Int J Antimicrob Agents. 2025 Jul 22:107579. doi: 10.1016/j.ijantimicag.2025.107579. Online ahead of print.

ABSTRACT

BACKGROUND: Due to the rise in antimicrobial resistance (AMR), there has been an increased interest in phage therapy to treat multi-drug resistant infections. In Australia, phage therapy is predominantly used in small clinical studies or for compassionate use, however, despite its potential expansion in modern medicine, the perception of phage therapy among medical professionals remains largely unknown.

METHODS: We conducted a national survey of Australian infectious diseases and clinical microbiology advanced trainees and specialists using an online mailing list to assess their knowledge, areas of interest, and concerns around the use of phage therapy in clinical practice in Australia; with 92 eligible respondents.

RESULTS: Most respondents believed that the current national plan for controlling AMR is inadequate and that phage therapy may be an effective solution; with 87 (97%) indicating that they would consider using phage therapy meeting established guidelines for purity and safety. There was a preference for bespoke therapy, with Gram-negative pathogens highlighted as priority targets. Alongside the phage therapy delivery protocols, therapeutic phage was considered important. Cystic fibrosis (CF), lung-infections, prosthetic device/related infections, and infections among patients following transplantation and/or immunosuppression were highly ranked in terms of priorities for clinical syndromes. Accessibility was highlighted as a barrier to phage therapy, specifically timely access (n=66; 72%) and logistics of phage procurement and administration (n=64; 70%).

CONCLUSION: These results suggest the support of phage therapy among infectious diseases and clinical microbiology advanced trainees and specialists in Australia, and highlights areas of focus and priority in order to advance phage therapy.

PMID:40706688 | DOI:10.1016/j.ijantimicag.2025.107579

Eur J Nutr. 2025 Jul 24;64(6):248. doi: 10.1007/s00394-025-03766-y.

NO ABSTRACT

PMID:40705145 | DOI:10.1007/s00394-025-03766-y

mBio. 2025 Jul 24:e0141125. doi: 10.1128/mbio.01411-25. Online ahead of print.

ABSTRACT

Microbial communities are often studied by measuring gene expression (mRNA levels), but translating these data into functional insights is challenging because mRNA abundance does not always predict protein levels. Here, we present a strategy to bridge this gap by deriving gene-specific RNA-to-protein conversion factors that improve the prediction of protein abundance from transcriptomic data. Using paired mRNA-protein data sets from seven bacteria and one archaeon, we identified orthologous genes where mRNA levels poorly predicted protein abundance, yet each gene's protein-to-RNA ratio was consistent across these diverse organisms. Applying the resulting conversion factors to mRNA levels dramatically improved protein abundance predictions, even when the conversion factors were obtained from distantly related species. Remarkably, conversion factors derived from bacteria also enhanced protein prediction in an archaeon, demonstrating the robustness of this approach. This cross-domain framework enables more accurate functional inference in microbiomes without requiring organism-specific proteomic data, offering a powerful new tool for microbial ecology, systems biology, and functional genomics.

IMPORTANCE: Deciphering the biology of natural microbial communities is limited by the lack of functional data. While transcriptomics enables gene expression profiling, mRNA levels often fail to predict protein abundance, the primary indicator of microbial function. Prior studies addressed this by calculating RNA-to-protein (RTP) conversion factors using conserved protein-to-RNA (ptr) ratios across bacterial strains, but their cross-species and cross-domain utility remained unknown. We generated comprehensive transcriptomic and proteomic data sets from seven bacteria and one archaeon spanning diverse metabolisms and ecological niches. We identified orthologous genes with conserved ptr ratios, enabling the discovery of RTP conversion factors that significantly improved protein prediction from mRNA, even between distant species and domains. This reveals previously unrecognized conservation in ptr ratios across domains and eliminates the need for paired proteomic data in many cases. Our approach offers a broadly applicable framework to enhance functional prediction in microbiomes using only transcriptomic data.

PMID:40704792 | DOI:10.1128/mbio.01411-25

Open Respir Arch. 2025 Jun 24;7(3):100460. doi: 10.1016/j.opresp.2025.100460. eCollection 2025 Jul-Sep.

