ERJ Open Res. 2025 Mar 3;11(2):00701-2024. doi: 10.1183/23120541.00701-2024. eCollection 2025 Mar.

ABSTRACT

CFTR modulators may be valuable therapy for patients with ABCA3 pathogenic variants https://bit.ly/3TMWKK9.

PMID:40040902 | PMC:PMC11874218 | DOI:10.1183/23120541.00701-2024

iScience. 2025 Feb 1;28(3):111942. doi: 10.1016/j.isci.2025.111942. eCollection 2025 Mar 21.

ABSTRACT

Cystic fibrosis (CF) is a life-shortening disease affecting >160,000 individuals worldwide predominantly with respiratory symptoms. About 80% of individuals with CF have the p.Phe508del variant that causes the CF transmembrane conductance regulator (CFTR) protein to misfold and be targeted for premature degradation by the endoplasmic reticulum (ER) quality control (ERQC), thus preventing its plasma membrane (PM) traffic. Despite the recent approval of a "highly effective" drug rescuing p.Phe508del-CFTR, maximal lung function improvement is ∼14%. To identify global modulators of p.Phe508del traffic, we performed a high-content small interfering RNA (siRNA) microscopy-based screen of >9,000 genes and monitored p.Phe508del-CFTR PM rescue in human airway cells. This primary screen identified 227 p.Phe508del-CFTR traffic regulators, of which 35 could be validated by additional siRNAs. Subsequent mechanistic studies established GRK5 as a robust regulator whose inhibition rescues p.Phe508del-CFTR PM traffic and function in primary and immortalized cells, thus emerging as a novel potential drug target for CF.

PMID:40040803 | PMC:PMC11876911 | DOI:10.1016/j.isci.2025.111942

Genome Med. 2025 Mar 4;17(1):19. doi: 10.1186/s13073-025-01443-7.

ABSTRACT

BACKGROUND: Non-tuberculous mycobacteria (NTM) are a diverse group of environmental bacteria that are increasingly associated with human infections and difficult to treat. Plasmids, which might carry resistance and virulence factors, remain largely unexplored in NTM.

METHODS: We used publicly available complete genome sequence data of 328 NTM isolates belonging to 125 species to study gene content, genomic diversity, and clusters of 196 annotated NTM plasmids. Furthermore, we analyzed 3755 draft genome assemblies from over 200 NTM species and 5415 short-read sequence datasets from six clinically relevant NTM species or complexes including M. abscessus, M. avium complex, M. ulcerans complex and M. kansasii complex, for the presence of these plasmids.

RESULTS: Between one and five plasmids were present in approximately one-third of the complete NTM genomes. The annotated plasmids varied widely in length (most between 10 and 400 kbp) and gene content, with many genes having an unknown function. Predicted gene functions primarily involved plasmid replication, segregation, maintenance, and mobility. Only a few plasmids contained predicted genes that are known to confer resistance to antibiotics commonly used to treat NTM infections. Out of 196 annotated plasmid sequences, 116 could be grouped into 31 clusters of closely related sequences, and about one-third were found across multiple NTM species. Among clinically relevant NTM, the presence of NTM plasmids showed significant variation between species, within (sub)species, and even among strains within (sub)lineages, such as dominant circulating clones of Mycobacterium abscessus.

CONCLUSIONS: Our analysis demonstrates that plasmids are a diverse and heterogeneously distributed feature in NTM bacteria. The frequent occurrence of closely related putative plasmid sequences across different NTM species suggests they may play a significant role in NTM evolution through horizontal gene transfer at least in some groups of NTM. However, further in vitro investigations and access to more complete genomes are necessary to validate our findings, elucidate gene functions, identify novel plasmids, and comprehensively assess the role of plasmids in NTM.

PMID:40038805 | DOI:10.1186/s13073-025-01443-7

Mol Cell Biochem. 2025 Mar 4. doi: 10.1007/s11010-025-05243-w. Online ahead of print.

