Am J Respir Crit Care Med. 2025 Mar 24. doi: 10.1164/rccm.202502-0338ED. Online ahead of print.

NO ABSTRACT

PMID:40126387 | DOI:10.1164/rccm.202502-0338ED

Physiol Rev. 2025 Mar 24. doi: 10.1152/physrev.00032.2024. Online ahead of print.

ABSTRACT

Nanosized extracellular vesicles (EVs) are released by all cells to convey cell-to-cell communication. EVs, including exosomes and microvesicles, carry an array of bioactive molecules, such as proteins and RNAs, encapsulated by a membrane lipid bilayer. Epithelial cells, endothelial cells, and various immune cells in the lung contribute to the pool of EVs in the lung microenvironment and carry molecules reflecting their cellular origin. EVs can maintain lung health by regulating immune responses, inducing tissue repair, and maintaining lung homeostasis. They can be detected in lung tissues and biofluids such as bronchoalveolar lavage fluid and blood, offering information about disease processes and can function as disease biomarkers. Here, we discuss the role of EVs in lung homeostasis and pulmonary diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, idiopathic pulmonary fibrosis, and lung injury. The mechanistic involvement of EVs in pathogenesis and their potential as disease biomarkers are discussed. Lastly, the pulmonary field benefits from EVs as clinical therapeutics in severe pulmonary inflammatory disease, as EVs from mesenchymal stem cells attenuate severe respiratory inflammation in multiple clinical trials. Further, EVs can be engineered to carry therapeutic molecules for enhanced and broadened therapeutic opportunities, such as the anti-inflammatory molecule CD24. Finally, we discuss the emerging opportunity of using different types of EVs for treating severe respiratory conditions.

PMID:40125970 | DOI:10.1152/physrev.00032.2024

F1000Res. 2025 Mar 6;11:1513. doi: 10.12688/f1000research.128260.2. eCollection 2022.

ABSTRACT

BACKGROUND: Vancomycin is an effective first-line therapy primarily in methicillin-resistant Staphylococcus aureus (MRSA) infection and Clostridium difficile, however, it has been shown that its effectiveness and the reduction of nephrotoxicity depend on maintaining adequate therapeutic levels. Population pharmacokinetic (PopPk) models attempt to parameterize the behavior of plasma concentrations in different target populations and scenarios such as renal replacement therapy, to successful therapeutic outcome and avoid these side effects.

METHODS: A scoping review was conducted following the guidelines of Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR), through a search in PubMed, LILACS, OVID Medline, Scopus, Web of Science, SAGE Journals, Google Scholar and previous known registers of PopPk models in non-critically ill adult patients, published between 1998 and 2024.

RESULTS: A total of 190 papers were fully screened, of which were included 36 studies conducted in different populations; 12 in general population, 23 in special populations (surgical, with impaired renal function, obese, elderly, with cancer and cystic fibrosis), and 1 in mixed population (general and with cancer). The main parameters in the models were renal clearance and volume of distribution. The principal covariables that affected the models were creatinine clearance and weight. All studies used internal evaluation and 4 of them used an external group.

DISCUSSION: The technology for the development and implementation of PopPk models requires experts in clinical pharmacology and is limited to university and research centers. The software is mostly expensive and, in most cases, the pharmacokinetic models and the heterogeneity in the parameters and evaluation methods depend on which compartmental model, parameters, covariates and software have been used.

CONCLUSIONS: These models require validation in the clinical context and conducting experiments to adapt them for precision dosing in different subpopulations.

PMID:40124851 | PMC:PMC11928783 | DOI:10.12688/f1000research.128260.2

Front Immunol. 2025 Mar 7;16:1508584. doi: 10.3389/fimmu.2025.1508584. eCollection 2025.

