Stem Cell Res. 2025 Jan 6;83:103653. doi: 10.1016/j.scr.2025.103653. Online ahead of print.

ABSTRACT

Cystic Fibrosis (CF) is a life-shortening disease that is caused by mutations in the CFTR gene, a gene that is expressed in multiple organs. There are several primary tissue models of CF disease, including nasal epithelial cultures and rectal organoids, that are effective in reporting the potential efficacy of mutation-targeted therapies called CFTR modulators. However, there is the well-documented variation in tissue dependent, therapeutic response amongst CF patients, even those with the same CF-causing mutation. Hence, there is an interest in developing strategies for comparing therapeutic efficacy in different organs relative to isogenic controls. In this study, we evaluated the CFTR chloride channel response to the highly effective CFTR modulator: Trikafta, in CF patient specific, iPSC-derived colonic and airway cultures relative to mutation-corrected (non-CF) tissues from that same individual. We measured pharmacological rescue in both tissues. This proof-of-concept study provides a roadmap for future comparisons of patient-specific CF therapeutic responses in both pulmonary and extra-pulmonary systems.

PMID:39793274 | DOI:10.1016/j.scr.2025.103653

Antimicrob Agents Chemother. 2025 Jan 10:e0104024. doi: 10.1128/aac.01040-24. Online ahead of print.

ABSTRACT

Tobramycin dosing in patients with cystic fibrosis (CF) is challenged by its high pharmacokinetic (PK) variability and narrow therapeutic window. Doses are typically individualized using two-sample log-linear regression (LLR) to quantify the area under the concentration-time curve (AUC). Bayesian model-informed precision dosing (MIPD) may allow dose individualization with fewer samples; however, the relative performance of these methods is unknown. This single-center retrospective analysis included adult patients with CF receiving tobramycin from 2015 to 2022. Tobramycin concentrations were predicted using LLR or Bayesian estimation with two population PK models (Hennig and Alghanem). Then, both methods were used to estimate the AUC for simulated patients. For Bayesian estimation, AUC estimation with flattened priors and limited sampling strategies were also assessed. Predictions were evaluated using normalized root mean square error (nRMSE), mean percent error (MPE), and accuracy. The data set included 70 treatment courses, with 32 not evaluable by LLR due to detection limits or timing issues. Bayesian estimation demonstrated worse accuracy (47.1%-50.7% vs 75.7%), higher MPE (24.2%-32.4% vs -2.4%), and higher nRMSE (35.0%-39.4% vs 24.8%) than LLR for peak concentrations but performed better on troughs (accuracy: 92.0%-92.9% vs 84.6%). Bayesian estimation with flattened priors and a single sample at 4 h was comparable to LLR performance, with better accuracy (42.9%-68.0% vs 41.1% LLR), comparable MPE (-2.3% to -3.7% vs -0.5%) and nRMSE (11.3%-21.6% vs 17.3%). Bayesian estimation with one concentration and flattened priors can match LLR prediction accuracy. However, popPK models must be improved to better estimate peak samples.

PMID:39791873 | DOI:10.1128/aac.01040-24

Healthcare (Basel). 2024 Dec 24;13(1):4. doi: 10.3390/healthcare13010004.

ABSTRACT

Background/Objectives: Exercise for children with cystic fibrosis leads to well-known health benefits. However, maintaining regular activity is challenging due to the daily demands of academics, clinical care, and family tasks. Home-based exercise programs offer a more adaptable alternative, fitting into family schedules. This study evaluated the effectiveness of the "KidMove" program, a parent-supervised, tailored, home exercise regimen. Methods: A quasi-experimental study was conducted with an intervention group (IG) and a wait-list control group (CG). The "KidMove" program lasted 12 weeks and included 35 exercises targeting endurance, resistance, flexibility, and neuromotor training. The primary outcome, endurance, was measured with the Modified Shuttle Walking Test, while secondary outcomes included body composition, resistance, flexibility, postural control, respiratory function, and health-related quality of life. Data were collected at baseline and post-intervention. A per-protocol analysis was conducted with generalized estimating equations (GEEs). Results: Forty-six children aged 10 ± 4 years (6 to 18 years), mostly male (n = 24; 52.2%), participated. Significant improvements were observed in the Modified Shuttle Walking Test [Wald χ2 = 14.24, p < 0.001], postural control [Wald χ2 = 3.89, p = 0.048], knee flexibility [Wald χ2 = 5.58, p = 0.018], and emotional functioning [Wald χ2 = 9.34, p = 0.002] categories. Conclusions: The "KidMove" program offers a practical, family friendly alternative to center-based exercise by empowering parents to support their children's physical activity at home, endurance, flexibility, and emotional well-being, while reducing the logistical challenges.

