Curr Opin Pediatr. 2025 Mar 27. doi: 10.1097/MOP.0000000000001458. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: The field of cystic fibrosis is experiencing dramatic changes, as the translation of a massive body of scientific knowledge accumulated from the day of the cloning of the CFTR gene has led to the identification of effective therapies to correct the basic defect. This has also allowed care providers and people with cystic fibrosis in low-income and middle-income countries (LMICs) to become more knowledgeable and proficient in cystic fibrosis cares.

RECENT FINDINGS: This review focuses on two main aspects highly relevant to understand the current status of cystic fibrosis in LMICs: The recognition of the universal occurrence of cystic fibrosis, as well as the varying incidence in different regions of the world, and the collaborative international efforts for dissemination of best care practices as an attempt to close gaps in care.

SUMMARY: As the field continues to change rapidly, multiple international efforts are attempting to close gaps and disparities clearly apparent between affluent countries and LMICs. However, these efforts are seriously hampered by limited access to effective therapies and most dramatically to CFTR modulator drugs.

PMID:40172290 | DOI:10.1097/MOP.0000000000001458

mBio. 2025 Apr 2:e0037425. doi: 10.1128/mbio.00374-25. Online ahead of print.

ABSTRACT

Staphylococcus aureus is one of the most common pathogens isolated from the lungs of people with cystic fibrosis (CF), but little is known about its ability to colonize this niche. We performed a transposon-sequencing (Tn-seq) screen to identify genes necessary for S. aureus growth in media prepared from ex vivo CF sputum. We identified 19 genes that were required for growth in all sputum media tested and dozens more that were required for growth in at least one sputum medium. Depleted mutants of interest included insertions in many genes important for surviving metal starvation, as well as the primary regulator of cysteine metabolism, cymR. To investigate the mechanisms by which these genes contribute to S. aureus growth in sputum, we quantified low-molecular-weight thiols, nutrient transition metals, and the host metal-sequestration protein calprotectin in sputum from 11 individuals with CF. In all samples, the abundance of calprotectin exceeded nutrient metal concentration, explaining the S. aureus requirement for metal-starvation genes. Furthermore, all samples contain potentially toxic quantities of cysteine and sufficient glutathione to satisfy the organic sulfur requirements of S. aureus. Deletion of the cysteine importer genes tcyA and tcyP in the ∆cymR background restored growth to wild-type levels in CF sputum, suggesting that the mechanism by which cymR is required for growth in sputum is to prevent uncontrolled import of cysteine or cystine from this environment. Overall, this work demonstrates that calprotectin and cysteine limit S. aureus growth in CF sputum.IMPORTANCEStaphylococcus aureus is a major cause of lung infections in people with cystic fibrosis (CF). This work identifies genes required for S. aureus growth in this niche, which represent potential targets for anti-Staphylococcal treatments. We show that genes involved in surviving metal starvation are required for growth in CF sputum. We also found that the primary regulator of cysteine metabolism, CymR, plays a critical role in preventing cysteine intoxication during growth in CF sputum. To support these models, we analyzed sputum from 11 individuals with CF to determine concentrations of calprotectin, nutrient metals, and low-molecular-weight thiols, which have not previously been quantified together in the same samples.

PMID:40172197 | DOI:10.1128/mbio.00374-25

Front Med (Lausanne). 2025 Mar 18;12:1527843. doi: 10.3389/fmed.2025.1527843. eCollection 2025.

ABSTRACT

BACKGROUND: Established morpho-functional chest magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in people with cystic fibrosis (pwCF) using a dedicated scoring system. Functional assessment is performed using contrast-enhanced (CE) perfusion MRI. Novel matrix pencil decomposition MRI (MP-MRI) is a contrast agent-free alternative, but further validation of this technique is needed.

OBJECTIVES: The aim of this study was to evaluate the applicability of the validated morpho-functional chest MRI score for CE perfusion and MP perfusion MRI in a multireader approach.