ABSTRACT

INTRODUCTION: Mycobacterium abscessus is a pathogen recently associated with patients with chronic lung conditions such as bronchiectasis and cystic fibrosis. M. abscessus is an environmental bacterium but recent evidence suggests that the pathogen is also transmitted from host-to-host. Because M. abscessus is known to form biofilms on the respiratory mucosa the release of bacteria from the biofilm becomes an important aspect on the transmission of the infection.

METHODS: A biofilm releasing system was established. A transposon library of M. abscessus was then screened to identify genes associated with the release from biofilms.

RESULTS: Several enzymes and genes of unidentified function were linked with the ability to detach from the biofilm. It was also shown that detached bacteria were increased capable of establish a new biofilm, attach to epithelial cells, and infect macrophages. To determine the surface molecules linked with the ability to infect new hosts, a surface proteomic was performed, showing that detaching bacteria express many proteins do not present in biofilm bacteria.

DISCUSSION: Detached M. abscessus, one of the possible infectious phenotypes, contains specific proteins and lipids in the surface that facilitate the infection of new hosts. In addition, we identified many small proteins that have the likelihood to be associated with the release of the biofilm bacteria.

PMID:40124375 | PMC:PMC11925935 | DOI:10.3389/fimmu.2025.1508584

Thorax. 2025 Mar 23:thorax-2024-221825. doi: 10.1136/thorax-2024-221825. Online ahead of print.

ABSTRACT

INTRODUCTION: Current bronchiectasis guidelines advise against the use of inhaled corticosteroids (ICS) except in patients with associated asthma, allergic bronchopulmonary aspergillosis (ABPA) and/or chronic obstructive pulmonary disease (COPD). This study aimed to describe the use of ICS in patients with bronchiectasis across Europe.

METHODS: Patients with bronchiectasis were enrolled into the European Bronchiectasis Registry from 2015 to 2022. Patients were grouped into ICS users and non-users at baseline and clinical characteristics associated with ICS use were investigated. Patients were followed up for clinical outcomes of exacerbation, hospitalisation and mortality for up to 5 years. We evaluated if elevated blood eosinophil counts (above the laboratory upper limit of normal) modified the effect of ICS on exacerbations.

RESULTS: 19 324 patients were included for analysis and 10 109 (52.3%) were recorded as being prescribed ICS at baseline. After exclusion of patients with a history of asthma, COPD and/or ABPA, 3174/9715 (32.7%) patients with bronchiectasis were prescribed ICS. Frequency of ICS use varied across countries, ranging from 17% to 85% of included patients. ICS users had more severe disease, with significantly worse lung function, higher Bronchiectasis Severity Index scores and more frequent exacerbations at baseline (p<0.0001). Overall, ICS users did not have a reduced risk of exacerbation or hospitalisation during follow-up, but a significant reduction in exacerbation frequency was observed in the subgroup of ICS users with elevated blood eosinophil counts (relative risk 0.70, 95% CI 0.59 to 0.84, p<0.001).

CONCLUSION: ICS use is common in bronchiectasis, including in those not currently recommended ICS according to bronchiectasis guidelines. ICS use may be associated with reduced exacerbation frequency in patients with elevated blood eosinophils.

PMID:40122611 | DOI:10.1136/thorax-2024-221825

Respir Med. 2025 Mar 21:108047. doi: 10.1016/j.rmed.2025.108047. Online ahead of print.

ABSTRACT

INTRODUCTION: Newborn screening (NBS) for cystic fibrosis (CF) facilitates early diagnosis and has been shown to significantly improve long-term clinical outcomes. In this study, we aimed to evaluate the 7-year results of the immunoreactive trypsinogen (IRT)/IRT NBS of Turkey.

METHODS: The study included all CF patients who were born after NBS implementation, and who were enrolled in the CF Registry of Turkey (CFRT) in 2022. Patients were divided into three groups according to NBS results: Group 1 with positive NBS, Group 2 with negative NBS, and Group 3 with no screening or unknown screening results. All clinical and demographic data were compared between the three groups.

