Respir Med. 2025 Mar 11:108036. doi: 10.1016/j.rmed.2025.108036. Online ahead of print.

ABSTRACT

BACKGROUND: Lung ultrasound is becoming increasingly important in the diagnosis of acute and chronic lung disease, especially in children and adolescents. In children with cystic fibrosis (CF), conventional radiography or computed tomography (CT) has been the main modality used to evaluate acute pneumonia or the progression of chronic lung disease. This Study aimed to evaluate Lung-Ultrasound as a diagnostic tool for children and adolescents with CF.

METHODS: We examined 30 CF patients with lung ultrasound before and after spirometry and compared them with lung ultrasounds of 15 lung-healthy children. We used a comprehensive and complete examination procedure with 12 probe positions to determine the best examination procedure in retrospect. In addition, an acceptance survey was conducted among the children and adolescents after the examination.

RESULTS: There was a significant difference in pleural irregularities, B-lines, consolidations and the adapted Peixoto et al. score between CF patients and healthy children before spirometry. We found excellent discrimination between patients and lung-healthy subjects using the Peixoto-score (AUC 0.968), pleural irregularities (AUC 0.890. CF patients had more B-lines, more consolidations, and a higher Peixoto score (mean difference 7.7 points).There was no significant difference in lung ultrasound results in children with CF before and after spirometry. Shortening our extended examination procedure would minimally compromise diagnostic accuracy. The lung ultrasound examination was well accepted by the children.

CONCLUSION: We could demonstrate that lung ultrasound is a sensitive and reliable method for assessing pulmonary changes in cystic fibrosis.

PMID:40081670 | DOI:10.1016/j.rmed.2025.108036

JBRA Assist Reprod. 2025 Mar 13. doi: 10.5935/1518-0557.20240102. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the carrier frequency of X-linked and autosomal recessive diseases in patients attending a human fertility institute in Colombia.

METHODS: This retrospective observational study included patients and gamete donors attending a Human Fertility Institute in Colombia between January 2017 and June 2023. Sociodemographic data and results of Next Generation Sequencing laboratory panels for screening of recessive disease-causing mutations were collected and analyzed.

RESULTS: Data from 746 samples were analyzed; 599 (80.3%) were Colombian origin individuals and 147 (19.7%) were foreigners. At least one mutation was detected in 526 (70.5%) individuals. Of note, 893 pathogenic genetic variants were identified.The genetic variants most frequently observed in all the individuals studied were associated with the following diseases (carrier frequency): alpha thalassemia (10.5%), alpha-1 antitrypsin deficiency (10%), congenital adrenal hyperplasia due to 21-hydroxylase deficiency (9.4%), cystic fibrosis (7.3%), spinal muscular atrophy type 1 (5.6%) and Stargardt disease type 1 (5.0%). The most frequent genetic variant observed in the subgroup of Colombian origin individuals was associated with alpha-1 antitrypsin deficiency (11.3%).

CONCLUSIONS: Information on the frequency of recessive diseases in Colombia is limited. This pioneering carrier genetic screening identified a high percentage of carriers for at least one recessive autosomal or X-linked in the population evaluated. Screening for recessive mutations could lead to an evolution in family planning programs and a decrease in the number of patients affected by recessive disorders. Furthermore, it could become a routine test not only in cases of assisted reproduction but also in cases of natural gestation.

PMID:40080775 | DOI:10.5935/1518-0557.20240102

J Exp Med. 2025 Jun 2;222(6):e20230803. doi: 10.1084/jem.20230803. Epub 2025 Mar 13.

ABSTRACT

To distinguish pathogens from commensals, the intestinal epithelium employs cytosolic innate immune sensors. Activation of the NAIP-NLRC4 inflammasome initiates extrusion of infected intestinal epithelial cells (IEC) upon cytosolic bacterial sensing. We previously reported that activation of the inflammasome in tuft cells, which are primarily known for their role in parasitic infections, leads to the release of prostaglandin D2 (PGD2). We observe that NAIP-NLRC4 inflammasome activation in tuft cells leads to an antibacterial response with increased IL-22 and antimicrobial protein levels within the small intestine, which is dependent on PGD2 signaling. A NKp46+ subset of ILC3 expresses the PGD2 receptor CRTH2 and is the source of the increased IL-22. Inflammasome activation in tuft cells also leads to better control of Salmonella Typhimurium in the distal small intestine. However, tuft cells in the cecum and colon are dispensable for antibacterial immunity. These data support that intestinal tuft cells can also induce antibacterial responses, possibly in a tissue-specific manner.

