Transl Pediatr. 2025 Jun 27;14(6):1332-1335. doi: 10.21037/tp-2024-584. Epub 2025 Jun 10.

ABSTRACT

BACKGROUND: Laparoscopic Nissen fundoplication is the standard treatment for gastroesophageal reflux disease in children. The proper dissection of the oesophagus and the hiatus is essential yet may be associated with higher morbidities in scenarios where dense adhesions obscuring a clear tissue plane were anticipated, for instance, patients with previous laparotomies, redo-fundoplication, etc. We hereby report the first experience of the novel use of a light-emitting nasogastric tube to enhance oesophageal dissection during laparoscopic fundoplication in children.

CASE DESCRIPTION: In this case report, we report a four-year-old girl with known cystic fibrosis who required supplemental milk to improve nutrition and medications administered via a nasogastric tube. Since long-term tube feeding was expected, the patient's parents were advised of the need for gastrostomy tube insertion and a pre-operative potential of hydrogen (pH) study. The 24-hour pH study revealed significant gastroesophageal reflux; therefore, laparoscopic fundoplication and gastrostomy were planned. An infrared illumination system urethral kit was put inside a feeding tube for identification of the boundary of the intra-abdominal oesophagus and aiding dissection in real time. Laparoscopic fundoplication and gastrostomy were smoothly performed. The patient resumed feeding 1 day after the procedure and was fit for discharge 3 days after the operation.

CONCLUSIONS: Light-emitting nasogastric tube is safe and potentially facilitates oesophageal dissection during laparoscopic fundoplication in children.

PMID:40688215 | PMC:PMC12268702 | DOI:10.21037/tp-2024-584

PNAS Nexus. 2025 Jul 4;4(7):pgaf211. doi: 10.1093/pnasnexus/pgaf211. eCollection 2025 Jul.

ABSTRACT

Cystic fibrosis (CF) is a genetic disorder resulting from mutations to the CF transmembrane regulator (CFTR) anion channel. CFTR correctors partially restore the folding and trafficking of mutant CFTR. We recently demonstrated that the correctors VX-445 and VX-121 directly potentiate large-conductance Ca2+-activated (BKCa) channels. We postulated that this could enhance the therapeutic potential of these drugs in the lung by increasing the driving force for transepithelial Cl- secretion. Herein, we evaluated the effect of acute addition of VX-445 on forskolin- and 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one-mediated Cl- secretion across primary human bronchial epithelial cells (HBEs) from wild type (WT) and F508del donors. Surprisingly, VX-445 (10 µM) induced a significant inhibition of forskolin-stimulated Cl- secretion in WT and F508del donor HBEs with corrected CFTR. We hypothesized that this was due to inhibition of the basolateral membrane Ca2+-activated K+ channel, KCa3.1 that maintains the driving force for Cl- secretion. Thus, we utilized patch-clamp techniques to evaluate VX-445 effects on isolated KCa3.1 currents. We demonstrate that VX-445 directly inhibits KCa3.1, as do similar molecules VX-659 and VX-121; however, only VX-659 inhibited KCa2.3 and KCa2.2 with a similar affinity to KCa3.1. To summarize, acute addition of CFTR correctors to HBEs reduces transepithelial Cl- secretion due to inhibition of KCa3.1.

PMID:40688096 | PMC:PMC12275099 | DOI:10.1093/pnasnexus/pgaf211

Front Microbiomes. 2024;3:1366948. doi: 10.3389/frmbi.2024.1366948. Epub 2024 Jun 2.

ABSTRACT

INTRODUCTION: The microbial interactions within the human microbiome are complex, and few methods are available to identify these interactions within a longitudinal microbial abundance framework. Existing methods typically impose restrictive constraints, such as requiring long sequences and equal spacing, on the data format which in many cases are violated.

METHODS: To identify microbial interaction networks (MINs) with general longitudinal data settings, we propose a stationary Gaussian graphical model (SGGM) based on 16S rRNA gene sequencing data. In the SGGM, data can be arbitrarily spaced, and there are no restrictions on the length of data sequences from a single subject. Based on the SGGM, EM-type algorithms are devised to compute the L1-penalized maximum likelihood estimate of MINs. The algorithms employ the classical graphical LASSO algorithm as the building block and can be implemented efficiently.