RESULTS: A total of 853 patients were included in the study, 668 (78.3%) patients were in Group 1, 90 (10.5%) in Group 2, and 95 (11.2%) in Group 3. The age at diagnosis was 0.17 (0.08-0.33) years in Group 1, 0.50 (0.25-1.0) in Group 2, and 0.33 (0.17-0.75) in Group 3 (p<0.001). The first and second sweat test results and frequency of pancreatic insufficiency were lowest in Group 2 (p<0.05). Median FEV1 (%) was 88 (77-103) in Group 1, 90 (71.5-104) in Group 2, 89.5 (81.75-97.5) in Group 3 (p>0.05). 49% of the patients had a severe genotype and it was detected most frequently in Group 1 (p=0.021).

CONCLUSIONS: Patients with pancreatic sufficiency may be missed by IRT/IRT NBS and lower and negative sweat test results may contribute to delays in CF diagnosis. Approximately 22% of patients are not diagnosed through this screening method.

PMID:40122405 | DOI:10.1016/j.rmed.2025.108047

Fertil Steril. 2025 Mar 21:S0015-0282(25)00162-1. doi: 10.1016/j.fertnstert.2025.03.014. Online ahead of print.

ABSTRACT

Male-factor infertility is a multifactorial, complex, and increasingly common condition, of which genetic factors have more frequently been implicated in. Not only are the causal relationships between genetic variation and male infertility phenotypes understudied, but also the differences in frequency of disease-causing genetic alterations within different geographic and ethnic groups. Guidelines remain inconsistent as to recommended genomic testing during the male infertility workup. Our current fund of knowledge limits our diagnostic capability where the etiology of male infertility remains idiopathic in about 40% of patients, despite advances in genomic sequencing and testing.

PMID:40122225 | DOI:10.1016/j.fertnstert.2025.03.014

Eur J Clin Nutr. 2025 Mar 22. doi: 10.1038/s41430-025-01589-y. Online ahead of print.

ABSTRACT

Elexacaftor/Tezacaftor/Ivacaftor (ETI) has led to improved lung function, life expectancy, and body mass index for people with Cystic Fibrosis (CF). The aim of this systematic review was to evaluate the impact that ETI has had on body composition in people with CF. A systematic review was performed using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials. Quality assessment using the Joanna Briggs Institute critical appraisal tools were performed. Results were summarised narratively. Five observational cohort studies involving a total of 185 participants were reviewed. Three studies showed an increase in fat mass (7.0-8.6 kg, 13.2-14.3 kg, and 13.4-15.5 kg). Two studies reported an increase in fat-free mass (49.4-50.1 kg, 52.5-55 kg), while one reported a decrease (50.5-48.9 kg). Two studies found an increase in fat mass index (4.1-6.3 kgm/2 and 4.7-5.4 kg/m2) and fat-free mass index (17.4-17.7 kg/m2 and 18.1-18.8 kg/m2). Two studies observed an increase in percentage body fat mass (12.1-15.4% and 23.1-27.6%). Four studies were classified as low quality, while one was considered medium quality. This review suggest that commencing ETI results in changes in body composition. Firm conclusions about the type and distribution of change in body composition cannot be made due to limited studies, high heterogeneity, and methodical weaknesses. It highlights the necessity for higher quality and longer-term studies to explore the impact that ETI is having on body composition.

PMID:40121317 | DOI:10.1038/s41430-025-01589-y

J Cyst Fibros. 2025 Mar 21:S1569-1993(25)00078-5. doi: 10.1016/j.jcf.2025.03.010. Online ahead of print.

ABSTRACT

BACKGROUND: CFTR modulators in post-transplant people with cystic fibrosis (pwCF) are less frequently used due to uncertainty regarding effectiveness and interactions with immunosuppressive agents. Elexacaftor/tezacaftor/ivacaftor (ETI) is a triple combination cystic fibrosis (CF) therapeutic with benefits in multiple organ systems where complications can impact lung transplant (LTx) outcomes, including malnutrition, diabetes, and sinus disease. ETI use in LTx recipients is variable.

