Int Forum Allergy Rhinol. 2025 May 15:e23591. doi: 10.1002/alr.23591. Online ahead of print.

NO ABSTRACT

PMID:40371719 | DOI:10.1002/alr.23591

Development. 2025 May 15:dev.204277. doi: 10.1242/dev.204277. Online ahead of print.

ABSTRACT

The small intestine is well known for its nutrient-absorbing enterocytes; yet equally critical for homeostasis is a diverse set of secretory cells, all presumed to originate from the same intestinal stem cell. Despite their major roles in intestinal function and health, understanding how the full spectrum of secretory cell types arises remains a longstanding challenge, largely due to their comparative rarity. Here, we investigate the specification of a rare population of small intestinal epithelial cells found in rats and humans but not mice: CFTR High Expressers (CHEs). Using pseudotime trajectory analysis of single-cell RNA-seq data from rat jejunum, we provide evidence that CHEs are specified along the secretory lineage and appear to employ a second wave of Notch-based signaling to distinguish themselves from other secretory cells. We validate the transcription factors directing these cells from crypt progenitors and demonstrate that Notch signaling is necessary to induce CHE fate in vivo and in vitro. Our findings suggest that Notch reactivation along the secretory lineage specifies CHEs, which may help regulate luminal pH and have direct relevance in cystic fibrosis pathophysiology.

PMID:40371707 | DOI:10.1242/dev.204277

JAMA Netw Open. 2025 May 1;8(5):e2510298. doi: 10.1001/jamanetworkopen.2025.10298.

ABSTRACT

IMPORTANCE: Patients with dementia have considerable supportive care needs. Specialist palliative care may be beneficial, but it is unclear which patients are most appropriate for referral and when they should be referred.

OBJECTIVE: To identify a set of consensus referral criteria for specialist palliative care for patients with dementia.

DESIGN, SETTING, AND PARTICIPANTS: In this survey study using 3 rounds of Delphi surveys, an international, multidisciplinary panel of clinicians from 5 continents with expertise in the integration of dementia and palliative care were asked to rate 83 putative referral criteria (generated from a previous systematic review and steering committee discussion). Specialist palliative care was defined as an interdisciplinary team consisting of practitioners with advanced knowledge and skills in palliative medicine offering consultative services for specialist-level palliative care in (nonhospice) inpatient, outpatient, community, and home-based settings.

MAIN OUTCOMES AND MEASURES: Consensus was defined a priori as at least 70% agreement among experts. A criterion was coded as major if the experts advocated that meeting 1 criterion alone was satisfactory to justify a referral. Data were summarized using descriptive statistics.

RESULTS: Of the 63 invited and eligible panelists, the response rate was 58 (92.1%) in round 1, 58 (92.1%) in round 2, and 60 (95.2%) in round 3. Of the 58 panelists who provided demographic data in round 1, most were aged 40 to 49 years (28 of 58 [48.3%]), and 29 panelists (50%) each were men and women. Panelists achieved consensus on 15 major and 42 minor criteria for specialist palliative care referral. The 15 major criteria were grouped under 5 categories, including dementia type (eg, rapidly progressive dementia), symptom distress (eg, severe physical symptoms), psychosocial factors or decision-making (eg, request for hastened death, assisted suicide, or euthanasia), comorbidities or complications (eg, ≥2 episodes of aspiration pneumonia in the past 12 months); and hospital use (eg, ≥2 hospitalizations within the past 3 months).

CONCLUSIONS AND RELEVANCE: In this Delphi survey study, international experts reached consensus on a range of criteria for referral to specialist palliative care. With testing and validation, these criteria may be used to standardize specialist palliative care access for patients with dementia across various care settings.

PMID:40366652 | PMC:PMC12079294 | DOI:10.1001/jamanetworkopen.2025.10298

Inn Med (Heidelb). 2025 May 14. doi: 10.1007/s00108-025-01912-6. Online ahead of print.

