Respir Care. 2025 Feb 10. doi: 10.1089/respcare.12352. Online ahead of print.

ABSTRACT

Asthma experienced by both adults and children is a phenotypically heterogeneous condition. Severe asthma, characterized by ongoing symptoms and airway inflammation despite high doses of inhaled and/or systemic corticosteroids, is the focus of research efforts to understand this underlying heterogeneity. Clinical phenotypes in both adult and pediatric asthma have been determined using supervised definition-driven classification and unsupervised data-driven clustering methods. Efforts to understand the underlying inflammatory patterns of severe asthma have led to the seminal discovery of type 2-high versus type 2-low phenotypes and to the development of biologics targeted at type 2-high inflammation to reduce the rates of severe asthma exacerbations. Type 2-high asthma is characterized by upregulation of T helper 2 immune pathways including interleukin (IL)-4, IL-5, and IL-13 along with eosinophilic airway inflammation, sometimes allergic sensitization, and responsiveness to treatment with corticosteroids. Type 2-low asthma is poorly responsive to corticosteroids and is not as well characterized as type 2-high asthma. Type 2-low asthma is limited by being defined as the absence of type 2-high inflammatory markers. Choosing a biologic for the treatment of severe asthma involves the evaluation of a panel of biomarkers such as blood eosinophils, total and specific immunoglobulin E/allergic sensitization, and fractional exhaled nitric oxide. In this review, we focus on the underlying pathobiology of adult and pediatric asthma, discuss the different phenotype-based treatment options for adult and pediatric type 2-high with or without allergic asthma and type 2-low asthma, and describe a clinical phenotyping approach to patients to guide out-patient therapy. Finally, we end with a discussion of whether pediatric asthma exacerbations necessitating admission to an ICU constitute their own high-risk phenotype and/or whether it is a part of other previously defined high-risk subgroups such as difficult-to-control asthma, exacerbation-prone asthma, and severe treatment-resistant asthma.

PMID:40013975 | DOI:10.1089/respcare.12352

Lung India. 2025 Mar 1;42(2):103-108. doi: 10.4103/lungindia.lungindia_404_24. Epub 2025 Feb 27.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder caused by genetic variant in the cystic fibrosis transmembrane regulator (CFTR) gene that affects around 89,000 people worldwide. Loss of the CFTR chloride channel due to pathogenic variants in the CFTR gene causes obstruction in the exocrine pancreas gland and reduced lung function.

OBJECTIVE: To determine the genotype and phenotype of patients with CF from western India.

MATERIALS AND METHODS: This was a single-center retrospective cross-sectional study conducted in a tertiary care super speciality paediatric hospital of Mumbai, India, comprising patients aged 0 to 18 years visiting a paediatric pulmonology clinic with suspected or confirmed diagnosis of CF.

RESULTS: The mean (SD) age of onset of symptoms was 6.8 (10.2) months and the mean (SD) age at diagnosis was 32.5 (50.5) months. The two most common genetic variants found in our patients were c. 1521_1523delCTT (F508del) (n = 21) and c.1367T>C (V456A) (n = 10). There were nine novel genetic variants identified that have not been reported so far. The mean (SD) age of onset of symptoms was 6.8 (10.2) months and mean (SD) age at diagnosis was 32.5 (50.5) months. The most common presenting features were recurrent respiratory infections (83%), malabsorption (79%), and failure to thrive (79%). Sweat chloride testing was conducted to establish the CFTR gene dysfunction and was positive in 79% (46/58) of patients and intermediate in 15% (n = 9/58) of patients. The two most common genetic variants found in our group of patients were c. 1521_1523delCTT (F508del) (n = 21) and c.1367T>C (V456A) (n = 10). There were nine novel genetic variants identified that have not been reported so far.

CONCLUSION: This study adds to the knowledge of genetic diversity in the pathogenic CFTR gene variants causing CF and highlights the importance of sequencing the entire CFTR gene as regional variations in the gene have been documented in India.

PMID:40013628 | DOI:10.4103/lungindia.lungindia_404_24

ERJ Open Res. 2025 Feb 25;11(1):00445-2024. doi: 10.1183/23120541.00445-2024. eCollection 2025 Jan.