METHODS: Twenty-seven pwCF (mean age 20.8 years, range 8.4-45.7 years) underwent morpho-functional MRI including CE perfusion and MP perfusion MRI in the same examination. Nine blinded chest radiologists of different experience levels assessed lung perfusion and applied the validated chest MRI score to CE- and MP-MRI. Inter-reader agreement of perfusion scores in CE- and MP-MRI were compared with each other and with the MRI morphology score. Differences according to the readers' experience were also analyzed.

RESULTS: The CE perfusion scores were overall lower than the MP perfusion scores (6.2 ± 3.3 vs. 6.9 ± 2.0; p < 0.05) with a strong correlation between both perfusion scores (r = 0.74; p < 0.01). The intraclass correlation coefficient (ICC) as measure for inter-reader agreement was good and significant for both perfusion scores, but higher for the CE perfusion score (0.75, p < 0.001) than for MP perfusion scores (0.61, p < 0.001). The Bland-Altman analysis revealed a difference in CE and MP perfusion scores with more extreme values in CE perfusion scores compared to MP perfusion scores (r = 0.62, p < 0.001). The morphology score showed a moderate to good correlation with the CE perfusion score (r = 0.73, p < 0.01) and the MP perfusion score (r = 0.55, p < 0.01). We did not find a difference in scoring according to the radiological experience level.

CONCLUSION: The established chest MRI score can be applied both to validated CE and novel MP perfusion MRI with a good interreader reliability. The remaining difference between CE and MP-MRI scores may be explained by a lack of routine in visual analysis of MP-MRI and may favor an automated analysis for use of MP-MRI as a noninvasive outcome measure.

PMID:40171501 | PMC:PMC11958188 | DOI:10.3389/fmed.2025.1527843

NEJM Catal Innov Care Deliv. 2025 Feb;6(2). doi: 10.1056/CAT.24.0095. Epub 2025 Jan 15.

ABSTRACT

Cystic fibrosis (CF) affects more than 160,000 individuals globally and has seen improved survival rates due to multidisciplinary care models and pharmacotherapy innovations. However, the associated costs remain substantial, prompting the authors to study and evaluate the expense of CF ambulatory care to understand how care structure influences costs. People with CF (PwCF) at large pediatric CF centers in both the United States and Ireland were recruited for parallel observational, prospective studies. Based upon the process of care, the lead clinicians at both sites identified and agreed on three strata of patients (0-11 months, 1-5 years, and 6-17 years of age). Process maps were developed for each of the age cohorts at each site, and the costs of ambulatory care - with emphasis on routine CF clinic visits - were measured utilizing time-driven activity-based costing (TDABC). A dollar-per-minute capacity cost rate (CCR) was calculated for all resources used in the care cycle. The total direct cost was obtained by multiplying the CCR for each resource by the time the resource was used during the patient's care cycle. The cost was summed across all resource types to obtain the cost over the entire care cycle for each site. Service operations were benchmarked to one site and variance analysis was performed. In total, 58 PwCF were included in the analysis (49 in the United States and 9 in Ireland); 4 were 0-11 months, 17 were 1-5 years, and 37 were 6-17 years of age. Physicians (United States) and respiratory consultants (Ireland) had the highest CCRs. Physicians and registered dietitians spent the most time with patients in the United States, compared with the clinical nurse specialists and dietitians in Ireland. The total variance in cost for clinical visits was largest in the 6- to 17-year-old group (28% variance, with 100% in the United States vs. 128% in Ireland). In the 6- to 17-year-old group, the largest drivers in total variance were quantity variance (variance in duration of time spent with patients), which was 108% greater in Ireland); the skill mix variance (variance in clinician type performing service for a given time), which was 49% greater in the United States; and the rate variance (variance in compensation levels across sites), which was 31% greater in the United States. The authors' use of TDABC to characterize the cost of multidisciplinary care during ambulatory clinic visits for PwCF, in combination with variance analysis (the quantitative investigation of the difference between actual and expected costs), provides new and innovative ways to compare costs across similar health care service delivery sites, providing insights into the distinctive features of each. A granular understanding of cost and comparison of resource utilization between centers provides valuable, organizationally relevant insights.

