Infect Immun. 2025 Mar 10:e0059124. doi: 10.1128/iai.00591-24. Online ahead of print.

ABSTRACT

Respiratory infections with multiresistant Pseudomonas aeruginosa are a major clinical problem, affecting mainly patients with pre-existing lung diseases such as cystic fibrosis (CF) or chronic obstructive pulmonary disease but also immunocompromised or elderly patients. We have previously shown that sphingosine, which is abundantly present on epithelial cells of the respiratory tract in healthy humans and wild-type mice, but almost undetectable on the surface of epithelial cells of the respiratory tract from CF patients and CF mice, efficiently kills many bacterial species in vitro and in vivo. Here, we show that sphingosine very rapidly induces marked changes in the membrane of P. aeruginosa with a rolling of the membrane followed by destruction of the bacteria. Sphingosine induced a degradation of cardiolipin via the maintenance of lipid asymmetry (Mla) system in P. aeruginosa. Degradation of cardiolipin induced by sphingosine is prevented in P. aeruginosa mutants of MlaY and reduced in mutants of MlaZ and MlaA. Mutants of MlaY and MlaZ were resistant to sphingosine-induced death of P. aeruginosa. In summary, our data indicate that sphingosine induces the death of P. aeruginosa by a persisting degradation of cardiolipin by the Mla system leading to severe membrane changes in bacteria, while leaving mammalian cells, devoid of cardiolipin in their plasma membrane, alive.

PMID:40062881 | DOI:10.1128/iai.00591-24

Pediatr Pulmonol. 2025 Mar;60(3):e71037. doi: 10.1002/ppul.71037.

ABSTRACT

BACKGROUND: Although modulator therapies have proven effective in cystic fibrosis (CF) access is limited due to reimbursement issues in Turkey. We aimed to examine anxiety and depression levels of people with CF (pwCF) and their caregivers according to their access to modulator treatment.

METHODS: Participants genetically eligible for elexacaftor/tezacaftor/ivacaftor (ETI) were divided into Group 1 (access via court decision, not yet on treatment) and Group 2 (unable to access due to reimbursement issues). Genetically ineligible participants formed Group 3. All pwCF and parents of those under 18 were screened for depression by the Patient Health Questionnaire-9 (PHQ-9) and for anxiety by the Generalized Anxiety Disorder-7 (GAD-7). Surveys for Group 1 patients were conducted just before starting ETI. Binary logistic regression analysis was performed to evaluate the effects of independent variables on anxiety and depression in pwCF and their primary caregivers.

RESULTS: A total of 389 pwCF and 285 caregivers were included. Group 3 (ineligible) had the highest depression rate (72.9%, n = 35), while Group 1 (pre-ETI) had the lowest (50.0%, n = 35). Median PHQ-9 scores were significantly lower in Group 1 (p < 0.006). Anxiety rates were higher in Groups 2 and 3 compared to Group 1 (p = 0.011 and p = 0.003, respectively). Access to ETI reduced the odds of anxiety by 67.7% (p = 0.029). Caregiver GAD-7 scores showed a weak negative correlation with pwCF age (r = -0.117).

CONCLUSION: Limited access to modulator therapies is associated with higher depression and anxiety symptoms among pwCF. Addressing these barriers is critical to improving their well-being.

PMID:40062574 | DOI:10.1002/ppul.71037

Front Nutr. 2025 Feb 21;12:1553674. doi: 10.3389/fnut.2025.1553674. eCollection 2025.