ABSTRACT

Adolescence represents a period of significant transformation for individuals with chronic conditions such as cystic fibrosis (CF) and asthma. Due to substantial progress in highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy, nearly everyone with CF now reaches adulthood, necessitating ongoing interdisciplinary medical care. Conversely, approximately 70% of children with asthma experience a resolution of symptoms as they reach adulthood. Factors contributing to the persistence of asthma into adulthood include the presence of severe asthma, diminished lung function in childhood and allergic comorbidities. Especially for young adults with severe asthma, continuous pneumological care including uninterrupted access to biologics, must be provided. During the transition process, considerations regarding career choices are pertinent for both patient groups. Additionally, issues related to family planning and prenatal diagnostics become particularly relevant for young adults with CF and should be addressed during the transition process. In both patient groups, an early and structured initiation of the transition process is essential. The use of checklists and transition plans can facilitate the transfer of critical information and ensure a seamless transition. Joint pediatric and internal medicine consultations foster trust and ensure medical quality. Ultimately, a successful transition should enable individuals with CF as well as those with asthma to assume responsibility for their condition and treatment, recognize clinical deterioration, and seek timely assistance.

PMID:40369362 | DOI:10.1007/s00108-025-01912-6

Eur Respir Rev. 2025 May 14;34(176):240220. doi: 10.1183/16000617.0220-2024. Print 2025 Apr.

ABSTRACT

INTRODUCTION: The Montreal Cystic Fibrosis Related Diabetes Screening Cohort (MCFC) was established in 2004 to study the prevalence, risk factors and management of cystic fibrosis-related diabetes, a significant extrapulmonary complication of cystic fibrosis with an increasing prevalence due to improved cystic fibrosis survival rates. The aims of this review are to highlight the key insights gained from monitoring the MCFC over 20 years, and to discuss the challenges and advantages of establishing such a cohort in a rare disease like cystic fibrosis.

METHODS: Adult people with cystic fibrosis were recruited from 2004 onward in Montreal, Canada, excluding those already diagnosed with cystic fibrosis-related diabetes. Clinical and biological results (including oral glucose tolerance tests) were recorded regularly.

RESULTS: Findings from the MCFC contributed to a better understanding of cystic fibrosis-related diabetes pathophysiology (in particular, the joint roles of reduced insulin secretion and added insulin resistance) and its relationship with lung function. Over the years, we observed a shift towards overweight and obesity among cystic fibrosis patients, along with improved lung function. This could be due to improved cystic fibrosis care and to the introduction of cystic fibrosis transmembrane conductance regulator modulators. We were also able to validate new, simplified screening modalities and management strategies (e.g. physical activity) for cystic fibrosis-related diabetes.

CONCLUSION: The MCFC has contributed to the understanding of cystic fibrosis-related diabetes and informed best practice guidelines. Future research will focus on how cystic fibrosis transmembrane conductance regulator modulators influence glycaemic control and cardiometabolic health in people with cystic fibrosis.

PMID:40368427 | DOI:10.1183/16000617.0220-2024

Eur Respir Rev. 2025 May 14;34(176):240261. doi: 10.1183/16000617.0261-2024. Print 2025 Apr.

ABSTRACT

The increasing life expectancy of people with cystic fibrosis (pwCF), largely driven by advancements in early diagnosis, multidisciplinary care and the recent introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, is likely to herald a shift in the focus of care toward managing the complexities of ageing. This review highlights key challenges and research priorities for addressing the health needs of an ageing CF population. A growing body of evidence underscores the heightened risks of cancers, cardiovascular diseases and changing nutritional and metabolic profiles as pwCF age. CFTR modulators have improved clinical outcomes, but their effects on inflammation, immunity and long-term disease trajectories remain incompletely understood. Nutritional management, particularly the implications of obesity and body composition, poses new challenges, as does the potential accelerated ageing of immune and pulmonary systems in CF. Emerging issues such as menopause in females with CF, lifetime antimicrobial resistance and the interplay between chronic inflammation and ageing further complicate the care landscape. The review emphasises the urgent need for multidisciplinary research programmes that integrate clinical, patient and community perspectives. Leveraging established CF registries, clinical trial networks and collaborations with ageing research frameworks is critical to addressing these challenges. Ultimately, the goal is to ensure that pwCF not only live longer but also experience improved quality of life and holistic wellbeing as they realise the full benefits of therapeutic advances.