PMID:40171477 | PMC:PMC11960789 | DOI:10.1056/CAT.24.0095

Front Pediatr. 2025 Mar 18;13:1564156. doi: 10.3389/fped.2025.1564156. eCollection 2025.

ABSTRACT

INTRODUCTION: Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder affecting motile cilia, leading to impaired mucociliary clearance and increased susceptibility to respiratory infections. These infections contribute to long-term complications such as bronchiectasis and lung function decline.

OBJECTIVES: This review explores both the acute and long-term impact of respiratory infections in children with PCD, while highlighting the multiple contributors to infection susceptibility. The review also evaluates emerging personalized approaches such as gene and mRNA therapy that hold promise for restoring ciliary function and reducing the burden of acute infections in pediatric PCD.

KEY FINDINGS AND CONCLUSIONS: Acute respiratory infections have a significant impact on morbidity in pediatric PCD, driving progressive airway remodeling. While current treatment strategies focus on managing infections directly, emerging therapies targeting inflammation and genetic causes hold promise for reducing infection burden and improving long-term outcomes. Future advances in personalized medicine could further enhance therapeutic approaches in this population.

PMID:40171169 | PMC:PMC11958984 | DOI:10.3389/fped.2025.1564156

Front Cell Infect Microbiol. 2025 Mar 18;15:1445660. doi: 10.3389/fcimb.2025.1445660. eCollection 2025.

ABSTRACT

Mycobacterium abscessus is a nontuberculous mycobacterium emerging as a significant pathogen in individuals with chronic lung diseases, including cystic fibrosis and chronic obstructive pulmonary disease. Current therapeutics have poor efficacy. Strategies of bacterial control based on host defenses are appealing; however, antimycobacterial immunity remains poorly understood and is further complicated by the appearance of smooth and rough morphotypes, which elicit distinct host responses. We investigated the role of serum components in neutrophil-mediated clearance of M. abscessus morphotypes. M. abscessus opsonization with complement enhanced bacterial killing compared to complement-deficient opsonization. Killing of rough isolates was less reliant on complement. Complement C3 and mannose-binding lectin 2 (MBL2) were deposited on M. abscessus morphotypes in distinct patterns, with a greater association of MBL2 on rough M. abscessus. Killing was dependent on C3; however, depletion and competition experiments indicate that canonical complement activation pathways are not involved. Complement-mediated killing relied on natural IgG and IgM for smooth morphotypes and on IgG for rough morphotypes. Both morphotypes were recognized by complement receptor 3 in a carbohydrate- and calcium-dependent manner. These findings indicate a role for noncanonical C3 activation pathways for M. abscessus clearance by neutrophils and link smooth-to-rough adaptation to complement activation.

PMID:40171164 | PMC:PMC11959001 | DOI:10.3389/fcimb.2025.1445660

Pediatr Pulmonol. 2025 Apr;60(4):e71078. doi: 10.1002/ppul.71078.

ABSTRACT

BACKGROUND: As the life expectancy of people with cystic fibrosis (PwCF) increases, understanding long-term complications, including CF-related bone disease (CFBD), is crucial.

OBJECTIVE: This study aimed to longitudinally characterize CFBD and to compare the bone status of pancreatic sufficient (PS) and pancreatic insufficient (PI) PwCF.

METHODS: This longitudinal analysis included PwCF older than 8 years of age who had at least one dual-energy X-ray absorptiometry test between 2008 and 2021. Data were collected on serum parameters of bone metabolism, nutritional history, habitual activity, and fractures in addition to other demographic and clinical characteristics.

RESULTS: The study included 80 PwCF: 32 (40%) were PS and 48 (60%) PI. Normal dual-energy X-ray absorptiometry results were found in 42 (53%) patients: 16 (50%) in the PS group and 26 (54%) in the PI group (p = 0.72). Three (9%) of the PS group and seven (15%) of the PI group had at least one Z-score below -2 (p = 0.49). The longitudinal bone density decline over a mean of 4.8 years was similar in the two groups. In a logistic regression analysis, pancreatic insufficiency was not found to be a risk factor for CFBD. Female sex was the only significant risk factor for a pathological Z-score.