ABSTRACT

Respiratory diseases are a leading cause of morbidity in children globally, with significant healthcare costs. The overuse of conventional treatments like antibiotics has raised concerns about antibiotic resistance and side effects. Lacticaseibacillus rhamnosus GG (LGG), one of the most extensively studied probiotics, has gained attention as a potential adjunct therapies due to their ability to modulate the gut microbiota and immune responses. This review aims to assess the effectiveness of LGG in managing pediatric respiratory diseases, including respiratory tract infections (RTI), cystic fibrosis (CF), and asthma. Clinical trials suggest LGG can reduce the incidence and severity of RTI, improving CF symptoms, and enhancing quality of life in children. However, evidence for its benefits in asthma remains inconclusive. Its mechanisms include modulating immune responses, enhancing gut barrier function, and maintaining a microbial homeostasis via the gut-lung axis. Existing studies are often limited by small sample sizes, heterogeneity in intervention protocols, and short follow-up periods. Emerging technologies and novel formulations, hold promise for unraveling the complex interactions among LGG, the gut-lung axis, and respiratory health. These advancements could pave the way for personalized probiotic therapies, highlighting the potential of LGG as a cost-effective, adjunctive therapy for pediatric respiratory diseases. This review underscores the broader significance of integrating LGG into pediatric healthcare, while calling for future research to overcome current limitations, optimize clinical protocols, and explore innovative therapeutic strategies.

PMID:40062233 | PMC:PMC11885142 | DOI:10.3389/fnut.2025.1553674

Cureus. 2025 Feb 5;17(2):e78551. doi: 10.7759/cureus.78551. eCollection 2025 Feb.

ABSTRACT

Introduction Non-cystic fibrosis bronchiectasis (bronchiectasis) is an increasingly recognized but understudied disease in children. National data on this disease are scarce. This study aimed to describe the clinical, radiological, and microbiological characteristics of Portuguese children with bronchiectasis. Methods A retrospective observational study was conducted at a tertiary pediatric pulmonology center in northern Portugal. Pediatric patients diagnosed with bronchiectasis and followed between July 2020 and September 2023 were included. Results A total of 38 patients were included, of whom 19 (50.0%) were male, with a median age at diagnosis of 6.3 years (3.8-11.0 years). Recurrent wheezing (n = 30, 78.9%) and chronic wet cough (n = 18, 47.4%) were the most common symptoms. An underlying etiology was identified in 36 (94.7%) patients, primarily postinfectious bronchiectasis (n = 18, 47.4%) and primary ciliary dyskinesia (n = 10, 26.3%). Multilobar involvement was observed in 25 (65.8%) patients, most frequently affecting the middle and lower lobes. Spirometry showed a mixed obstructive-restrictive pattern in 10 (33.3%) patients and a predominantly obstructive pattern in nine (30.0%) patients. Haemophilus influenzae and Streptococcus pneumoniae were the most frequently isolated microorganisms, both in bronchoalveolar lavage and sputum cultures. Pseudomonas aeruginosa was detected in nine (7.4%) sputum samples. Conclusion This study highlights the diverse clinical presentations, etiologies, and microbiological findings in pediatric bronchiectasis. Identifiable causes were present in most cases, emphasizing the importance of clinical vigilance for early diagnosis and intervention. Further research is warranted to explore long-term outcomes and refine treatment approaches based on microbiological profiles.

PMID:40062141 | PMC:PMC11887590 | DOI:10.7759/cureus.78551

World J Clin Pediatr. 2025 Mar 9;14(1):97537. doi: 10.5409/wjcp.v14.i1.97537. eCollection 2025 Mar 9.

ABSTRACT

BACKGROUND: Neonatal screening (NS) is a public health policy to identify genetic pathologies such as cystic fibrosis (CF), sickle cell disease, and other diseases. Sickle cell disease is the comprehensive term for a group of hemoglobinopathies characterized by the presence of hemoglobin S. CF is an autosomal recessive multisystemic disease with pathophysiology involving deleterious mutations in the transmembrane regulatory gene that encodes a protein that regulates the activity of chloride and sodium channels in the cell surface epithelium. NS is crucial for early diagnosis and management, which ensures a better quality of life.

AIM: To report a case of the coexistence of sickle cell anemia (SCA) and CF and perform an integrative literature review.

METHODS: This is an observational study and a review of the literature focusing on two rare genetic pathologies identified simultaneously in NS from the perspective of a clinical case. The authors identified only 5 cases of SCA associated with CF. No clinical trials or review articles were identified considering the rarity of the coexistence of these two pathologies.

RESULTS: Herein, the authors reported the case of a girl who after undergoing NS on day 8 of life was diagnosed with SCA with an alteration in the dosage of immunoreactive trypsin. The diagnosis of CF was confirmed by the Coulometry Sweat Test. The rarity of the co-occurrence of these two severe genetic pathologies (CF and SCA) is a challenge for medical science.