PMID:40079814 | DOI:10.1084/jem.20230803

J Antimicrob Chemother. 2025 Mar 13:dkaf073. doi: 10.1093/jac/dkaf073. Online ahead of print.

ABSTRACT

BACKGROUND: Mycobacterium abscessus is an important cause of pulmonary infections, particularly among people with cystic fibrosis. Current treatment options for M. abscessus are suboptimal. Apramycin is a promising alternative aminoglycoside for M. abscessus, in part due to its ability to avoid intrinsic aminoglycoside-modifying enzymes in this pathogen.

OBJECTIVES: Define the pharmacodynamic activity of apramycin doses against M. abscessus.

METHODS: Apramycin and amikacin pharmacodynamics were assessed against two amikacin-susceptible M. abscessus subsp. abscessus isolates (ATCC 19977 and NR-44261) using a 14-day hollow fibre infection model (HFIM). Viable bacterial counts were determined during exposure to amikacin (15-20 mg/kg q24h) and 3 fractionated doses of apramycin (15 mg/kg q12h, 30 mg/kg q24h, 60 mg/kg q48h) using pharmacokinetic profiles predicted in epithelial lining fluid.

RESULTS: Against ATCC 19977, apramycin activity exceeded that of amikacin, with maximum bacterial reductions between 1.51 and 2.18 log10 cfu/mL for the different doses. Apramycin 15 mg/kg q12h displayed slightly better killing compared with the other apramycin dosing regimens between 96 and 144h before regrowth occurred. NR-44261 was not inhibited by amikacin and the activity of apramycin against this isolate was similar between the three doses (∼0.5 log10 cfu/mL reductions). After 14 days of exposure to apramycin monotherapy, ATCC 19977 and NR-44261 became apramycin resistant with MICs of >32 mg/L.

CONCLUSIONS: Apramycin exhibited greater pharmacodynamic activity than amikacin against amikacin-susceptible M. abscessus isolates and may be a promising therapy for this pathogen. However, antibiotic combination strategies to minimize apramycin resistance from emerging may be necessary.

PMID:40079270 | DOI:10.1093/jac/dkaf073

Can J Respir Ther. 2025 Mar 3;61:20-32. doi: 10.29390/001c.129988. eCollection 2025.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) is a severe autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This condition disrupts chloride channels and leads to the production of thick, sticky mucus, affecting the respiratory and gastrointestinal systems. CF's prevalence is particularly high in Saudi Arabia, where the incidence has increased from 1 in 2,000 to 1 in 1,000 births. Effective management of CF is essential for improving patient outcomes, yet there is a notable lack of understanding regarding respiratory therapists' (RTs) adherence to established CF management protocols.

METHODS: This descriptive quantitative study aimed to assess RTs' adherence to the Cystic Fibrosis Foundation's guidelines. Using a convenience sampling technique, a self-report survey was distributed to 750 members of the Saudi Society for Respiratory Care (SSRC), resulting in 351 responses, of which 166 were fully completed and met the inclusion criteria. The survey focused on RTs' knowledge and management practices related to CF. Data analysis was conducted using SPSS version 25, with descriptive statistics (mean, standard deviation, frequency, percentage, and mode) and non-parametric tests. The Kruskal-Wallis Test was employed to evaluate differences in adherence scores across demographic groups (e.g., education level, years of experience). Chi-square analysis was applied to examine relationships between categorical demographic variables (e.g., region of practice) and adherence to guidelines.

RESULTS: The analysis revealed significant gaps in RTs' adherence to CF guidelines, with only 42.8% accurately identifying the sweat chloride threshold for CF diagnosis and a limited 36.1% recognizing Pseudomonas aeruginosa as a common CF pathogen. Additionally, just 56.6% correctly identified the gold-standard airway clearance therapy. The Wilcoxon signed-ranks test further highlighted a statistically significant disparity (p = 0.00) between RTs' theoretical knowledge and practical application of CF management techniques, emphasizing the need for improved training.

DISCUSSION: The findings suggest a need for enhanced training and resources to bridge the gap between theoretical knowledge and practical management of CF. The lack of adherence to clinical guidelines could impact patient outcomes and survival rates.