PMID:40368426 | DOI:10.1183/16000617.0261-2024

J Allergy Clin Immunol Pract. 2025 May 12:S2213-2198(25)00437-4. doi: 10.1016/j.jaip.2025.05.013. Online ahead of print.

ABSTRACT

The pathophysiology of atopic dermatitis (AD) involves cutaneous inflammation, predominantly mediated by innate immunity and T cells, with Immunoglobulin E (IgE) playing a marginal role in most patients. Over previous decades, however, there has been an ongoing debate regarding the relevance of IgE-mediated allergy testing in AD patients. Patients with AD have a defective skin barrier that facilitates a high inflammatory response to environmental antigens, placing them at greater risk for food allergies. Nevertheless, because these patients often produce very high levels of IgE, the positive predictive value of skin prick tests and specific IgE measurements is low; such tests should be performed only when there is a concordant immediate hypersensitivity reaction (i.e. urticaria or angioedema) rather than eczema. In recent years, numerous studies have emphasized the importance of maintaining oral exposure to foods in order to prevent the development or progression of food allergies in atopic patients. While acknowledging that food allergens may contribute to AD in certain cases, it is critical that patients understand the risk of developing IgE-mediated food allergies if they exclude allergenic foods from their diet. Ultimately, controlling AD while retaining these foods in the diet should be the goal for all patients.

PMID:40368248 | DOI:10.1016/j.jaip.2025.05.013

Einstein (Sao Paulo). 2025 May 12;23:eAO1312. doi: 10.31744/einstein_journal/2025AO1312. eCollection 2025.

ABSTRACT

BACKGROUND: Santos et al. analyzed the clinical characteristics and pulmonary function of children with cystic fibrosis infected with SARS-CoV-2. Infected children showed higher rates of dyspnea, coughing, hospitalization, and pulmonary exacerbations. Despite a temporary decline in pulmonary function, the recovery rates matched those of the uninfected children during follow-up. ■ SARS-CoV-2 infection leads to mild-to-moderate disease in children with cystic fibrosis. ■ No worsening of cystic fibrosis was observed months after infection.

OBJECTIVE: This study aimed to evaluate the clinical manifestations of SARS-CoV-2 in children and adolescents with cystic fibrosis.

METHODS: This was a case-control analysis of clinical variables and pulmonary function test results in 43 children with cystic fibrosis, 17 (39.5%) of whom tested positive for SARS-CoV-2.

RESULTS: The infected children exhibited a higher frequency of dyspnea and cough and a greater need for hospitalization. One infected child died. Pulmonary exacerbations were more frequent among the infected children. Additional data indicated a subsequent reduction in pulmonary function in the infected children, although this was not significantly different from that in the uninfected children.

CONCLUSION: Children with cystic fibrosis who contracted SARS-CoV-2 experienced mild to moderate symptoms and required hospitalization but generally had high recovery rates.

PMID:40367008 | DOI:10.31744/einstein_journal/2025AO1312

J Man Manip Ther. 2025 May 14:1-7. doi: 10.1080/10669817.2025.2505096. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a severe hereditary disease that affects multiple organ systems. Among these, the musculoskeletal system is an under-explored area. This interview study aimed to explore experiences of musculoskeletal symptoms and of manual therapies as complementary care in this context.

METHODS: Semi-structured interviews were used to collect data from ten respondents. The data were subsequently analyzed through content analysis with an inductive approach in accordance with the method of Elo and Kyngäs.

RESULTS: The analysis resulted in three main categories; 1) Living with CF involves musculoskeletal health challenges, 2) Manual therapies impact daily life for people with CF, and 3) People with CF aspire for broader and more collaborative respiratory care.

CONCLUSION: The respondents described musculoskeletal symptoms in and around the thoracic cage. They experienced symptom relief and increased body awareness following manual therapy interventions (MTI) and recommended that these methods be offered as complementary care to enhance quality of life.

PMID:40366667 | DOI:10.1080/10669817.2025.2505096

mBio. 2025 May 14;16(5):e0133824. doi: 10.1128/mbio.01338-24. Epub 2025 Apr 9.

