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

Respir Res. 2025 Feb 28;26(1):77. doi: 10.1186/s12931-025-03140-w.

ABSTRACT

BACKGROUND: Non-cystic fibrosis bronchiectasis is associated with frequent and diverse microbial infections, yet an overall understanding of microbial presence across different disease stages is lacking.

METHODS: A meta-analysis assessed lung microbes in adults with non-CF bronchiectasis, collecting data using both culture-based and sequencing approaches through three international databases and three Chinese databases. Subgroups were categorized by disease stage: the stable group (S), the exacerbation group (E), and unclassified data consolidated into the undetermined group (U). Culture data were analysed in random-effects meta-analyses while sequencing data were processed using QIIME 2.

RESULTS: A total of 98 studies were included with data from 54,384 participants worldwide. Pseudomonas aeruginosa was the most frequently isolated bacterium (S: 26[19-34]%, E: 23[20-25]%, U: 20[16-25]%), while not specified Mycobacterium avium complex exhibited the highest mycobacterial prevalence (S: 3[1-5]%, E: 4[2-5]%, U: 15[3-27]%). Aspergillus spp. (S: 15[-10-39]%, E: 2[1-3]%, U: 10[5-15]%) and Candida spp. (S: not applicable, E: 11[2-20]%, U: 10[-8-27]%) were predominant in fungi culture with variable distributions among groups. Rhinovirus was the most commonly detected virus with varying prevalence across airway sample types rather than disease stages (S-sputum: 18[-16-53]%, S-nasopharyngeal: 4[-1-9]%, E-sputum: 22[16-29]%, E-nasopharyngeal: 6[4-8]%). Sequencing results revealed notable antibiotic persistence of Pseudomonas in 16S, and significant domination of Candida in ITS.

CONCLUSION: Our findings indicate consistent bacterial patterns throughout bronchiectasis stages in both culture and sequencing results. Viruses are extensively detected in stable patients but vary across different airway sample types. Lower bacterial diversity and higher fungal diversity may be associated with exacerbation risks.

PMID:40022075 | DOI:10.1186/s12931-025-03140-w

Mol Med. 2025 Feb 28;31(1):81. doi: 10.1186/s10020-025-01133-5.

ABSTRACT

BACKGROUND AND PURPOSE: Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disease belonging to the inherited bone marrow failure syndromes and characterized by hypocellular bone marrow, exocrine pancreatic insufficiency, and skeletal abnormalities. SDS is associated with increased risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). Although SDS is not primarily considered an inflammatory disorder, some of the associated conditions (e.g., neutropenia, pancreatitis and bone marrow dysfunction) may involve inflammation or immune system dysfunctions. We have already demonstrated that signal transducer and activator of transcription (STAT)-3 and mammalian target of rapamycin (mTOR) were hyperactivated and associated with elevated IL-6 levels in SDS leukocytes. In this study, we analyzed the level of phosphoproteins involved in STAT3 and mTOR pathways in SDS lymphoblastoid cells (LCLs) and the secretomic profile of soluble pro-inflammatory mediators in SDS plasma and LCLs in order to investigate the systemic inflammation in these patients and relative pathways.

METHODS: Twenty-six SDS patients and seven healthy donors of comparable age were recruited during the programmed follow-up visits for clinical evaluation at the Verona Cystic Fibrosis Center Human. The obtained samples (plasma and/or LCLs) were analyzed for: phosphoproteins, cytokines, chemokines and growth factors levels by Bio-plex technology; microRNAs profiling by next generation sequencing (NGS) and microRNAs expression validation by Real Time-PCR (RT-PCR) and droplet digital PCR (ddPCR) .

RESULTS: We demonstrated dysregulation of ERK1/2 and AKT phosphoproteins in SDS, as their involvement in the hyperactivation of the STAT3 and mTOR pathways confirmed the interplay of these pathways in SDS pathophysiology. However, both these signaling pathways are strongly influenced by the inflammatory environment. Here, we reported that SDS is characterized by elevated plasma levels of several soluble proinflammatory mediators. In vitro experiments show that these pro-inflammatory genes are closely correlated with STAT3/mTOR pathway activation. In addition, we found that miR-181a-3p is down-regulated in SDS. Since this miRNA acts as a regulator of several pro-inflammatory pathways such as STAT3 and ERK1/2, its down-regulation may be a driver of the constitutive inflammation observed in SDS patients.

