Clin Nutr ESPEN. 2025 Apr 24:S2405-4577(25)00274-8. doi: 10.1016/j.clnesp.2025.04.006. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Elexacaftor, Tezacaftor, Ivacaftor has enhanced clinical outcomes, expected lifespan and quality of life for people with cystic fibrosis. Increased body mass index post- Elexacaftor, Tezacaftor, Ivacaftor is well documented, suggesting high-energy, high-fat recommendations may no longer be appropriate. This study aims to identify changes in dietary intake and nutritional parameters post gene modulator therapy Elexacaftor, Tezacaftor, Ivacaftor.

METHODS: A retrospective cohort study assessed diet and nutritional parameters of adults with cystic fibrosis (n=40) pre- and post- Elexacaftor, Tezacaftor, Ivacaftor (9 ± 3 months). Dietary intake was analysed (24hr recalls), for total energy intake, macronutrient distribution, sodium, core food groups, and discretionary intakes being compared to Nutrition Guidelines for people with cystic fibrosis, and general population guidelines.

RESULTS: Total energy intake decreased from 139.3 to 116.6kJ/kg/day (p=0.012) and was below the estimated energy requirement for people with cystic fibrosis by 4457.3kJ (p<0.001), despite body mass index increasing (p=<0.001). Median dietary sodium decreased from 1364mg to 1251mg (p=0.028). Intake of protein was above, and total fat intake met the higher end of guidelines for people with cystic fibrosis. Saturated fat intake did not change (p=0.403) however exceeded general guidelines of <10% total energy intake in line with general population intake of 15.9%. A decrease in discretionary foods (5.1 to 4.5 serves/d, p=0.038) and increase in vegetable intake (interquartile range 1.0-2.9 to 1.5-3.7 serves/d, p=0.036) was noted. Serum retinol levels increased from 1.7μmol/L to 2.0μmol/L (p=0.003).

CONCLUSION: Dietary patterns of people with cystic fibrosis change following Elexacaftor, Tezacaftor, Ivacaftor commencement. While total energy intake decreased and vegetable intake increased, saturated fat and discretionary intake remained high, increasing risk of metabolic disease. An individualised approach is needed with modulator therapy and recognition that changing diet is a modifiable risk factor for chronic disease.

PMID:40287067 | DOI:10.1016/j.clnesp.2025.04.006

Transplant Rev (Orlando). 2025 Apr 23;39(3):100933. doi: 10.1016/j.trre.2025.100933. Online ahead of print.

ABSTRACT

BACKGROUND: Whether survival differs between urgent lung transplantation (ULTx) and standard lung transplantation (LTx) remains unclear. This systematic review and meta-analysis aimed to evaluate survival and other post-transplant outcomes between ULTx and standard LTx.

METHODS: PubMed, Embase, and Cochrane Library were searched up to July 31, 2024 for relevant studies. A meta-analysis of baseline characteristics and postoperative outcomes was then performed, with subgroup analyses by study designs and indications. Overall survival (OS) was set as the primary outcome in this study. Risk ratio (RR), mean differences (MD) with 95 % confidence interval (CI) were assessed using fixed-effects or random-effects models.

RESULTS: Nine studies with 934 ULTx and 2980 standard LTx patients were included. ULTx group exhibited lower donor PaO2/FiO2 (P = 0.03) and higher pre-operative life support use (P < 0.001) than standard LTx group. No statistical difference in waiting list mortality was found between groups (28.4 % vs. 12.6 %; P = 0.54). ULTx was associated with significantly lower 1-year, 3-year, and 5-year OS than standard LTx (70.2 % vs. 80.0 %, 57.7 % vs. 66.7 %, 46.5 % vs. 56.2 %; all P < 0.001). At each time point, about 10 % OS rate differences were found consistently. In most subgroups, ULTx was associated with worse outcomes, but no difference in OS was observed in cystic fibrosis (CF) patients.