CONCLUSIONS: The prevalence and severity of CFBD were not found to correlate with pancreatic sufficiency. The similar prevalence of CFBD between patients with PS and PI suggests that screening, and eventually treatment, should be offered to all PwCF, irrespective of pancreatic status.

PMID:40170622 | DOI:10.1002/ppul.71078

Br J Clin Pharmacol. 2025 Apr 2. doi: 10.1002/bcp.70027. Online ahead of print.

ABSTRACT

AIM: Dipeptidyl peptidase-1 (DPP-1) inhibitors have been studied for the treatment of neutrophil-mediated inflammatory diseases including bronchiectasis, bronchial asthma and cystic fibrosis. This study evaluated the pharmacokinetics, pharmacodynamics, safety and tolerability of DPP-1 inhibitor HSK31858 in healthy Chinese volunteers.

METHODS: Volunteers in Part A randomly received single doses of HSK31858 (15, 40, 60 and 80 mg) or placebo in fasted states. The 40-mg cohort also received HSK31858 40 mg or placebo in fed states. In Part B, volunteers randomly received HSK31858 10, 20 and 40 mg or placebo once daily for 28 days in fasted states. The primary endpoints were safety and tolerability of HSK31858.

RESULTS: Among 38 volunteers in Part A and 36 in Part B, HSK31858 was well tolerated; no deaths, serious adverse events, or discontinuations due to adverse events occurred. The median Tmax was 0.75 to 1.0 h and the mean terminal t1/2 was 16.5 to 21.0 h in the fasted state with single doses of HSK31858. Both Cmax and AUC0-t exhibited a dose-dependent rise. Food had no effect on AUC. Multiple doses of HSK31858 demonstrated a similar pharmacokinetics profile, with about 2-fold accumulation in AUC. HSK31858 dose-dependently inhibited neutrophil count-normalized neutrophil elastase (NEnorm) activity. The maximal percentage decrease in NEnorm activity relative to baseline during 28 days of HSK31858 treatments was 13.6% and 76.4% with HSK31858 10 and 40 mg once-daily, respectively.

CONCLUSION: HSK31858 was safe and well tolerated. The pharmacokinetics and pharmacodynamics profile of HSK31858 supports further clinical development for the treatment of neutrophil-mediated inflammatory diseases.

TRIAL REGISTRATION: NCT05663593.

PMID:40170587 | DOI:10.1002/bcp.70027

Ther Adv Respir Dis. 2025 Jan-Dec;19:17534666251329792. doi: 10.1177/17534666251329792. Epub 2025 Apr 1.

NO ABSTRACT

PMID:40170358 | DOI:10.1177/17534666251329792

Commun Biol. 2025 Apr 2;8(1):540. doi: 10.1038/s42003-025-07944-w.

ABSTRACT

Preterm birth disrupts intestinal epithelial maturation, impairing digestive and absorptive functions. This study integrates analysis of single-cell RNA sequencing datasets, spanning fetal to adult stages, with human preterm intestinal models derived from the ileal tissue of preterm infants. We investigate the potential of extracellular vesicles (EVs) derived from human Wharton's jelly mesenchymal stem cells to promote intestinal maturation. Distinct enterocyte differentiation trajectories are identified during the transition from immature to mature stages of human intestinal development. EV treatment, particularly with the EV39 line, significantly upregulates maturation-specific gene expression related to enterocyte function. Gene set enrichment analysis reveals an enrichment of TGFβ1 signaling pathways, and proteomic analysis identifies TGFβ1 and FGF2 as key mediators of EV39's effects. These treatments enhance cell proliferation, epithelial barrier integrity, and fatty acid uptake, primarily through CFTR-dependent mechanisms-unique to human preterm models, not observed in mouse intestinal organoids. This highlights the translational potential of EV39 and CFTR activation in promoting the functional maturation of the premature human intestine.