METHODS: We conducted a pharmacokinetics (PK) study of concentrations of ETI parent compounds and the four major metabolites (M23-ELX, M1-TEZ, M1-IVA, M6-IVA) in a prospective non-randomized observational study, with all transplant participants concomitantly taking tacrolimus for LTx immunosuppression and excluded if taking any other medication with known interactions (e.g., azole antifungals) and compared to a non-transplant group of pwCF. We completed non-compartmental analysis (NCA) for both groups and compared the transplant to non-transplant PK parameters, as well as to published data from the manufacturer for non-transplant pwCF. Area under the curve (AUC), average concentrations (Cavg), minimum and maximum concentrations, clearance, and other parameters were determined.

RESULTS: Twelve transplant and fourteen non-transplant participants with CF completed the study. There were no significant differences between the mean values for any PK parameters for the transplant and non-transplant groups and no substantial differences in frequency of concentrations outside the therapeutic ranges in the two groups.

CONCLUSIONS: Our data suggest there are not significant differences in concentrations of ELX, TEZ, IVA, or their major human metabolites in LTx recipients compared to non-transplant pwCF.

PMID:40121139 | DOI:10.1016/j.jcf.2025.03.010

Trends Mol Med. 2025 Mar 21:S1471-4914(25)00034-6. doi: 10.1016/j.molmed.2025.02.001. Online ahead of print.

NO ABSTRACT

PMID:40121136 | DOI:10.1016/j.molmed.2025.02.001

Tissue Cell. 2025 Mar 19;95:102865. doi: 10.1016/j.tice.2025.102865. Online ahead of print.

ABSTRACT

The lungs are constantly subjected to enormous amounts of air and potentially transmitted agents, leading to a high incidence of severe and complex ailments urging the demand for defensive actions to maintain their regular function. Numerous studies have demonstrated how certain probiotics have many advantages including hindering pulmonary exacerbations in individuals with cystic fibrosis, which encourages the idea of combining them with approved antibiotics as a therapeutic choice for treatment patients with lung fibrosis who also have bacterial infections. This investigation aimed to test the possibility of a combination of Torulaspora delbrueckii as a probiotic with ciprofloxacin in an animal model having pulmonary fibrosis with a moderate load of Klebsiella pneumonia. Ninety adult male rats were split into six groups (15 rats/each): GI (control), GII (lung fibrosis), GIII (lung fibrosis infected by K. pneumonia), GIV (lung fibrosis infected by K. pneumonia then treated with ciprofloxacin), GV (lung fibrosis infected by K. pneumonia and fed with T. delbrueckii) and GVI (lung fibrosis infected by K. pneumonia then treated with combined therapy of ciprofloxacin and T. delbrueckii) for 28 days. Survival rate and bacterial load were determined in various experimental animal groups. Histological variations were examined as well as scanning electron microscopy. Gene expression, various levels of cytokines, redox enzymes, and oxidative stress markers were assessed and compared in different tested groups. The treatment using a combination of T. delbrueckii and ciprofloxacin is suggested as a new method to treat induced lung fibrosis in animals and infected with K. pneumonia as a possible option in complicated infection.

PMID:40120428 | DOI:10.1016/j.tice.2025.102865

Biochem Biophys Res Commun. 2025 Mar 14;758:151645. doi: 10.1016/j.bbrc.2025.151645. Online ahead of print.