ABSTRACT

INTRODUCTION: The use of intravenous antibiotic formulations delivered by inhalation is controversial. Tolerance can be an issue and some treatment guidelines discourage this route of administration if the same antibiotic is available in an inhalation formulation.

MATERIAL AND METHODS: This was a retrospective, observational, single-center study comparing tolerance to three antibiotics delivered by nebulization (intravenous formulations of ampicillin and gentamicin, and an inhalation formulation of colistimethate sodium) in patients with bronchial infection (BI), chronic bronchial infection (CBI), and/or recurrent respiratory infections. The study also aimed to identify factors potentially associated with tolerability.

RESULTS: A total of 330 antibiotic tolerance tests were performed in 135 patients (mean age 68 years; 48.9% female; mean post-bronchodilator FEV1% predicted 65.9%). Of these patients, 62.2% had bronchiectasis and 39.3% had chronic obstructive pulmonary disease (COPD). The best tolerated antibiotic was colistimethate. Overall, 89.6% of colistimethate doses were tolerated, compared to 69.5% of inhaled gentamicin doses (P < 0.001) and 69.1% of ampicillin doses (P < 0.001). Compared with colistimethate administration, the odds of intolerance were 5.69 times higher for gentamicin (P < 0.001) and 6.21 times higher for ampicillin (P < 0.001). In the univariate analysis, factors that may have been associated with antibiotic intolerance included smoking habit, worse post-bronchodilator FEV1% predicted and a diagnosis of COPD. In the multivariate analysis, after adjustment for antibiotic type, smoking habit, post-bronchodilator FEV1 and COPD diagnosis, the only factor influencing tolerance was the type of antibiotic used.

CONCLUSION: In patients with BI and/or CBI and/or recurrent respiratory infections, inhaled sodium colistimethate is significantly better tolerated than intravenous formulations of gentamicin and ampicillin for the inhalation route. The only factor influencing tolerance is the type of antibiotic used.

PMID:40704060 | PMC:PMC12284521 | DOI:10.1016/j.opresp.2025.100460

Case Rep Pediatr. 2025 Jul 16;2025:5569829. doi: 10.1155/crpe/5569829. eCollection 2025.

ABSTRACT

Background and Objectives: Enteroviruses (EV) mainly cause mild infections but have been found to affect neonates more severely. The aim of this study is the description of symptoms, laboratory findings, treatment, duration of hospital stay, imaging, and outcome in five neonates presenting with EV infection of the central nervous system (CNS). Case Study: All patients had signs of sepsis and/or CNS infection at first presentation and were diagnosed using cerebrospinal fluid (CSF) reverse transcriptase polymerase chain reaction (RT-PCR). One developed seizures and dilated coronary arteries and recovered after treatment with levetiracetam, intravenous immunoglobulins (IVIGs), prednisolone, and acetylsalicylic acid. This patient was also the only one to show CSF abnormalities including mononuclear pleocytosis. C-reactive protein in blood was slightly elevated in 3/5, while interleukin-6 was normal at onset and later increased (58.7-310 mg/dL) in all patients. Neutrophil-to-lymphocyte ratio was elevated (1.02-4.83) in 5/5. Antibiotics were given for 4-7 days; hospital stay lasted 7-13 days. Cerebral ultrasound was done in 2/5 and was normal in both. The patient who developed seizures underwent brain magnetic resonance imaging without pathological findings. The clinical outcome was favorable in all of our five patients. Conclusions: In neonates who appear septic without an apparent focus, EV CNS infection should be considered and can be diagnosed by CSF PCR testing. Diagnosis leads to earlier discontinuation of antibiotic treatment and shorter hospital stay. Neonates with EV infection should be screened for cardiac complications and in severe cases treated with IVIG. CSF abnormalities might predict a more severe disease course and justify closer monitoring.

PMID:40703496 | PMC:PMC12286663 | DOI:10.1155/crpe/5569829

Front Med (Lausanne). 2025 Jul 9;12:1554300. doi: 10.3389/fmed.2025.1554300. eCollection 2025.