ABSTRACT

Strict and facultative anaerobic bacteria are widely associated with both acute and chronic airway diseases. However, their potential role(s) in disease pathophysiology remains poorly understood due to inherent limitations of existing laboratory models and conflicting oxygen demands between anaerobes and host cells. To address these limitations, here, we describe a dual oxic-anoxic culture (DOAC) approach that maintains an oxygen-limited microenvironment at the apical epithelial interface while host cells are oxygenated basolaterally. This platform enables epithelial-anaerobe co-culture for ~48 h, and we demonstrate its utility by evaluating reciprocal interactions between the oxygen-sensitive anaerobic bacterium, Fusobacterium nucleatum, and oxygen-demanding airway epithelial cells at the transcriptional level. Using bulk RNAseq, we demonstrate that epithelial colonization results in altered gene expression by F. nucleatum, highlighted by the differential expression of genes associated with virulence, ethanolamine and lysine metabolism, metal uptake, and other transport processes. We also combine DOAC with single-cell RNA sequencing to reveal a cell type-specific transcriptional response of the airway epithelium to F. nucleatum infection, including the increased expression of inflammatory marker genes and cancer-associated pathways. Together, these data illustrate the versatility of DOAC while revealing new insights into anaerobe-host interactions and their mechanistic contributions to airway disease pathophysiology.IMPORTANCEConflicting oxygen demands between anaerobes and host cells present a significant barrier to in vitro modeling of how these cell types interact. To this end, the significance of our dual oxic-anoxic culture (DOAC) approach lies in its ability to maintain anaerobe and epithelial viability during co-culture, paving the way for new insights into the role(s) of anaerobic microbiota in disease. We use DOAC to interrogate reciprocal interactions between the airway epithelium and Fusobacterium nucleatum-an anaerobic commensal with pathogenic potential. Given its link to a range of diseases, from localized infections to various cancers, these data showing how F. nucleatum bacterium re-shapes its metabolism and virulence upon epithelial colonization provide new mechanistic insight into F. nucleatum physiology and how the host responds. We use F. nucleatum as our model, but the DOAC platform motivates additional studies of the gut, lung, and oral cavity, where host-anaerobe interactions and the underlying mechanisms of pathogenesis are poorly understood.

PMID:40366160 | DOI:10.1128/mbio.01338-24

mSphere. 2025 May 14:e0013725. doi: 10.1128/msphere.00137-25. Online ahead of print.

ABSTRACT

Sickle cell disease (SCD) is a chronic blood disorder that disrupts multiple organ systems and can lead to severe morbidity. Persistent and acute symptoms caused by immune system dysregulation in individuals with SCD could contribute to disease either directly or indirectly via dysbiosis of commensal microbes and increased susceptibility to infection. Here, we explored the nasal and oral microbiomes of children with SCD (cwSCD) to uncover potential dysbiotic associations with the blood disorder. Microbiota collected from nasal and oral swabs of 40 cwSCD were compared to eight healthy siblings using shotgun metagenomic sequencing. Commensal taxa were present at similar levels in the nasal and oral microbiome of both groups. However, the nasal microbiomes of cwSCD contained a higher prevalence of Pseudomonadota species, including pathobionts such as Yersinia enterocolitica and Klebsiella pneumoniae. Furthermore, the oral microbiome of cwSCD displayed lower α-diversity and fewer commensal and pathobiont species compared to the healthy siblings. Thus, subtle but notable shifts seem to exist in the nasal and oral microbiomes of cwSCD, suggesting an interaction between SCD and the microbiome that may influence health outcomes.

IMPORTANCE: The oral and nasal cavities are susceptible to environmental exposures including pathogenic microbes. In individuals with systemic disorders, antibiotic exposure, changes to the immune system, or changes to organ function could influence the composition of the microbes at these sites and the overall health of individuals. Children with sickle cell disease (SCD) commonly experience respiratory infections, such as pneumonia or sinusitis, and may have increased susceptibility to infection because of disrupted microbiota at these body sites. We found that children with SCD (cwSCD) had more pathobiont bacteria in the nasal cavity and reduced bacterial diversity in the oral cavity compared to their healthy siblings. Defining when, why, and how these changes occur in cwSCD could help identify specific microbial signatures associated with susceptibility to infection or adverse outcomes, providing insights into personalized treatment strategies and preventive measures.