ABSTRACT

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) triple modulator therapy, elexacaftor-tezacaftor-ivacaftor (ETI) has transformed care for people with cystic fibrosis (CF) who have eligible mutations. It is, however, not curative. Response to treatment also varies and lung disease, although slowed, remains progressive. We have previously demonstrated inhibition of the epithelial sodium channel (ENaC) by selective furin inhibition to be an alternative, mutation-agnostic approach that can enhance airways hydration and restore mucociliary transport (MCT) in CF. Inhibition of furin therefore, offers a potential therapeutic strategy for those ineligible, intolerant or nonresponsive to ETI and may provide a further opportunity for clinical benefit for those currently treated with ETI. The aim of this study was to determine the impact of furin inhibition on ETI responses to assess its utility as an adjunct therapy.

METHODS: Differentiated primary CF human bronchial epithelial cells (HBECs) were treated with the highly selective furin inhibitor BOS-318 and with ETI. Ion channel function was measured using a 24-channel Transepithelial Current Clamp (TECC-24) system and airways surface hydration was investigated by measuring airway surface liquid (ASL) height and MCT rate.

RESULTS: The presence of BOS-318 had no effect on the ability of ETI to stimulate CFTR-mediated Cl- secretion but contributed a reduced Na+ transport via robust inhibition of ENaC. This altered ion transport profile effected an improved ASL height and MCT rate, which were significantly greater than improvements observed with ETI alone, demonstrating the benefits of the dual approach.

CONCLUSIONS: Selective furin inhibition has the potential to further improve clinical outcomes for all people with CF and offers opportunity as an adjunct to improve responses to currently available CFTR modulator therapies.

PMID:40013020 | PMC:PMC11863070 | DOI:10.1183/23120541.00445-2024

Cell Death Dis. 2025 Feb 26;16(1):134. doi: 10.1038/s41419-025-07447-w.

ABSTRACT

Acyl CoA binding protein encoded by diazepam binding inhibitor (ACBP/DBI) is a tissue hormone that stimulates lipo-anabolic responses and inhibits autophagy, thus contributing to aging and age-related diseases. Protein expression profiling of ACBP/DBI was performed on mouse tissues to identify organs in which this major tissue hormone is expressed. Transcriptomic and proteomic data bases corroborated a high level of human-mouse interspecies conservation of ACBP/DBI expression in different organs. Single-cell RNA-seq data confirmed that ACBP/DBI was strongly expressed by parenchymatous cells from specific human and mouse organs (e.g., kidney, large intestine, liver, lung) as well as by myeloid or glial cells from other organs (e.g., adipose tissue, brain, eye) following a pattern that was conserved among the two species. We identified a panel of 44 mRNAs that are strongly co-expressed with ACBP/DBI mRNA in normal and malignant human and normal mouse tissues. Of note, 22 (50%) of these co-expressed mRNAs encode proteins localized at mitochondria, and mRNAs with metabolism-related functions are strongly overrepresented (66%). Systematic data mining was performed to identify transcription factors that regulate ACBP/DBI expression in human and mouse. Several transcription factors, including growth response 1 (EGR1), E2F Transcription Factor 1 (E2F1, which interacts with retinoblastoma, RB) and transformation-related protein 53 (TRP53, best known as p53), which are endowed with oncosuppressive effects, consistently repress ACBP/DBI expression as well as its co-expressed mRNAs across multiple datasets, suggesting a mechanistic basis for a coregulation network. Furthermore, we identified multiple transcription factors that transactivate ACBP/DBI gene expression together with its coregulation network. Altogether, this study indicates the existence of conserved mechanisms determining the expression of ACBP/DBI in specific cell types of the mammalian organism.

PMID:40011442 | DOI:10.1038/s41419-025-07447-w

J Exp Biol. 2025 Feb 26:jeb.250110. doi: 10.1242/jeb.250110. Online ahead of print.