CONCLUSIONS: ULTx reduces waiting list mortality in critical patients, but is associated with worse OS than standard LTx. ULTx may limit short-term survival rather than long-term survival compared with standard LTx.

PMID:40286583 | DOI:10.1016/j.trre.2025.100933

Microorganisms. 2025 Mar 24;13(4):730. doi: 10.3390/microorganisms13040730.

ABSTRACT

This study examines the impact of inhaled tobramycin therapy on the within-host changes in P. aeruginosa strains isolated from Bulgarian patients with CF prior to and post treatment. Genotypic comparison by RAPD-PCR indicated that most of the pre-treatment isolates had a high similarity and were genetically comparatively close to strains from other countries with known increased morbidity or treatment requirements. Most of the post-treatment isolates were, however, genetically distant from their pre-treatment counterparts, showing genotypic diversification after the treatment. Phenotypic comparisons showed a lower ODmax reached during groswth and an increased lag-time in the post-treatment isolates. All strains were capable of invasion and intracellular reproduction within A549 cultured cells. The addition of sub-inhibitory amounts (1/4 or 1/2 MIC) of tobramycin during growth showed the higher relative fitness (as a percentage of the untreated control) of the post-treatment strains. The effects of sub-MICs on biofilm growth did not show such a pronounced trend. However, when a resazurin-based viability test was applied, the advantage of the post-treatment strains was confirmed for both broth and biofilm cultures. In spite of that, according to the determined MIC values, all isolates were tobramycin-sensitive, and the data from this study imply the development of tolerance to the antibiotic in the strains that survived the treatment.

PMID:40284567 | DOI:10.3390/microorganisms13040730

J Clin Med. 2025 Apr 18;14(8):2807. doi: 10.3390/jcm14082807.

ABSTRACT

Background/Objective: Cystic fibrosis (CF) is a chronic genetic disease affecting multiple body systems and having a significant impact on mental health and sleep. Patients with CF frequently suffer from anxiety, depression, and sleep disturbances, but non-pharmacological strategies are understudied. Although progressive muscle relaxation (PMR) has recognized benefits, its impact on CF remains insufficiently explored. The study aimed to analyze the effect of integrating PMR into a standard pulmonary rehabilitation (PR) program on mental health, sleep quality, and quality of life in adults with CF. Methods: A total of 22 adult patients with CF were randomly assigned to either the intervention group (PR + PMR) or the control group (PR only). Assessments were performed at baseline, after 21 days of intervention, and at the 48-day follow-up. Outcome measures included the CFQ-R for quality of life, the HADS for mental health, and the PSQI for sleep. Results: Compared to the control group, participants who practiced PMR experienced significant reductions in anxiety (p = 0.05) and depression (p = 0.02) at the final assessment. A significant improvement in sleep quality was also observed (p < 0.01). No relevant differences were found in pulmonary function or performance on the six-minute walk test. Conclusions: Integrating PMR into pulmonary rehabilitation programs may be an effective strategy for improving mental health and sleep in patients with CF. Due to its accessibility and ease of implementation, PMR could be adopted as a complementary method in the holistic care of these patients.

PMID:40283637 | DOI:10.3390/jcm14082807

J Clin Med. 2025 Apr 9;14(8):2583. doi: 10.3390/jcm14082583.