CONCLUSION: Improving RTs' adherence to CF management guidelines through ongoing education and updated clinical standards is essential. Addressing these gaps could elevate the standard of care and contribute to better patient outcomes and survival rates in Saudi Arabia.

PMID:40078596 | PMC:PMC11901341 | DOI:10.29390/001c.129988

Front Med (Lausanne). 2025 Feb 26;12:1479638. doi: 10.3389/fmed.2025.1479638. eCollection 2025.

ABSTRACT

BACKGROUND: Little information is available regarding whether active physical activity lowers mortality risk in individuals with bronchiectasis.

METHODS: We used the Korean National Health Insurance Service database from 2010 to 2016 to evaluate the association between changes in physical activity and mortality risk in individuals with bronchiectasis. Of 552,510 individuals with newly diagnosed bronchiectasis, we enrolled 165,842 individuals who had two consecutive health examinations before and after bronchiectasis diagnosis, within two years, as the study aimed to measure changes in exercise habits between the two time points. Active physical activity was defined as engaging in moderate- or vigorous-intensity physical activity at least once a week, either before or after bronchiectasis diagnosis. The outcome measure was all-cause mortality.

RESULTS: During a mean follow-up of 6.2 ± 2.1 years, 10,535 (6.4%) individuals with bronchiectasis died. Individuals with bronchiectasis who were physically active exhibited a lower mortality rate than those who were physically inactive. Mortality reduction was particularly evident in the exercise maintainers group (aHR [adjusted hazard ratio] = 0.69, 95% confidence interval [CI] = 0.64-0.74) and individuals with physical activity ≥1,000 metabolic equivalent of task-min per week (aHR = 0.73, 95% CI = 0.70-0.77) compared to those who were physically inactive.

CONCLUSION: Engaging in active physical activity is associated with a decreased risk of mortality in individuals with bronchiectasis.

PMID:40078390 | PMC:PMC11896819 | DOI:10.3389/fmed.2025.1479638

Nutrients. 2025 Feb 28;17(5):868. doi: 10.3390/nu17050868.

ABSTRACT

BACKGROUND: Exocrine pancreatic insufficiency in cystic fibrosis (CF) increases fecal choline losses, but the postnatal course of plasma choline and its metabolites in these patients is unknown. While choline homeostasis is crucial for cellular, bile, and lipoprotein metabolism, via phosphatidylcholine (PC) and via betaine as a methyl donor, choline deficiency is associated with impaired lung and liver function, including hepatic steatosis.

OBJECTIVE: The goal of our study was to evaluate the plasma levels of choline, betaine, trimethylamine oxide (TMAO), PC, and PC subclasses in CF patients from infancy to adulthood and compare those with exocrine pancreatic insufficiency (EPI) to those with pancreatic sufficiency (EPS).

METHODS: Retrospective analysis of target parameters in plasma samples (July 2015-November 2023) of CF patients (0.64-24.6 years) with tandem mass spectrometry.

RESULTS: A total of 477 samples from 162 CF patients were analyzed. In CF patients with EPI (N = 148), plasma choline and betaine concentrations were lower and decreased with age compared to EPS patients showing normal values. TMAO concentrations, indicating intestinal choline degradation by bacterial colonization, were frequently elevated in EPI from infancy onwards, and inversely related to plasma choline and betaine levels. PC-containing linoleic acid levels were lower in EPI, but arachidonic and docosahexaenoic acid content was similar in both patient groups.

CONCLUSION: CF patients with EPI are at risk of choline and betaine deficiency compared to exocrine pancreas-sufficient CF patients. Elevated TMAO concentrations in EPI patients indicate increased bacterial colonization leading to choline degradation before absorption. These findings indicate that laboratory testing of choline, betaine, and TMAO as well as clinical trials on choline supplementation are warranted in CF patients.

PMID:40077735 | DOI:10.3390/nu17050868

Int J Mol Sci. 2025 Mar 6;26(5):2336. doi: 10.3390/ijms26052336.