CONCLUSION: This study adds to the few case reports present in the literature that highlight the identification of two severe diseases via NS.

PMID:40059892 | PMC:PMC11686575 | DOI:10.5409/wjcp.v14.i1.97537

J Cyst Fibros. 2025 Mar 8:S1569-1993(25)00070-0. doi: 10.1016/j.jcf.2025.03.002. Online ahead of print.

ABSTRACT

OBJECTIVES: Recent therapeutic advances, mainly with the advent of CFTR modulators, have been associated with an increasing number of pregnancies in females with cystic fibrosis (fwCF). This study aimed to evaluate the safety of the use of CFTR modulators, specifically elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) during pregnancy.

METHODS: A nationwide cohort study was conducted using the French health insurance data warehouse (SNDS), covering nearly all singleton pregnancies ending between January 2018 and December 2023. Exposure to CFTR modulators was defined as using prescriptions through pregnancy, including one month in the preconception period. The study compared pregnancy outcomes amongst fwCF between pregnancies exposed and unexposed to CFTR modulators.

RESULTS: Among 590 pregnancies in fwCF, 148 (24.7 %) were exposed to CFTR modulators, including 136 during first trimester. Of these, 147 (99.3 %) resulted in livebirths. The most common CFTR modulator used was ELX/TEZ/IVA, in 121 (81.8 %) pregnancies. The prevalence of major birth defects was similar between exposed and unexposed fwCF (3.38 % vs. 4.66 %; p = 0.72). The rate of small for gestational age (SGA, <10th percentile) was significantly lower in pregnancies exposed compared to unexposed (6.8 % vs. 16.1 %; p < 0.01).

DISCUSSION: The study provides early reassurance about the safety of CFTR modulators during pregnancy, particularly in terms of teratogenicity and adverse pregnancy outcomes. While findings suggest potential benefits, such as halved rate of SGA, further research is required to confirm these outcomes and investigate long-term effects on the development of children prenatally exposed to CFTR modulators.

PMID:40058987 | DOI:10.1016/j.jcf.2025.03.002

Methods Cell Biol. 2025;194:119-133. doi: 10.1016/bs.mcb.2024.01.007. Epub 2024 Feb 26.

ABSTRACT

Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expression in high endothelial venules is regulated by bacterial metabolites emanating from the gut and the interaction of MAdCAM-1 with α4β7 integrin mediates lymphocyte diapedesis into gut-associated secondary lymphoid tissues. MAdCAM-1 thus controls the abundance of circulating immunosuppressive T cells that can reach malignant tissue and compromise the therapeutic efficacy of anticancer immunotherapy. Here we describe a biosensor-based phenotypic assessment that facilitates the high throughput screening (HTS)-compatible assessment of MAdCAM-1 regulation in response to exposure to bacterial metabolites. This screening routine encompasses high endothelial venule cells expressing green fluorescent protein (GFP) under the control of the MAdCAM-1 promoter combined with robot-assisted bioimaging and a multistep image analysis pipeline. Altogether this system facilitates the discovery of bacterial composites that control anticancer immunity via the sequestration of Th17-specific regulatory T cells (Treg17) in the gut.

PMID:40058956 | DOI:10.1016/bs.mcb.2024.01.007

J Obstet Gynaecol Can. 2025 Mar 7:102809. doi: 10.1016/j.jogc.2025.102809. Online ahead of print.

ABSTRACT

INTRODUCTION: Survival in cystic fibrosis (CF) is increasing and more women are considering their reproductive options, however there is limited data on pregnancy and neonatal outcomes in this population. The objectives of this study were to describe maternal and neonatal outcomes in women with CF and the general Canadian maternal population (general population).

METHODS: Maternal and neonatal clinical outcomes and healthcare utilization for in-hospital live births was retrieved from the Canadian Institute for Health Information's Discharge Abstract Database. Mothers with CF were identified using the ICD-10-CA code for CF. The observation period was fiscal year (FY) 2006-2007 to FY2020-2021 for mothers with CF, and FY2019-2020 for the general population.