ABSTRACT

Bronchiectasis is a chronic and heterogeneous respiratory condition, which is characterized by irreversible abnormal dilatation of the bronchial tree, chronic cough, copious sputum production, and increased risk of acute exacerbations that contribute to the development of chronic respiratory failure, poor exercise tolerance and, consequently, poor quality of life (QoL). A large amount of published data explore regarding the diagnostic approach, the clinical management, and the development of novel therapeutic strategies. Moreover, it is well-known that the exercise-training rehabilitation can be helpful in reducing disease deterioration and relieve symptoms. However, the effect of exercise in patients with non-cystic fibrosis-related bronchiectasis (NCFB) is scarce, and no athletic programs have been fully developed. Thus, the aim of the present study is to investigate the results obtained by administering a specific athletic/physical protocol to these patients. Among all patients affected by NCFB and followed in our Institution, those with the highest scores of performance status will be addressed to the Interdipartimental Centre in Motor and Sport Activities, Sport Medicine Centre, University of Pavia for a work protocol based on mesocycles of 3 times/week for 6 months. A patient-tailored active training regimen will be set up considering major complaints-endurance training for patients with dyspnea, strength training for patients with cough and difficult sputum expectoration, and a balanced aerobic and anaerobic training for patients with asthenia. To the best of our knowledge, the ATHOS study is the first perspective clinical trial, encompassing athletic programs for non-CF bronchiectasis patients, and rationale and in itinere, partial results will be presented, analyzed, and discussed in comparison to standard disease management.

PMID:40703269 | PMC:PMC12283567 | DOI:10.3389/fmed.2025.1554300

Ear Nose Throat J. 2025 Jul 24:1455613251361237. doi: 10.1177/01455613251361237. Online ahead of print.

ABSTRACT

The management of refractory chronic rhinosinusitis (CRS) in children with cystic fibrosis (CF) remains a challenge, especially in those who are not candidates for highly effective modulator therapy. These patients often have severe sinus disease that does not improve with medical treatment, requiring surgery as the definitive treatment. We report a case of a 9-year-old female patient with CF and refractory CRS presenting with significant nasal obstruction, postnasal drainage, and frontal headaches that severely impacted her quality of life. A hybrid technique that involved balloon catheter dilation (BCD) along with endoscopic sinus surgery (ESS) allowed the management of complex anatomical problems associated with the severe polyposis, copious purulence, and narrow frontal recesses during the surgery. This improved our ability to visualize the surgical field, minimize blood loss, and better preserve the mucosa, which ultimately led to better surgical and clinical outcomes. Our findings suggest that hybrid BCD-assisted ESS may offer an effective solution to manage severe CRS in pediatric CF patients, particularly for those who have limited therapeutic options.

PMID:40702974 | DOI:10.1177/01455613251361237

Ital J Pediatr. 2025 Jul 23;51(1):242. doi: 10.1186/s13052-025-02056-x.

ABSTRACT

Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition that affects the esophagus and is marked by the presence of eosinophils. This disease is becoming more common in children and adolescents and can result in symptoms like swallowing difficulties, food impaction and abdominal pain. Managing pediatric EoE requires a team effort including gastroenterologists, allergists and dietitians. Medical treatments may include topical corticosteroids, proton pump inhibitors, and elimination diets. Endoscopy plays a key role in the diagnosis, management and monitoring of the condition. The management of pediatric EoE is distinct from that of adult EoE, due to differences in anatomy, physiology and treatment options. Thus, it is recommended that children with EoE see a pediatric gastroenterologist when possible. However, adult gastroenterologists can also contribute to the management of pediatric EoE when a pediatric gastroenterologist is not accessible. A guideline for the management of pediatric EoE in Italy has been created by Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) to encourage collaboration between adult gastroenterologists and pediatricians, and it has been endorsed by major adult gastroenterology Italian societies including AIGO, SIGE and SIED, highlighting the importance of collaboration in the diagnosis and management of pediatric EoE.

PMID:40702503 | DOI:10.1186/s13052-025-02056-x

Mol Cancer. 2025 Jul 23;24(1):204. doi: 10.1186/s12943-025-02392-w.