RESULTS: Extensive simulation studies show that the proposed algorithms can significantly outperform the conventional algorithms if the correlations among the longitudinal data are reasonably high. When the assumptions in the SGGM areviolated, e.g., zero inflation or data from heterogeneous microbial communities, the proposed algorithms still demonstrate robustness and perform better than the other existing algorithms. The algorithms are applied to a 16S rRNA gene sequencing data set from patients with cystic fibrosis. The results demonstrate strong evidence of an association between the MINs and the phylogenetic tree, indicating that the genetically related taxa tend to have more/stronger interactions. These results strengthen the existing findings in literature.

DISCUSSION: The proposed algorithms can potentially be used to explore the network structure in genome, metabolome etc. as well.

PMID:40687607 | PMC:PMC12276884 | DOI:10.3389/frmbi.2024.1366948

EClinicalMedicine. 2025 Jul 8;85:103334. doi: 10.1016/j.eclinm.2025.103334. eCollection 2025 Jul.

ABSTRACT

BACKGROUND: Portable ex vivo lung perfusion and ventilation with the Organ Care System (OCS) Lung system is a safe, effective method for preserving extended criteria donor (ECD) organs before transplant. Although this technology is increasingly used in the United States, no published data describe its effects on long-term graft function and patient outcomes. This study assessed long-term clinical outcomes after transplantation of ECD lungs that were preserved, recruited, and assessed with the OCS Lung.

METHODS: The EXPAND Lung Trial was a prospective, single-arm, multicenter, international trial conducted between January 2014 and July 2016; 5-year follow-up data were collected until December 2021. Double-lung donors were included who met any of four ECD criteria: age ≥55 years, PaO2/FiO2 ≤300 mmHg, expected ischemic time >6 h, and donation after circulatory death (DCD). Transplant recipients' overall survival and 5-year incidence of bronchiolitis obliterans syndrome (BOS) were compared between the EXPAND cohort (n = 79) and a control cohort from the same centers within the same time period, who received donor lungs preserved with ice but not OCS (n = 644). This study is registered with ClinicalTrials.gov (NCT04194398).

FINDINGS: Overall survival was similar between the EXPAND and control cohorts; 5-year overall survival was 68.1% versus 66.5%, respectively (P = 0.795). The risk factors associated with overall survival were the degree of urgency for lung transplant and recipient age; 5-year survival was much greater for patients designated as non-urgent than for patients designated as urgent (73% versus 41%, P = 0.021). 5-Year BOS3-free survival was 60.4% for the EXPAND cohort and 63.7% for the control cohort (P = 0.599). Overall survival, development of BOS3, and development of any grade of BOS did not differ between the EXPAND and control cohorts.

INTERPRETATION: Among patients who underwent lung transplantation with ECD lungs, the use of OCS Lung resulted in excellent long-term clinical outcomes. This study's findings support the use of OCS Lung to expand the donor pool and provide a foundation for future studies comparing lung-preservation strategies.

FUNDING: This study was funded by TransMedics.

PMID:40686680 | PMC:PMC12273511 | DOI:10.1016/j.eclinm.2025.103334

Heart Lung. 2025 Jul 19:S0147-9563(25)00157-8. doi: 10.1016/j.hrtlng.2025.07.008. Online ahead of print.

ABSTRACT

BACKGROUND: As most cystic fibrosis (CF) patients progress to respiratory failure, lung functionality assessment is pivotal. We previously developed a test that monitors airways measuring the spin-spin relaxation time (T2m) of water hydrogens present in sputum using Low Field-Nuclear Magnetic resonance (LF-NMR).

OBJECTIVES: To investigate further the significance of T2m exploring: 1) T2m correlation with the effects of chest physiotherapy (CP); 2) the influence of sputum contamination by saliva on T2m; 3) T2m relation with sputum mesh size; 4) T2m correlation with the effects of the CFTR-modulator Elexa-caftor/Tezacaftor/Ivacaftor (ETI).