RESULTS: During the 15-year observation period, there were 154 newborns from 146 deliveries among 124 mothers with CF. Relative to the general population, mothers with CF were younger (median age 28 vs. 31 years), had more comorbidities, induction of labour, epidural, assisted delivery and use of assisted reproductive technologies, but fewer cesarean sections. Nearly 85% of mothers with CF delivered in a hospital that had a CF clinic. 6.8% of mothers with CF were admitted to the intensive care unit (ICU). Neonates born to mothers with CF had high rates of multiple births, preterm delivery, and jaundice. 26.6% of neonates born to mothers with CF were admitted to the neonatal ICU.

CONCLUSIONS: While no inferential analyses were done, mothers with CF and their newborns may experience worse post-delivery outcomes and may require greater use of healthcare resources than the general population.

PMID:40058495 | DOI:10.1016/j.jogc.2025.102809

Nat Commun. 2025 Mar 8;16(1):2334. doi: 10.1038/s41467-025-57532-z.

ABSTRACT

Fatty acids are a primary source of carbon for Pseudomonas aeruginosa (PA) in the airways of people with cystic fibrosis (CF). Here, we use tandem mass-tag proteomics to analyse the protein expression profile of a CF clinical isolate grown on different fatty acids. Two fatty acyl-CoA dehydrogenases (designated FadE1 and FadE2) are strongly induced during growth on fatty acids. FadE1 displays a strong preference for long-chain acyl-CoAs, whereas FadE2 exclusively utilizes medium-chain acyl-CoAs. Structural analysis of the enzymes enables us to identify residues comprising the substrate selectivity filter in each. Engineering these residues enables us to invert the substrate specificity of each enzyme. Mutants in fadE1 displayed impaired virulence in an infection model, and decreased growth on long chain fatty acids. The unique features of the substrate binding pocket enable us to identify an inhibitor that is differentially active against FadE1 and FadE2.

PMID:40057486 | DOI:10.1038/s41467-025-57532-z

Int J Antimicrob Agents. 2025 Mar 6:107488. doi: 10.1016/j.ijantimicag.2025.107488. Online ahead of print.

ABSTRACT

Hypermutable P. aeruginosa isolates frequently display resistance emergence during treatment. Mechanisms of such resistance emergence have not been explored using dynamic hollow-fiber studies and multi-omics-informed mathematical modeling. Two hypermutable and heteroresistant P. aeruginosa isolates, CW8 (MICmeropenem=8mg/L, MICtobramycin=8mg/L) and CW44 (MICmeropenem=4mg/L, MICtobramycin=2mg/L), were studied. Both isolates had genotypes resembling those of carbapenem- and aminoglycoside-resistant strains. Achievable lung fluid concentration-time profiles following meropenem at 1 or 2g every 8h (3-h infusion) and tobramycin at 5 or 10mg/kg body weight every 24h (0.5-h infusion), in monotherapy and combinations, were simulated over 8 days. Total and resistant bacterial counts were determined. Resistant colonies and whole population samples at 191h were whole-genome sequenced, and population transcriptomics performed at 1 and 191h. The multi-omics analyses informed mechanism-based modeling of total and resistant populations. While both isolates eventually displayed resistance emergence against all regimens, the high-dose combination synergistically suppressed resistant regrowth of only CW8 up to ∼96h. Mutations that emerged during treatment were in pmrB, ampR, and multiple efflux pump regulators for CW8, and in pmrB and PBP2 for CW44. At 1h, mexB, oprM and ftsZ were differentially downregulated in CW8 by the combination. These transcriptomics results informed inclusion of mechanistic synergy in the mechanism-based model for only CW8. At 191h, norspermidine genes were upregulated (without a pmrB mutation) in CW8 by the combination, and informed the adaptive loss of synergy in the model. Multi-omics information enabled mechanism-based modeling to describe the bacterial response of both isolates simultaneously. IMPORTANCE: Pseudomonas aeruginosa causes serious bacterial infections in people with cystic fibrosis (pwCF), and has numerous resistance mechanisms. Current empirical approaches to informing antibiotic regimen selection have important limitations. This study exposed two P. aeruginosa clinical isolates to concentration-time profiles of meropenem and tobramycin as would be observed in lung fluid of pwCF. The combination elicited different bacterial count profiles between the isolates, despite similar bacterial baseline characteristics. We found differences between the isolates in the expression of a key resistance mechanism against meropenem at 1h, and expression that implied a loss of cell membrane permeability for tobramycin without the expected DNA mutation. This information enabled mathematical modeling to accurately describe all bacterial profiles over time. For the first time, this multi-omics informed modeling approach using DNA and RNA data was applied to a hollow-fiber infection study. Using bacterial molecular insights with mechanism-based mathematical modeling has high potential for ultimately informing personalized antibiotic therapy.