PMID:39791611 | DOI:10.3390/healthcare13010004

Hum Gene Ther. 2025 Jan 10. doi: 10.1089/hum.2024.215. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). While gene therapy holds promise as a cure, the cell-type-specific heterogeneity of CFTR expression in the lung presents significant challenges. Current CF ferret models closely replicate the human disease phenotype but have limitations in studying functional complementation through cell-type-specific CFTR restoration. To address this, we developed a new transgenic ferret line, CFTRint1-eGFP(lsl), in which a Cre-recombinase (Cre)-excisable enhanced fluorescent protein (eGFP) reporter cassette is knocked in (KI) to intron 1 of the CFTR locus. Breeding this reporter line with CFTRG551D CF ferret resulted in a novel CF model, CFTRint1-eGFP(lsl)/G551D, with disease onset manageable via the administration of CFTR modulator VX770. In this study, we confirmed two key properties of the CFTRint1-eGFP(lsl)/G551D CF ferrets: (1) cell-type-specific expression of the CFTR(N-24)-eGFP fusion protein, driven by the intrinsic CFTR promoter, in polarized epithelial cultures and selected tissues, and (2) functional reversion of the KI allele via Cre-mediated excision of the reporter cassette. This model provides a valuable tool for studying the effects of targeted CFTR reactivation in a cell-type-specific manner, which is crucial for enhancing our understanding of CFTR's roles in modulating airway clearance and innate immunity, and for identifying relevant cellular targets for CF gene therapy.

PMID:39791230 | DOI:10.1089/hum.2024.215

Am J Rhinol Allergy. 2025 Jan 10:19458924241311354. doi: 10.1177/19458924241311354. Online ahead of print.

ABSTRACT

BACKGROUND: Thymic stromal lymphopoietin (TSLP) plays an important role in mediating the type-2-inflammatory response. This study examined how TSLP and interleukin (IL)-4 levels in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) correlated with clinical and postoperative outcomes.

METHODS: Solid-phase sandwich ELISA was used to analyze TSLP and IL-4 levels in mucus (n = 47), plasma (n = 17), polyp (n = 30), inferior (n = 25), and middle (n = 26) turbinate tissue collected during functional endoscopic sinus surgery (FESS) in CRSwNP patients (n = 76) and controls (n = 11). Inclusion criteria includes patients with medical treatment refractory CRSwNP confirmed by endoscopy or maxillofacial CT. Exclusion criteria include history of immunodeficiency, coagulation disorders, fungal sinusitis, or cystic fibrosis. Levels of TSLP and IL-4 were correlated with SNOT-22, UPSIT, and fractional exhaled nitric oxide (FeNO) using MannWhitney U two-tailed test and linear regression with Spearman correlation coefficient test.

RESULTS: TSLP is elevated in the inferior turbinates (effect size = 2.695, p = 0.0007) of CRSwNP patients compared to controls. IL-4 is expressed at elevated levels in the inferior (effect size = 3.092, p < 0.0001) and middle turbinates (effect size = 2.041, p = 0.019) compared to controls. Mucus TSLP (r = 0.4013, p = 0.0153) and IL-4 (r = 0.6138, p < 0.0001) positively correlate with preoperative FeNO levels. Lower TSLP in the inferior (r = -0.5179, p = 0.0231) and middle turbinates (r = -0.5075, p = 0.0224) and lower IL-4 in the inferior turbinates (r = -0.5205, p = 0.0223) correlate with a greater improvement in SNOT-22 post-FESS.

CONCLUSION: TSLP and IL-4 are elevated in patients with CRSwNP and correlated with increased preoperative FeNO levels and decreased sinonasal quality of life benefit after FESS. Expression of TSLP and IL-4 may play a role in guiding postoperative expectations in patients with treatment refractory CRSwNP.

PMID:39791191 | DOI:10.1177/19458924241311354

BMC Pediatr. 2025 Jan 9;25(1):22. doi: 10.1186/s12887-024-05369-8.