NO ABSTRACT

PMID:40702467 | DOI:10.1186/s12943-025-02392-w

Nat Commun. 2025 Jul 23;16(1):6799. doi: 10.1038/s41467-025-61168-4.

ABSTRACT

Bacteria evolving within human hosts encounter selective tradeoffs that render mutations adaptive in one context and deleterious in another. Here, we report that the cystic fibrosis-associated pathogen Burkholderia dolosa overcomes in-human selective tradeoffs by acquiring successive point mutations that alternate phenotypes. We sequenced the whole genomes of 931 respiratory isolates from two recently infected cystic fibrosis patients and an epidemiologically-linked, chronically-infected patient. These isolates are contextualized using 112 historical genomes from the same outbreak strain. Within both newly infected patients, convergent mutations that disrupt O-antigen expression quickly arose, comprising 29% and 63% of their B. dolosa communities by 3 years. The selection for loss of O-antigen starkly contrasts with our previous observation of parallel O-antigen-restoring mutations after many years of chronic infection in the historical outbreak. Experimental characterization reveals that O-antigen loss increases uptake in immune cells while decreasing competitiveness in the mouse lung. We propose that the balance of these pressures, and thus whether O-antigen expression is advantageous, depends on tissue localization and infection duration. These results suggest that mutation-driven phenotypic alternation may be underestimated without dense temporal sampling, particularly for microbes with prolonged infection or colonization.

PMID:40701980 | DOI:10.1038/s41467-025-61168-4

J Cyst Fibros. 2025 Jul 22:S1569-1993(25)01532-2. doi: 10.1016/j.jcf.2025.07.009. Online ahead of print.

NO ABSTRACT

PMID:40701925 | DOI:10.1016/j.jcf.2025.07.009

J Cyst Fibros. 2025 Jul 23:S1569-1993(25)01534-6. doi: 10.1016/j.jcf.2025.07.010. Online ahead of print.

ABSTRACT

BACKGROUND: Abdominal symptoms (AS) relevantly impair quality of life (QoL) in people with Cystic fibrosis (CF). Following FDA guidelines, we previously developed and validated the CFAbd-Score©, the first CF-specific gastrointestinal patient-reported outcome-measure (PROM) for people with CF. Therewith, we demonstrated that AS significantly and markedly decrease during treatment with the new game-changing CF-therapy elexacaftor-tezacaftor-ivacaftor (ETI). However, for children with CF (cwCF), a pediatric-focused PROM could improve self- or proxy-assisted reporting of AS.

AIMS: Development and validation of the CFAbd-Score.kid©, the pediatric version of the CFAbd-Score©, following FDA- and COSMIN-guidelines, anticipating ETI approval in younger cwCF.

METHODS: We iteratively developed the CFAbd-Score.kid© together with CF-specialists from different fields, cwCF and their proxies. We implemented pictograms and easy language to optimize comprehension of questions by cwCF aged <12years, as well as adapted response strategies. We devised a scoring algorithm, weighting items (n = 29) and domains (n = 5) differently, to optimize the PROM´s sensitivity (range: 0-100pts).

RESULTS: In 5 German CF-centers, n = 102 cwCF (7.6 ± 2.3yrs) completed n = 257 CFAbd-Score.kid© questionnaires. For known-groups validity analysis, n = 72 healthy children (HC) were included. Good to excellent test-retest reliability was observed (intraclass correlation-coefficient=0.89, p < 0.001). Median total CFAbd-Score.kid© resulted significantly higher in cwCF, compared to HC (16.2 vs.10.1pts, p < 0.01). CwCF also scored significantly higher in domains "Disorders of bowel movement", "Disorders of appetite" and "Quality of life".

CONCLUSION: The novel CFAbd-Score.kid©, well accepted among children, allows recording of AS in cwCF. The total CFAbd-Score.kid© and three of its five domains reveal a significantly and markedly elevated burden of AS in cwCF, compared to HC.

PMID:40701924 | DOI:10.1016/j.jcf.2025.07.010

PLoS One. 2025 Jul 23;20(7):e0328051. doi: 10.1371/journal.pone.0328051. eCollection 2025.