PMID:40057138 | DOI:10.1016/j.ijantimicag.2025.107488

Tuberculosis (Edinb). 2025 Mar 4;152:102629. doi: 10.1016/j.tube.2025.102629. Online ahead of print.

ABSTRACT

Animal models that can mimic progressive granulomatous pulmonary disease (PD) due to non-tuberculous mycobacteria (NTM) have not been established in rats to date. These models could assist with the study of the pathophysiology of NTM-PD as well as the preclinical development of new therapies. In the present study, an immunocompetent rat model of progressive Mycobacterium abscessus (MABs)- PD was developed using MABs originating from a patient with cystic fibrosis. MABs was embedded in agarose beads and delivered intratracheally to the lungs of Sprague Dawley rats two times at a one-week time interval. The bacterial burden of lysed lungs, spleen and liver was assessed by calculating colony forming units (CFUs) on day 28. Lung CFUs indicated a ∼1.2-2 log10 total CFU increase compared to the initial total bacterial load instilled into the lungs. In all infected rats, multinodular granulomatous inflammatory lesions containing MABs were found in the lung. These findings support the establishment of an immunocompetent MABs PD rat model, characterised by an increase in mycobacterial burden over time and a chronic granulomatous inflammatory response to the MABs infection.

PMID:40056658 | DOI:10.1016/j.tube.2025.102629

NPJ Biofilms Microbiomes. 2025 Mar 7;11(1):40. doi: 10.1038/s41522-025-00673-2.

ABSTRACT

Cyclic diguanylate (c-di-GMP) is a central biofilm regulator in Pseudomonas aeruginosa, where increased intracellular levels promote biofilm formation and antibiotic tolerance. Targeting the c-di-GMP network may be a promising anti-biofilm approach, but most strategies studied so far aimed at eliminating surface-attached biofilms, while in vivo P. aeruginosa biofilms often occur as suspended aggregates. Here, the expression profile of c-di-GMP metabolism-related genes was analysed among 32 P. aeruginosa strains grown as aggregates in synthetic cystic fibrosis sputum. The diguanylate cyclase SiaD proved essential for auto-aggregation under in vivo-like conditions. Virtual screening predicted a high binding affinity of echinacoside towards the active site of SiaD. Echinacoside reduced c-di-GMP levels and aggregate sizes and potentiated tobramycin activity against aggregates in >80% of strains tested. This synergism was also observed in P. aeruginosa-infected 3-D alveolar epithelial cells and murine lungs, demonstrating echinacoside's potential as an adjunctive therapy for recalcitrant P. aeruginosa infections.

PMID:40055321 | DOI:10.1038/s41522-025-00673-2

Chest. 2025 Mar 5:S0012-3692(25)00272-7. doi: 10.1016/j.chest.2025.02.023. Online ahead of print.

ABSTRACT

BACKGROUND: Persistent tachypnea of infancy (PTI)/neuroendocrine cell hyperplasia of infancy (NEHI) is a form of childhood interstitial lung disease (chILD) that predominantly affects young children. Although it is one of the most common chILDs, there is no unified diagnostic approach specific to this condition.

RESEARCH QUESTION: Is there a difference in the clinical presentation and the diagnostic approach in PTI/NEHI patients between the European countries?