ABSTRACT

Emerging evidence indicates that chloride channels (ClCs) significantly affect the pathogenesis of inflammatory bowel disease (IBD) through their regulatory roles in mast cell function and epithelial integrity. IBD, encompassing conditions such as Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract, where channels influence immune responses, fluid balance, and cellular signalling pathways essential for maintaining mucosal homeostasis. This review examines the specific roles of ClC in mast cells, focussing on the regulation of mast cell activation, degranulation, cytokine release, and immune cell recruitment in inflamed tissues. Key channels, including Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and ClC-2, are discussed in detail because of their involvement in maintaining intestinal epithelial barrier function, a critical factor disrupted in IBD. For example, CFTR facilitates chloride ion transport across epithelial cells, which is essential for mucosal hydration and maintenance of the intestinal barrier. Reduced CFTR function can compromise this barrier, permitting microbial antigens to penetrate the underlying tissues and triggering excessive immune responses. ClC-2, another chloride channel expressed in mast cells and epithelial cells, supports tight junction integrity, contributes to barrier function, and reduces intestinal permeability. Dysregulation of these channels is linked to altered mast cell activity and excessive release of pro-inflammatory mediators, exacerbating IBD symptoms, such as diarrhoea, abdominal pain, and tissue damage. Here, we review recent pharmacological strategies targeting ClC, including CFTR potentiators and ClC-2 activators, which show the potential to mitigate inflammatory responses. Additionally, experimental approaches for selective modulation of chloride channels in mast cells have been explored. Although targeting ClC offers promising therapeutic avenues, challenges remain in achieving specificity and minimizing side effects. This review highlights the therapeutic potential of Cl channel modulation in mast cells as a novel approach for IBD treatment, aiming to reduce inflammation and restore intestinal homeostasis in affected patients.

PMID:40038149 | DOI:10.1007/s11010-025-05243-w

Eur J Prev Cardiol. 2025 Mar 4:zwaf122. doi: 10.1093/eurjpc/zwaf122. Online ahead of print.

ABSTRACT

AIM: To assess the impact of antimicrobial resistance (AMR) on major adverse cardiovascular event (MACE) risk in patients with bronchiectasis.

METHODS: This retrospective study utilized data from the TriNetX research network, analysing patients with bronchiectasis categorized by the presence or absence of AMR. Primary outcomes included the risk of MACE (myocardial infarction, stroke and systemic thromboembolism, and cardiac arrest) and all-cause death. Cox regression analysis with 1:1 propensity score matching (PSM) was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the primary outcomes. Subgroup analyses were conducted to validate results in clinically relevant subgroups.

RESULTS: Prior to PSM, patients with AMR (n=6,543, 61.0±22.0 years, 55.8% female) were younger, more often male, and presented a higher prevalence of cardiovascular risk factors than those without AMR (n=154,685, 67.3±16.0 years, 59.4% female). After PSM, no significant differences were found between groups. However, AMR patients showed a higher risk of MACE (HR 1.29, 95% CI 1.17-1.41) and all-cause death (HR 1.49, 95% CI 1.38-1.61) compared to non-AMR patients. The MACE risk was notably elevated among AMR patients without prior cardiovascular events (HR 1.56, 95% CI 1.34-1.81). Similar MACE risks were observed in cystic fibrosis (HR 1.24, 95% CI 0.86-1.78) and non-cystic fibrosis subgroups (HR 1.28, 95% CI 1.16-1.41), with consistent findings across different AMR types.

CONCLUSIONS: In patients with bronchiectasis, AMR is associated with an increased risk of MACE and all-cause death, suggesting that controlling AMR spread may confer broader health benefits, particularly in reducing cardiovascular risk.

PMID:40037796 | DOI:10.1093/eurjpc/zwaf122

PLoS One. 2025 Mar 4;20(3):e0318085. doi: 10.1371/journal.pone.0318085. eCollection 2025.