ABSTRACT

Mycobacterium abscessus (M. abscessus) is an emerging, rapidly growing mycobacterium that causes chronic lung infection, particularly in patients with cystic fibrosis, as well as skin and soft tissue infections. Adipose tissue is recognized as an important niche that supports M. tuberculosis persistence. However, the dormancy, latency, and persistence mechanisms of M. abscessus in the host remain poorly understood. This study investigated how adipose tissue serves as a niche for M. abscessus using both a human adipose tissue ex vivo infection model and a murine adipose tissue in vivo infection model. M. abscessus infected not only the cytosol of adipocytes but also entered host lipid droplets, where it formed intracytoplasmic lipid inclusions in the bacterial cell. To our knowledge, this unique localization has never been reported for M. abscessus or any other mycobacterium. Within host lipid droplets, M. abscessus lost acid-fastness and gained Nile Red positivity. These results suggest that M. abscessus acquires a dormancy-like phenotype within host lipid droplets of adipocytes, potentially contributing to its persistence, virulence, and resistance to treatment. These findings provide valuable insights into mycobacterial persistence mechanisms and could offer a promising foundation for developing novel therapeutic approaches.

PMID:40120350 | DOI:10.1016/j.bbrc.2025.151645

J Cyst Fibros. 2025 Mar 20:S1569-1993(25)00074-8. doi: 10.1016/j.jcf.2025.03.006. Online ahead of print.

ABSTRACT

We present a case of a carrier mother treated with elexacaftor/tezacaftor/ivacaftor (ETI) for in-utero management of meconium ileus in a fetus diagnosed with cystic fibrosis (CF), homozygous for the F508del variant. Following multidisciplinary discussion and shared decision-making involving the parents, ETI was initiated at 27 weeks of gestation. At 38+4 weeks, the infant was delivered. Despite the treatment, the newborn developed meconium ileus, necessitating emergency surgery after birth. We explore potential factors contributing to the lack of success in our case compared to previously reported successful cases in USA and Spain. Drug levels measured in neonatal blood and in maternal breast milk indicated minimal drug exposure, raising questions about whether variability in placental transfer and excretion in breast milk or suboptimal ETI dosing in the overweight mother impacted the outcome. Additionally, the natural variability in meconium ileus outcome, which can range from spontaneous resolution to severe complications must be considered. In our case, ETI may have mitigated the severity of the condition, preventing serious complications like bowel perforation or peritonitis. However, given that about 20 % of all fetal bowel dilation resolves spontaneously, it remains uncertain whether the positive outcomes in prior cases were attributable to ETI or the natural course of the disease. We emphasize the need for more evidence on in utero ETI exposure by advocating for the collection of cases involving ETI treatment for fetal meconium ileus, regardless of outcomes. Developing guidelines will be essential to optimize benefits for both mother and fetus while minimizing risks.

PMID:40118755 | DOI:10.1016/j.jcf.2025.03.006

Arch Bronconeumol. 2025 Mar 1:S0300-2896(25)00071-7. doi: 10.1016/j.arbres.2025.02.010. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis causes exercise limitation due to impaired lung function and other complications, which in turn increases the chance of mortality. CFTR modulators, particularly the elexacaftor/tezacaftor/ivacaftor (ETI) combination, improve lung function in children older than 6 years in real-life studies.

OBJECTIVE: This study aimed to assess the impact of ETI on aerobic capacity in children with CF aged 6-11 years under real-life conditions and to evaluate whether prior CFTR modulator treatment affects these outcomes.

METHODS: A multicenter, prospective cohort study was conducted with pediatric CF patients. Participants underwent evaluations 6-8 months before ETI (T1), at the start of ETI (T2), and 6-8 months post-treatment (T3). Primary outcomes included cardiorespiratory fitness assessed via peak oxygen consumption (VO2peak) during a cardiopulmonary exercise test (CPET), and secondary outcomes encompassed lung function, quality of life, physical activity, and functional mobility.

RESULTS: Of the 28 patients (mean age 9.02±1.59 years), 19 were ETI-naive, and 9 had prior CFTR modulator treatment. Significant improvements were observed in FEV1 (p<0.001), and several functional mobility tests (30CST, Stair Climb Test, 10MWT). However, VO2peak showed no significant changes between T1 and T3. Quality of life scores improved notably in emotional, eating, and respiratory domains, and a slight improvement was noted in physical activity levels (p=0.037).