STUDY DESIGN AND METHODS: This was a European multicenter, retrospective, observational study. Data on clinical characteristics and diagnostic strategies in PTI/NEHI patients were analyzed and compared across participating countries.

RESULTS: The study included 378 children with PTI/NEHI from 17 countries (63.5% male, 97.4% Caucasian), diagnosed at the median age of 9 months (IQR: 6-13). The most common baseline symptoms were tachypnea, chest retractions, crackles on auscultation, hypoxemia, and failure to thrive. High-resolution computed tomography (HRCT) was performed on all patients, with most undergoing chest X-rays, echocardiography, and immunology tests. Lung biopsy was done on 23.5% of patients, with a decreasing trend over time and variation by country; its use was associated with longer diagnostic delay. Histopathology showed a hyperplasia of pulmonary neuroendocrine cells in 52.8% of cases. Genetic testing was rare, and its application varied significantly between countries. Additional investigations that do not have an established role, such as assessment for gastroesophageal reflux disease and obstructive sleep apnea, infant pulmonary function tests, and lung ultrasounds were limited to single countries.

INTERPRETATION: Diagnosis of PTI/NEHI relies on clinical symptoms and HRCT results, with lung biopsies less commonly performed. Differences exist between countries regarding the number and type of investigations. There is a need for guidelines that will uniform the diagnostic approach.

PMID:40054602 | DOI:10.1016/j.chest.2025.02.023

J Cyst Fibros. 2025 Mar 6:S1569-1993(25)00069-4. doi: 10.1016/j.jcf.2025.03.001. Online ahead of print.

ABSTRACT

Cystic fibrosis is caused by biallelic mutations in the gene encoding the CFTR conductor channel. The recent approval of the Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy has marked a milestone in the management of this disease, alleviating respiratory and digestive symptoms. However, this treatment has no impact on the increased susceptibility to bacterial infections. In this scenario, phage therapy, viruses capable of selectively targeting and killing bacteria, is an emerging option. In the exploration of phages as therapeutic agents, a crucial consideration is their interaction with host cells, especially the immune system. In a previous study, we established the anti-inflammatory effect of four selected phages using the cftr loss-of-function (LoF) zebrafish embryos. In this study, we dissected the interactions of one of them, i.e. the phage DEV, with two cell types crucial in the context of cystic fibrosis: bronchial epithelial cells carrying biallelic CFTR F508del mutation (CuFi-1) and macrophages chemically CFTR inhibited. DEV administration to both human cell types showed anti-inflammatory effects by decreasing the expression of pro-inflammatory cytokines. We further demonstrated that, when in contact with CuFi-1 cells, DEV is internalized and degraded through the lysosomal compartment. In zebrafish, we showed that DEV interacts with tissue-resident macrophages and, in turn, reduces neutrophil recruitment toward the inflammation site. This information sheds light on a previously undocumented aspect of phage therapy as a modulator of the immune response, inducing anti-inflammatory effects. This could be particularly noteworthy within the context of excessive inflammation observed in the airways of individuals with cystic fibrosis.

PMID:40055113 | DOI:10.1016/j.jcf.2025.03.001

Gene. 2025 Mar 5:149384. doi: 10.1016/j.gene.2025.149384. Online ahead of print.

ABSTRACT

BACKGROUND: Nonsense mutations in the CFTR gene are responsible for approximately 8 % of cystic fibrosis (CF) cases worldwide. The consequent premature termination of translation leads to the production of a truncated and non-functional CFTR protein. Despite the intensive research in the field, these patients cannot benefit from specific and approved therapies yet. To address this issue, in this study we evaluated a potential therapeutic strategy to overcome the nonsense G542X (UGG > UGA) mutation in the CFF-16HBEge human bronchial epithelial cells by restoring the full-length CFTR protein.

METHODS: We applied the RESTORE (Recruiting endogenous ADAR to specific transcripts for oligonucleotide-mediated RNA editing) approach, based on specifically designed antisense RNA oligonucleotides (ASOs) to recruit endogenous ADAR (adenosine deaminase acting on RNA) enzymes. The ADAR's recruitment to the target CFTR mRNA is expected to promote the deamination of adenosine (A) into inosine (I) within the premature termination codon (UGA). As the ribosome reads the inosine as guanosine (G), the stop codon could be recoded as a tryptophan (UGG), thereby allowing the synthesis of a full-length CFTR protein, albeit with a different amino acid.