PMID:40366139 | DOI:10.1128/msphere.00137-25

Pediatr Pulmonol. 2025 May;60(5):e71124. doi: 10.1002/ppul.71124.

NO ABSTRACT

PMID:40365926 | DOI:10.1002/ppul.71124

J Clin Med. 2025 May 5;14(9):3187. doi: 10.3390/jcm14093187.

ABSTRACT

Cystic fibrosis (CF) is a multisystemic disease caused by a genetic defect, namely a mutation in the CFTR gene, that results in the production of an abnormal protein that regulates the flow of chloride ions through epithelial cells, leading to the dehydration of secreted mucus and changes in its biological properties. Chronic inflammation and recurrent respiratory infections progressively damage lung tissue, leading to respiratory and cardiorespiratory failure. This study aims to present a clinical case and explore the clinical changes in CF that may influence the provision of pre-hospital first aid. The study presents a case report of a 23-year-old CF patient undergoing evaluation for lung transplantation, infected with Pseudomonas aeruginosa and Staphylococcus aureus with the MSSA phenotype, and in a severe condition due to infectious exacerbation. Despite antibiotic treatment, the patient's condition deteriorated, leading to respiratory failure and cardiac arrest. Emergency measures were taken to maintain airway patency-the patient was sedated, intubated, and connected to a ventilator. CF involves systemic complications that, during exacerbations, may require urgent interventions. Cystic fibrosis is associated with multiple systemic complications, some of which may, during exacerbations, require emergency medical interventions. Providing care to this patient group involves specific procedures addressing the consequences of the underlying disease. Due to increasing survival rates and the emergence of new phenotypes, there is a need for the continuous education of medical personnel, including emergency responders, regarding the management of genetically determined diseases. This study underscores the importance of recognizing CF's complex nature and adapting emergency care accordingly to ensure timely and effective intervention in life-threatening situations.

PMID:40364218 | DOI:10.3390/jcm14093187

J Clin Med. 2025 Apr 30;14(9):3118. doi: 10.3390/jcm14093118.

ABSTRACT

Background: The global health burden of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS) affects billions of people and is associated with high levels of healthcare expenditure. Conventional therapies (bronchodilators and corticosteroids) provide symptomatic benefit but take no effect on disease progression, demonstrating the need to develop new therapies. Emerging therapies treat the underlying mechanisms of these chronic diseases, which provide symptomatic relief and benefit the underlying disease. Methods: This review assesses the evolution of therapeutic interventions for chronic lung diseases from a series of established inhaled combination therapies to biologics, gene therapy, and even AI-based stratification of therapies for patients. In addressing these issues, we review the mechanisms of action, evidence of efficacy, and clinical trial evidence, while discussing access issues affecting the implementation of these therapies and ethical issues in relation to their use. Results: The review highlights recent developments in treatment approaches, such as gene therapies aimed at cystic fibrosis mutations, advanced drug delivery pathways for more accurate targeting, and stem cell-based therapies designed to replace damaged lung tissue. These developments have the potential to improve outcomes for chronic lung diseases, but the challenges, including a lack of access, adequate patient selection, and long-term safety, need to be addressed. Conclusions: New therapies offer tremendous potential, but their transition from laboratory to clinic still face numerous barriers including access, regulation, and a need for personalized therapy approaches. The review indicates that future research should develop strategies to reduce barriers to access, improve distribution, and improve clinical guidelines to successfully implement these new therapies.

PMID:40364149 | DOI:10.3390/jcm14093118

J Clin Med. 2025 Apr 25;14(9):2979. doi: 10.3390/jcm14092979.