METHODS: T2m was measured in the sputum of 16 CF-patients before/after CP and in 9/16 patients before/after ETI administration. FEV1/C reactive protein (CRP)/erythrocyte-sedimentation rate (ESR) and sweat chloride concentration were measured using standard techniques. Sputum contamination by saliva/sputum mesh size were determined mathematically.

RESULTS: We prove that T2m can be used to detect the lack of significant effects on lung function by CP (confirmed by FEV1). Moreover, we developed of a mathematical approach to correct T2m value in sputum samples contaminated by saliva and to determine the relationship between T2m and sputum mesh size. Finally, we show that T2m can effectively detect the positive effects of ETI on lung function (evaluated by FEV1) and that T2m inversely correlates with the CRP/ESR/chloride sweat concentration.

CONCLUSION: This data strengthens the rationale for T2m employment in CF lung disease monitoring and show that T2m can be profitably used to complement the FEV1 test.

PMID:40685258 | DOI:10.1016/j.hrtlng.2025.07.008

J Control Release. 2025 Jul 18:114053. doi: 10.1016/j.jconrel.2025.114053. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a severe monogenic disease characterized by debilitating lung dysfunction caused by loss-of-function mutations in the CFTR gene. While CRISPR-based gene editing holds promise for correcting these mutations and potentially curing CF, efficient delivery of gene editors to the lung epithelium through the mucosal barrier remains a major challenge. In this study, we developed a lung-optimized gene editing strategy using lipid nanoparticles (LNPs) and evaluated it in increasingly complex, biomimetic human-based and patient-derived models. Systematic optimization of helper lipids, genetic cargo, guide RNA modifications, and gene editor ratios, alongside analysis of innate immune responses, achieved ~50 % editing efficiency in the model gene HPRT in two-dimensional models. Editing efficiency significantly dropped to ~5 % in biomimetic three-dimensional CF bronchial epithelial tissue models following topical LNP application. Pretreatment with the approved mucolytic agent dornase alpha increased editing efficiency to ~12.7 %. Finally, in CF patient-derived cells harboring the CFTRR1162X mutation, our optimized LNP formulation achieved ~12 % correction on gene level, offering a potential treatment avenue for this yet untreatable mutation. Taken together, this study demonstrates that optimizing the genetic cargo as well as the delivery vehicle is key when striving for clinically applicable treatment approaches. It further provides insights into gene editing rates in human-based normal and CF patient-derived bronchial tissue models which express all relevant biological barriers and, thus, can pave the way for topically applicable treatment options for patients with CF and other genetic lung diseases.

PMID:40684992 | DOI:10.1016/j.jconrel.2025.114053

J Cyst Fibros. 2025 Jul 17:S1569-1993(25)01525-5. doi: 10.1016/j.jcf.2025.07.002. Online ahead of print.

ABSTRACT

INTRODUCTION: Infection is a primary cause of progressive pulmonary disease in people with cystic fibrosis (pwCF). Researchers frequently utilize data registries or centre-based cohort studies to study infections in CF. We examine challenges encountered in conducting two multi-centre non-interventional investigator-led cohort studies undertaken a decade apart.

METHODS: The Australian Clonal Pseudomonas Study (ACPinCF, 1294 participants) and the National NTM in CF study (1314 participants) leveraged clinical practice, with data was supplied by clinics and the Australian CF Data Registry. Diagnostic laboratories performed cultures according to local protocols.

RESULTS: Site approval times were lengthy; 16 months for the ACPinCF study and between 21-44 months for the National NTM in CF study. The latter required individual contract negotiation with each clinical site as a requirement of governance approval. Changing clinical demands and unforeseen challenges such as the SARS-CoV-2 pandemic significantly impacted the NTM study. Despite these challenges, participant retention remained robust, with minimal loss to follow-up. Changes in CF centre leadership and health service policy on cost-recovery for research participation further exacerbates the challenges of maintaining longitudinal cohort CF studies.