ABSTRACT

All ionoregulating marine fishes examined to date utilize seawater-type ionocytes expressing the apical Cl- channel, cystic fibrosis transmembrane conductance regulator (Cftr) to secrete Cl-. We performed transcriptomic, molecular, and functional studies to identify Cl- transporters in the seawater-type ionocytes of sea lamprey (Petromyzon marinus). Gill cftr expression was minimal or undetectable in larvae and post-metamorphic juveniles. We identified other Cl- transporters highly expressed in the gills and/or upregulated following metamorphosis and further investigated two candidates that stood out in our analysis, a Ca2+-activated Cl- channel, anoctamin 1 (ano1), and the Clc chloride channel family member 2 (clcn2). Of these, ano1 was expressed 10-100 times more than clcn2 in the gills; moreover, ano1 was upregulated during seawater acclimation, while clcn2 was not. Using an antibody raised against sea lamprey Ano1, we did not detect Ano1 in the gills of larvae, found elevated levels in juveniles and observed a 4-fold increase in juveniles after seawater acclimation. Ano1 was localized to seawater-type branchial ionocytes but, surprisingly, was localized to the basolateral membrane. In vivo pharmacological inhibition experiments demonstrated that a DIDS-sensitive mechanism was critical to the maintenance of osmoregulatory homeostasis in seawater- but not freshwater-acclimated sea lamprey. Taken together, our results provide evidence of a Cftr-independent mechanism for branchial Cl- secretion in sea lamprey that leverages Ano1-expressing ionocytes. Once further characterized, the Cftr-independent, Ano1-rich ionocytes of sea lamprey could reveal novel strategies for branchial Cl- secretion, whether by Ano1 or some other Cl- transporter, not previously known in ionoregulating marine organisms.

PMID:40007443 | DOI:10.1242/jeb.250110

Viruses. 2025 Jan 29;17(2):189. doi: 10.3390/v17020189.

ABSTRACT

Pseudomonas aeruginosa, an opportunistic pathogen, causes various biofilm-associated infections like pneumonia, infections in cystic fibrosis patients, and urinary tract and burn infections with high morbidity and mortality, as well as low treatment efficacy due to the extremely wide spread of isolates with multidrug resistance. Here, we report the new bacteriophage Pseudomonas phage Ka2 isolated from a tributary stream of Lake Baikal and belonging to the Pbunavirus genus. Transmission electron microscopy resolved that Pseudomonas phage Ka2 has a capsid of 57 ± 9 nm and a contractile and inflexible tail of 115 ± 10 nm in the non-contracted state. The genome consists of 66,310 bp with a GC content of 55% and contains 96 coding sequences. Among them, 52 encode proteins have known functions, and none of them are potentially associated with lysogeny. The bacteriophage lyses 21 of 30 P. aeruginosa clinical isolates and decreases the MIC of amikacin, gentamicin, and cefepime up to 16-fold and the MIC of colistin up to 32-fold. When treating the biofilms with Ka2, the biomass was reduced by twice, and up to a 32-fold decrease in the antibiotics MBC against biofilm-embedded cells was achieved by the combination of Ka2 with cefepime for the PAO1 strain, along with a decrease of up to 16-fold with either amikacin or colistin for clinical isolates. Taken together, these data characterize the new Pseudomonas phage Ka2 as a promising tool for the combined treatment of infections associated with P. aeruginosa biofilms.

PMID:40006944 | DOI:10.3390/v17020189

Pharmaceutics. 2025 Feb 6;17(2):200. doi: 10.3390/pharmaceutics17020200.

ABSTRACT

Background: The combination of ivacaftor, tezacaftor and elexacaftor (ETI) is approved for patients with cystic fibrosis (CF) aged two years and older and at least one F508del mutation in the CFTR gene. Variability in ETI treatment response has been repeatedly reported, and its reasons are unclear and understudied. Objectives: We present a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the rapid and simultaneous quantification of ETI in plasma, dried plasma spots (DPS), and whole blood volumetric absorptive microsampling (VAMS). Methods: The method utilizes a rapid extraction protocol with 200 μL methanol after the addition of deuterated internal standards. Chromatographic separation was achieved using a reversed-phase Hypersil Gold aQ column (Thermo Fisher Scientific). The method was validated according to ICH (International Council on Harmonisation) guidelines M10 for bioanalytical method validation, demonstrating linearity in the concentration range 0.020-12.000 µg/mL. It was also proved accurate and reproducible with no matrix effect. This method was applied to anonymized samples from patients undergoing ETI treatment: eight plasma and DPS and five VAMS samples were analyzed. Results: ETI concentrations measured in plasma and DPS were interchangeable, whereas ETI concentrations in VAMS were lower than in plasma, as expected for molecules with high plasma protein binding (99%). A correction factor based on the hematocrit value was used to calculate the equivalent plasma concentration from VAMS concentrations. Conclusions: This method is suitable for pharmacokinetic (PK) studies and could facilitate the centralization of samples to specialized laboratories, supporting multicenter studies.