CONCLUSIONS: The results obtained in this study shed light on the complex pathogenetic mechanism underlying bone marrow failure and leukemogenesis in SDS, suggesting the need for anti-inflammatory therapies for SDS patients.

PMID:40021961 | DOI:10.1186/s10020-025-01133-5

NPJ Antimicrob Resist. 2025 Feb 28;3(1):17. doi: 10.1038/s44259-025-00088-1.

ABSTRACT

R-pyocins, bacteriocin-like proteins produced by Pseudomonas aeruginosa, present a promising alternative to phage therapy and/or adjunct to currently used antimicrobials in treating bacterial infections due to their targeted specificity, lack of replication, and stability. This review explores the structural, mechanistic, and therapeutic aspects of R-pyocins, including their potential for chronic infection management, and discusses recent advances in delivery methods, paving the way for novel antimicrobial applications in clinical settings.

PMID:40021925 | DOI:10.1038/s44259-025-00088-1

Transplant Proc. 2025 Feb 27:S0041-1345(25)00102-2. doi: 10.1016/j.transproceed.2025.02.020. Online ahead of print.

ABSTRACT

Although active malignancy is a contraindication to lung transplantation, there is increasing uncertainty as to what constitutes "active" malignancy given the rapidly changing therapeutic armamentarium and overall survival of patients with malignancy. Chronic myeloid leukemia (CML) is an example of a previously fatal malignancy that has been transformed into a chronic disease with close-to-normal life expectancy since the advent of tyrosine kinase inhibitor (TKI) therapy. However, it remains relatively unknown if lung transplantation could successfully be performed in patients with CML. We describe the course of a 34-year-old woman with cystic fibrosis and advanced lung disease who was diagnosed with CML while undergoing lung transplant evaluation. She was initiated on imatinib with optimal treatment response; she achieved major molecular response (MMR) and deep molecular response (DMR) at 8 and 10 months of treatment, respectively. She developed progressive respiratory failure and underwent bilateral lung transplantation at close to 3 years after achieving MMR. At 6 years post-transplant, she has excellent graft function and remains in DMR on imatinib. Treated CML in DMR should be regarded as inactive malignancy and should not preclude patients from life-saving transplant consideration. Our case also demonstrates the feasibility of long-term immunosuppression on TKI therapy.

PMID:40021434 | DOI:10.1016/j.transproceed.2025.02.020

Sci Adv. 2025 Feb 28;11(9):eads1568. doi: 10.1126/sciadv.ads1568. Epub 2025 Feb 28.

ABSTRACT

A reduced sense of smell is a common condition in people with cystic fibrosis (CF) that negatively affects their quality of life. While often attributed to nasal mucosa inflammation, the underlying causes of the olfactory loss remain unknown. Here, we characterized gene expression in olfactory epithelium cells from patients with CF using single-nuclei RNA sequencing and found altered expression of olfactory receptors (ORs) and genes related to progenitor cell proliferation. We confirmed these findings in newborn, inflammation-free samples of a CF animal model and further identified ultrastructural alterations in the olfactory epithelium and bulbs of these animals. We established that CFTR, the anion channel whose dysfunction causes CF, is dispensable for odor-evoked signaling in sensory neurons, yet CF animals displayed defective odor-guided behaviors consistent with the morphological and molecular alterations. Our study highlights CF's major role in modulating epithelial structure and OR expression, shedding light on the mechanisms contributing to olfactory loss in CF.

PMID:40020072 | DOI:10.1126/sciadv.ads1568

Pediatr Pulmonol. 2025 Mar;60(3):e71021. doi: 10.1002/ppul.71021.

ABSTRACT

BACKGROUND: People with CF (pwCF) frequently have gastrointestinal symptoms (GI), including abdominal pain and irregular bowel movements. These are often embarrassing, difficult to report, and frequently missed. Thus, a GI Symptom Tracker was created and validated in the USA and translated and validated in Dutch. This questionnaire consists of four subscales: Eating Challenges, Stools, Adherence Challenges, and Abdominal Symptoms. The aim of this study was to investigate the relationship between GI symptoms, anxiety/depression, and health-related quality of life (HRQoL) in Dutch pwCF.