PMID:40169914 | DOI:10.1038/s42003-025-07944-w

Basic Clin Androl. 2025 Apr 1;35(1):13. doi: 10.1186/s12610-025-00260-7.

ABSTRACT

BACKGROUND: Azoospermia, the most severe form of male infertility, is categorized into two types: non-obstructive azoospermia (NOA) and obstructive azoospermia (OA), which exhibit significant genetic heterogeneity. Azoospermia factor (AZF) deletion is a common cause of NOA, whereas congenital bilateral absence of the vas deferens (CBAVD), a severe subtype of OA, is frequently linked to cystic fibrosis transmembrane conductance regulator (CFTR) gene variants. This case report is the first to document the coexistence of a partial AZFa microdeletion and a homozygous CFTR variant in a CBAVD-affected azoospermic patient with intact spermatogenesis.

CASE PRESENTATION: A 32-year-old man presented with primary infertility and azoospermia. Clinical evaluation revealed CBAVD (normal hormone levels, low semen volume, pH 6.0, and absence of the vas deferens). Genetic analysis accidentally revealed a 384.9 kb AZFa deletion (sY84 and sY86, but not sY1064, 1182) that removed USP9Y but retained DDX3Y in the proband, his fertile brother, and his father. A homozygous CFTR variant (TG12-5T) was also detected in the proband and his brother and was inherited from heterozygous parental carriers. Microdissection testicular sperm extraction (micro-TESE) revealed intact spermatogenesis, confirmed by histology and immunofluorescence, indicating normal germ cell development.

CONCLUSION: This case expands the intricate genetic spectrum of azoospermia by illustrating the critical role of DDX3Y in the AZFa region in spermatogenesis and the variable penetrance of CFTR variant (TG12-5T) in CBAVD. These insights may refine diagnostic strategies and underscore the necessity for tailored fertility management in individuals with multifactorial genetic anomalies.

PMID:40169970 | DOI:10.1186/s12610-025-00260-7

Biomed Pharmacother. 2025 Mar 31;186:117957. doi: 10.1016/j.biopha.2025.117957. Online ahead of print.

ABSTRACT

BACKGROUND: Overactive neutrophilic inflammation causes damage to the airways and death in people with cystic fibrosis (CF), a genetic disorder resulting from mutations in the CFTR gene. Reducing the impact of inflammation is therefore a major concern in CF. Evidence indicates that dysfunctional NRF2 signaling in CF individuals may impair their ability to regulate their oxidative and inflammatory responses, although the role of NRF2 in neutrophil-dominated inflammation and tissue damage associated with CF has not been determined. Therefore, we examined whether curcumin, an activator of NRF2, might provide a beneficial effect in the context of CF.

METHODS: Combining Cftr-depleted zebrafish as an innovative biomedical model with CF patient-derived airway organoids (AOs), we aimed to understand how NRF2 dysfunction leads to abnormal inflammatory status and tissue remodeling and determine the effects of curcumin in reducing inflammation and tissue damage in CF.

RESULTS: We demonstrate that NFR2 is instrumental in regulating neutrophilic inflammation and repair processes in vivo, thereby preventing inflammatory damage. Importantly, curcumin treatment restores NRF2 activity in both CF zebrafish and AOs. Curcumin reduces neutrophilic inflammation in CF context, by rebalancing the production of epithelial ROS and pro-inflammatory cytokines. Furthermore, curcumin improves tissue repair by reducing CF-associated fibrosis. Our findings demonstrate that curcumin prevents CF-mediated inflammation via activating the NRF2 pathway.

CONCLUSIONS: This work highlights the protective role of NRF2 in limiting inflammation and injury and show that therapeutic strategies to normalize NRF2 activity, using curcumin or others NRF2 activators, might simultaneously reduce airway inflammation and damage in CF.

PMID:40168724 | DOI:10.1016/j.biopha.2025.117957

PLoS Pathog. 2025 Apr 1;21(4):e1013017. doi: 10.1371/journal.ppat.1013017. Online ahead of print.