CONCLUSIONS: ETI treatment significantly enhances lung function and certain aspects of quality of life and physical fitness in pediatric CF patients. However, it does not significantly alter aerobic capacity (VO2peak) within the observed period.

PMID:40113488 | DOI:10.1016/j.arbres.2025.02.010

Obstet Gynecol. 2025 Apr 1;145(4):e141-e142. doi: 10.1097/AOG.0000000000005865.

NO ABSTRACT

PMID:40112310 | DOI:10.1097/AOG.0000000000005865

Otolaryngol Head Neck Surg. 2025 Mar 20. doi: 10.1002/ohn.1231. Online ahead of print.

ABSTRACT

OBJECTIVE: To differentiate pediatric chronic rhinosinusitis (CRS) into clinically relevant primary and secondary phenotypes based on clinical, radiographic, and laboratory findings.

STUDY DESIGN: Retrospective chart review of patients with CRS who underwent endoscopic sinus surgery over a 5-year period.

SETTING: Tertiary referral children's hospital.

METHODS: Relevant medical and surgical history inclusive of disease onset, clinical and radiographic findings, laboratory data, and operative culture results was recorded. Data analysis resulted, where appropriate, in phenotype and endotype characterization.

RESULTS: In total, 94 patients, aged 6.8 to 22.0 years, with a mean age of 15.4 years, satisfied the inclusion criteria. Eosinophilic CRS was the most common primary phenotype (n = 19, 20.2%), and this group was the most likely to have recurrent disease requiring revision surgery. Additional primary phenotypes identified included allergic fungal rhinosinsusitis (n = 10, 10.6%) and central compartment atopic disease (n = 2, 2.1%). CRS associated with cystic fibrosis was the most common secondary CRS category (n = 13, 13.8%). Based on available data, over one-third of patients (n = 36, 38.2%) could not be categorized into a specific phenotype based on current clinical and radiologic criteria.

CONCLUSION: A phenotype and endotype-based classification system for CRS is evolving for the adult population. This study highlights that such a classification system is possible in the pediatric and adolescent age group, facilitating targeted biologic therapies at the underlying inflammatory mechanism. Further investigation is clearly required given an etiologic source of paranasal sinus inflammation could not be identified in approximately one-third of patients.

PMID:40111215 | DOI:10.1002/ohn.1231

Int J Popul Data Sci. 2025 Feb 20;8(5):2924. doi: 10.23889/ijpds.v8i5.2924. eCollection 2023.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) heterozygotes (also known as 'carriers') are people who have one mutated copy of the CFTR gene. Research into the health risks of CF carriers has been limited by a lack of large cohorts tested for CF carrier status, but routine clinical testing identifies CF carriers in the population. Such test records additionally contain large amounts of clinical information, making them a valuable research resource to not only identify CF carriers in the population but also to provide additional data not found elsewhere.

METHODS: Following governance approvals, we adapted 30 years worth of CF genetic testing records generated by the All-Wales Medical Genomics Service (AWMGS) and submitted them to the SAIL Databank for anonymised linkage.

RESULTS: Unexpected obstacles meant that a minimum amount of clinical information could be annotated ahead of linkage. The raw data were highly heterogeneous due to the records' longitudinal collection and clinical origins, making standardisation difficult. Moreover, the presence of unique identifiers in the clinical data violated the separation principle, requiring manual annotation to produce a cleaned dataset. Explicit identification of patients or their relatives throughout the records complicated split file anonymisation.

CONCLUSION: Extracting useful information from historical clinical genetic test records is a significant challenge with technical and governance aspects. The mixing of unique identifiers with clinical data in heterogeneous, unstructured free text combined with a lack of automated tools meant that manual annotation was required to adhere to the separation principle. As such, only a minimum of the available clinical data was annotatable within the project timeline and mutually exclusive access to the identifiable and pseudonymised data meant that annotations could not later be validated. Future efforts to link clinical genetic test records for research must consider these challenges in their approach.