METHODS: In this prospective, cross-sectional single-center pilot study, pwCF completed the Dutch GI Symptom Tracker, GAD-7 (anxiety), PHQ-9 (depression), and CFQ-R (HRQoL) from September 2021 to June 2022. Regression analyses were used to analyze the univariable associations between GI symptoms, anxiety/depression, and HRQoL.

RESULTS: A total of 51 pwCF were enrolled consecutively (n = 41 adults, 66% female, mean age (y) [range] = 32.7 [19-71] and n = 10 adolescents, 70% female, mean age (y) [range] = 14.2 [12-17]). Elevated levels of anxiety (scores ≥ 10 on GAD-7) were found in 17% of adults and 0% of adolescents. Elevated depression scores (≥ 10 on PHQ-9) were found in 9% of adults and 20% of adolescents. GI scales "Abdominal Symptoms" and "Stools" were significantly, positively associated with elevated symptoms of anxiety and depression. Most GI scales were associated with lower HRQoL.

CONCLUSION: This is the first study investigating the link between GI symptoms assessed by the Dutch GI Symptom Tracker and anxiety/depression and HRQoL in Dutch pwCF. More GI symptoms were associated with higher anxiety and depression scores and worse HRQoL. Additional research is needed to better understand how mental and physical health are linked in GI symptoms in CF.

PMID:40019138 | DOI:10.1002/ppul.71021

Pediatr Pulmonol. 2025 Mar;60(3):e71017. doi: 10.1002/ppul.71017.

ABSTRACT

BACKGROUND: Substance use has increased among people with CF (pwCF), yet communication about use remains understudied between pwCF and their healthcare providers.

OBJECTIVE: Investigate pwCF's perceptions regarding their healthcare team's discussions surrounding substance use, comfort level discussing such usage, and barriers encountered during these discussions.

METHODS: This cross-sectional study used a one-time electronic survey to assess communication regarding substance use between pwCF aged 13 years and older and their CF healthcare team.

RESULTS: Of 226 participants, 74% (n = 167) reported being asked about marijuana, 57% (n = 128) about CBD, 70% (n = 150) about e-cigarettes, and 88% (n = 189) about cigarettes by their CF healthcare team. Fewer providers discussed the risks and benefits of each substance: 47% (n = 107) for marijuana, 40% (n = 90) for CBD, 44% (n = 99) for e-cigarettes, and 61% (n = 138) for cigarettes. Provider knowledge was rated higher for cigarettes and e-cigarettes compared to marijuana and CBD. Most participants felt comfortable discussing substance use, though a minority expressed discomfort, mainly due to concerns about documentation in medical records and perceived lack of support.

CONCLUSION: This study highlights variability in communication between pwCF and their healthcare teams regarding substance use, particularly when it comes to marijuana and CBD. The findings suggest a need for standardized guidelines and educational resources to improve recreational substance screening and discussion in CF clinical care, especially given the changing landscape of marijuana regulations and increasing use among pwCF.

PMID:40019020 | DOI:10.1002/ppul.71017

Pediatr Pulmonol. 2025 Mar;60(3):e71019. doi: 10.1002/ppul.71019.

ABSTRACT

RATIONALE: The introduction of elexacaftor/tezacaftor/ivacaftor (ETI), a highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy, to younger ages and the COVID-19 pandemic have significantly reduced pulmonary exacerbations requiring hospitalization among children with CF.

OBJECTIVE: To assess demographic and clinical characteristics of children and young adults with CF hospitalized for pulmonary exacerbations before and after pediatric ETI approval.

METHODS: A retrospective chart review was conducted at five United States CF Foundation-accredited care centers. Hospitalization data from children and young adults with CF in 2018 and 2022 were analyzed.

RESULTS: Hospitalizations decreased from 471 cases (241 individuals) in 2018 to 163 cases (110 individuals) in 2022. The racial distribution shifted, with more hospitalized patients identifying as people of color in 2022 (28% vs. 14%; p = 0.018). A greater proportion of hospitalized children in 2022 had two non-F508del mutations compared with children hospitalized in 2018 (38% vs. 19%) and were less likely to be infected with methicillin-resistant Staphylococcus aureus (MRSA). Comparing 2022-2018, children on CFTR modulator therapy, including ETI (76%), showed reduced infections with Pseudomonas aeruginosa and Achromobacter xylosoxidans.