ABSTRACT

Preterm infants are at high risk of developing respiratory distress syndrome (RDS). Mutations in the genes encoding for surfactant proteins B and C or the ATP-binding cassette transporter A3 (ABCA3) are rare but known to be associated with severe RDS and interstitial lung diseases. The exact prevalence of these mutations in the general population is difficult to determine, as they are usually studied in connection with clinical symptoms. Most cases are not captured due to variability in expression or diagnosis. It is estimated that they affect a small percentage of the population, with mutations in ABCA3 most commonly identified in association with severe lung diseases in newborns. Even heterozygous ABCA3-mutations can increase the risk and severity of RDS in neonates. The expression of these proteins is developmentally regulated, increases with gestational age, and is crucial for the function of pulmonary surfactant at birth. Additional lung stressors, such as meconium aspiration syndrome or pulmonary infections, can lead to a complex clinical picture associated with severe courses. This case report describes an extremely preterm female infant with suspected meconium aspiration syndrome, severe RDS, Mycoplasma pneumoniae infection, and a heterozygous ABCA3-mutation. The report discusses the clinical presentation, diagnostic evaluation, and therapeutic interventions, emphasizing the complexities associated with multiple pulmonary conditions in the context of extreme prematurity. At the limits of viability, therapeutic options for severe respiratory insufficiency are limited compared to older children. The developmental neurological prognosis following prolonged relative hypoxia is a crucial factor to consider in discussions about changing treatment goals. Particularly in severe cases, pulmonary infections and genetic changes in surfactant metabolism must be considered in newborns with RDS.

PMID:39789505 | DOI:10.1186/s12887-024-05369-8

Transplant Proc. 2025 Jan 8:S0041-1345(24)00687-0. doi: 10.1016/j.transproceed.2024.12.024. Online ahead of print.

ABSTRACT

Infectious complications significantly impact morbidity and mortality following lung transplantation (LuTx), with over 25% of post-transplant deaths attributed to infections. Antibiotic prophylaxis during the surgical procedure is crucial for reducing early infections, though the current use of wide-spectrum antibiotics, especially in cases of multidrug-resistant organisms (MDROs), is contentious and varies widely across centre. This practice raises concerns about antimicrobial resistance (AMR), particularly in immunosuppressed patients requiring lifelong healthcare access. Syndromic multiplex polymerase chain reaction (mPCR) tests, which detect multiple pathogens simultaneously, have shown promise in quickly identifying pathogens and resistance mechanisms, thus enabling targeted treatments. However, their application in LuTx has been limited.

PMID:39788793 | DOI:10.1016/j.transproceed.2024.12.024

J Med Internet Res. 2025 Jan 9;27:e60689. doi: 10.2196/60689.

ABSTRACT

BACKGROUND: Home spirometers have been widely implemented in the treatment of people with cystic fibrosis (CF). Frequent spirometry measurements at home could lead to earlier detection of exacerbations. However, previous research indicates that the long-term use of home spirometry is not well maintained by people with CF.

OBJECTIVE: We aimed to gain insight into the long-term uptake of home spirometry in regular multicenter CF care.

METHODS: Home spirometers combined with a remote monitoring platform were introduced in the treatment of people with CF in 5 Dutch CF centers starting in April 2020. Usage data from April 2020 to December 2022 were analyzed retrospectively. Survival analyses were conducted to assess use consistency over time, and t tests were used to evaluate the impact of increased pulmonary symptoms on home spirometry frequency. The effect of the initiation of a new treatment, Elexacaftor/Tezacaftor/Ivacaftor, on use frequency over time was assessed in a subgroup of participants with repeated measures ANOVA.

RESULTS: During the observation period, a total of 604 people with CF were enrolled in the remote monitoring platform and 9930 home spirometry measurements were performed. After the initiation of home spirometry use, the number of users declined rapidly. One year after the initiation, 232 (54.2%) people with CF stopped using home spirometry. During the observation period, 67 (11.1%) users performed more than 20 measurements. Furthermore, the number of consistent home spirometry users decreased over time. After 600 days, only 1% of users had measured their lung function consistently every 31 days. Use frequency slightly increased during periods with increased pulmonary symptoms (ΔMean=0.45, t497.278=-4,197; P<.001) and showed an initial rise followed by a decrease after starting treatment with Elexacaftor/Tezacaftor/Ivacaftor (ΔMean=0.45, t497.278=-4,197; P<.001).

CONCLUSIONS: Consistent uptake of home spirometry in people with CF is low but increases around periods of changing symptoms. A clear strategy for the organization of remote care seemed to improve the long-term uptake of home spirometry. Nevertheless, home spirometry and its intensity are not a goal on their own but should be used as a tool to reach individual goals within local contexts.

PMID:39788554 | DOI:10.2196/60689

Pediatr Pulmonol. 2025 Jan;60(1):e27473. doi: 10.1002/ppul.27473.