ABSTRACT

Background/Objectives: Olfactory dysfunction (OD) is a common symptom among people with cystic fibrosis (PwCF) and contributes to environmental safety concerns, nutritional challenges, and an overall diminished quality of life. OD is perceived to progress along the lifespan in PwCF, often due to worsening sinonasal disease. Among children with cystic fibrosis (CwCF), OD is poorly characterized as limited resources and tolerance contribute to challenges in psychophysical olfactory evaluation among pediatric populations. The Children's Personal Significance of Olfaction (ChiPSO) questionnaire was recently proposed as a tool to assess olfaction and the importance of olfactory stimulation among children. This pilot study aimed to evaluate the utility of ChiPSO among a cohort of ethnically diverse CwCF. Methods: Individuals aged 7-17 with physician-diagnosed CF were asked to complete questionnaires, including ChiPSO and the brief questionnaire on olfactory dysfunction (bQOD-NS), prior to undergoing psychophysical olfactory evaluation with the U-Sniff Identification test. Potential associations between questionnaires and olfactory performance, pulmonary function, and demographic characteristics were evaluated using Pearson and Spearman correlations, independent-sample t-tests, Wilcoxon rank sum tests, and multiple linear regression. Results: U-Sniff Identification score positively correlated with the overall ChiPSO total score [r(13) = 0.640, p = 0.010] and its environmental subdomain score [r(13) = 0.774, p < 0.001], though not with the food subdomain [r(13) = 0.450, p = 0.093], the social subdomain [r(13) = 0.343, p = 0.2], or bQOD-NS score [r(11) = -0.125, p = 0.7]. Hispanic ethnicity is associated with ChiPSO (p = 0.041). Conclusions: In this preliminary study, olfactory importance increases with olfactory function among an ethnically diverse sample of CwCF, with a preferential influence of olfactory function on personal importance of environmental olfactory information. While these results should be interpreted with limitations imposed by the pilot nature of our sample size, our pilot data highlights associations with early adolescent development of importance of olfaction that can be disrupted in the setting of progressive disease among CwCF.

PMID:40283411 | DOI:10.3390/jcm14082583

Medicina (Kaunas). 2025 Apr 2;61(4):653. doi: 10.3390/medicina61040653.

ABSTRACT

Background and Objectives: In the present systematic review and meta-analysis, we aimed to discover the overall efficacy of azithromycin in children with cystic fibrosis (CF) and with or without Pseudomonas aeruginosa infection, specifically regarding its effect on respiratory parameters such as forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in addition to its effect on exacerbations and the need to use additional antibiotics. Materials and Method: We conducted this systematic review and meta-analysis by searching for all eligible articles on PubMed, Web of Science, and Scopus published between inception and September 2024. We used the following search strategy for our searching process: "Cystic fibrosis" AND "Azithromycin" and "Children" OR "Pediatric" OR "Infant". We conducted the meta-analysis by pooling the mean difference (MD) and comparing the continuous variables and odds ratio (OR) for dichotomous variables at 95% confidence intervals (CI), at a p-value of 0.05. Results: Azithromycin was observed to be associated with increased FEV1 compared with the control, showing an MD of 1.91 (95% CI: 1.09, 2.74, p < 0.00001) and non-significant heterogeneity. However, no significant difference was observed between azithromycin and control groups regarding FVC with MD = 0.62 (95% CI: -0.01, 1.25, p = 0.06). Compared with the control group, azithromycin was significantly associated with lower risk and a lower number of exacerbations, with OR = 0.48 (95% CI: 0.34, 0.67, p < 0.0001) and MD = -0.82 (95% CI: -1.32, -0.33, p = 0.001), respectively, with non-significant heterogeneity. Regarding the need for new antibiotic usage, azithromycin showed a significantly lower need, with OR = 0.35 (95% CI: 0.13, 0.94, p = 0.04), I2 = 75%, p = 0.02. No significant difference was observed between both groups regarding hospitalization rate, with OR = 0.88 (95% CI: 0.55, 1.4, p = 0.59). Conclusions: This systematic review and meta-analysis showed the efficacy of azithromycin in pediatric patients with CF, as it improved lung function by increasing FEV1, reduced exacerbations of CF, which is the most common symptom of CF that leads to mortality, and reduced the number of antibiotics that needed to be administered to patients with CF, which reduces the risk of antibiotic resistance. Therefore, the long-term use of azithromycin is recommended for pediatric patients with CF as part of their treatment regimen.