CONCLUSIONS: The decline in hospitalizations for pulmonary exacerbations likely reflects the benefits of ETI therapy, as a higher proportion of children and young adults hospitalized in 2022 had two non-F508del mutations and were not eligible for ETI. A greater percentage of those hospitalized in 2022 identified as belonging to minority racial groups, highlighting ongoing health disparities in the ETI era. Additionally, there were notable changes in the microbiological characteristics between 2018 and 2022.

PMID:40018992 | DOI:10.1002/ppul.71019

Front Biosci (Landmark Ed). 2025 Jan 24;30(2):25765. doi: 10.31083/FBL25765.

ABSTRACT

BACKGROUND: A number of association studies have linked ribosomal DNA gene copy number (rDNA CN) to aging and pathology. Data from these studies are contradictory and depend on the quantitative method.

METHODS: The hybridization technique was used for rDNA quantification in human cells. We determined the rDNA CN from healthy controls (HCs) and patients with schizophrenia (SZ) or cystic fibrosis (CF) (total number of subjects N = 1124). For the first time, rDNA CN was quantified in 105 long livers (90-101 years old). In addition, we conducted a joint analysis of the data obtained in this work and previously published by our group (total, N = 3264).

RESULTS: We found increased rDNA CN in the SZ group (534 ± 108, N = 1489) and CF group (567 ± 100, N = 322) and reduced rDNA CN in patients with mild cognitive impairment (330 ± 60, N = 93) compared with the HC group (422 ± 104, N = 1360). For the SZ, CF, and HC groups, there was a decreased range of rDNA CN variation in older age subgroups compared to child subgroups. For 311 patients with SZ or CF, rDNA CN was determined two or three times, with an interval of months to several years. Only 1.2% of patients demonstrated a decrease in rDNA CN over time. We did not find significant rDNA CN variation in eight different organs of the same patient or in cells of the same fibroblast population.

CONCLUSIONS: The results suggest that rDNA CN is a relatively stable quantitative genetic trait statistically associated with some diseases, which however, can change in rare cases under conditions of chronic oxidative stress. We believe that age- and disease-related differences between the groups in mean rDNA CN and its variance are caused by the biased elimination of carriers of marginal (predominantly low) rDNA CN values.

PMID:40018927 | DOI:10.31083/FBL25765

BMJ Public Health. 2024 Nov 27;2(2):e001459. doi: 10.1136/bmjph-2024-001459. eCollection 2024 Dec.

ABSTRACT

INTRODUCTION: Newborn screening (NBS) is an essential public health initiative for early diagnosis of inborn errors of metabolism (IEM), where timely intervention can reduce morbidity and mortality. While routine in developed countries, NBS is not widely practised in India. This study aimed to implement NBS programme in a tertiary care hospital in South India and validate predetermined cut-off values tailored to the regional population.

METHODS: Between 2020 and 2022, 5157 neonates were screened for congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), cystic fibrosis (CF), glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDD), phenylketonuria (PKU), galactosemia and biotinidase deficiency. Screening was performed using dissociation-enhanced lanthanide fluorescent immunoassay technology on Victor2D platform (Revvity). Markers assessed included 17-α-OH progesterone, neonatal thyroid stimulating hormone, total galactose, immunoreactive trypsinogen, G6PD enzyme, biotinidase enzyme and phenylalanine levels. Data analysis was conducted using R V.4.1.1 software.

RESULTS: Of the 5157 neonates, the recall rates were consistent with those reported in similar studies. However, only 26.7% of screen-positive newborns returned for retesting, indicating a significant gap in awareness about IEMs and the importance of follow-up. Of these, none were diagnosed with CAH; however, four were found to have CH, two had galactosemia, three had G6PDD, one had CF, one had PKU and none had biotinidase deficiency. The confirmed cases were promptly treated and monitored regularly. The distribution of each marker's values fell within 2.5th-97.5th percentiles suggesting consistency.

CONCLUSION: The reference ranges provided by the manufacturer appear valid in the Indian context. A key challenge identified was low follow-up compliance for screen-positive infants, highlighting the need for enhanced public education on IEM and NBS. Future research will focus on determining the incidence of IEMs and improving parental awareness and follow-up rates.

PMID:40018536 | PMC:PMC11816103 | DOI:10.1136/bmjph-2024-001459