CONCLUSIONS: Conducting and sustaining longitudinal non-interventional studies present significant challenges. Even after costs for centre participation, sample processing, data curation, data analysis and results output are covered by grant funding, these studies will still heavily depend on significant support provided by the centres without substantial funding.

PMID:40681450 | DOI:10.1016/j.jcf.2025.07.002

Qual Life Res. 2025 Jul 18. doi: 10.1007/s11136-025-04021-x. Online ahead of print.

ABSTRACT

PURPOSE: Informal carers of people with cystic fibrosis (PwCF) play a critical role in care provision, yet the impact of caregiving on their quality of life (QoL) remains underexplored. We aimed to assess the effect of caregiver burden on the quality of life of informal caregivers of people with cystic fibrosis in the UK.

METHODS: We conducted a cross-sectional online survey study administering a structured questionnaire with four validated measures (EQ-5D-5L, CarerQol-7D, ReQoL-10 and ASCOT-Carer). We used a carer-reported severity scale of cystic fibrosis to define severity groups. Statistical methods included descriptive analyses and ordinary least squares (OLS) regression to examine the association between carer utility and CF severity.

RESULTS: We find significant decrements in carers' quality of life due to their care burden, with the most affected dimensions being mental health (79% of carers reported some anxiety or depression) and social health (60% reported negative impacts on social contact). We find this QoL to be significantly worse for those caring for people with severe CF compared to those with mild CF (-0.03 to -0.1), for the majority of the measures used (EQ-5D, ReQoL-10 and CarerQol-7D).

CONCLUSION: Our paper shows the negative impact on QoL for carers of PwCF, correlated with increasing CF severity due to their carer duties, and the negative impacts on their various health aspects, especially mental health. This indicates the importance of including carer QoL and additional measures to fully capture burden in health technology assessments (HTA) for CF.

PMID:40679537 | DOI:10.1007/s11136-025-04021-x

JHLT Open. 2025 Jun 18;9:100323. doi: 10.1016/j.jhlto.2025.100323. eCollection 2025 Aug.

ABSTRACT

The year 2025 marks an important landmark: almost 40 years since the first pediatric lung transplant (LTX), over 3-5 years since the availability of elexacaftor/tezacaftor/ivacaftor in several countries, and 5-10 years since striking shifts were reported in the diagnoses that accounted for pediatric LTX. We review historic indications for pediatric LTX, highlighting shifts in these over time, and analyze data from the ISHLT International Thoracic Organ Transplant Registry, United Network of Organ Sharing, Canadian Cystic Fibrosis (CF) Registry, and other databases up to the present day. Currently, pediatric CF-related LTX cases are at record lows in many countries. Non-retransplant bronchiolitis obliterans seems to be on the rise as a transplant indication in pediatrics, which is particularly true in the younger age group per ISHLT data. Childhood interstitial lung disease is increasing as an indication, especially in North America. Idiopathic pulmonary arterial hypertension (IPAH) and pulmonary hypertension as a whole now account for record highs as indications for pediatric LTX around the world, with IPAH alone now accounting for nearly 20% of pediatric LTX in the United States, for instance. This information will help guide future international pediatric thoracic transplant consensus guidelines around candidate selection and optimization, placing more emphasis on non-CF considerations.

PMID:40678364 | PMC:PMC12270605 | DOI:10.1016/j.jhlto.2025.100323

Adv Healthc Mater. 2025 Jul 17:e2501776. doi: 10.1002/adhm.202501776. Online ahead of print.