PMID:40006567 | DOI:10.3390/pharmaceutics17020200

Pharmaceuticals (Basel). 2025 Feb 7;18(2):225. doi: 10.3390/ph18020225.

ABSTRACT

Background/Objectives: Mycobacterium abscessus (MAB) is a highly resilient pathogen that causes difficult-to-treat pulmonary infections, particularly in individuals with cystic fibrosis (CF) and other underlying conditions. Its ability to form robust biofilms within the CF lung environment is a major factor contributing to its resistance to antibiotics and evasion of the host immune response, making conventional treatments largely ineffective. These biofilms, encased in an extracellular matrix, enhance drug tolerance and facilitate metabolic adaptations in hypoxic conditions, driving the bacteria into a persistent, non-replicative state that further exacerbates antimicrobial resistance. Treatment options remain limited, with multidrug regimens showing low success rates, highlighting the urgent need for more effective therapeutic strategies. Methods: In this study, we employed artificial sputum media to simulate the CF lung environment and conducted high-throughput screening of 24,000 compounds from diverse chemical libraries to identify inhibitors of MAB biofilm formation, using the Crystal Violet (CV) assay. Results: The screen established 17 hits with ≥30% biofilm inhibitory activity in mycobacteria. Six of these compounds inhibited MAB biofilm formation by over 60%, disrupted established biofilms by ≥40%, and significantly impaired bacterial viability within the biofilms, as confirmed by reduced CFU counts. In conformational assays, select compounds showed potent inhibitory activity in biofilms formed by clinical isolates of both MAB and Mycobacterium avium subsp. hominissuis (MAH). Key compounds, including ethacridine, phenothiazine, and fluorene derivatives, demonstrated potent activity against pre- and post-biofilm conditions, enhanced antibiotic efficacy, and reduced intracellular bacterial loads in macrophages. Conclusions: This study results underscore the potential of these compounds to target biofilm-associated resistance mechanisms, making them valuable candidates for use as adjuncts to existing therapies. These findings also emphasize the need for further investigations, including the initiation of a medicinal chemistry campaign to leverage structure-activity relationship studies and optimize the biological activity of these underexplored class of compounds against nontuberculous mycobacterial (NTM) strains.

PMID:40006039 | DOI:10.3390/ph18020225

Pharmaceuticals (Basel). 2025 Jan 27;18(2):175. doi: 10.3390/ph18020175.

ABSTRACT

This manuscript provides a comprehensive review of advancements in dry powder inhaler (DPI) technology for pulmonary and systemic drug delivery, focusing on proteins, peptides, nucleic acids, and small molecules. Innovations in spray-drying (SD), spray freeze-drying (SFD), and nanocarrier engineering have led to enhanced stability, bioactivity, and aerosol performance. Studies reveal the critical role of excipients, particle morphology, and device design in optimizing deposition and therapeutic efficacy. Applications include asthma, cystic fibrosis, tuberculosis (TB), and lung cancer, with emerging platforms such as ternary formulations and siRNA-loaded systems demonstrating significant clinical potential. Challenges such as stability, scalability, and patient adherence are addressed through novel strategies, including Quality by Design (QbD) approaches and advanced imaging tools. This work outlines pathways for future innovation in pulmonary drug delivery.

PMID:40005989 | DOI:10.3390/ph18020175

J Clin Med. 2025 Feb 18;14(4):1362. doi: 10.3390/jcm14041362.

ABSTRACT

The Hungarian Pancreatic Study Group (HPSG) was established with the aim of advancing pancreatology. Our summary outlines the methodologies, key results, and future directions of the HPSG. Methodological elements included, the formation of strategic national and international collaborations, the establishment of patient registries and biobanks, and a strong focus on education and guideline development. Key results encompassed, pioneering research on pancreatic ductal function and the role of cystic fibrosis transmembrane conductance regulator (CFTR) in inflammation, significant advancements in understanding acute and chronic pancreatitis, and the execution of numerous clinical trials to explore new therapeutic approaches. Despite challenges, such as securing funding and translating research into clinical practice, the HPSG's commitment to patient care and scientific innovation has been unwavering. The group aims to deepen research into pancreatic cancer and chronic pancreatitis, conduct more randomized controlled trials (RCTs), and expand its efforts internationally by involving global staff and patients. The authors hope that this summary inspires others to undertake similar initiatives and contribute to the global advancement of medical research and patient care in pancreatology.