ABSTRACT

Background/Objectives: Patients with chronic lung diseases, such as cystic fibrosis, were considered a risk group for a severe course of coronavirus disease 2019 at the beginning of the pandemic. However, mounting evidence suggests that this group may not face an elevated risk for a severe SARS-CoV-2 infection. Methods: Here, we present data on the incidence and clinical course of SARS-CoV-2 infections in a single pediatric CF centre in Austria. Clinical variables were analyzed for their potential impact on disease acquisition and severity. A total of 135 young people with CF were assessed from February 2020 until December 2022. Results: Eighty-four patients were infected with SARS-CoV-2, out of which nine patients reported re-infection, resulting in 93 SARS-CoV-2 infections. Most infections, 76/93 (82%), occurred during the period of omicron variant predominance. Higher body mass index and respiratory colonization with Haemophilus influenzae before the beginning of the pandemic were significantly associated with the risk of acquiring SARS-CoV-2 infection. All patients had an uncomplicated COVID-19 course, regardless of the SARS-CoV-2 variant and COVID-19 vaccine status at infection. The most frequent symptoms were rhinitis (53%), fatigue (49%), cephalea (43%), and fever (38%). Neither oxygen therapy nor hospitalization were needed for any of the patients. Lung function parameters (FEV1, FVC, FEF50, LCI), both in the early post-viral as well as late post-viral stages, were not significantly impacted by SARS-CoV-2 infections. No long-term post-COVID-19 effects were reported. Conclusions: Our single-centre experience suggests that the course of SARS-CoV-2 infections in children and adolescents with CF is primarily mild and uncomplicated.

PMID:40364010 | DOI:10.3390/jcm14092979

J Clin Med. 2025 Apr 25;14(9):2977. doi: 10.3390/jcm14092977.

ABSTRACT

Objectives: In this retrospective study, we performed a volumetric analysis of paranasal cavity pneumatization in a population of adult patients with cystic fibrosis compared to healthy controls, providing parcel evaluation of each sinus, and analyzing the prevalence of major anatomical sinonasal variants in the two groups. Methods: We compared paranasal sinus volumes of 89 adult patients with cystic fibrosis and 144 healthy controls who underwent paranasal sinus computed tomography. Volumes were segmented and extracted on tomographic images using the freely available software MRIcron 2019, then compared using a t-test; the z-score test was used to determine whether the two groups differ significantly in terms of major anatomical variants prevalence. Results: Overall sinus volumes in patients with cystic fibrosis patients differ significantly as compared to the healthy population (p < 0.00001). Furthermore, with the only exception of ethmoid sinus pneumatization, which was similar in both populations, all the other sinuses were statistically different. No significant difference emerged concerning anatomical variants' prevalence. Conclusions: Our results further stress the impact of cystic fibrosis on sinus structure in adult patients, better revealing the consequences of the disease on upper airways and in optimizing the management of patients with sinonasal manifestations.

PMID:40364008 | DOI:10.3390/jcm14092977

Molecules. 2025 Apr 22;30(9):1866. doi: 10.3390/molecules30091866.

ABSTRACT

Cystic fibrosis (CF) is a life-threatening disorder caused by mutations in the CFTR gene, leading to defective chloride ion transport and thickened mucus in the respiratory and gastrointestinal systems. CFTR modulators, including ivacaftor, lumacaftor, tezacaftor, and elexacaftor, have improved patient outcomes, but interindividual pharmacokinetic variability and potential drug-drug interactions require therapeutic drug monitoring (TDM) for optimal efficacy and safety. In this context, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous quantification of CFTR modulators and their major active metabolites in human plasma to support pharmacokinetic studies and routine TDM. The multiplex LC-MS/MS assay was established using plasma protein precipitation, followed by chromatographic separation on an Xselect HSS T3 (Waters®) column and positive electrospray ionization mode detection. The method was validated based on FDA and EMA guidelines for specificity, linearity, accuracy (89.8-107.8%), repeatability (1.1-8.1%), intermediate fidelity (1.3-10.9%), matrix effects, and stability, demonstrating a robust performance with excellent precision and accuracy. International interlaboratory comparisons confirmed the reliability of the assay. The developed method can be applied for the clinical monitoring of caftors' plasma concentrations and preliminary data suggest that it can also be applied to alternative matrices, such as breast milk. This method will serve to characterize caftors' pharmacokinetic variability and monitor drug-drug interactions to further refine personalized dosing strategies and enhance precision medicine treatments for patients with CF.

PMID:40363673 | DOI:10.3390/molecules30091866

Int J Mol Sci. 2025 May 3;26(9):4350. doi: 10.3390/ijms26094350.