ABSTRACT

The biliary system is vital to hepatobiliary function, yet diseases like primary sclerosing cholangitis, biliary atresia, cystic fibrosis, and cholangiocarcinoma remain poorly understood due to the limitations of traditional two-dimensional (2D) cell cultures and animal models, which fail to replicate complex human biliary physiology. Biliary organoids, an innovative three-dimensional (3D) in vitro model, have emerged to bridge this gap, closely mimicking tissue structure and function. This review systematically summarizes the construction methods of biliary organoids-matrix-independent methods and matrix-dependent methods, as well as tissue engineering-based strategies, such as bioprinting and microfluidics-and cell sources, including primary tissues, pluripotent stem cells, and tumor-derived cells. It also explores the potential roles of key signaling pathways that drive biliary development and disease in guiding cell differentiation, proliferation, and tissue organization during biliary organoid construction. It explores recent applications in disease modeling and clinical translation, leveraging gene editing, chemical induction, inflammatory stimulation, and co-culture systems. Despite their potential, challenges persist in model stability, long-term culture, and immune microenvironment simulation. Future advances, integrating multi-omics, dynamic culture systems, and emerging bioengineering technologies, promise to enhance physiological relevance. Biliary organoids are poised to transform fundamental research, drug screening, and personalized medicine, accelerating clinical breakthroughs in hepatobiliary disease management.

PMID:40677219 | DOI:10.1002/adhm.202501776

J Pediatr Gastroenterol Nutr. 2025 Jul 18. doi: 10.1002/jpn3.70097. Online ahead of print.

ABSTRACT

OBJECTIVES: Despite advances in the management of ambulatory paediatric ulcerative colitis (UC), challenges remain as many patients are refractory to therapy and some require colectomy. The aim of these guidelines is to provide an update on optimal care for UC through detailed recommendations and practice points.

METHODS: These guidelines are an update to those published in 2018 and are a joint effort of the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation. An extensive literature search with subsequent evidence appraisal using the Oxford methodology was performed, followed by three online voting sessions and a consensus face-to-face meeting. Thirty-nine recommendations and 77 practice points were endorsed by the 25 experts with at least an 84% consensus rate.

RESULTS: Robust evidence-based recommendations and detailed practice points are provided. In addition to reemphasising and updating the role of more 'traditional' UC therapies, these guidelines outline optimising the use of antitumour necrosis factor therapies and integrating newer biologics and small molecules, as well as supportive therapy, to improve outcomes and provide an updated management algorithm. Measurement and monitoring tools and decision aids are provided, and additional aspects, including nutritional support, extraintestinal manifestations, pouchitis, inflammatory bowel disease-unclassified and patient support, are discussed. Some aspects, including surgery and thromboprophylaxis, are covered in the acute severe UC guidelines.

CONCLUSIONS: These guidelines serve as an aid in managing children with UC through a combination of evidence-based recommendations and more practical practice points in the ambulatory setting.

PMID:40677018 | DOI:10.1002/jpn3.70097

J Cyst Fibros. 2025 Jul 16:S1569-1993(25)01522-X. doi: 10.1016/j.jcf.2025.06.008. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to assess unmet needs of pwCF in the earthquake zone by income level.

METHODS: Following the February 6, 2023 Earthquake in Turkiye, the shorter version of the 'Your Current Life Situation' (YCLS) survey was adapted for post-earthquake conditions. The adapted YCLS was administered through face-to-face interviews at participants in seven earthquake-affected provinces to determine the insecurity areas and unmet needs in pwCF. Parents completed the survey for those pwCF under 18 years old; those over 18 completed it themselves.

RESULTS: Among 255 participants, 91.7% (n=234) had incomes below the poverty threshold and 71.8% (n=183) below the hunger threshold. Post-earthquake, 69% (n=176) lived in overcrowded conditions and 37.6% (n=96) relocated to temporary housing. Under these challenging circumstances, 34.5% (n=88) of pwCF experienced disruptions in routine visits, and 20.8% (n=53) reported disruption in daily CF care routine. Financial and food insecurities were prevalent, with 77.3% (n=197) and 53.3% (n=136) of participants affected, respectively. The potential impact of earthquake-induced relocation on the participants' insecurity status was analyzed. Among those who relocated, financial, transportation, and housing insecurity appeared to be more prevalent (p<0.001).

CONCLUSION: This is the first study to analyze association between income level and unmet needs among pwCF living in earthquake-affected zone. The study revealed significant financial and food insecurity among pwCF in these areas. The findings emphasize the need for disaster-specific emergency action plans to address these vulnerabilities, ensuring access to healthcare and basic needs during crises.