PMID:40004893 | DOI:10.3390/jcm14041362

Children (Basel). 2025 Jan 28;12(2):157. doi: 10.3390/children12020157.

ABSTRACT

BACKGROUND/OBJECTIVES: Cystic fibrosis (CF) is a life-limiting genetic disorder affecting multiple organ systems. This study compared clinical outcomes, hospitalization rates, and survival between children and adolescents with CF who received CFTR modulator therapies (ivacaftor, lumacaftor, tezacaftor, and elexacaftor).

METHODS: A retrospective cohort study was conducted using data from the TriNetX global collaborative network. Patients with CF aged 2-12 years (children) and 13-18 years (adolescents) who received CFTR modulator therapies were included. The propensity score matching balanced baseline characteristics between the two age groups.

RESULTS: After propensity score matching, 946 patients per group were analyzed. The incidence of respiratory failure (3.81% vs. 1.06%, p < 0.001) and respiratory infections (62.7% vs. 57.5%, p = 0.021) were significantly higher in adolescents compared to children. Adolescents had a higher risk of respiratory failure (HR = 3.6, 95% CI = 1.79-7.21, p < 0.001) and respiratory infections (HR = 1.09, 95% CI = 1.01-1.17, p < 0.001). Adolescents also had a higher hospitalization rate (29.6% vs. 20.3%, p < 0.001), with a 47% higher risk (HR = 1.47, 95% CI = 1.22-1.77, p = 0.001), more hospital visits per person (8.8 vs. 3.7, p = 0.004), and longer hospital stays (32.7 vs. 20.4 days, p = 0.006). Mortality rates were similar between the groups (1.58% vs. 1.26%, p = 0.56).

CONCLUSIONS: CF patients who initiated CFTR modulator therapies during adolescence had a higher incidence of respiratory failure, respiratory infections, hospitalization rates, and healthcare resource utilization compared to those who started therapy in childhood, despite similar mortality rates. These findings highlight the importance of the early initiation of CFTR modulator therapies.

PMID:40003259 | DOI:10.3390/children12020157

Diagnostics (Basel). 2025 Feb 16;15(4):474. doi: 10.3390/diagnostics15040474.

ABSTRACT

Hyperpolarized xenon-129 MRI (129XeMRI) has emerged as a powerful tool in the identification, evaluation, and assessment of disease endotyping and in response to interventions for a myriad of pulmonary diseases. Growing investigative efforts ranging from basic science to application in translational research have employed 129XeMRI in the evaluation of pulmonary conditions such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and cystic fibrosis (CF). The novel feature of 129XeMRI is its ability to generate anatomic and physiologic readouts of the lung with resolution from the whole lung down to the lobar level. Additional advantages include being non-invasive and non-radioactive, and utilizing an inexpensive and ubiquitous noble gas as an inhalation contrast agent: xenon-129. In this review, we outline the clinical advances provided by 129XeMRI among common pulmonary diseases with high healthcare burdens in recent decades.

PMID:40002625 | DOI:10.3390/diagnostics15040474

Antibiotics (Basel). 2025 Feb 11;14(2):177. doi: 10.3390/antibiotics14020177.

ABSTRACT

Background/Objectives: The pulmonary administration of antibiotics can be advantageous in treating pulmonary infections by promoting high intrapulmonary drug concentrations with reduced systemic exposure. However, limited benefits have been observed for pulmonary administration versus other administration routes due to its rapid clearance from the lung. Here, the effects of structural modifications on the epithelial permeability and antibacterial potency of a third-generation cephalosporin were investigated to improve the understanding of drug properties that promote intrapulmonary retention and how they may impact efficacy. Methods: Ceftazidime was modified by attaching 18 hydrophobic, hydrophilic, and mucus-binding motifs to the carboxylic acid distant from the beta-lactam by amidation. Epithelial permeability was investigated by drug transport assays using human bronchial epithelial air-liquid interface cultures. Antibacterial potency was determined by microtiter MIC assays with B. pseudomallei, P. aeruginosa, E. coli, and S. aureus. Results: A 40-50% reduction in the transepithelial transport rate was exhibited by two PEGylated ceftazidime analogs (mPEG8- and PEG5-pyrimidin-2-amine-ceftazidime) and n-butyl-ceftazidime. An increase in the transport rate was exhibited by four analogs bearing small and hydrophobic or negatively charged motifs (n-heptane-, phenyl ethyl-, glutamic acid-, and 4-propylthiophenyl boronic acid-ceftazidime). The antibacterial potency was reduced by ≥10-fold for most ceftazidime analogs against B. pseudomallei, P. aeruginosa, and E. coli but was retained by seven ceftazidime analogs primarily bearing hydrophobic motifs against S. aureus. Conclusions: The covalent conjugation of PEGs with MW > 300 Da reduced the epithelial permeability of ceftazidime, but these modifications severely reduced antibacterial activity. To improve the pulmonary retention of antibiotics with low membrane permeability, this work suggests future molecular engineering studies to explore high-molecular-weight prodrug strategies.