PMID:40282944 | DOI:10.3390/medicina61040653

Genes (Basel). 2025 Apr 7;16(4):439. doi: 10.3390/genes16040439.

ABSTRACT

BACKGROUND: Psychosis, particularly schizophrenia (SZ), is influenced by genetic and environmental factors. The neurodevelopmental hypothesis suggests that genetic factors affect neuronal circuit connectivity during perinatal periods, hence causing the onset of the diseases. In this study, we performed a genome-wide association study (GWAS) in a sample of the first episode of psychosis (FEP).

METHODS: A sample of 147 individuals diagnosed with non-affective psychosis and 102 controls were recruited and assessed. After venous blood and DNA extraction, the samples were genotyped. Genetic data underwent quality controls, genotype imputation, and a case-control genome-wide association study (GWAS). After the GWAS, results were investigated using an in silico functional mapping and annotation approach.

RESULTS: Our GWAS showed the association of 27 variants across 13 chromosomes at genome-wide significance (p < 1 × 10-7) and a total of 1976 candidate variants across 188 genes at suggestive significance (p < 1 × 10-5), mostly mapping in non-coding or intergenic regions. Gene-based tests reported the association of the SUFU (p = 4.8 × 10-7) and NCAN (p = 1.6 × 10-5) genes. Gene-sets enrichment analyses showed associations in the early stages of life, spanning from 12 to 24 post-conception weeks (p < 1.4 × 10-3) and in the late prenatal period (p = 1.4 × 10-3), in favor of the neurodevelopmental hypothesis. Moreover, several matches with the GWAS Catalog reported associations with strictly related traits, such as SZ, as well as with autism spectrum disorder, which shares some genetic overlap, and risk factors, such as neuroticism and alcohol dependence.

CONCLUSIONS: The resulting genetic associations and the consequent functional analysis displayed common genetic liability between the non-affective psychosis, related traits, and risk factors. In sum, our investigation provided novel hints supporting the neurodevelopmental hypothesis in SZ and-in general-in non-affective psychoses.

PMID:40282399 | DOI:10.3390/genes16040439

Genes (Basel). 2025 Mar 30;16(4):402. doi: 10.3390/genes16040402.

ABSTRACT

Cystic fibrosis (CF), a genetic disorder characterized by mutations in the CFTR gene, has seen significant advances in treatment through cutting-edge approaches such as gene therapy and personalized medicine. This review examines the current and emerging strategies shaping CF care, focusing on novel therapies that target the root cause of CF and optimize patient outcomes. CFTR modulators have transformed cystic fibrosis management by enhancing protein function for specific mutations, leading to improved lung function and quality of life. Concurrently, gene therapy offers transformative potential by aiming to correct CFTR mutations using tools like CRISPR/Cas9 or prime editing, though challenges remain in delivery and long-term efficacy. The integration of precision medicine, facilitated by genomic and computational technologies, allows for personalized treatment plans that account for genetic variability and disease severity. Complementing these approaches, holistic management emphasizes the importance of psychological support and nutritional optimization, acknowledging CF's multi-system impact. Future directions include exploring anti-inflammatory agents and microbiome modulation to further mitigate disease morbidity. However, global disparities in treatment access continue to challenge equitable healthcare delivery, underscoring the need for policy reform and international cooperation. By synthesizing these developments, this review highlights the transformative potential of modern CF treatments, advocating for continued innovation and global healthcare equity, with the ultimate goal of dramatically improving life expectancy and quality of life for individuals with CF.

PMID:40282362 | DOI:10.3390/genes16040402

Healthcare (Basel). 2025 Apr 17;13(8):923. doi: 10.3390/healthcare13080923.

ABSTRACT

Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.

PMID:40281872 | DOI:10.3390/healthcare13080923

Int J Tuberc Lung Dis. 2025 May 25;29(5):199-201. doi: 10.5588/ijtld.25.0157.