PMID:40675865 | DOI:10.1016/j.jcf.2025.06.008

BMJ. 2025 Jul 17;390:r1501. doi: 10.1136/bmj.r1501.

NO ABSTRACT

PMID:40675624 | DOI:10.1136/bmj.r1501

Exp Physiol. 2025 Jul 17. doi: 10.1113/EP092423. Online ahead of print.

ABSTRACT

Computed cardiopulmonography (CCP) is a technique that measures lung volumes (functional residual capacity and deadspace) together with novel parameters reflecting lung inhomogeneities (non-uniformities in lung inflation and deadspace path length). First, highly precise measurements of gas exchange are made during a nitrogen washout with a purpose-built molecular flow sensor. Second, an individual's lung physiology is then described by personalising the parameters of a bespoke cardio-respiratory model obtained by fitting the model to the data. The present study examines the effects of participants' physical characteristics on these parameter values, and from this also provides preliminary estimates for normal ranges. Data from 92 healthy individuals (27% female, age 40 ± 19 (mean ± SD) years, height 1.75 ± 0.09 m, mass 74 ± 14 kg) were used. A prediction equation for each CCP parameter was written as: y = α + βln(age) + γln(height) + δln(BMI) + ε(is_Female) + error, where BMI is body mass index. Non-significant terms (P > 0.1) were removed sequentially to identify just the significant characteristics. Physical characteristics exerted a large influence on volume-related CCP parameters. In contrast, only age had a significant influence on inhomogeneity-related CCP parameters. The prediction equations, together with their mean squared errors, were used to calculate z-scores for CCP data from three previously published studies in asthma, chronic obstructive pulmonary disease, and early cystic fibrosis. Values for these z-scores often lay beyond those commonly used to define a normal range (±1.65). In conclusion, reference values for inhomogeneity-based CCP parameters may only need correcting for age, and often appear as abnormal in airways disease.

PMID:40673629 | DOI:10.1113/EP092423

Crit Rev Clin Lab Sci. 2025 Jul 17:1-11. doi: 10.1080/10408363.2025.2527288. Online ahead of print.

ABSTRACT

Over the past 60 years, preventative public health screening programs have evolved since their inception and now include newborn screening (NBS) aimed at identifying infants after birth for a number of rare, congenital, inherited diseases. Most of the conditions detected through NBS are autosomal recessive disorders or exhibit X-linked inheritance, meaning that family members of individuals with these conditions have a higher risk for being either affected or obligate heterozygotes. For example, the X-linked adrenoleukodystrophy (X-ALD) in the screening panel identifies affected newborns and asymptomatic relatives through subsequent testing. Thus, NBS becomes a gateway to family-wide prevention, through the application of reverse cascade testing (RCS). In this paper we examined the scenarios where RCS may be appropriate. Accordingly, we have identified a list of criteria assessing whether a NBS disease would benefit from RCS: (1) autosomal recessive or X-linked inheritance; (2) high carrier rates, (3) variable expressivity, (4) mild or late-onset forms; and (5) association with diagnostic delays and recent addition to the screening panel. More than one criterion usually needs to be met for a disease to benefit from RCS. We have identified a list of diseases and highlighted the potential benefits of RCS: X-ALD, Cystic Fibrosis, Sickle Cell Disease, Spinal Muscular Atrophy and Pompe disease. There are additional scenarios within NBS where disease maternal conditions (3-methylcrotonyl-CoA carboxylase deficiency and carnitine uptake deficiency) or nutritional maternal conditions (vitamin B12 deficiency) may cause a screen-positive NBS result. Whenever a maternal nutritional deficiency is a potential reason for a positive NBS, this is indicative of a non-inherited condition that may require treatment in the newborn owing to possible neurological damage and delay in normal growth in newborns with certain secondary deficiencies. For these cases RCS is recommended, as the mother's status may put her at risk for future adverse events (i.e. cardiovascular and musculoskeletal disorders, hepatic involvement, and neurodegeneration). The RCS-NBS strategy discussed in this paper offers a set of criteria against which diseases can be assessed for the potential need for RCS. Implementation of this strategy requires several considerations including educational needs, ethical issues, uptake of testing, logistics and costs for this expanded screening and counseling, and availability of appropriate specialists for ongoing management.