ABSTRACT

BACKGROUND: Current diagnostic tools are limited in their ability to diagnose cystic fibrosis liver disease (CFLD) as disease is often focal in nature. Magnetic resonance extracellular volume quantification (MRI ECV) in the liver may have diagnostic utility in CFLD as a more selective liver volume is assessed and can be performed using equipment readily available in clinical practice on a standard MRI protocol.

METHODS: Healthy volunteers (HV), CF participants with no liver disease (CF-noLD) and CF participants with cirrhosis (CF-C) aged 18 years and above had MRI ECV measured using a 3T Siemens scanner. An additional retrospective analysis was performed to calculate MRI ECV in individuals who had available images obtained using a 1.5T Siemens scanner from a previous study.

RESULTS: 16 individuals had MRI ECV measured using a 3T Siemens scanner. Mean (SD) MRI ECV was 0.316 (0.058) for HV (n = 5), 0.297 (0.034) for CF-noLD (n = 5) and 0.388 (0.067) for CF-C (n = 6 ). Post-hoc analysis showed a significant difference between CF-noLD and CF-C (p = 0.046). Of 18 individuals with available images using a 1.5T scanner, mean (SD) MRI ECV was 0.269 (0.048) in HV (n = 8), 0.310 (0.037) in CF-noLD (n = 8) and 0.362 (0.063) in CF-C (n = 2).

CONCLUSIONS: Liver MRI ECV quantification was feasible in adults with CF with no significant difference in results between 1.5T and 3T obtained images suggesting applicability across different types of MRI scanner. A higher MRI ECV was demonstrated in CF participants with cirrhosis suggesting potential utility as a diagnostic tool for those with advanced CFLD. Further evaluation in larger cohorts is warranted.

PMID:40036270 | DOI:10.1371/journal.pone.0318085

Appl Environ Microbiol. 2025 Mar 4:e0240224. doi: 10.1128/aem.02402-24. Online ahead of print.

ABSTRACT

Quorum sensing (QS) plays a crucial role in regulating key traits, including the upregulation of phage receptors, which leads to heightened phage susceptibility in Pseudomonas aeruginosa. As a result, higher cell densities typically increase the risk of phage invasions. This has led to speculation that bacteria may have evolved strategies to counterbalance this increased susceptibility. Additionally, non-synonymous mutations in LasR, the master regulator of QS, are common among cystic fibrosis patients, but the impact of these mutations on phage interactions remains poorly understood. Here, we systematically investigated the role of QS in shaping these interactions using bacterial strains with functional or altered QS systems. In the QS-functional strain ZS-PA-35, disruption of the Las system reduces cell susceptibility to the type IV pili-dependent phage phipa2, delaying bacterial lysis during the early logarithmic growth phase. At high cell densities, Las-induced dormancy further inhibits phage proliferation despite enhanced phage adsorption. Notably, nutrient supplementation fully restores phage proliferation in the strains with a functional Las system. In contrast, the QS-deficient strain ZS-PA-05, carrying a LasR mutation, fails to regulate phage-host interactions via QS. Moreover, our findings reveal that within mixed microbial populations, cells benefit from the presence of closely related kin, which collectively reduce prey density and limit phage-host interaction frequencies under nutrient-rich conditions. These results underscore the flexibility of QS-regulated defense strategies, highlighting their critical role in optimizing bacterial resilience against phage predation, particularly in heterogeneous communities most vulnerable to phages.IMPORTANCEBacteria have developed various strategies to combat phage infection, posing challenges to phage therapy. In this study, we demonstrate that Pseudomonas aeruginosa strains with functional or altered quorum sensing (QS) systems may adapt different survival tactics for prolonged coexistence with phages, contingent upon bacterial population dynamics. The dynamics of phage infection highlight the influence of intrinsic heterogeneity mediated by QS, which leads to the emergence of different phage-host outcomes. These variants may arise as a result of coevolutionary processes or coexistence mechanisms of mutational and non-mutational defense strategies. These insights enhance our comprehension of how bacteria shield themselves against phage attacks and further underscore the complexity of such approaches for successful therapeutic interventions.