ABSTRACT

Until relatively recently, bronchiectasis (not due to cystic fibrosis) was considered an orphan disease, lacking clinical and commercial interest, and was rarely diagnosed. Since the 2000s, several working groups have emerged in Europe and the US - with the first register for bronchiectasis launching in Spain - and these have demonstrated the impact bronchiectasis has on health. Today, bronchiectasis is considered the third most common chronic inflammatory disease of the airways, after COPD and asthma, and represents a significant economic burden. We make the case for further characterization of these registries to better understand the heterogeneous epidemiology of bronchiectasis.

PMID:40281677 | DOI:10.5588/ijtld.25.0157

Lung. 2025 Apr 25;203(1):57. doi: 10.1007/s00408-025-00811-9.

ABSTRACT

PURPOSE: Combined lung-liver transplant (CLLT) is a complex yet life-saving procedure for patients with simultaneous end-stage lung and liver disease. Given the geographical allocation change to the lung allocation score (LAS) in 2017 and the recent SARS-CoV-2 outbreak in 2019, we aim to provide an updated analysis of the patient selection and outcomes of CLLTs.

METHODS: The UNOS registry was used to identify all patients who underwent CLLT between January 2014 and June 2023. To account for the changes made to LAS in 2017, baseline characteristics and outcomes were compared between era 1 (before 2017) and era 2 (after 2017). Risk factors for mortality were analyzed using the Cox regression hazard models. Recipient survival of up to 3 years was analyzed using the Kaplan-Meier method.

RESULTS: 117 CLLTs were performed (77.8% in era 2). Donor organs experienced significantly longer ischemic times (p = 0.039) and traveled longer distances (p = 0.025) in era 2. However, recipient (p = 0.79) and graft (p = 0.41) survival remained comparable at up to 3 years post-transplant between eras. CLLTs demonstrated similar long-term survival to isolated lung transplants (p = 0.73). Higher recipient LAS was associated with an increased mortality risk (HR 1.14, p = 0.034). Recipient diagnosis of idiopathic pulmonary fibrosis carried a 5.03-fold risk of mortality (p = 0.048) compared to those with cystic fibrosis.

CONCLUSION: In the post-2017 LAS change era, CLLTs are increasingly performed with comparable outcomes to isolated lung transplants. A careful, multidisciplinary approach to patient selection and management remains paramount to optimizing outcomes for this rare patient population.

PMID:40281222 | DOI:10.1007/s00408-025-00811-9

Br Dent J. 2025 Apr;238(8):648-654. doi: 10.1038/s41415-024-8269-8. Epub 2025 Apr 25.

ABSTRACT

Objectives To measure past dental caries experience in people with cystic fibrosis and to compare the results with a control group of people without cystic fibrosis.Methods A cross-sectional study of 92 adults with cystic fibrosis and 92 adults without cystic fibrosis was undertaken in Cork University Dental School and Hospital. The median age for study group and control group participants was 31 years and 27 years, respectively. All participants completed a detailed questionnaire before undergoing a clinical examination that recorded demographic, social and oral health variables. Caries was recorded using the Decayed, Missing and Filled Teeth (DMFT) index. All data were statistically analysed using the Wilcoxon rank-sum test, chi-squared test and Fisher's test. Negative binomial models were also used to analyse data.Results The study group had a higher mean DMFT score compared to the control group (6.52, 0.99, 0.41, 3.89 versus 5.33, 0.18, 0.11, 3.68). While the study group had a higher DMFT, the only component that was statistically significant between the groups was the Decayed Teeth component (p <0.001).Conclusion In this study, the cohort of people with cystic fibrosis had more caries than people without cystic fibrosis. Further research is required to establish if underlying systemic conditions, social and behavioural factors, or a combination of the aforementioned are responsible for a higher caries experience in this study group.

