzymes and subsequent malabsorption of nutrients. Case reports have described preserved pancreatic function with prenatal elexacaftor/tezacaftor/ivacaftor (ETI) exposure. However, little is known about pancreatic function and injury as ETI exposure decreases postnatally. Here, we discuss four infants with cystic fibrosis (CF) who were prenatally exposed to ETI, with pancreatic function ranging from preserved to mild insufficiency. All four developed elevated serum lipase, a marker of pancreatic cell injury, as ETI exposure diminished after birth. These cases illustrate the relationship between sweat chloride as a biomarker of CFTR function, fecal elastase as a biomarker of pancreatic function, and serum lipase a biomarker of pancreatic cell injury. While prenatal ETI exposure can preserve pancreatic function in infants with CF, ongoing postnatal ETI exposure may be necessary to prevent pancreatic damage, suggesting a role for early ETI therapy in prenatally exposed infants.

PMID:40713201 | DOI:10.1016/j.jcf.2025.07.013

J Cyst Fibros. 2025 Jul 24:S1569-1993(25)01530-9. doi: 10.1016/j.jcf.2025.07.005. Online ahead of print.

ABSTRACT

BACKGROUND: Five cystic fibrosis transmembrane conductance regulator (CFTR) modulator (CFTRm) therapies are approved for patients with cystic fibrosis (CF). Despite the established efficacy and safety of CFTRm therapy, variability exists in prescribing amongst CF physicians. Here, we describe prescriber factors influencing CFTRm use.

METHODS: This observational study used clinical vignettes of patients with CF. Participants were adult pulmonologists and pediatricians specializing in respiratory medicine from Germany, Italy, UK, Ireland, and the Netherlands. Participants took part in a 3-step data collection process: (i) 60-minute individual telephone interview; (ii) decision exercise where physicians made a treatment decision about CFTRm on 10 clinical vignettes; and (iii) 30-minute web-assisted interview to provide rationale for treatment decisions. Univariate analysis, dimensionality reduction via factor analysis, and a random-effects logistic regression model were used to identify factors impacting CFTRm prescribing.

RESULTS: Thirty-eight pulmonologists and 42 pediatricians provided 800 clinical decisions. Only 45 % of pulmonologists and 29 % of pediatricians prescribed a CFTRm for all eligible adult or pediatric vignettes. Pancreatic sufficiency decreased odds of prescribing a CFTRm (OR 0.106; 95 % CI 0.046, 0.244) whereas odds increased for patients' age >12 years (OR 3.779; 95 % CI 1.579, 9.042). Physician characteristics associated with CFTRm prescribing were being proactive/pushing boundaries (OR 1.772; 95 % CI 1.153, 2.722), having previously prescribed LUM/IVA (OR 2.732; 95 % CI 1.070, 6.974), and belief CFTRm therapies could improve adherence (OR 1.440; 95 % CI 0.946, 2.192).

CONCLUSIONS: Behavioral characteristics, attitudes toward CFTRm therapies, and experience with CFTRm therapies impact physician CFTRm prescribing more than individual disease factors.

PMID:40713199 | DOI:10.1016/j.jcf.2025.07.005

BMJ Case Rep. 2025 Jul 25;18(7):e267573. doi: 10.1136/bcr-2025-267573.

ABSTRACT

Fetal liver calcifications (FLCs) are relatively common findings on prenatal imaging, typically appearing as punctate, hyperechogenic areas with posterior acoustic shadowing. Although they may suggest genetic, infectious or vascular anomalies, isolated cases are often clinically insignificant. We are reporting a case of a pregnant woman in her late 30s whose routine second-trimester ultrasound revealed isolated, coarse FLCs. Despite their ultrasonographic appearance, prenatal investigations-including karyotyping, infection screening and cystic fibrosis testing-were unremarkable. The pregnancy progressed normally, culminating in the term delivery of a healthy male infant. Postnatal imaging confirmed isolated intrahepatic calcifications with no identifiable aetiology. Early vascular events during development were hypothesised. Prenatal diagnosis of FLCs requires consideration of multiple aetiologies and, consequently, targeted investigation. Once potential causes are excluded, isolated FLCs, even when coarse, do not appear to impact fetal or neonatal outcomes. The literature regarding the characterisation and management of coarse FLCs remains limited.

PMID:40713069 | DOI:10.1136/bcr-2025-267573

Eur Radiol. 2025 Jul 25. doi: 10.1007/s00330-025-11835-3. Online ahead of print.

ABSTRACT

OBJECTIVES: Cystic fibrosis (CF) is a prevalent autosomal recessive disorder, with lung complications being the primary cause of morbidity and mortality. In paediatric patients, structural lung changes begin early, necessitating prompt detection to guide treatment and delay disease progression. This study evaluates ultra-low-dose CT (ULDCT) versus chest x-rays (CXR) for children with CF (CwCF) lung disease assessment. ULDCT uses AI-enhanced deep-learning iterative reconstruction to achieve radiation doses comparable to a CXR.

MATERIALS AND METHODS: This prospective study recruited radiographers and radiologists to assess the image quality (IQ) of ten paired ULDCT and CXR images of CwCF from a single centre. Statistical analyses, including the Wilcoxon Signed Rank test and visual grading characteristic (VGC) analysis, compared diagnostic confidence and anatomical detail.