ABSTRACT

Defective CFTR (cystic fibrosis transmembrane conductance regulator) is pathognomonic for cystic fibrosis (CF), which is characterized by an accumulation of tenacious secretions in pulmonary airways, as well as by abnormal ductal secretions in other organs, including the pancreas and prostate. The advent of CFTR modulating therapies has markedly improved the clinical status and survival of CF patients, primarily attributable to improved lung function. Previous publications reported that a decline in CFTR function was associated with a decline in activity and expression of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB). ARSB removes 4-sulfate groups from N-acetylgalactosamine 4-sulfate residues and is required for the degradation of chondroitin 4-sulfate (chondroitin sulfate A) and dermatan sulfate, two sulfated glycosaminoglycans which accumulate in cystic fibrosis. Declines in both ARSB and in CFTR have been associated with the development of malignancies, including prostate malignancy. The experiments in this report show that similar effects on invasiveness are present when either CFTR or ARSB is inhibited in human prostate epithelial cells, and these effects resemble findings detected in malignant prostate tissue. The effects of CFTR inhibition are reversed by treatment with recombinant human ARSB in prostate cells. These results suggest that treatment by rhARSB may benefit patients with cystic fibrosis and prostate cancer.

PMID:40362587 | DOI:10.3390/ijms26094350

Int J Mol Sci. 2025 May 1;26(9):4320. doi: 10.3390/ijms26094320.

ABSTRACT

Cyclodextrins (CDs) enhance the solubility of poorly water-soluble drugs like ibuprofen (IBU), making them promising carriers for pulmonary drug delivery. This route lowers the required dose, minimizing side effects, which could be beneficial in treating cystic fibrosis. In this study, a nano-spray-drying technique was applied to prepare CD/IBU complexes using sulfobutylether-β-cyclodextrin (SBECD) or (2-Hydroxy-3-N,N,N-trimethylamino)propyl-beta-cyclodextrin chloride (QABCD) as carriers as well as mannitol (MAN) and leucine (LEU) as aerosolization excipients. Various investigation techniques were utilized to examine and characterize the samples, including a Master Sizer particle size analyzer, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). We applied in vitro Andersen Cascade Impactor measurements and in silico simulation analysis to determine the sample's aerodynamic properties. We also performed in vitro dissolution and diffusion tests. Applying formulations with optimal aerodynamic properties, we achieved an improved ~50% fine particle fraction values based on the Andersen Cascade Impactor measurements. The in vitro dissolution and diffusion studies revealed rapid IBU release from the formulations; however, the QABCD-based sample exhibited reduced membrane diffusion compared to SBECD due to the formation of electrostatic interactions.

PMID:40362557 | DOI:10.3390/ijms26094320

Healthcare (Basel). 2025 May 7;13(9):1084. doi: 10.3390/healthcare13091084.

ABSTRACT

Background/Objectives: Cystic fibrosis (CF) is a chronic genetic disease that impacts both physical and psychological health, increasing vulnerability to anxiety, depression, and reduced quality of life (QoL). Psychological interventions, particularly cognitive behavioral therapy (CBT), have demonstrated promising results in enhancing emotional resilience, treatment adherence, and QoL. This systematic review aims to evaluate the role and effectiveness of psychological interventions in improving the QoL among individuals with CF. Methods: A comprehensive literature search was conducted across the PubMed, Scopus, and PsycINFO databases for studies published between 2014 and 2024, in line with PRISMA guidelines and a registered PROSPERO protocol. Out of 162 initially identified articles, six clinical studies met the inclusion criteria. Intervention included cognitive behavioral therapy-based interventions, employing several digital or telehealth formats such as fibrosis-specific cognitive behavioral therapy (CF-CBT) and the coping and learning to manage stress (CALM) program, often delivered via telehealth. Results: Most interventions demonstrated significant reductions in depression, anxiety, and perceived stress, alongside improvements in coping self-efficacy and vitality. Cohen's d-effect sizes ranged from moderate to large for core psychological outcomes. QoL measures, particularly vitality and emotional functioning, were significantly enhanced in most studies. Conclusions: Psychological interventions, particularly CBT and ACT, significantly improve mental health and QoL in individuals with CF, supporting their integration into routine care.

PMID:40361862 | DOI:10.3390/healthcare13091084