PMID:40673334 | DOI:10.1080/10408363.2025.2527288

J Clin Transl Endocrinol. 2025 Jun 23;41:100403. doi: 10.1016/j.jcte.2025.100403. eCollection 2025 Sep.

ABSTRACT

Cystic fibrosis-related diabetes (CFRD) is the most prevalent extrapulmonary comorbidity in CF. While insulin remains the standard treatment, increasing rates of overweight and obesity due to CFTR modulators highlight the need for new therapies. SGLT2 inhibitors, effective in type 2 diabetes, have not been studied in CFRD. This case series presents eight CFRD patients treated with SGLT2 inhibitors alongside insulin for one year. Half had BMI reductions (1.33-2.89 kg/m2); others had increases. Glycemic control improved in six, worsened in two due to insulin nonadherence. Insulin adjustments showed no pattern. One patient discontinued due to genital infections; overall tolerance was high.

PMID:40672774 | PMC:PMC12264597 | DOI:10.1016/j.jcte.2025.100403

bioRxiv [Preprint]. 2025 Jul 8:2025.07.08.663034. doi: 10.1101/2025.07.08.663034.

ABSTRACT

Acute respiratory viral infections are an important driver of morbidity and mortality in people with chronic lung disease and are frequently associated with pulmonary exacerbations and a transition from intermittent to chronic bacterial infection of the airways. Chronic Pseudomonas aeruginosa infections are associated with worsened lung function, poor outcomes, and increased hospital visits. We sought to improve understanding of the effects of respiratory viral infections and host immune response on the resident bacterial community of the airways, using cystic fibrosis as a model. We performed an observational longitudinal study of 38 adults with CF and collected sinus and sputum samples at 6-month intervals from 2017 - 2021. We performed 16S rRNA amplicon sequencing to characterize the airway microbiota, real-time RT-PCR for viral infection detection, and cytokine quantification. We observed viral positivity rates of 19% and 14% in sinus and sputum samples, respectively. Human rhinovirus was the most frequently observed viral pathogen in both sinus and sputum samples. We measured a significant perturbance of the bacterial community during viral infection that did not return to baseline following resolution of the viral infection. This perturbation was driven by a significant increase in Pseudomonas relative abundance during viral infection. Furthermore, we found significant associations with increased Pseudomonas relative abundance for several pro-inflammatory and antiviral cytokines, including interleukin (IL)-2, IL-8, and interferon (IFN)- λ 1. These findings indicate an important role for respiratory viral infections and the host immune response in the development and maintenance of chronic Pseudomonas infections in the context of CF airway disease and broadly expand our understanding of viral-bacterial coinfection of the airways.

IMPORTANCE: Respiratory infections are a leading cause of morbidity and mortality worldwide, and co-infections are associated with worsened disease outcomes. In viral-bacterial co-infection, clinical and mechanistic studies show that a preceding acute respiratory viral infection promotes the establishment and exacerbation of bacterial infections, leading to increased morbidity. Although people with cystic fibrosis do not experience more frequent acute respiratory viral infections, their outcomes are worse, with prolonged symptoms and hospitalizations. When examining how acute viral infections shape the microbiota in the respiratory tract of pwCF, we observe a disturbance of the microbial community composition during viral infections that does not return to baseline after the acute viral infection resolves. Moreover, we show that Pseudomonas relative abundance is significantly increased in the airways of pwCF during viral infection and that increased concentrations of antiviral cytokines - such as interferon (IFN)- λ 1 - are associated with increased Pseudomonas abundance. These findings offer evidence that the progression of chronic Pseudomonas infections in pwCF are influenced by acute respiratory viral infections and the subsequent antiviral response in the airways. This study furthers our understanding of viral-bacterial coinfection in the context of CF.