ABSTRACT

Cystic Fibrosis (CF) is a hereditary condition and can cause permanent respiration problems leading to degraded life quality. The most common variation leading to CF is the F508del variation. CF can cause damage to not just the lungs but also digestive system, pancreas, and other organs. CF decreases the life expectancy of the individuals affected with the constant fear of lung complications. The current methods of treatment include using a combination of drugs to manage the symptoms. The combination of drugs has many side effects and causes damage to other organs like liver, heart or kidneys. In this study, we aim to find a drug that can relieve the symptoms of CF. We began by creating a dataset of potential drug molecules, which was subsequently refined by removing harmful compounds through an ADMET scan. All these compounds were then docked to the mutated Cystic Fibrosis Transmembrane Regulator (CFTR) protein. The compounds with the best docking affinity were Galicaftor and Bamocaftor. A currently approved drug, Ivacaftor was selected as control for the 200 ns Molecular Dynamics (MD) Simulation. The simulation revealed that the CFTR protein remained more stable and compact when complexed with Bamocaftor, when compared to Ivacaftor and Galicaftor. Moreover, the MMPBSA free energy calculations revealed that the free energy of the CFTR-bamocaftor complex is the lowest compared to the other complexes. Our findings reveal the action of bamocaftor on CFTR protein with p.Phe508del variation. However, the absence of in-vivo or in-vitro studies is a limitation, and further experimental validation is necessary to confirm its efficacy and safety.

PMID:40700450 | DOI:10.1371/journal.pone.0328051

Infect Dis Rep. 2025 Jul 7;17(4):80. doi: 10.3390/idr17040080.

ABSTRACT

Background: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Modulator therapies have the ability to improve CFTR function in CF patients, but despite the clear evidence of benefits regarding CFTR modulator therapy, including improved lung function, the reduced rate of exacerbations, and an overall improved quality of life, studies focusing on the reduction rates of P. aeruginosa infections during modulator therapy expressed the need for future research on this topic. Objective: This study aimed to evaluate the impact of CFTR modulator therapies on the prevalence, density, and persistence of P. aeruginosa infection in CF patients and to explore the mechanisms involved. Methods: A systematic literature review was performed by searching five major databases (PubMed, Cochrane Library, Scopus, Google Scholar, and Web of Science), and 21 relevant articles investigating the link between CFTR therapy and P. aeruginosa infections were selected following the PRISMA guidelines. Results: The data indicated that Ivacaftor and the combination Elexacaftor/Tezacaftor/Ivacaftor (ETI) can reduce total bacterial load and markers of systemic inflammation. However, clonal lines of P. aeruginosa persist in most cases, and complete eradication is rare, mainly due to biofilm formation and antimicrobial resistance. Conclusions: Although CFTR-modulating therapies help to improve clinical condition and reduce inflammation, they do not consistently lead to the elimination of P. aeruginosa.

PMID:40700326 | DOI:10.3390/idr17040080

Int J Neonatal Screen. 2025 Jul 17;11(3):54. doi: 10.3390/ijns11030054.

ABSTRACT

An essential link in the cystic fibrosis (CF) newborn screening (NBS) process is communication of results. While this is described between NBS programs and primary care providers, data of this occurrence is limited with neonatologists. Neonatology providers represent a group caring for critically ill infants with conditions that can impact their ability to complete diagnostic testing after an abnormal NBS. Delays in testing can prolong time to diagnosis. We fielded a survey to assess neonatology provider knowledge and awareness of the Pennsylvania state CF NBS algorithm after an update occurred. Provider demographics, awareness of CF NBS update, and knowledge of the diagnostic testing process were measured. 86% of respondents were unaware of Pennsylvania CF NBS updates. Provider comfort with interpreting CF NBS results varied. 40% of providers identified the next diagnostic testing steps for a critically ill infant following an abnormal CF NBS. Our survey emphasizes the need for educating neonatology providers about CF NBS to improve knowledge and awareness of CF NBS algorithms to facilitate the early diagnosis of affected infants.

PMID:40700046 | DOI:10.3390/ijns11030054

Int J Neonatal Screen. 2025 Jul 11;11(3):52. doi: 10.3390/ijns11030052.