PMID:40281172 | DOI:10.1038/s41415-024-8269-8

Eur J Hum Genet. 2025 Apr 25. doi: 10.1038/s41431-025-01851-8. Online ahead of print.

NO ABSTRACT

PMID:40281080 | DOI:10.1038/s41431-025-01851-8

Int J Infect Dis. 2025 Apr 23:107913. doi: 10.1016/j.ijid.2025.107913. Online ahead of print.

ABSTRACT

Diffuse panbronchiolitis (DPB) is a chronic inflammatory disease predominantly affecting East Asians. It is characterized by persistent Pseudomonas aeruginosa colonization and progressive respiratory failure. Lung transplantation (LTx) serves as a definitive treatment option for advanced cases, but post-transplant recurrence poses significant challenges. This report describes a Japanese woman who experienced DPB recurrence after bilateral LTx. Persistent P. aeruginosa colonization and recurrent respiratory symptoms were managed with off-label tobramycin solution for inhalation (TSI), which is commonly used in cystic fibrosis. TSI treatment led to significant clinical and radiological improvements, clearance of P. aeruginosa from sputum cultures, and no further hospitalizations during six months of therapy. This case suggests the potential of TSI as a therapeutic approach for managing recurrent DPB and indicates its role in stabilizing post-transplant outcomes. Further studies may clarify its efficacy and expand its application in broader DPB management strategies.

PMID:40280231 | DOI:10.1016/j.ijid.2025.107913

J Med Chem. 2025 Apr 25. doi: 10.1021/acs.jmedchem.5c00405. Online ahead of print.

ABSTRACT

Chronic lung infections caused by Pseudomonas aeruginosa and Burkholderia cenocepacia pose a severe threat to immunocompromised patients, particularly those with cystic fibrosis. These pathogens often infect the respiratory tract, and available treatments are limited due to antibiotic resistance. Targeting bacterial lectins involved in biofilm formation and host-pathogen interactions represents a promising therapeutic strategy. In this study, we evaluate the potential of synthetic fucosylamides as inhibitors of the two lectins LecB (P. aeruginosa) and BC2L-C-Nt (B. cenocepacia). Using a suite of biophysical assays, we assessed their binding affinities, identifying three β-fucosylamides as promising dual-target ligands, while crystallography studies revealed the atomic basis of these ligands to interact with both bacterial lectins. The emerged classes of compounds represent a solid starting point for the necessary hit-to-lead optimization for future dual inhibitors aiming at the treatment of coinfections with these two bacterial pathogens.

PMID:40279549 | DOI:10.1021/acs.jmedchem.5c00405

Metabolites. 2025 Mar 29;15(4):236. doi: 10.3390/metabo15040236.

ABSTRACT

BACKGROUND/OBJECTIVES: Amino acids (AAs) play a critical role in diseases such as cystic fibrosis where Pseudomonas aeruginosa PAO1 adapts its metabolism in response to host-derived nutrients. The adaptation influences virulence and complicates antibiotic treatment mainly for the antimicrobial resistance context. D- and L-AAs have been analyzed for their impact on quorum sensing (QS), a mechanism that regulates virulence factors. This research aimed to reconstruct the genome-scale metabolic model (GEM) of P. aeruginosa PAO1 to investigate the metabolic roles of D- and L-AAs in QS-related pathways.

METHODS: The updated GEM, iJD1249, was reconstructed by using protocols to integrate data from previous models and refined with well-standardized in silico media (LB, M9, and SCFM) to improve flux balance analysis accuracy. The model was used to explore the metabolic impact of D-Met, D-Ala, D-Glu, D-Ser, L-His, L-Glu, L-Arg, and L-Ornithine (L-Orn) at 5 and 50 mM in QS-related pathways, focusing on the effects on bacterial growth and carbon flux distributions.