ABSTRACT

Atherosclerosis (AS) is a disease characterised by the accumulation of atherosclerotic plaques on the inner walls of blood vessels, resulting in their narrowing. In its early stages, atherosclerosis remains asymptomatic and undetectable by conventional pathological methods. However, as the disease progresses, it can lead to a series of cardiovascular diseases, which are a leading cause of mortality among middle-aged and elderly populations worldwide. Neutrophil extracellular traps (NETs) are composed of chromatin and granular proteins released by neutrophils. Upon activation by external stimuli, neutrophils undergo a series of reactions, resulting in the release of NETs and subsequent cell death, a process termed NETosis. Research has demonstrated that NETosis is a means by which neutrophils contribute to immune responses. However, studies on neutrophil extracellular traps have identified NETs as the primary cause of various inflammation-induced diseases, including cystic fibrosis, systemic lupus erythematosus, and rheumatoid arthritis. Consequently, the present review will concentrate on the impact of neutrophil extracellular traps on atherosclerosis formation, analysing it from a molecular biology perspective. This will involve a systematic dissection of their proteomic components and signal pathways.

PMID:40076955 | DOI:10.3390/ijms26052336

Int J Mol Sci. 2025 Feb 27;26(5):2066. doi: 10.3390/ijms26052066.

ABSTRACT

The introduction of CFTR modulators in the clinics has improved body mass index in cystic fibrosis (CF) individuals. Leptin is a major regulator of appetite and energy expenditure but is also involved in bone metabolism. Whether circulating leptin levels are associated with low bone mineral density (BMD) and fracture risk in CF remains unknown. Therefore, the present study aims to analyze and integrate the current evidence linking leptin and bone loss in CF. As no scientific evidence was found, we focused on secondary dysregulations of bone loss in CF that may be linked to pathologies that are similar to the various dysregulations and multisystemic manifestations in CF. Studies published from 2001 to 2022 were identified through the PubMed, Scopus, and Web of Science databases, and screening was performed following the PRISMA guidelines. The included studies were assessed using a quality checklist. From the 774 records identified, 28 studies met the inclusion criteria. Although no evidence has been found directly related to bone loss in CF individuals, some studies revealed a positive association between leptin levels and BMD, while others found an inverse association. Current evidence suggests that for circulating leptin levels to be a predictive biomarker of bone health, further research will be needed to reveal the direct and indirect mechanisms behind leptin and bone loss and to understand whether changes in leptin levels correlate with changes in BMD. Of note, studies with CF people would be of high importance to understand the role of leptin in CF-related bone disease.

PMID:40076690 | DOI:10.3390/ijms26052066

Int J Mol Sci. 2025 Feb 25;26(5):2012. doi: 10.3390/ijms26052012.

ABSTRACT

Pseudomonas aeruginosa is an opportunistic pathogen with a multidrug-resistant profile that has become a critical threat to global public health. It is one of the main causes of severe nosocomial infections, including ventilator-associated pneumonia, chronic infections in patients with cystic fibrosis, and bloodstream infections in immunosuppressed individuals. Development of vaccines against P. aeruginosa is a major challenge owing to the high capacity of this bacterium to form biofilms, its wide arsenal of virulence factors (including secretion systems, lipopolysaccharides, and outer membrane proteins), and its ability to evade the host immune system. This review provides a comprehensive historical overview of vaccine development efforts targeting this pathogen, ranging from early attempts in the 1970s to recent advancements, including vaccines based on novel proteins and emerging technologies such as nanoparticles and synthetic conjugates. Despite numerous promising preclinical developments, very few candidates have progressed to clinical trials, and none have achieved final approval. This panorama highlights the significant scientific efforts undertaken and the inherent complexity of successfully developing an effective vaccine against P. aeruginosa.

PMID:40076637 | DOI:10.3390/ijms26052012

Int J Mol Sci. 2025 Feb 21;26(5):1871. doi: 10.3390/ijms26051871.

ABSTRACT

Cystic fibrosis (CF) is characterized by chronic respiratory infections and excessive inflammation, driven by both host- and pathogen-derived proteases. The dysregulated activity of proteolytic enzymes such as neutrophil elastase (NE), cathepsin G, and matrix metalloproteases (MMPs) degrades lung tissue, exacerbates airway remodeling, and perpetuates inflammatory cycles. Concurrently, bacterial proteases from pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus contribute to immune evasion and tissue destruction, compounding disease severity. Despite advances in antimicrobial and anti-inflammatory therapies, protease-driven lung damage remains a critical challenge. This review examines the dual role of host and bacterial proteases in CF pathophysiology, highlighting emerging protease-targeted therapies aimed at mitigating lung damage and inflammation. Strategies explored include the inhibition of NE, MMPs, and bacterial proteases, with a focus on innovative therapeutic approaches such as dual-function inhibitors, biologics, and advanced drug delivery systems. By restoring the protease-antiprotease balance, these interventions offer the potential to improve clinical outcomes and quality of life for CF patients.