ABSTRACT

Cystic Fibrosis Screen Positive Inconclusive Diagnosis/CFTR-related Metabolic Syndrome (CFSPID/CRMS) presents a significant clinical challenge due to its variable diagnostic outcomes and uncertain disease progression. Current diagnostic strategies, including sweat chloride testing and genetic analysis fall short in delivering clear guidance for clinical decision-making and risk assessment. Here, we comment on the potential of CFTR functional tests in patient-derived intestinal organoids (PDIOs) to enhance early risk stratification in CFSPID/CRMS cases. Using four hypothetical cases based on real-world data, we illustrate diverse clinical trajectories: diagnosis of cystic fibrosis (CF), reclassification as a CFTR-related disorder (CFTR-RD), non-CF designation, and persistent diagnostic uncertainty. Organoid-based assays-such as forskolin-induced swelling (FIS), steady-state lumen area (SLA) analysis, and rectal organoid morphology analysis (ROMA)-offer functional insights into CFTR activity and drug responsiveness. Compared to existing CFTR functional tests, such as Intestinal Current Measurement (ICM) and Nasal Potential Difference (NPD), these assays are more accessible, highly reproducible, and when needed support personalized medicine approaches. PDIO-based assays could help identify infants at high risk of disease progression, facilitating earlier interventions while minimizing unnecessary follow-ups for those unlikely to develop CF-related symptoms. Although not yet widely implemented, these assays hold promise for refining CFSPID diagnostics and management. Future research should focus on establishing standardized protocols allowing validation of clinical utility.

PMID:40700044 | DOI:10.3390/ijns11030052

Curr Issues Mol Biol. 2025 Apr 10;47(4):268. doi: 10.3390/cimb47040268.

ABSTRACT

Cancer gene therapy is attracting considerable attention as a new treatment method for overcoming intractable cancers. CAR-T cell therapy has already achieved remarkable results, particularly for hematological tumors. Because CAR-T cells can increase within the body, they have the advantage of requiring only a single administration. In addition, CAR-T cell therapy targeting the CD19 antigen has been established for relapsed or refractory disease in young people with CD19-positive acute B-cell leukemia (B-acute lymphoblastic leukemia, B-ALL) and diffuse large B-cell lymphoma (DLBCL). In addition to CAR-T cell therapy, oncolytic viruses represent a promising approach for cancer treatment, with some already in clinical use and others being researched for their potential benefits. These viruses infect and kill cancer cells, triggering an immune response that helps the body recognize and fight cancer. Oncolytic virus therapy is a form of immunotherapy that uses modified viruses to target and destroy tumor cells while potentially stimulating antitumor immune responses. These viruses have shown promising activity in clinical trials, with some approved for specific cancers like melanoma. Research is ongoing to improve their efficacy, expand their use to other cancer types, and overcome the logistical challenges associated with their delivery. Gene therapy can potentially treat diseases caused by recessive gene disorders like cystic fibrosis, hemophilia, muscular dystrophy, and sickle cell anemia, as well as acquired genetic diseases, such as cancer and viral infections like acquired immunodeficiency syndrome (AIDS).

PMID:40699667 | DOI:10.3390/cimb47040268

Antimicrob Agents Chemother. 2025 Jul 23:e0027825. doi: 10.1128/aac.00278-25. Online ahead of print.

ABSTRACT

Tobramycin is commonly used for the treatment of pulmonary exacerbations in children with cystic fibrosis (CF). Currently, a standard dose of 10 mg/kg daily is used in all children. We aim to develop a population pharmacokinetic (popPK) model of tobramycin in children with CF and determine the: (i) effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on tobramycin pharmacokinetics (PK); (ii) attainment of the commonly used serum steady state area under the concentration-time curve target (AUC24,ss) of 80-110 mg/L⋅h with standard dosing; and (iii) generate an optimized fully individualized dosing strategy to improve target attainment. Multicenter prospective observational study of children with CF aged 0-19 years receiving IV tobramycin who had ≥1 serum concentration measured. A popPK model was developed using nonlinear mixed-effect modeling, and simulations were performed to assess study aims. Overall, 63 children had 450 serum tobramycin concentrations. A one-compartment popPK model, including age, weight, a renal maturation model, and estimated glomerular filtration rate as covariates, was developed. With standard dosing, 1/3 of children achieved the target AUC24,ss with younger children (<2 years) having the lowest probability of target attainment (PTA) (15%). The optimized dosing regimen improved target attainment in all children, increasing the PTA in children <2 years to 62%. CFTR modulator drugs did not affect tobramycin PK. Standard tobramycin dosing in children with CF achieves poor attainment of target serum AUC24,ss, particularly in children <2 years. A fully individualized approach (available at https://www.kidscalc.org/) improved target attainment in all children. CFTR modulators had a negligible effect on tobramycin PK.