RESULTS: Our results indicate that in the CFF-16HBEge G542X cell line, the transfection of a specific ASO allows the rescue of the CFTR transcript and protein expression, compared to the untransfected mutated cells. Next generation sequencing of CFTR cDNA also confirmed the occurrence of the expected RNA editing outcome.

CONCLUSIONS: The obtained results suggest that the RESTORE approach might be explored as a promising strategy to treating nonsense mutations in CFTR, potentially contributing to novel therapeutic options for CF patients.

PMID:40054708 | DOI:10.1016/j.gene.2025.149384

J Particip Med. 2025 Mar 6;17:e59686. doi: 10.2196/59686.

ABSTRACT

BACKGROUND: Newborn screening aims to identify babies affected by rare but serious genetic conditions. As technology advances, there is the potential to expand the newborn screening program following evaluation of the likely benefits and drawbacks. To inform these decisions, it is important to consider the family experience of screening and the views of the public. Engaging in public dialogue can be difficult. The conditions, screening processes, and associated moral and ethical considerations are complex.

OBJECTIVE: This study aims to develop a stand-alone online resource to enable a range of stakeholders to understand whether and how next-generation sequencing should be incorporated into the CF screening algorithm.

METHODS: Around 4 development workshops with policymakers, parents, and other stakeholders informed the design of an interactive activity, including the structure, content, and questions posed. Stakeholders were recruited to take part in the development workshops via purposeful and snowball sampling methods to achieve a diversity of views across roles and organizations, with email invitations sent to representative individuals with lived, clinical, and academic experience related to CF and screening. Ten stakeholders informed the development process including those with lived experience of CF (2/10, 20%), clinicians (2/10, 20%), and representatives from relevant government, charity, and research organizations (6/10, 60%). Vignettes constructed using interview data and translated into scripts were recorded to provide short films to represent and provoke consideration of families' experiences. Participants were recruited (n=6, adults older than 18 years) to test the resulting resource. Study advertisements were circulated via physical posters and digital newsletters to recruit participants who self-identified as having a reading difficulty or having English as a second language.

RESULTS: An open access online resource, "Cystic Fibrosis Newborn Screening: You Decide," was developed and usability and acceptability tested to provide the "user" (eg, a parent, the general public, or a health care professional) with an interactive scenario-based presentation of the potential outcomes of extended genetic testing, allowing them to visualize the impact on families. This included a learning workbook that explains key concepts and processes. The resulting tool facilitates public engagement with and understanding of complex genetic and screening concepts.

CONCLUSIONS: Online resources such as the one developed during this work have the potential to help people form considered views and facilitate access to the perspectives of parents and the wider public on genetic testing. These may be otherwise difficult to obtain but are of importance to health care professionals and policymakers.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06299566; https://clinicaltrials.gov/study/NCT06299566.

PMID:40053726 | DOI:10.2196/59686

Med Lett Drugs Ther. 2025 Mar 17;67(1724):41-43. doi: 10.58347/tml.2025.1724a.

NO ABSTRACT

PMID:40053374 | DOI:10.58347/tml.2025.1724a

Curr Gastroenterol Rep. 2025 Mar 7;27(1):20. doi: 10.1007/s11894-025-00969-5.

ABSTRACT

PURPOSE OF REVIEW: Cystic fibrosis is a chronic condition that has significant effects on the nutritional status of pediatric patients. Malnutrition is frequently encountered in this population and has been shown to contribute to poor pulmonary and overall disease outcomes. This article will provide an overview of the physiologic and psychosocial challenges toward attaining optimal nutrition in pediatric cystic fibrosis patients.