PMID:40110575 | PMC:PMC11922013 | DOI:10.23889/ijpds.v8i5.2924

J Cyst Fibros. 2025 Mar 18:S1569-1993(25)00058-X. doi: 10.1016/j.jcf.2025.02.009. Online ahead of print.

ABSTRACT

INTRODUCTION: The Liverpool Epidemic Strain (LES) of Pseudomonas aeruginosa is one of several known strains to be transmissible between persons with cystic fibrosis (CF) (pwCF) and the only known strain to have infected large proportions of CF populations on two continents. Despite its prevalence, efforts to understand its spread have proven elusive.

METHODS: We leveraged a prospective collection of P. aeruginosa isolates from pwCF attending the Southern Alberta Adult CF clinic from 1986 to 2020 to identify all individuals with LES infection. LES isolates collected every 1-2 years from each pwCF were sequenced and compared with 171 published LES genomes by phylogenetic analysis.

RESULTS: Of 395 pwCF screened, ten pwCF infected with the LES were identified, from whom 46 LES isolates were sequenced. The earliest LES isolate was recovered in 1986, ∼2 years earlier than the previously oldest published LES isolate recovered in the UK. Phylogenetic analysis identified a diverse set of isolates at the root of the LES phylogeny that formed four clades, one of which gave rise to a "classic LES" clade. Canadian isolates formed a paraphyletic group that included the root of this clade and out of which the UK LES clade emerged. We estimated the date of the most recent common ancestor (MRCA) of the UK LES clade as 1977.

CONCLUSIONS: Our study provides genomic evidence in support of a silent epidemic of LES infection occurring in the late 1970s among pwCF first originating in Canada and being spread to the UK, where transmission markedly accelerated.

PMID:40107913 | DOI:10.1016/j.jcf.2025.02.009

J Cyst Fibros. 2025 Mar 18:S1569-1993(25)00072-4. doi: 10.1016/j.jcf.2025.03.005. Online ahead of print.

NO ABSTRACT

PMID:40107911 | DOI:10.1016/j.jcf.2025.03.005

Pediatr Pulmonol. 2025 Mar;60(3):e71048. doi: 10.1002/ppul.71048.

ABSTRACT

OBJECTIVE: To describe variants in the CFTR gene and demographic and clinical characteristics of individuals with Cystic Fibrosis (CF) from a Brazilian State pediatric reference center upon diagnosis.

METHODS: Cross-sectional retrospective cohort study of individuals with CF under 18 years old treated in a referral center between 2007 and 2023. Data was derived from medical records. A descriptive analysis of the variables at diagnosis, including pathogenic genetic variants in the CFTR gene, clinical findings, and demographic data.

RESULTS: The population of 110 patients was predominantly male (54.5%) and white (66.4%). Age at diagnosis ranged from 13 days to 17 years (median = 2 months), 78.2% were diagnosed at < 2 years, and 50.9% were diagnosed following neonatal screening. The most frequent clinical manifestations at diagnosis were steatorrhea (70.0%), persistent respiratory symptoms (58.2%), and malnutrition (36.4%). The most common CFTR variants were F508del (49.0%), G542X (7.3%), and 3120+1G>A (5.9%). Eighty-four (76.4%) were eligible to use at least 1 of the 4 CFTR modulator therapies available in Brazil, and 29 were eligible for 3 therapies because they are homozygous for F508del.

CONCLUSION: Identification of CFTR variants at diagnosis can provide many benefits to patients, such as early interventions and CFTR modulator therapy, and is feasible in Brazil. Because each country may have different distributions of CFTR variants, it is essential to evaluate these distributions as we advance methodologies for gene variant detection, particularly in the contexts of newborn screening and diagnostic testing.

PMID:40105401 | DOI:10.1002/ppul.71048