PMID:40001420 | DOI:10.3390/antibiotics14020177

Antibiotics (Basel). 2025 Feb 8;14(2):169. doi: 10.3390/antibiotics14020169.

ABSTRACT

Background/Objectives: Pulmonary delivered tobramycin (TOB) is a standard treatment for Pseudomonas aeruginosa lung infections, that, along with Staphylococcus aureus, is one of the most common bacteria causing recurring infections in CF patients. However, the only available formulation on the market containing tobramycin, TOBI®, is sold at a price that makes the access to the treatment difficult. Therefore, this work focuses on the development and characterization of an ionic complex between a polyelectrolyte, hyaluronic acid (HA) and its salt, sodium hyaluronate (NaHA), and TOB to be formulated as an inhalable dry powder. Methods: The solid state complex obtained by spray drying technique was physicochemically characterized by infrared spectroscopy, thermal analysis and X-ray diffraction, confirming an ionic interaction for both complexes. Results: The powder density, geometric size, and morphology along with the aerodynamic performance showed suitable properties for the powder formulations to reach the deep lung. Moisture uptake was found to be low, with the complex HA-TOB remaining physicochemically unchanged, while the NaHA-TOB required significant protection against humidity. The biopharmaceutical in vitro experiments showed a rapid dissolution which can have a positively impact in reducing side effects, while the drug release study demonstrated a reversible polyelectrolyte-drug interaction. Microbiological experiments against P. aeruginosa and S. aureus showed improved bacterial growth inhibition and bactericidal efficacy, as well as better inhibition and eradication of biofilms when compared with to TOB. Conclusions: A simple polyelectrolyte-drug complex technique represents a promising strategy for the development of antimicrobial dry powder formulations for pulmonary delivery in the treatment of cystic fibrosis (CF) lung infections.

PMID:40001413 | DOI:10.3390/antibiotics14020169

Antibiotics (Basel). 2025 Feb 7;14(2):165. doi: 10.3390/antibiotics14020165.

ABSTRACT

The lack of available treatments in pediatric non-cystic fibrosis (non-CF) bronchiectasis is a major concern, especially in the context of the increasing disease burden due to better detection rates with advanced imaging techniques. Recurrent infections in these patients are the main cause of deterioration, leading to impaired lung function and increasing the risk of morbidity and mortality. Since pediatric non-CF bronchiectasis with early recognition and appropriate treatment can be reversible, optimal management is an issue of growing significance. The use of inhaled antibiotics as a treatment option, although a standard of care for CF patients, has been poorly studied in patients with non-CF bronchiectasis, especially in children. In this review, we present the current data on the potential use of inhaled antibiotics in the treatment of non-CF bronchiectasis and assess their safety and efficacy profile, focusing mainly on children. We conclude that inhaled antibiotics as an adjuvant maintenance treatment option could be tried in a subgroup of patients with frequent exacerbations and recent or chronic Pseudomonas aeruginosa infection as they appear to have beneficial effects on exacerbation rate and bacterial load with minimal safety concerns. However, the level of evidence in children is extremely low; therefore, further research is needed on the validity of this recommendation.

PMID:40001409 | DOI:10.3390/antibiotics14020165

Antimicrob Resist Infect Control. 2025 Feb 25;14(1):17. doi: 10.1186/s13756-025-01527-4.

ABSTRACT

BACKGROUND/INTRODUCTION: Antipseudomonal antibiotics are frequently used in patients admitted to hospitals. Many of these substances are classified as a reserve or watch status by the WHO. Inappropriate risk assessment of invasive detection of P. aeruginosa (PAE) can be a reason for overuse of antipseudomonal antibiotics. Therefore it is important to define relevant and specific risk factors for invasive PAE detection.