RESULTS: Among the tested AAs, D-Met was the only one that did not enhance the growth rate of P. aeruginosa PAO1, while L-Arg and L-Orn increased fluxes in the L-methionine biosynthesis pathway, influencing the metH gene. These findings suggest a differential metabolic role for D-and L-AAs in QS-related pathways.

CONCLUSIONS: Our results shed some light on the metabolic impact of AAs on QS-related pathways and their potential role in P. aeruginosa virulence. Future studies should assess D-Met as a potential adjuvant in antimicrobial strategies, optimizing the concentration in combination with antibiotics to maximize its therapeutic effectiveness.

PMID:40278365 | DOI:10.3390/metabo15040236

J Imaging. 2025 Apr 21;11(4):124. doi: 10.3390/jimaging11040124.

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 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.

PMID:40278040 | DOI:10.3390/jimaging11040124

Biomimetics (Basel). 2025 Apr 17;10(4):247. doi: 10.3390/biomimetics10040247.

ABSTRACT

Airway mucus plays a critical role in respiratory health, with diseases such as cystic fibrosis (CF) being characterized by mucus that exhibits increased viscosity and altered viscoelasticity. In vitro models that emulate these properties are essential for understanding the impact of CF mucus on airway function and for the development of therapeutic strategies. This study characterizes a mucus mimic composed of xanthan gum and locust bean gum, which is designed to exhibit the rheological properties of CF mucus. Mucus concentrations ranging from 0.07% to 0.3% w/v were tested to simulate different states of bacterial infection in CF. Key rheological parameters, including yield stress, storage modulus, loss modulus, and viscosity, were measured using an HR2 rheometer with strain sweep, oscillation frequency, and flow ramp tests. The results show that increasing the concentration enhanced the mimic's elasticity and yield stress, with values aligning with those reported for CF mucus in pathological states. These findings provide a quantitative framework for tuning the rheological properties of mucus in vitro, allowing for the simulation of CF mucus across a range of concentrations. This mucus mimic is cost-effective, readily cross-linked, and provides a foundation for future studies examining the mechanobiological effects of mucus yield stress on epithelial cell layers, particularly in the context of bacterial infections and airway disease modeling.

PMID:40277645 | DOI:10.3390/biomimetics10040247

Stat Med. 2025 Apr;44(8-9):e70057. doi: 10.1002/sim.70057.

ABSTRACT

Joint models for longitudinal and survival data have become a popular framework for studying the association between repeatedly measured biomarkers and clinical events. Nevertheless, addressing complex survival data structures, especially handling both recurrent and competing event times within a single model, remains a challenge. This causes important information to be disregarded. Moreover, existing frameworks rely on a Gaussian distribution for continuous markers, which may be unsuitable for bounded biomarkers, resulting in biased estimates of associations. To address these limitations, we propose a Bayesian shared-parameter joint model that simultaneously accommodates multiple (possibly bounded) longitudinal markers, a recurrent event process, and competing risks. We use the beta distribution to model responses bounded within any interval ( a , b ) $$ \left(a,b\right) $$ without sacrificing the interpretability of the association. The model offers various forms of association, discontinuous risk intervals, and both gap and calendar timescales. A simulation study shows that it outperforms simpler joint models. We utilize the US Cystic Fibrosis Foundation Patient Registry to study the associations between changes in lung function and body mass index, and the risk of recurrent pulmonary exacerbations, while accounting for the competing risks of death and lung transplantation. Our efficient implementation allows fast fitting of the model despite its complexity and the large sample size from this patient registry. Our comprehensive approach provides new insights into cystic fibrosis disease progression by quantifying the relationship between the most important clinical markers and events more precisely than has been possible before. The model implementation is available in the R package JMbayes2.

PMID:40277342 | DOI:10.1002/sim.70057

Mikrobiyol Bul. 2025 Apr;59(2):145-157. doi: 10.5578/mb.20250232.