PMID:40076497 | DOI:10.3390/ijms26051871

Hum Genomics. 2025 Mar 12;19(1):25. doi: 10.1186/s40246-025-00736-7.

ABSTRACT

BACKGROUND: Global fertility decline has led to increased use of assisted reproductive technology (ART), raising concerns about genetic risks to offspring. This study aimed to investigate cystic fibrosis transmembrane conductance regulator (CFTR) variants in Chinese families and assess their association with pregnancy complications and neonatal outcomes.

METHODS: This prospective cohort study included 446 Chinese families (148 natural conceptions, 298 ART conceptions) who underwent whole genome sequencing. We analyzed the frequency of pathogenic/likely pathogenic CFTR variants and their association with preterm birth (PTB), pregnancy complications, and neonatal outcomes.

RESULTS: Twelve pathogenic/likely pathogenic CFTR variants were identified, with K464N (c.1392G > T) being the most prevalent (2.9% of cohort). PTB incidence was significantly higher in pregnancies with fetal CFTR variants (43.1%, 22/51) compared to those without (17.5%, 69/395; p < 0.001). Fetuses carrying the CFTR K464N variant exhibited a 3.39-fold increased risk of PTB (95% confidence interval (CI): 1.39-8.23, p = 0.007) after adjusting for confounders. Neither fetal nor maternal CFTR variants were significantly associated with other neonatal outcomes, including neonatal weight, Apgar scores, respiratory distress, or hyperbilirubinemia (p > 0.050).

CONCLUSION: These findings suggest a potential association between fetal CFTR K464N variant and increased risk of preterm birth in Chinese families, highlighting the importance of considering CFTR genotyping in prenatal care.

PMID:40075526 | DOI:10.1186/s40246-025-00736-7

Cell Mol Life Sci. 2025 Mar 13;82(1):109. doi: 10.1007/s00018-025-05627-7.

ABSTRACT

Cystic fibrosis (CF) is a life-shortening genetic disorder, caused by mutations in the CF transmembrane conductance regulator (CFTR) protein that regulates ion and fluid transport in epithelial tissue. Female CF patients face considerable fertility challenges, with higher prevalence of deficient fertility compared to healthy women. Not much is known about the underlying causes. In particular, the pathobiology of the endometrium, the uterus' inner lining essential for pregnancy and expressing fluctuating CFTR levels during the menstrual cycle, is unexplored in CF. To address this gap, we developed organoid models from CF patient endometrium. The organoids recapitulated CF characteristics and revealed molecular and pathway differences in cycle-recapitulating hormone responses compared to healthy endometrial organoids. Furthermore, specific functional aberrations were restored by CFTR modulator treatment. To further complement human organoid models for unraveling endometrial pathobiology in CF, we also developed organoids from a genetic CF mouse model that were also found to recapitulate CF characteristics. Moreover, single-cell RNA-sequencing analysis of the CF mouse uterus revealed molecular traits in the endometrium similar to the human CF endometrium (as evidenced by its organoid model). Our study provides new endometrium models to advance our understanding of CF-associated endometrial pathobiology, particularly regarding menstrual cycle aberrations that impact fertility. This research is timely since improved CF therapeutics result in increased life expectancy, allowing more CF patients to consider starting a family.

PMID:40074868 | DOI:10.1007/s00018-025-05627-7

J Cyst Fibros. 2025 Mar 11:S1569-1993(25)00073-6. doi: 10.1016/j.jcf.2025.03.004. Online ahead of print.

ABSTRACT

Fatigue is common among adults with cystic fibrosis (awCF) and may be associated with systemic inflammation. This study examines systemic inflammation, measured by C-reactive protein (CRP), and fatigue, assessed using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) vitality domain, in individuals initiating elexacaftor/tezacaftor/ivacaftor (ETI) therapy. In a cohort of 61 awCF from St. Paul's Hospital, Vancouver, CRP and vitality were measured at baseline and at 1, 3, 6, and 12 months post-ETI initiation. We observed reductions in CRP and increases in vitality over the 12-month period. Linear mixed-effects models were used to examine the relationship between CRP and vitality adjusted for age, sex, BMI, and lung function. Our findings demonstrated a significant, independent inverse association between CRP and vitality. These results highlight the potential role of systemic inflammation in influencing vitality in awCF undergoing ETI therapy. Further research incorporating additional inflammatory markers and psychosocial variables is warranted to deepen our understanding of fatigue mechanisms in this population.