ABSTRACT

INTRODUCTION: Lumacaftor/ivacaftor (lum/iva) was introduced in the Netherlands in 2017. We investigated 1-year efficacy of lum/iva on lung function and small airway and structural lung disease evaluated by multiple breath nitrogen washout and CT scan. Additionally, we investigated effects of lum/iva on exacerbations, anthropometry, sweat chloride and safety in children with CF in the Netherlands.

METHODS: Children with CF aged 6-18 years and homozygous for F508del treated in one of the seven Dutch CF centers for at least 12 months were eligible. Data were extracted from the Dutch CF Registry and electronic patient records. Primary outcome was change in percent predicted FEV1 (ppFEV1) after 12 months.

RESULTS: Nationwide, 247 children with CF were eligible for lum/iva. Eight patients discontinued lum/iva due to side effects. In total, 223/247 children (90.3%) were evaluated. Mean (range) age at baseline was 11.0 (6.0-17.1) years. There was no change in FEV1 after 12 months of lum/iva. In a subgroup, markers of small airway function and structural lung disease, such as LCI (n = 28), mean change (SD) -10.0% (15.8), and bronchus-artery (BA) analysis on CT scan (n = 81), showed significant improvement (p < 0.01). Moreover, BMI (n = 192), exacerbations (n = 219) and sweat chloride measurements (n = 105) improved.

CONCLUSION: Lum/iva was generally well tolerated in a real-life, nationwide pediatric cohort. The efficacy of lum/iva was comparable to phase 3 studies in children. LCI and BA analysis as markers of small airway and structural lung disease showed significant improvement which indicates the importance of these parameters to evaluate treatment effects of CF modulators in children.

PMID:39785291 | DOI:10.1002/ppul.27473

Pediatr Pulmonol. 2025 Jan;60(1):e27475. doi: 10.1002/ppul.27475.

ABSTRACT

BACKGROUND: People with cystic fibrosis (CF) may not expectorate sputum at young ages or after they receive CFTR modulators. While oropharyngeal swabs are commonly used to test for lower airway pathogens, it is unknown whether Staphylococcus aureus from the oropharynx matches the strain(s) infecting the lungs. Our goal was to determine whether oropharyngeal and sputum isolates of S. aureus are genetically distinct in a cohort of patients with CF.

METHODS: We obtained historical S. aureus isolates from patients who intermittently expectorated sputum in 2018, and we prospectively cultured S. aureus from oropharyngeal swabs and sputum from subjects with CF between August 2020 and February 2022. We performed short-read whole genome sequencing, determined sequence type, and performed phylogenetic analysis using S. aureus core genome single nucleotide polymorphisms (SNPs). We assigned isolates from a patient to the same strain if they had the same sequence type and differed by ≤ 60 SNPs or the isolates were not disturbed by clade breaker analysis.

RESULTS: 36 subjects had S. aureus in ≥ 1 oropharyngeal swab and ≥ 1 sputum in 2018. In the prospective collection, 31 subjects had synchronous oropharyngeal swab and sputum collections. Although polyclonal infections were detected, sputum and oropharyngeal isolates of S. aureus typically matched the same strain within study subjects, both over the span of 2018 (31/36 patients) and when collected simultaneously from 2020 to 2022 (29/31 patients).

CONCLUSIONS: In patients with CF who intermittently produce sputum, oropharyngeal swabs identify S. aureus with genetic and phenotypic similarity to those cultured from sputum.

PMID:39785222 | DOI:10.1002/ppul.27475

Monaldi Arch Chest Dis. 2025 Jan 9. doi: 10.4081/monaldi.2025.3068. Online ahead of print.

ABSTRACT

With the increasing use of highly effective modulator therapy (HEMT) in adults with cystic fibrosis (awCF), it is necessary to determine the evolution of the most dynamic physiological markers of this disease, such as the 6-minute walk test (6MWT) and the Glittre-activities of daily living test (TGlittre). The present study aimed to evaluate the 1-year changes in the 6- minute walking distance (6MWD), TGlittre time, and quality of life (QoL) in awCF before the initiation of HEMT and to determine the impact of habitual physical activity (HPA) and chest physiotherapy (CP). This longitudinal study enrolled 24 awCF who completed the 6MWT and TGlittre. Pulmonary function tests, handgrip strength (HGS), and the Cystic Fibrosis Questionnaire-Revised (CFQ-R) were conducted. Measurements were collected at baseline (T1) and 1 year later (T2). The median body mass index increased between T1 and T2 [19.8 (18-24) vs. 21.4 (19-24) kg/m2, p=0.038]. TGlittre time decreased both in relation to the absolute values [3.10 (2.52-3.39) vs. 2.40 (2.00-3.00) minutes, p=0.001] and in relation to the predicted values [127 (116-150) vs. 108 (102-140) % predicted, p=0.001]. Although there was no increase in 6MWD relative to the predicted values, it increased relative to the absolute values [545 (463-654) vs. 617 (540-658) meters, p=0.041]. In relation to the group that did not engage in HPA, individuals who had HPA showed an increase in HGS between T1 and T2 [7.1 (0-20) vs. 0 (-12-3) kgf, p=0.031]. In relation to the group that did not undergo CP, individuals undergoing CP showed an increase in the 'treatment burden'-CFQ-R between T1 and T2 [16.1 (-3-18) vs. -11.2 (-28-1) points, p=0.049]. In conclusion, awCF performed better on TGlittre than on 6MWT. They experienced an improvement in body composition. HPA was correlated with peripheral muscle strength, as were CP and QoL.