OBJECTIVE: The objective of this study was to identify risk factors for invasive detection of PAE in patients upon hospital admission.

METHODS: All patients 18 years of age and older with a detection of PAE and/or Enterobacterales in clinical samples taken within 48 h of admission to one of the hospitals of Charité Universitätsmedizin Berlin between 2015 and 2020 were included into this retrospective cohort study.

RESULTS: Overall, we included a total of 27,710 patients. In 3,764 (13.6%) patients PAE was detected in clinical samples taken within 48 h after admission. The most frequently detected Enterobacterales was E. coli in 14.142 (51%) patients followed by Klebsiella spp. in 4.432 (16%) patients. Multivariable regression analysis identified that prior colonisation with a multi drug resistant PAE or detection of a PAE in clinical samples during a previous hospitalisation increased the risk for invasive detection of PAE (OR 39.41; 95% CI 28.54-54.39) and OR 7.87 (95% CI 6.60-9.38) respectively. Admission to a specialised ward for patients with cystic fibrosis was associated with an increased risk (OR 26.99; 95% CI 20.48-35.54). Presence of chronic pulmonary disease (OR 2.05; 95% CI 1.85-2.26), hemiplegia (OR 2.16; 95% CI 1.90-2.45) and male gender (OR 1.60; 95% CI 1.46-1.75) were associated with a modest increase in risk for presence of PAE.

CONCLUSION: Patients with a prior detection of P. aeruginosa or admission to a cystic fibrosis ward had the highest risk for invasive detection of P. aeruginosa. Adherence to specific risk scores based on local risk factors could help to optimize prescription of anti-pseudomonal antibiotics that categorized as reserve and watch.

PMID:40001254 | DOI:10.1186/s13756-025-01527-4

Nutrition. 2025 Jan 27;133:112694. doi: 10.1016/j.nut.2025.112694. Online ahead of print.

ABSTRACT

OBJECTIVES: Having an optimal nutritional status and getting adequate energy and nutrients are important factors that affect the success of the treatment of cystic fibrosis (CF) and increase survival. The objective of this study was to determine the nutritional status, nutritional intake, and dietary quality among children aged 2 to 14 with CF. We aimed to assess the impact of a nutrition education intervention provided to mothers on these parameters and compare the results with a control group.

METHODS: Participants (n = 46) were divided into two groups, one group received nutrition education, the other group did not receive any intervention, and all participants were followed up in the 1st and 3rd months of the study. Each participant completed a questionnaire form prepared by the researcher including general information about the patient, anthropometric data, 3-day dietary intake, and Mediterranean Diet Quality Index.

RESULTS: While the children's Mediterranean Diet Quality Index scores did not change significantly during the study period, the proportion of children in the education group who had adequate nutrition according to body mass index percentile for age increased from 42.0% to 48.0%. In addition, energy (kcal), fat (g), and monounsaturated fatty acids (g) intake, vitamin D, E, K, B6, biotin, and iron intakes of the education group increased significantly during the study (P < 0.05).

CONCLUSIONS: This study contributes to the literature by showing that nutrition education given to mothers for CF children, improves the nutritional status of children and increases their energy and nutrient intakes.

PMID:39999653 | DOI:10.1016/j.nut.2025.112694

Pediatr Pulmonol. 2025 Feb;60(2):e71018. doi: 10.1002/ppul.71018.

ABSTRACT

BACKGROUND: Patients with primary ciliary dyskinesia (PCD) are commonly treated for pulmonary exacerbations with intravenous tobramycin, but data on tobramycin pharmacokinetics in PCD is lacking. The objective of this study was to compare tobramycin pharmacokinetics in pediatric patients with PCD to those with cystic fibrosis (CF).

METHODS: This retrospective study included pediatric patients hospitalized for a pulmonary exacerbation between January 2018 and June 2023. Included patients were treated with systemic tobramycin and had two concentrations usable to calculate patient-specific pharmacokinetics. Each patient with PCD was matched 1:2 to patients with CF based on age. The primary outcome was tobramycin elimination rate constant.