PMID:40035599 | DOI:10.1128/aem.02402-24

Res Sq [Preprint]. 2025 Feb 17:rs.3.rs-5938603. doi: 10.21203/rs.3.rs-5938603/v1.

ABSTRACT

BACKGROUND: In a healthy lung, the airway epithelium regulates glucose transport to maintain low glucose concentrations in the airway surface liquid (ASL). However, hyperglycemia and chronic lung diseases, such as cystic fibrosis (CF), can result in increased glucose in bronchial aspirates. People with CF are also at increased risk of lung infections caused by bacterial pathogens, including methicillin-resistant Staphylococcus aureus. Yet, it is not known how increased airway glucose availability affects bacteria in chronic CF lung infections or impacts treatment outcomes.

METHODS: To model the CF airways, we cultured immortalized CF (CFBE41o-) and non-CF (16HBE) human bronchial epithelial cells at air liquid interface (ALI). Glucose concentrations in the basolateral media were maintained at 5.5 mM or 12.5 mM, to mimic a normal and hyperglycemic milieu respectively. 2-deoxyglucose was added to high glucose culture media to restrict glucose availability. We collected ASL, basolateral media, and RNA from ALI cultures to assess the effects of elevated glucose. We also inoculated S. aureus onto the apical surface of normal or high glucose ALI cultures and observed the results of antibiotic treatment post-inoculation. S. aureus growth was measured by enumerating viable colony forming units (CFU) and with fluorescence microscopy. The effects of elevated glucose on in vitro growth and antibiotic treatment were also evaluated in standard bacterial culture medium and synthetic CF medium (SCFM).

RESULTS: We found that glucose concentrations in the ASL of ALI cultures maintained in normal or high glucose mimicked levels measured in breath condensate assays from people with CF and hyperglycemia. Additionally, we found hyperglycemia increased S. aureus aggregation and antibiotic resistance during infection of cells maintained in high glucose compared to normal glucose conditions. Heightened antibiotic tolerance or resistance as not observed during in vitro growth with elevated glucose. Limiting glucose with 2-deoxyglucose both decreased aggregation and reduced antibiotic resistance back to levels comparable to non-hyperglycemic conditions.

CONCLUSIONS: These data indicate hyperglycemia alters S. aureus growth during infection and may reduce efficacy of antibiotic treatment. Glucose restriction is a potential option that could be explored to limit bacterial growth and improve treatment outcomes in chronic airway infections.

PMID:40034435 | PMC:PMC11875303 | DOI:10.21203/rs.3.rs-5938603/v1

ANZ J Surg. 2025 Mar 3. doi: 10.1111/ans.70005. Online ahead of print.

ABSTRACT

BACKGROUND: Distal intestinal obstruction syndrome (DIOS) presents significant management challenges for people with cystic fibrosis (pwC). We evaluated the treatment outcomes and identified risk factors associated with the need for surgical intervention in patients admitted with DIOS.

METHOD: We conducted a retrospective case series of 96 encounters of DIOS over a 20-year period, observing outcomes between cases of medical management versus those requiring for operative intervention. To our knowledge, this is the largest Australian study to review intervention in DIOS.

RESULTS: Among the patients studied, 94.8% were successfully treated non-surgically. Using computed tomography (CT) confirmation of DIOS as the gold standard, only 9.1% of abdominal x-rays were accurate in finding DIOS. Gastrografin was used in half of cases and was associated with a shorter recovery time. One in 16 patients required operative management, with two cases experiencing surgery following prolonged medical treatment. A history of previous laparotomy increased the odds of requiring surgical intervention by 16 times (95% CI: 1.2-209.9, P = 0.035), while a history of meconium ileus increased the odds by 15.6 times (95% CI: 1.2-204.8, P = 0.036). All patients who underwent surgery also had pancreatic insufficiency.