ABSTRACT

Kistik fibrozis (KF), solunum yollarında yoğun mukus birikimi nedeniyle kronik enfeksiyonlara yol açan genetik bir hastalıktır. Pseudomonas aeruginosa, KF hastalarında sık rastlanan ve uzun süreli enfeksiyonlara ve kolonizasyona neden olan önemli bir patojendir. Bu çalışma, KF çocuk hastalarının solunum yolu örneklerinden ardışık olarak elde edilen P.aeruginosa izolatlarının antibiyotik duyarlılık profillerinin ve biyofilm oluşturma yeteneklerinin karşılaştırılmasını amaçlamıştır. Hacettepe Üniversitesi İhsan Doğramacı Çocuk Hastanesi KF Ünitesinde 2021-2023 yılları arasında prospektif olarak takip edilen KF hastalarından (n= 80) alınan solunum yolu örneklerinde üreyen ardışık kronik P.aeruginosa izolatları incelenmiştir. Bakteri tür tanımlaması MALDI-TOF MS ile yapılmış ve konvansiyonel yöntemlerle doğrulanmıştır. Antibiyotik duyarlılık testleri EUCAST önerileri doğrultusunda sıvı mikrodilüsyon ve gradiyent test yöntemleriyle gerçekleştirilmiştir. Antibiyotik direnç genleri (blaVIM, blaIMP, blaNDM, blaKPC) polimeraz zincir reaksiyonu yöntemiyle incelenmiştir. Biyofilm oluşumu, kristal viyole mikrotitrasyon plak yöntemiyle değerlendirilmiştir. Kistik fibrozis hastalarında eşlik eden en sık sistemik bulgu ekzokrin pankreas yetmezliği (n= 58) ve bronşektazi (n= 44) olarak saptanmıştır. P.aeruginosa dışında 56 hastada başka bir etkenin daha ürediği [metisiline duyarlı Staphylococcus aureus (n= 46), metisiline dirençli S.aureus (n= 31), Acinetobacter spp. (n= 2) ve tüberküloz dışı mikobakteri (n= 2)] saptanmıştır. Bu çalışmada, izolatların antibiyotik direnci seftazidime en yüksek (%3.75), kolistine en düşük (%1.25) bulunmuştur. Tobramisin, meropenem ve levofloksasine direnç %2.5 olarak saptanırken, siprofloksasine direnç tespit edilmemiştir. Antibiyotik direnç genleri açısından en sık saptanan gen blaVIM olup ilk izolatlarda %12.5, sonraki izolatlarda ise %10 oranında belirlenmiştir. Çalışmaya dahil edilen izolatların hiçbrisinde blaKPC, blaIMP ve blaNDM direnç genleri saptanmamıştır. Biyofilm oluşumu değerlendirildiğinde, ilk izolatların %77.5'inde, sonraki ardışık 80 izolatın 59 (%73.7)'unda kantitatif olarak biyofilm oluşumu gösterilmiştir. İzolatların 11 (%18.6)'inin güçlü pozitif, 33 (%55.9)'ünün orta pozitif ve 15 (%25.4)'inin zayıf pozitif biyofilm oluşturduğu saptanmıştır. Sonuç olarak, P.aeruginosa'nın KF hastalarında yüksek biyofilm oluşturma kapasitesine sahip olduğu belirlenirken antibiyotik tedavisinin mikroorganizmanın eradikasyonunda etkin rol oynamadığı saptanmıştır. Bu çalışma, ardışık izolatların biyofilm yapımı ve antibiyotik direnç paternlerinde anlamlı değişiklikler göstermediğini ortaya koymuştur. Benzer antibiyotik duyarlılık ve biyofilm yapımı gösteren ardışık P.aeruginosa izolatlarında bakterinin yok edilmesi için antibiyofilm duyarlılık testlerinin yapılması ve yeni antibiyofilm tedavi stratejilerinin geliştirilmesi önem arz etmektedir.

PMID:40277263 | DOI:10.5578/mb.20250232