ABSTRACT

Anthrax lethal toxin (LT) and edema toxin (ET) are two of the major virulence factors of Bacillus anthracis, the causative pathogen of anthrax disease. While the roles of LT in anthrax pathogenesis have been extensively studied, the pathogenic mechanism of ET remains poorly understood. ET is a calmodulin-dependent adenylate cyclase that elevates intracellular cAMP by converting ATP to cAMP. Thus, it was postulated that the ET-induced in vivo toxicity is mediated by certain cAMP-dependent events. However, mechanisms linking cAMP elevation and ET-induced damage have not been established. Cholera toxin is another bacterial toxin that increases cAMP. This toxin is known to cause severe intestinal fluid secretion and dehydration by cAMP-mediated activation of protein kinase A (PKA), which in turn activates cystic fibrosis transmembrane conductance regulator (CFTR). The cAMP-activated PKA phosphorylation of CFTR on the surface of intestinal epithelial cells leads to an efflux of chloride ions accompanied by secretion of H2O into the intestinal lumen, causing rapid fluid loss, severe diarrhea and dehydration. Due to similar in vivo effects, it was generally believed that ET and cholera toxin would exhibit a similar pathogenic mechanism. Surprisingly, in this work, we found that cAMP-mediated PKA/CFTR activation is not essential for ET to exert its in vivo toxicity. Instead, our data suggest that ET-induced ATP depletion may play an important role in the toxin's pathogenesis.

PMID:40168442 | DOI:10.1371/journal.ppat.1013017

Pediatr Pulmonol. 2025 Apr;60(4):e71076. doi: 10.1002/ppul.71076.

ABSTRACT

BACKGROUND: The effects of CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), on exercise capacity in people with cystic fibrosis (pwCF) remain unclear, with no data available on their impact within the context of an exercise intervention. Therefore, this study aimed to assess the effects of an exercise intervention on exercise capacity in adults with CF, comparing those treated with and without ETI.

METHODS: A total of 56 adult pwCF participated in this quasi-experimental study as part of a rehabilitation program, which included a 3.5-week exercise intervention. The program involved five weekly 45-min sessions, including endurance training on a cycle ergometer. VO2 peak and Wpeak were the primary outcomes used to assess changes in exercise capacity.

RESULTS: The intervention significantly increased VO2 peak and Wpeak in all pwCF, regardless of ETI use, with similar improvements between groups. PwCF with lower baseline fitness (VO2 peak ≤ 81%pred) showed greater improvements than those with higher fitness (VO2 peak ≥ 82%pred). ppFEV1 remained unchanged, while BMI increased in both groups. Notably, the ETI group spent significantly more time in physical activity (PA) at hard and very hard intensities compared to the non-ETI group. Additionally, a positive correlation was observed between PA intensity and VO2 peak and Wpeak in the ETI group.

CONCLUSION: Independent of ETI treatment, adult pwCF improve their exercise capacity by participating in a regular exercise program. ETI treatment appears to enhance time spent in higher PA intensities. Despite the effectiveness of CFTR modulators, regular PA and exercise remain essential to maintain and improve exercise capacity in pwCF.

PMID:40167900 | DOI:10.1002/ppul.71076

Disabil Rehabil. 2025 Apr 1:1-9. doi: 10.1080/09638288.2025.2484779. Online ahead of print.

ABSTRACT

Purpose: Adherence to airway clearance therapy (ACT) among individuals with cystic fibrosis (CF) is often inconsistent. This study aims to explore the perceptions of adults with CF regarding their experiences with ACT and what influences their selection of specific ACTs. Findings may help inform clinician approaches to patient care and ACT. Materials and Methods: A qualitative descriptive study was conducted using individual, semi-structured interviews. Eight participants [six male and two female, median (min-max) age 42.5 (27-52)] were purposively recruited from the Toronto Adult CF Centre at St. Michael's Hospital, Unity Health Toronto. Results: Four key themes were generated from participants' accounts. First, they described the intensive nature of CF self-management and its influence on their perceptions and selection of ACT techniques. Second, they emphasized the importance of healthcare professional guidance in treatment decisions. Third, physical health status, exercise, and CF transmembrane conductance regulator modulator therapy also shaped participants' self-management approaches. Lastly, their social context influenced how they navigated self-management, which evolved over time. Conclusion: This study shows that ACT technique selection is influenced by various evolving needs across the lifespan. Understanding the role that patient experiences play in ACT technique selection may help clinicians personalize recommendations and promote patient-centred care.