CONCLUSION: Medical management was successful in the majority of DIOS presentations. Our study emphasizes a low threshold for abdominal CT scans to identify complete DIOS in high-risk patients, particularly those with a history of laparotomy or meconium ileus, who may require surgical intervention. Furthermore, we advocate for the adjunctive use of Gastrografin alongside medical management. Future research should refine protocols for these high-risk groups to improve outcomes and reduce morbidity.

PMID:40033632 | DOI:10.1111/ans.70005

J Gen Intern Med. 2025 Mar 3. doi: 10.1007/s11606-025-09449-y. Online ahead of print.

ABSTRACT

BACKGROUND: Despite guideline recommendations to offer continuous glucose monitoring (CGM) to all patients with diabetes using insulin, prescription rates for CGM remain low in primary care.

OBJECTIVE: This quality improvement project aimed to improve access to CGM in primary care for patients with type 2 diabetes on insulin.

DESIGN: This was a quality improvement project conducted by a joint endocrinology/primary care team at a single primary care community health clinic. After defining the problem through process mapping, driver diagrams, and Pareto charts, several interventions were trialed through Plan-Do-Study-Act (PDSA) cycles.

PARTICIPANTS: The study team consisted of four endocrinologists, two primary care providers (MD/NP), the lead primary care nurse, and the primary care population health specialist.

INTERVENTIONS: Interventions included a directory for durable medical equipment (DME) suppliers, nursing education with device company representatives, a new electronic ordering system for DME, and a nursing outreach program to patients eligible for CGM.

MAIN MEASURES: The primary outcome was percentage of eligible patients using CGM. Process measures included the number of CGM orders started weekly. Nursing comfort with CGM, knowledge of CGM, and perceptions of communication with DME suppliers were also measured.

KEY RESULTS: The percentage of eligible patients using CGM increased from 28 to 42%, and the percentage of patients using CGM started in primary care increased from 8 to 14%. Weekly orders increased from 0.3 per week to 2.3 per week. Nursing reported feeling more comfortable and knowledgeable about CGM after the interventions and reported improved communication with DME suppliers.

CONCLUSIONS: CGM is known to improve outcomes for patients with diabetes but is an underutilized tool in primary care. Collaborative quality improvement projects between endocrinology and primary care can rapidly build capacity within primary care to prescribe CGM and expand access for patients with diabetes who do not have endocrinologists.

PMID:40032724 | DOI:10.1007/s11606-025-09449-y

FEBS J. 2025 Mar 3. doi: 10.1111/febs.70050. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to chronic, unresolved inflammation of the airways due to uncontrolled recruitment of polymorphonuclear leukocytes (PMNs). Evidence indicates that CFTR loss-of-function, in addition to promoting a pro-inflammatory phenotype, is associated with an increased risk of developing cancer, suggesting that CFTR can exert tumor-suppressor functions. Three-dimensional (3D) in vitro culture models, such as the CF lung airway-on-a-chip, can be suitable for studying PMN recruitment, as well as events of cancerogenesis, that is epithelial cell invasion and migration, in CF. To gather insight into the pathobiology of CFTR loss-of-function, we generated CFTR-knockout (KO) clones of the 16HBE14o- human bronchial cell line by CRISPR/Cas9 gene editing, and performed a comparative proteomic analysis of these clones with their wild-type (WT) counterparts. Systematic signaling pathway analysis of CFTR-KO clones revealed modulation of inflammation, PMN recruitment, epithelial cell migration, and epithelial-mesenchymal transition. Using a latest-generation organ-on-a-chip microfluidic platform, we confirmed that CFTR-KO enhanced PMN recruitment and epithelial cell invasion of the endothelial layer. Thus, a dysfunctional CFTR affects multiple pathways in the airway epithelium that ultimately contribute to sustained inflammation and cancerogenesis in CF.

PMID:40029006 | DOI:10.1111/febs.70050

Phys Occup Ther Pediatr. 2025 Mar 3:1-16. doi: 10.1080/01942638.2025.2469567. Online ahead of print.