RESULTS: Seventy-five participants were enrolled, 25 radiologists and 50 radiographers. The majority (88%) preferred ULDCT over CXR for monitoring CF lung disease due to higher perceived confidence (p ≤ 0.001) and better IQ ratings (p ≤ 0.05), especially among radiologists (area under the VGC curve and its 95% CI was 0.63 (asymmetric 95% CI: 0.51-0.73; p ≤ 0.05). While ULDCT showed no significant differences in anatomical visualisation compared to CXR, the overall IQ for lung pathology assessment was rated superior.

CONCLUSION: ULDCT offers superior IQ over CXR in CwCF, with similar radiation doses. It also enhances diagnostic confidence, supporting its use as a viable CXR alternative. Standardising CT protocols to optimise IQ and minimise radiation is essential to improve disease monitoring in this vulnerable group.

KEY POINTS: Question How does chest X-ray (CXR) IQ in children compare to ULDCT at similar radiation doses for assessing CF-related lung disease? Findings ULDCT offers superior IQ over CXR in CwCF. Participants preferred ULDCT due to higher perceived confidence levels and superior IQ. Clinical relevance ULDCT can enhance diagnosis in CwCF while maintaining comparable radiation doses. ULDCT also enhances diagnostic confidence, supporting its use as a viable CXR alternative.

PMID:40711551 | DOI:10.1007/s00330-025-11835-3

J Bacteriol. 2025 Jul 25:e0014925. doi: 10.1128/jb.00149-25. Online ahead of print.

ABSTRACT

The PA7-clade (or group 3) of Pseudomonas aeruginosa is now recognized as a distinct species, Pseudomonas paraeruginosa. We report here the genomic sequences of six new strains of P. paraeruginosa: Zw26 (the first complete genome of a cystic fibrosis isolate of P. paraeruginosa), draft genomes of four burn and wound strains from Argentina very closely related to PA7, and of Pa5196, the strain in which arabinosylation of type IV pili was documented. We compared the genomes of 82 strains of P. paraeruginosa and confirmed that the species is divided into two sub-clades. Core genomes are very similar, while most differences are found in "regions of genomic plasticity" (RGPs). Several genomic deletions were identified, and most are common to the CR1 sub-clade that includes Zw26 and Pa5196. All strains lack the type 3 secretion system (T3SS) and instead use an alternative virulence strategy involving an exolysin, a characteristic shared with group 5 P. aeruginosa. All strains tend to be multiresistant like PA7, with a significant proportion of carbapenem-resistant strains, either oprD mutants or carrying carbapenemase genes. Although P. paraeruginosa is still relatively rare, it has a worldwide distribution. Its multiresistance and its alternative virulence strategy need to be considered in future therapeutic development.IMPORTANCEPseudomonas aeruginosa is an important opportunistic pathogen causing respiratory infections, notably in cystic fibrosis, and burn and wound infections. Our study reports six new genomes of Pseudomonas paraeruginosa, a new species recently reported as distinct from P. aeruginosa. The number of sequenced genomes of P. paraeruginosa is only about 1% that of P. aeruginosa. We compare the genomic content of nearly all strains of P. paraeruginosa in GenBank, highlighting the differences in core and accessory genomes, antimicrobial resistance genes, and virulence factors. This novel species is very similar in environmental spectrum to P. aeruginosa but is notably resistant to last-line antibiotics and uses an alternative virulence strategy based on exolysin-this strategy being shared with some P. aeruginosa outliers.

PMID:40709931 | DOI:10.1128/jb.00149-25

Immun Inflamm Dis. 2025 Jul;13(7):e70232. doi: 10.1002/iid3.70232.

ABSTRACT

BACKGROUND: Bitter taste receptors (TAS2Rs), originally identified for their role in gustation, are now recognized for their functions in extraoral tissues, particularly in innate immune responses. TAS2Rs detect bacterial quorum sensing molecules (QSMs) and other metabolites, enabling the host to sense and respond to pathogenic threats across mucosal surfaces.

OBJECTIVE: This review synthesizes current knowledge of TAS2Rs in the context of bacterial infection, emphasizing their mechanisms of immune modulation, genetic polymorphisms, tissue-specific expression, and therapeutic potential.

METHODS: A comprehensive literature review was conducted, incorporating in vitro, ex vivo, and in vivo studies investigating TAS2R expression, signaling pathways, and immune functions in response to bacterial pathogens across respiratory, gastrointestinal, and oral tissues.

RESULTS: TAS2Rs detect bacterial QSMs, triggering calcium signaling cascades, nitric oxide (NO) release, antimicrobial peptide secretion, and cytokine responses. In respiratory epithelium, TAS2R38 and TAS2R14 modulate mucociliary clearance and NO-mediated bacterial killing. In the oral cavity, TAS2R14 and TAS2R38 influence cytokine production, bacterial uptake, and antimicrobial responses. Intestinal TAS2Rs regulate host defense via genotype-specific pathways, as seen with TAS2R10 and TAS2R43. Polymorphisms in TAS2Rs affect infection susceptibility and immune responses, with implications for diseases like cystic fibrosis, chronic rhinosinusitis, dental caries, and periodontitis. Notably, TAS2R-mediated responses are highly tissue- and bacteria-dependent, with distinct signaling and outcomes observed depending on the pathogen and the local immune environment.

CONCLUSIONS: TAS2Rs play an essential role in host-pathogen interactions across multiple mucosal surfaces. Their ability to detect bacterial signals and activate innate immune defenses positions them as promising therapeutic targets. Future studies should focus on in vivo validation, genetic diversity, and receptor-ligand specificity using emerging tools like cryo-electron microscopy and transgenic models.

PMID:40709685 | DOI:10.1002/iid3.70232