PMID:40167245 | DOI:10.1080/09638288.2025.2484779

Biopsychosoc Sci Med. 2025 Mar 24. doi: 10.1097/PSY.0000000000001387. Online ahead of print.

ABSTRACT

OBJECTIVE: An emerging body of evidence suggests that psychological flexibility may be an important and underexamined determinant of overall psychological functioning. The chronic nature of Cystic Fibrosis (CF) may require a greater level of flexibility to navigate complex and dynamic health concerns in an increasingly aging population.

METHODS: We examined associations between psychological flexibility, coping styles, psychological grit, and negative affectivity (anxiety and depressive symptoms) from baseline assessments of randomized trial among adults with CF. Regression models controlling for age, gender, income, psychotropic medication use and pulmonary function were used to characterize associations between psychological flexibility, coping styles and negative affect.

RESULTS: A total of 124 individuals were included in analyses, 74 (60%) of whom were taking a psychotropic medication. Depressive (BDI-II=18.6 [SD=9.9]) and anxious (BAI=13.8 [SD=9.3]) symptoms were both elevated. Greater levels of psychological flexibility were associated with lower negative affect, such that individuals reporting less cognitive fusion (B=-0.59, P<0.001) and greater psychological acceptance (B=-0.51. P<0.001) exhibited lesser levels of anxiety and depressive symptoms. Psychological flexibility was the most robust correlate of negative affect after accounting for other coping variables (B=-0.50, P<0.001) and this association was not moderated by FEV1/FVC levels.

CONCLUSIONS: Psychological flexibility is robustly associated with decreased negative affect among individuals with CF, independent of background and clinical characteristics.

PMID:40167140 | DOI:10.1097/PSY.0000000000001387

J Pediatr Gastroenterol Nutr. 2025 Mar 31. doi: 10.1002/jpn3.70029. Online ahead of print.

ABSTRACT

OBJECTIVES: We determined the prevalence of anemia and its characteristics in children with newly diagnosed inflammatory bowel disease (IBD) and investigated its trend during follow-up.

METHODS: An observational, multicenter cohort study of IBD children with anemia at the diagnosis enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition IBD registry. Data were collected at the diagnosis and at 1 year.

RESULTS: Five hundred eighty-nine (295 Crohn's disease [CD] [50%] and 294 ulcerative colitis [UC]/IBD unclassified [IBDU] [50%]) of 1634 patients with IBD presented with anemia (36%). Anemia rate was higher in CD than in UC (39% vs. 33%, p = 0.009), and most patients had moderate anemia (55%). Children with CD had higher rates of mild anemia than UC (38% vs. 33%, p < 0.0001), while severe anemia was more common in UC (13% vs. 6%, p = 0.001). In CD, lower age at the diagnosis and lower albumin level correlated with anemia severity (p = 0.0007 and <0.0001, respectively). In UC, severe disease was more common in patients with severe anemia compared to those with mild and moderate anemia (20.6% vs. 43.6%, p = 0.01; 17% vs. 43.6%, p = 0.001). At 1 year, 99 children (22.9%) were persistently anemic and were characterized by a more severe disease compared to those who had resolved their anemia.

CONCLUSIONS: More than one third of IBD children present with anemia, most commonly moderate. Severe anemia is more common in UC compared to CD. One in four patients is still anemic after 1 year from the diagnosis, suggesting inadequate attention to the issue and the need for dedicated therapeutic management and careful monitoring.

PMID:40165528 | DOI:10.1002/jpn3.70029

Stat Methods Med Res. 2025 Mar 31:9622802251316971. doi: 10.1177/09622802251316971. Online ahead of print.