ABSTRACT

AIMS: To evaluate the effects of telerehabilitation (TG) compared with an unsupervised home exercise training program (HG) on muscle function, physical activity (PA), and sleep in children with cystic fibrosis (CF).

METHODS: Thirty children with CF (mean age = 10.2 ± 1.9 years) were randomly allocated to TG or HG. The exercise protocol was applied thrice a week for six weeks in the TG via Skype. The same exercises were sent in an exercise booklet to the HG, and phone contact was made once a week. Muscle function (one-minute sit-to-stand (1-min STS), sit-up, pushup, squat, and plank tests)), PA (Physical Activity Questionnaire for Older Children), and sleep (Epworth Sleepiness Scale (ESS) and Pediatric Sleep Questionnaire (PSQ)) were assessed before and after the 6-week study period.

RESULTS: The 1-min STS significantly improved in the TG compared with the HG (p ≤ .001, ηp2 = 0.474). The sit-up (p = .005, ηp2 = 0.247), pushup (p = .002, ηp2 = 0.180), squat (p = .002, ηp2 = 0.284), and plank (p < .001, ηp2 = 0.360) test scores were significantly improved in the TG compared to the HG. No significant changes between groups were seen for PA (p = .261, ηp2 = 0.045), ESS (p = .160, ηp2 = 0.069), or PSQ (p = .763, ηp2 = 0.003).

CONCLUSION: Children who received TG improved muscle function more than children who received an HG. The effectiveness of longer term TG programs should be investigated in children with CF.

PMID:40028780 | DOI:10.1080/01942638.2025.2469567

Genet Med Open. 2025 Jan 7;3:101962. doi: 10.1016/j.gimo.2025.101962. eCollection 2025.

ABSTRACT

PURPOSE: Newborn screening identifies rare diseases that result from the recessive inheritance of pathogenic variants in both copies of a gene. Long-read genome sequencing (LRS) is used for identifying and phasing genomic variants, but further efforts are needed to develop LRS for applications using low-yield DNA samples.

METHODS: In this study, genomic DNA with high molecular weight was obtained from 2 cystic fibrosis patients, comprising a whole-blood sample (CF1) and a newborn dried blood spot sample (CF2). Library preparation and genome sequencing (30-fold coverage) were performed using 20 ng of DNA input on both the PacBio Revio system and the Illumina NovaSeq short-read sequencer. Single-nucleotide variants, small indels, and structural variants were identified for each data set.

RESULTS: Our results indicated that the genotype concordance between long- and short-read genome sequencing data was higher for single-nucleotide variants than for small indels. Both technologies accurately identified known pathogenic variants in the CFTR gene (CF1: p.(Met607_Gln634del), p.(Phe508del); CF2: p.(Phe508del), p.(Ala455Glu)) with complete concordance for the polymorphic poly-TG and consecutive poly-T tracts. Using PacBio read-based haplotype phasing, we successfully determined the allelic phase and identified compound heterozygosity of pathogenic variants at genomic distances of 32.4 kb (CF1) and 10.8 kb (CF2).

CONCLUSION: Haplotype phasing of rare pathogenic variants from minimal DNA input is achieved through LRS. This approach has the potential to eliminate the need for parental testing, thereby shortening the time to diagnosis in genetic disease screening.

PMID:40027236 | PMC:PMC11869909 | DOI:10.1016/j.gimo.2025.101962

Obstet Med. 2025 Feb 26:1753495X251319588. doi: 10.1177/1753495X251319588. Online ahead of print.

ABSTRACT

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) was made available to eligible women in September 2020 by NHS Scotland.

METHODS: Retrospective data collection for the 13 pregnancies in women taking ETI from the West of Scotland Adult Cystic Fibrosis Unit, September 2020-December 2023.