RESULTS: Seven patients with PCD were matched to 14 patients with CF. Baseline characteristics were similar between groups. The final tobramycin dose was not significantly different between groups (9.3 vs. 11.8 mg/kg, p = 0.192). All doses were infused over 30 min every 24 h. Tobramycin elimination rate constant (0.510 vs. 0.493 h-1, p = 0.433) and volume of distribution (0.31 vs. 0.23 L/kg, p = 0.640) were not different between groups. No patient experienced acute kidney injury. Additionally, both groups experienced similar duration of tobramycin therapy (12.3 vs. 9.6 days, p = 0.184) and length of stay (12.0 vs. 12.6 days, p = 0.801).

CONCLUSIONS: No difference in tobramycin elimination rate constant was found between patients with PCD and those with CF. Clinical outcomes were not significantly different between groups. Although not statistically significant, a lower tobramycin dose was observed in patients with PCD.

PMID:39998853 | DOI:10.1002/ppul.71018

Radiology. 2025 Feb;314(2):e241793. doi: 10.1148/radiol.241793.

ABSTRACT

Background Although pericardial calcification has been observed on chest CT scans in patients with cystic fibrosis (CF), its prevalence and characteristics have not been elucidated. Purpose To determine the prevalence and characteristics of pericardial calcification, and identify clinical variables associated with it, in adult patients with CF and to compare this prevalence with that in individuals without CF. Materials and Methods This was a retrospective, single-center case-control study including consecutive patients with CF who underwent chest CT between January 2021 and December 2022. Control group 1 included individuals without CF matched for age and sex. Control group 2 included individuals with previous Mycobacterium tuberculosis infection and no concomitant diagnosis of CF matched for sex. Control group 3 included patients with primary ciliary dyskinesia. Qualitative and quantitative evaluations of pericardial calcification were performed. The χ2 test and Fisher exact test were used for comparisons of categorical variables; the Kruskal-Wallis test and Mann-Whitney U test were used for comparisons of continuous variables. Results Of the 348 adult patients with CF (mean age, 35 years ± 13 [SD]; 193 [55%] male patients), 62 (18%) had pericardial calcification at CT. The prevalence of pericardial calcification was 1% (four of 348) in control group 1, 2% (two of 100) in control group 2, and 4% (one of 24) in control group 3 (P < .001). Pericardial calcification developed de novo in 66% (41 of 62) and progressed in 21% (13 of 62) of patients with CF. The distribution of pericardial calcification in patients with CF was most frequently multifocal (58%; 36 of 62). The median calcium score of pericardial calcification was 65 (IQR, 28-375). In patients with CF, older age, lower forced expiratory volume in 1 second, higher vitamin D level, and a higher prevalence of Burkholderia cenocepacia ET12 infection were associated with pericardial calcification. Conclusion Pericardial calcification was more prevalent in adult patients with CF than in individuals without CF and progressed over time in some patients. © RSNA, 2025 Supplemental material is available for this article.

PMID:39998371 | DOI:10.1148/radiol.241793

Respirology. 2025 Feb 25. doi: 10.1111/resp.70009. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: β-ENaC-Tg mice serve as a relevant model of muco-obstructive lung disease and diffuse-type emphysema, with impaired mucociliary clearance, mucus obstruction, chronic airway inflammation, structural lung damage, and altered lung function. The aim of this study was to undertake a comprehensive analysis of lung function and mechanics of the adult β-ENaC-Tg model.

METHODS: Adult β-ENaC-Tg and wild-type littermates underwent X-ray velocimetry (XV) scans using a Permetium XV scanner (4DMedical, Melbourne, Australia). For comparative lung mechanics, lung function assessments were conducted with a flexiVent system (SCIREQ, Montreal, Canada).

RESULTS: XV imaging demonstrated elevated ventilation defect percentage, mean specific ventilation, and ventilation heterogeneity in β-ENaC-Tg mice. Spatial analysis of ventilation maps indicated increased ventilation variability in the peripheral lung regions, as well as an increased proportion of under-ventilated areas. The flexiVent analysis indicated that compared to wild types, β-ENaC-Tg mice have a significantly more compliant lungs with increased inspiratory capacity, reduced tissue elastance, and increased hysteresivity (heterogeneity), suggesting loss of parenchymal integrity.

CONCLUSION: This research highlights the utility of XV imaging in evaluating ventilation defects in the β-ENaC-Tg model and provides a comprehensive lung function analysis.

PMID:39998270 | DOI:10.1111/resp.70009