ABSTRACT

G-formula is a popular approach for estimating the effects of time-varying treatments or exposures from longitudinal data. G-formula is typically implemented using Monte-Carlo simulation, with non-parametric bootstrapping used for inference. In longitudinal data settings missing data are a common issue, which are often handled using multiple imputation, but it is unclear how G-formula and multiple imputation should be combined. We show how G-formula can be implemented using Bayesian multiple imputation methods for synthetic data, and that by doing so, we can impute missing data and simulate the counterfactuals of interest within a single coherent approach. We describe how this can be achieved using standard multiple imputation software and explore its performance using a simulation study and an application from cystic fibrosis.

PMID:40165440 | DOI:10.1177/09622802251316971

BMJ Open Respir Res. 2025 Mar 31;12(1):e002546. doi: 10.1136/bmjresp-2024-002546.

ABSTRACT

BACKGROUND: A person's beliefs about treatment influence their engagement and adherence to that treatment. The Necessity-Concerns Framework suggests that adherence is influenced by a person's judgement of their own need for treatment (necessity beliefs) and concerns about the potential adverse consequences of taking the treatment. This study was conducted to explore the Necessity-Concerns Framework for elexacaftor-tezacaftor-ivacaftor (ETI) therapy (Kaftrio) in adults with cystic fibrosis (CF).

METHODS: A total of 64 adults with CF were maintained on ETI therapy as part of their routine CF care, and completed the Beliefs about Medicines Questionnaire. Patient demographics, lung function, body mass index and quality of life using the Cystic Fibrosis Questionnaire Revised were collected as part of routine clinical care. Duration of ETI therapy along with medicines possession ratio was recorded.

RESULTS: Patients reported strong beliefs about the necessity of ETI therapy. The majority of patients (78%) reported low concerns about ETI therapy while 22% of patients reported high concerns. A small number of patients (n=4) had concerns which were stronger than their beliefs about necessity.

DISCUSSION: Patients reported strong beliefs in the necessity of ETI therapy. Although concerns were lower, a significant proportion of the sample had strong concerns about their ETI therapy. By being aware of people with CF's necessity and concerns beliefs around ETI therapy clinical teams will be better armed to engage them in treatment decisions and support optimal adherence.

PMID:40164471 | DOI:10.1136/bmjresp-2024-002546

Respir Physiol Neurobiol. 2025 Mar 29:104423. doi: 10.1016/j.resp.2025.104423. Online ahead of print.

ABSTRACT

Physical activity is a leading trigger of dyspnea in chronic cardiopulmonary diseases. Recently, there has been a renewed interest in uncovering the mechanisms underlying this distressing symptom. We start by articulating a conceptual framework linking cardiorespiratory abnormalities with the central perception of undesirable respiratory sensations during exercise. We specifically emphasize that exertional dyspnea ultimately reflects an imbalance between (high) demand and (low) capacity. As such, the symptom arises in the presence of a heightened inspiratory neural drive - the will to breathe - secondary to a) increased ventilatory output relative to the instantaneous ventilatory capacity (excessive breathing) and/or b) its impeded translation into the act of breathing due to constraints on tidal volume expansion (constrained breathing). In patients with chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, and interstitial lung disease (ILD), constrained breathing assumes a more dominant role as the disease progresses. Excessive breathing due to heightened wasted ventilation in the physiological dead space is particularly important in the initial stages of COPD, while alveolar hyperventilation has a major contributory role in hypoxemic patients with ILD. Hyperventilation is also a leading driver of dyspnea in heart failure (HF) with reduced ejection fraction (EF), while high physiological dead space is the main underlying mechanism in HF with preserved EF. Similarly, wasted ventilation in poorly perfused lung tissue dominates the scene in pulmonary vascular disease. New artificial intelligence-based approaches to expose the contribution of excessive and constrained breathing may enhance the yield of cardiopulmonary exercise testing in investigating exertional dyspnea in these patients.

PMID:40164293 | DOI:10.1016/j.resp.2025.104423