PMID:40074570 | DOI:10.1016/j.jcf.2025.03.004

J Obstet Gynaecol Can. 2025 Mar 10:102811. doi: 10.1016/j.jogc.2025.102811. Online ahead of print.

ABSTRACT

COVID-19 outcomes are worse in non-pregnant patients that are cystic fibrosis carriers; however, no studies have examined COVID-19 outcomes in pregnant patients that are cystic fibrosis carriers. We evaluated the cystic fibrosis carrier status of pregnant patients with COVID-19 in three geographical regions in the United States and compared outcomes between non-carriers and carriers. Out of 2430 pregnant patients with COVID-19, 229 had a cystic fibrosis screen. Pregnant cystic fibrosis carriers were associated with 47.90 times greater odds of hospitalization with COVID-19 than non-carriers. A larger cohort will be needed to draw strong conclusions.

PMID:40074033 | DOI:10.1016/j.jogc.2025.102811

Am J Respir Crit Care Med. 2025 Mar 12. doi: 10.1164/rccm.202409-1824OC. Online ahead of print.

ABSTRACT

RATIONALE: Mycobacterium abscessus group bacteria (MABS) cause lethal infections in people with chronic lung diseases. Transmission mechanisms remain poorly understood; the detection of dominant circulating clones (DCCs) has suggested potential for person-to-person transmission.

OBJECTIVES: This study aimed to determine the role of drinking water in the transmission of MABS.

METHODS: A total of 289 isolates were cultured from respiratory samples (231) and drinking water sources (58) across Queensland, Australia.

MEASUREMENTS AND MAIN RESULTS: Whole genome sequences were analysed to identify DCCs and determine relatedness. Half of the isolates (144, 49·8%) clustered with previously described DCCs, of which 30 formed a clade within DCC5. Pangenomic analysis of the water-associated DCC5 clade revealed an enrichment of genes associated with copper resistance. Four instances of plausible epidemiological links were identified between genomically-related clinical and water isolates.

CONCLUSIONS: We provide evidence that drinking water is a reservoir for MABS and may be a vector in the chain of MABS infection.

PMID:40072241 | DOI:10.1164/rccm.202409-1824OC

Pediatr Pulmonol. 2025 Mar;60(3):e71044. doi: 10.1002/ppul.71044.

ABSTRACT

BACKGROUND: People with cystic fibrosis (pwCF) often have multifactorial peripheral muscle abnormalities attributed to, for example, malnutrition, steroid use, altered redox balance and, potentially, CF-specific intrinsic alterations. Malnutrition in CF now includes an increasing prevalence of overweight and obesity, particularly in those receiving CF transmembrane conductance regulator (CFTR) modulator therapy (CFTRm). We aimed to characterise peripheral muscle function and body composition in pwCF on Elexacaftor/Tezacaftor/Ivacaftor (ETI) CFTRm, compared to healthy controls.

METHODS: Fifteen pwCF on ETI, and 15 healthy age- and sex-matched controls (CON), underwent whole-body dual-energy X-ray absorptiometry scans, and a comprehensive evaluation of peripheral muscle function. Tests included quadriceps maximal isometric force measurement, an intermittent isometric quadriceps fatiguing protocol, handgrip strength dynamometry, squat jump height assessment, and 1-min sit-to-stand testing.

RESULTS: No significant differences in quadriceps maximal isometric force (CON: 181.60 ± 92.90 Nm vs. CF: 146.15 ± 52.48 Nm, p = 0.21, d = 0.47), handgrip strength (CON: 34 ± 15 kg vs. CF: 31 ± 11 kg, p = 0.62, d = 0.18), peripheral muscle endurance, fatigue, or power were observed between the groups. Moreover, no significant differences in whole-body, trunk or limb lean mass, fat-free mass, fat mass, or whole-body bone mineral density were evident.

CONCLUSION: Comparable peripheral muscle mass and function has been demonstrated in pwCF on ETI, albeit a group with good lung function. Research is needed to confirm these findings longitudinally in pwCF, including those with more severe lung disease, who are less physically active, and have less optimal nutrition and exercise support.

PMID:40071679 | DOI:10.1002/ppul.71044

Pediatr Pulmonol. 2025 Mar;60(3):e71042. doi: 10.1002/ppul.71042.