RESULTS: Mean pre-pregnancy FEV1 was 2.26L, 70% predicted (range 1.25-3.19); (38-86% predicted). Mean FEV1 post-pregnancy was 2.29L, 71% predicted (range 1.49-3.40); (45-92% predicted). The mean age at conception (29 years) and mean percentage predicted FEV1 (70%) were higher than in other UK studies. Two pregnancies resulted in miscarriage, the remaining 11 pregnancies resulted in a live birth. Seven women had a pulmonary exacerbation of CF during pregnancy. Three of four women with FEV1 < 60% predicted had uncomplicated pregnancies with no pulmonary exacerbations.

CONCLUSION: We demonstrate that people with CF and varying spectrums of lung disease who take CFTR modulators can have uncomplicated pregnancies with positive lung function outcomes.

PMID:40027072 | PMC:PMC11866333 | DOI:10.1177/1753495X251319588

Eur J Clin Nutr. 2025 Mar 1. doi: 10.1038/s41430-025-01591-4. Online ahead of print.

ABSTRACT

OBJECTIVES: Malnutrition is prevalent among children with cystic fibrosis (CF), often resulting from frequent pulmonary exacerbations and intestinal malabsorption. In addition to providing sufficient calorie intake through enteral formulas, appetite stimulants may help address nutritional deficiencies and improve overall prognosis.

METHODS: This retrospective study included children who received cyproheptadine (CH) as an appetite stimulant for at least three consecutive months. Data on CH-related adverse effects, z-scores for weight, height, body mass index (BMI), and percentage of forced expiratory volume in 1 s (FEV1%) were collected from medical records. Z-scores of growth parameters were calculated at baseline (CH initiation), three months before baseline, and three and six months after treatment.

RESULTS: The study included 45 children with a mean age of 11 years. One patient was on modulator therapy, one was pancreatic sufficient, and another one had diabetes. Only one patient was using enteral supplementation simultaneously with CH. Significant improvements in weight and BMI z-scores were observed from baseline to three months of CH therapy (p = 0.004 and p = 0.006, respectively), with no significant changes noted in the three months before treatment. A modest increase in weight and BMI z-scores was seen from three to six months of therapy. Additionally, FEV1 z-scores significantly increased from baseline to three months of therapy, with no further improvement observed in the subsequent three months.

CONCLUSION: Six months of CH therapy was associated with significant improvements in weight and BMI z-scores, particularly within the first three months. No adverse effects were reported. Given the deceleration in the rate of increase in anthropometric z-scores from the third to sixth month, a three-month duration of CH therapy appears to be optimal and sufficient for children with CF.

PMID:40025246 | DOI:10.1038/s41430-025-01591-4

Int Forum Allergy Rhinol. 2025 Mar 2:e23555. doi: 10.1002/alr.23555. Online ahead of print.

ABSTRACT

BACKGROUND: Severe chronic rhinosinusitis (CRS) is a near universal manifestation of cystic fibrosis. Elexacaftor/tezacaftor/ivacaftor (ETI) is an oral, small molecule, highly effective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) corrector-potentiator drug. In people with cystic fibrosis age > 12 years, ETI improves sinonasal symptoms, endoscopy findings, polyp size, and radiologic findings. This study evaluates changes in CRS in children ages 6-12 years newly started on ETI.

METHODS: This was a prospective, three center, pre-post study of 11 children age 6-11 years newly started on ETI. Study endpoints included the SN-5 sinonasal health survey, Sniffin' Kids olfaction test, a sinus computerized tomography (CT) scan, and nasal endoscopy with mucus sampling for full-length 16S rRNA sequencing microbiome analysis. Study visits were conducted before ETI and at a median of 9 months after treatment initiation.

RESULTS: ETI lead to improvement in symptoms, endoscopy scores and radiologic findings of CRS. Olfaction was below normal at baseline and did not improve. The sinonasal microbiome was dominated by typically commensal organisms before and after treatment for most participants. Additionally, Staphylococcus aureus was found in five participants at baseline and six participants on treatment.