PMID:40672159 | PMC:PMC12265526 | DOI:10.1101/2025.07.08.663034

Pediatr Pulmonol. 2025 Jul;60(7):e71210. doi: 10.1002/ppul.71210.

ABSTRACT

BACKGROUND: Cystic Fibrosis Bone Disease (CFBD) is a known complication in children with CF and may cause serious problems in adulthood or transplantation processes. This study aimed to identify potential predictable risk factors for the development of low BMD by evaluating pediatric patients screened with DXA as a "Heart-Lung Transplantation Center" and created new strategic plans to improve our CFBD screening program by evaluating our results in literature and guidelines recommendations.

METHODS: This retrospective cohort study includes 86 children ages 6-18 years with CF who underwent at least one DXA scan between August 2016 and October 2024. Participants were compared according to BMD z scores and the relationship between BMD and disease-related parameters was evaluated.

RESULTS: The rate of DXA screening in our center was 81.1% over 8 years of age and 72.8% over 6 years of age. 41.8% of our population had abnormal BMD (z scores < -1), and the rate of very low BMD (z scores < -2) was 17.4%. The frequency of abnormal BMD was higher in children with BMI< 50th percentile, SKS ≤ 70, low FEV1 z score, respiratory microorganism colonization, ≥ 2 annual pulmonary exacerbations, required respiratory support, low albumin, and high CRP levels. Systemic inflammation marker CRP increase was the most predictable parameter for low BMD.

CONCLUSION: This study informs clinical practice by highlighting the need for multidisciplinary interventions, such as earlier evaluation of DXA scans due to the risk factors and poor clinical conditions, a consistent follow-up protocol, individualized nutrition programs with the dietitian, and enhanced physical therapy.

PMID:40671433 | DOI:10.1002/ppul.71210

Pediatr Pulmonol. 2025 Jul;60(7):e71200. doi: 10.1002/ppul.71200.

ABSTRACT

BACKGROUND: With routine newborn screening for cystic fibrosis (CF) now considered standard of care, the designation of CFTR Related Metabolic Syndrome (CRMS) or CF screen positive, indeterminate diagnosis (CFSPID) has been established. The majority of CRMS/CFSPID patients remain asymptomatic; however, 3.8%-44% of these patients may progress to a diagnosis of CF. This raises the question of how to optimally manage CRMS/CFSPID patients. We set out to gain a better understanding of the past practices employed at CF centers across Canada in the care of patients with a diagnosis of CRMS/CFSPID.

METHODS: An invitation to participate in an online survey was disseminated to CF centers in Canada through the REDCap database. The survey was completed in 2018. It included questions addressing patient population, timing of follow-up of CRMS/CFSPID patients, and details around specific investigations ordered.

RESULTS: Twelve out of 20 qualifying clinics completed the survey. The total patient population compiled included 1412 patients, of which 171 (12%) were classified as CRMS/CFSPID. There was wide variability in the timing of follow-up with a median (IQR) of 6 (5.25-12) months and a range of 3-12 months. There was also wide variability in the timing of repeat investigations such as sweat chloride, respiratory cultures, chest x-rays and spirometry.

CONCLUSIONS: With current evidence showing that a considerable number of CRMS/CFSPID patients may progress to CF, ensuring these patients are identified as early as possible and followed in a consistent manner is essential. The Cystic Fibrosis Foundation and European Cystic Fibrosis Society have recently developed guidelines regarding the care of these patients. This survey describes historical practices for follow up of CRMS/CFSPID patients to help inform the development of Canadian consensus guidelines.

PMID:40671429 | DOI:10.1002/ppul.71200

Microbes Infect. 2025 Jul 14:105546. doi: 10.1016/j.micinf.2025.105546. Online ahead of print.

ABSTRACT

Staphylococcus aureus infections remain a great concern in people with cystic fibrosis also after the introduction of modulator therapy. Here we describe the state of the art of traditional and novel therapeutic strategies to fight both acute and chronic infections caused by sensitive and drug resistant strains.

PMID:40669745 | DOI:10.1016/j.micinf.2025.105546