PMID:40698812 | DOI:10.1128/aac.00278-25

Expert Opin Pharmacother. 2025 Jul 23. doi: 10.1080/14656566.2025.2538275. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) treatment has been transformed by CF transmembrane conductance regulator (CFTR) modulator therapies, yet significant gaps remain for those with non-responsive or modestly responsive (below therapeutically relevant levels) genotypes and advanced disease. Emerging agents for genetic therapies and targeting symptoms are in development and offer hope for broader, more durable clinical benefits. This review synthesizes the latest clinical advances aiming to shape the future of CF care.

AREAS COVERED: We examine investigational agents in clinical development, including: alternative CFTR modulators (e.g. potentiators, correctors, and amplifiers); gene-based therapies utilizing viral and non-viral vectors; anti-inflammatory approaches; and infection-targeted therapies. Clinical trial data and combination strategies are discussed.

EXPERT OPINION: Despite dramatic improvements in clinical outcomes and survival in PwCF on modulator drugs, further efforts are warranted for ineligible/non-responsive individuals or intolerant to modulators. In addition, it remains vital to identify novel therapeutic strategies to mitigate lung damage and disease progression as infection and inflammation persist even in PwCF receiving 'highly effective' modulator therapy.

PMID:40698678 | DOI:10.1080/14656566.2025.2538275

Cureus. 2025 Jun 22;17(6):e86516. doi: 10.7759/cureus.86516. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Non-cystic fibrosis bronchiectasis (NCFB) remains underdiagnosed in pediatric populations, particularly in the Middle East.

OBJECTIVE: To characterize the high-resolution computed tomography (HRCT) features of NCFB in pediatric patients, including extent, morphological subtype, and lobar distribution, and to evaluate their associations with underlying clinical diagnoses at a tertiary care center in Oman.

METHODS: We conducted a retrospective cross-sectional study at Sultan Qaboos University Hospital (SQUH), a tertiary center in Oman, reviewing pediatric patients ≤18 years diagnosed with NCFB between January 2000 and December 2022. High-resolution computed tomography (HRCT) reports prepared by pediatric radiologists were reviewed. Data on clinical features, radiological patterns, lobar involvement, and etiologies were analyzed descriptively using IBM SPSS Statistics for Macintosh, Version 19.0 (IBM Corp., Armonk, NY).

RESULTS: Of the 150 patients reviewed, 61 met the inclusion criteria. The mean age at diagnosis was 7.3 years, with 35 (57.4%) being male. Diffuse bronchiectasis was predominant, observed in 48 patients (78.7%), and involved more than two lobes in 40 cases (65.6%). The left lower lobe was the most frequently affected, seen in 13 patients (21.6%). Cylindrical bronchiectasis was present in all patients, while cystic in 25 patients (41.0%) and varicose in 19 patients (31.1%) forms were more common in those with systemic disorders, such as primary immunodeficiency (PID, 18 patients; 37.5%) and primary ciliary dyskinesia (PCD, 8 patients; 16.7%). Patients diagnosed at age ≥5 years had a significantly higher prevalence of diffuse disease.

CONCLUSION: HRCT is a crucial diagnostic tool for pediatric NCFB, particularly in children with recurrent infections or systemic comorbidities, such as PID or PCD. Early imaging may prevent irreversible damage and guide targeted treatment. Establishing national guidelines for pediatric chest CT utilization and incorporating multidisciplinary assessments may improve diagnostic timeliness and outcomes.

PMID:40698238 | PMC:PMC12281239 | DOI:10.7759/cureus.86516