ABSTRACT

BACKGROUND: Genetic modifiers have been identified that increase the risks of lung disease and other complications, such as diabetes in people with cystic fibrosis (CF). Variants in the hemochromatosis gene (HFE) were reported in a study of adults to be associated with worse lung disease.

OBJECTIVES: To ascertain the frequency of HFE variants, particularly C282Y (c.845G > A) and H63D (c.187C > G) and to determine if they are associated with variations in the onset and early severity of CF lung disease as well as abnormalities in iron status.

DESIGN: We studied with whole genome sequencing and clinical outcome measures in a cohort of 104 children with CF at 5-6 years old who were previously found to show an association between aggregated genetic modifiers and an earlier onset and a more severe lung disease phenotype.

RESULTS: In our cohort, 23% have H63D and 11% have C282Y. Lung function at age 6 years and Pseudomonas aeruginosa infections did not differ by HFE variants, but having C282Y was associated with more pulmonary exacerbations in the first 6 years of life. Three patients have H63D/C282Y genotype, and all showed phenotypic expression of hemochromatosis with abnormal iron indices.

CONCLUSION: Our study revealed that the presence of HFE variant C282Y in people with CF may lead to more severe lung disease manifestations beginning in early childhood. There is a risk of hemochromatosis in CF patients with two HFE variants, and thus they should be followed for evidence of iron overload.

PMID:40071665 | DOI:10.1002/ppul.71042

Ther Adv Respir Dis. 2025 Jan-Dec;19:17534666251323181. doi: 10.1177/17534666251323181. Epub 2025 Mar 12.

ABSTRACT

Nontuberculous mycobacteria (NTM) are ubiquitous, opportunistic pathogens that can cause lung disease in people with non-cystic fibrosis bronchiectasis (NCFB) and cystic fibrosis (CF). The incidence of NTM pulmonary infections and lung disease has continued to increase worldwide over the last decade among both groups. Notably, women with NCFB NTM pulmonary disease (NTM-PD) bear a disproportionate burden with NTM rates increasing in this population as well as having consistently higher incidence of NTM-PD compared to men. In contrast, among people with CF, an overall increased risk among women has not been observed. In the United States, the majority of people with CF are taking highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators, and these numbers are increasing worldwide. The long-term impact of CFTR modulator medications on NTM infections is not entirely understood. Guidelines for the screening, diagnosis, and management of NTM-PD exist for people with NCFB and CF, but do not consider unique implications relevant to women. This review highlights aspects of NTM-PD among women with NCFB and CF, including the epidemiology of NTM infection, special considerations for treatment, and unmet research needs relevant to women with NTM-PD.

PMID:40071337 | DOI:10.1177/17534666251323181

Ital J Pediatr. 2025 Mar 11;51(1):71. doi: 10.1186/s13052-025-01918-8.

ABSTRACT

INTRODUCTION: Children with congenital lung disease (CLD) may suffer from long-term complications, such as impairments in lung growth, decreased total lung volume, recurrent lower respiratory tract infections and, in some cases, malignant transformation.

OBJECTIVE AND METHODS: we described retrospective data on diagnostic process, clinical and functional data regarding a cohort of symptomatic and asymptomatic children with CLD followed in a single third level center in the last twenty years.

RESULTS: 91 children were included in the study. Five classes of disease were examined. Bronchial tree and pulmonary abnormalities represent the most common anomalies. Despite the improved resolution of prenatal diagnosis, most of patients underwent chest CT scan to confirm the initial diagnostic suspicion. The most reported symptoms were wheezing, recurrent respiratory infections and acute respiratory failure. According to malformation type, patients underwent to surgery, endoscopic and/or medical treatment. Improvement of symptoms occurred faster in patients surgically and endoscopically treated. No statistical difference in the number of exacerbations before and after treatment was recorded, as well as no differences in spirometry values were observed among surgically and non-surgically treated children. No malignant transformation was observed in two patients with intra-lobar sequestration and hybrid lesion during the follow up period.

CONCLUSION: the clinical presentation of congenital airway and lung disorders varies significantly depending on the type of malformation, making it challenging to standardize treatment strategies and follow-up programs. Based on our experience, prompt surgical or endoscopic intervention in early symptomatic children leads to faster symptom improvement and normal lung function in the follow-up period. However, further prospective studies are needed to better define optimal treatment strategies for these rare conditions, particularly for asymptomatic patients, for whom management approaches remain poorly established.

PMID:40069796 | DOI:10.1186/s13052-025-01918-8