RECENT FINDINGS: Newer therapies such as CFTR modulators have played significant roles in improving the nutritional status of patients with cystic fibrosis. There is also a greater focus on becoming more aware of psychosocial and cultural barriers in the care of cystic fibrosis patients. Many challenges exist in optimizing nutritional support including but not limited to the patient's clinical manifestations and disease severity, caregiver ability, and access to care. Both gastrointestinal and non-gastrointestinal disorders lead to insufficient caloric intake, increased loss and metabolic needs, and micronutrient and macronutrient deficiency. Social factors including stressful patient and caregiver relationships and altered body image also contribute to poor nutritional status.

PMID:40053205 | DOI:10.1007/s11894-025-00969-5

Physiol Rep. 2025 Mar;13(5):e70264. doi: 10.14814/phy2.70264.

ABSTRACT

Intestinal tuft cells have recently been the focus of many studies due to their function in chemosensation and type 2 immunity in human gastrointestinal diseases. This study investigated the impact of acute tuft cell loss on intestinal physiological function. Tuft cell deletion was induced in DCLK1-IRES-GFP-CreERT2/+;Rosa-DTA (DCLK1-DTA) mice by a single tamoxifen injection, concomitant with littermate controls. Transient deletion of intestinal and biliary tuft cells was maximal on day 4 and recovered by day 7 post tamoxifen. DCLK1-DTA mice presented with significantly shortened small intestinal length and greater body weight loss by day 4. The activity of Na+-dependent glucose transporter 1 (SGLT1) and cystic fibrosis transmembrane regulator (CFTR) was reduced. Correlated with tuft cell reduction, the frequency of cholecystokinin (CCK)+ enteroendocrine and intermediate secretory cells, which co-express Paneth and goblet cell markers, was increased. In the lamina propria, fewer mast cells and leukocytes were found in the Day 4 DCLK1-DTA mice compared to controls. Ablation of tuft cells may induce nutrient malabsorption through alterations in epithelial cell proliferation and differentiation, along with changes in the mucosal defense response. These observations identify a new role for tuft cells in regulating intestinal absorption and mucosal regeneration.

PMID:40051209 | DOI:10.14814/phy2.70264

Ital J Pediatr. 2025 Mar 6;51(1):67. doi: 10.1186/s13052-025-01904-0.

ABSTRACT

BACKGROUND: Currently, there is a lack of data concerning the organization and characteristics of Italian pediatric physiotherapy units for the treatment of patients with chronic lung diseases, especially those with rare conditions such as Primary Ciliary Dyskinesia (PCD) and non-Cystic Fibrosis bronchiectasis (NCFB).

METHODS: A national descriptive study based on a survey questionnaire was conducted. The questionnaire consisted of three different sections: distribution and characteristics of the centres, services provided by respiratory therapists, physiotherapists' perception of the unit. The survey was distributed to all healthcare providers via an online platform, and a descriptive data analysis was performed.

RESULTS: The survey had a response rate of 97.5% with twenty-nine responses collected. The centers are heterogeneously distributed: thirteen in the northern regions, eight in the central regions and eight in the southern regions. Of the 29 centers with a physiotherapy unit, 19 had a specialized respiratory therapy unit. Respiratory therapy was provided in different care settings: regular wards (28/29 centers, 97%), outpatient service (29/29 centers, 100%), and intensive or semi-intensive care units (17/29 centers, 59%). The interventions provided by respiratory therapists involved more than just airway clearance (29/29). More specific interventions, such as pulmonary function tests (23/29), functional tests (27/29), educational training (26/29), management of workout exercise programs (25/29) and interventions developed in collaboration with physicians such as non-invasive ventilation (NIV) (23/29) and oxygen titration (21/29) are performed. It is interesting to note that therapists are also involved in various activities, such as telemedicine, physiotherapists' research projects, and supporting alongside physicians, for the prescription at home of medical devices. Perception of the unit was also evaluated.

CONCLUSIONS: The involved centers are heterogeneous in terms of distribution and treatments offered. The role of respiratory physiotherapists still seems to be fragmented. This first descriptive analysis of the physiotherapy units and the main differences between centers opens queries on the clinical approaches used for pediatric patients with PCD in terms of respiratory physiotherapy. However,in response to evolving treatment needs, a more specialized and standardized approach to patient care is required.

PMID:40050996 | DOI:10.1186/s13052-025-01904-0