CONCLUSIONS: ETI improves sinonasal symptoms and endoscopy findings in children 6-11 years of age. Olfaction did not improve with ETI treatment in this age group, suggesting that olfactory dysfunction associated with CF is established early in life. This younger cohort of pediatric patients presented with abundant Staphylococcus aureus and only very rare Pseudomonas aeruginosa at baseline or after treatment.

PMID:40024881 | DOI:10.1002/alr.23555

Microb Pathog. 2025 Feb 28:107378. doi: 10.1016/j.micpath.2025.107378. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa, a formidable opportunistic pathogen, is notorious for its ability to form biofilms and produce virulence factors that favor chronic infections, especially in cystic fibrosis patients. The misuse of disinfectants, combined with environmental leakage and biodegradation, has led to widespread exposure of microorganisms to sub-lethal concentrations of disinfectants, particularly quaternary ammonium compounds (QACs). This study investigates the interaction between QACs, specifically ethylbenzalkyl dimethyl ammonium chloride (EBAC), and the quorum sensing (QS) mechanisms governing P. aeruginosa behavior. The results demonstrate that exposure to sub-minimum inhibitory concentrations (sub-MICs) of EBAC not only enhances the biofilm-forming capability of P. aeruginosa isolates but also modulates the expression of crucial QS-regulated genes. Notably, the bacteria exhibit increased production of biofilm-associated virulence factors such as pyocyanin and elastase, and altered antibiotic susceptibility profiles, indicating a shift towards persistent infection phenotypes. These findings reveal that QAC exposure can significantly increase resistance to antibiotics and external stressors like hydrogen peroxide. These results emphasize the need to reassess the efficacy of QACs in clinical disinfection settings, particularly against P. aeruginosa infections, and highlight the potential for unintended consequences of their use regarding bacterial behavior and virulence. This study provides novel insights into the role of QACs in modulating QS-mediated virulence and antibiotic resistance, offering a new perspective on the risks associated with sub-lethal disinfectant exposure.

PMID:40024542 | DOI:10.1016/j.micpath.2025.107378

J Pediatr Adolesc Gynecol. 2025 Feb 28:S1083-3188(25)00226-8. doi: 10.1016/j.jpag.2025.02.009. Online ahead of print.

ABSTRACT

This case report highlights a rare occurrence of urethral prolapse (UP) in a 7-year-old girl diagnosed with cystic fibrosis (CF). The patient displayed a protruding, swollen, and bleeding mass at the urinary orifice, accompanied by chronic constipation and a recent respiratory syncytial virus (RSV) infection. Cystovaginoscopy and circumferential excision were performed, leading to a successful outcome. Since the operation, the patient has been pain-free. The association between CF and UP underscores the need for heightened awareness among clinicians. The report focuses on recognizing and managing UP in pediatric CF patients to provide the best possible care.

PMID:40024430 | DOI:10.1016/j.jpag.2025.02.009

J Cyst Fibros. 2025 Feb 28:S1569-1993(25)00068-2. doi: 10.1016/j.jcf.2025.02.018. Online ahead of print.

NO ABSTRACT

PMID:40023749 | DOI:10.1016/j.jcf.2025.02.018

Rev Mal Respir. 2025 Feb 28:S0761-8425(25)00047-6. doi: 10.1016/j.rmr.2025.02.004. Online ahead of print.

ABSTRACT

Cystic fibrosis is a genetic disease in which phenotypic variability is still poorly understood. Our hypothesis is that the exposome, and more specifically exposure to air pollution and/or anxiety, could play a role in this phenomenon. In this context, we have developed an experimental study in which cystic fibrosis mice were exposed to stress (anxiety) and then to complex realistic atmospheres. Our results should provide mechanistic elements for a better understanding of the phenotypic variability observed in cystic fibrosis patients and thus be able to propose new avenues for better management of these patients.

PMID:40023717 | DOI:10.1016/j.rmr.2025.02.004