PMID:39783834 | DOI:10.4081/monaldi.2025.3068

Expert Rev Respir Med. 2025 Jan 9. doi: 10.1080/17476348.2025.2451960. Online ahead of print.

ABSTRACT

INTRODUCTION: Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by the production of sickle hemoglobin, leading to red blood cells sickling and hemolysis in hypoxic conditions. The resulting acute and chronic endothelial inflammation leads to chronic organ damage. Respiratory manifestations in SCD usually start from childhood and represent the leading causes of morbidity and mortality. Nevertheless, they are generally poorly addressed or recognized later in life, often contributing to a more severe course and complications.

AREAS COVERED: This narrative review aims to outline the significant acute and chronic respiratory manifestations in children with SCD, focusing on prevention and clinical management. Compelling issues that need to be addressed in the future are also discussed. We searched the PubMed database for original papers written in English. Age restrictions were set for children (birth to 18 years). No limitations were set for the date and study country.

EXPERT OPINION: Early detection and treatment of respiratory manifestations in SCD should be central to follow-up with patients affected by SCD. Nonetheless, studies are lacking, especially in pediatric age, and there is still no consensus on their management. Further research is strongly needed to accomplish universally accepted guidelines to guarantee patients the best care possible.

PMID:39783770 | DOI:10.1080/17476348.2025.2451960

Sci Diabetes Self Manag Care. 2025 Jan 9:26350106241306058. doi: 10.1177/26350106241306058. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of the study was to identify the most common reasons for and timing of continuous glucose monitoring (CGM) attrition in youth with type 1 diabetes (T1DM).

METHODS: This single center retrospective chart review included youth with T1DM <22 years seen between November 1, 2021, and October 31, 2022. Data were gathered from CGM cloud-based software and the electronic medical record.

RESULTS: Among 2663 youth, 88.3% (n = 2351) actively used CGM, and 5.9% (n = 311) had CGM attrition. Those who discontinued CGM were older (17.0 vs 14.9 years, P = .0001), had a longer T1DM duration (7.4 vs 5.1 years), higher A1C (9% vs 7.4%), and were non-Hispanic Black (NHB; 34.0% vs 11.5%). The odds of CGM attrition were 5.0 and 2.8 times higher in NHB and Latine youth, respectively, compared to non-Hispanic White youth. Median time to CGM discontinuation was 4 months, 21 days after initiation; 57% of youth who discontinued did so in the first 6 months of use. The most common reasons for CGM attrition were problems with device adhesion (18.4%), dislike device on the body (10.8%), insurance problems (9.5%), pain with device use (8.3%), and system mistrust due to inaccurate readings (8.2%). NHB and Latine youth were more likely to discontinue CGM due to insurance problems (3.2% vs 15.1% vs 16.7%).

CONCLUSIONS: To support equitable, uninterrupted CGM use, education at CGM initiation should address practical approaches to improve adhesion and wearability and provide a clear pathway to obtaining supplies. Interventions to support sustained CGM use should occur within the first 6 months of initiation.

PMID:39783011 | DOI:10.1177/26350106241306058

Ann Pharmacother. 2025 Jan 8:10600280241310595. doi: 10.1177/10600280241310595. Online ahead of print.

ABSTRACT

BACKGROUND: Among people with cystic fibrosis (PwCF), methicillin-resistant Staphylococcus aureus (MRSA)-associated acute pulmonary exacerbations (APEs) have been increasing in prevalence and can cause rapid declines in lung function and increased mortality. Fortunately, since 2019, incidence has started to decline.

OBJECTIVE: The purpose of this study was to evaluate if doxycycline has comparable efficacy to vancomycin for the treatment of APEs in PwCF. Given the potential toxicities and intolerances associated with vancomycin, evaluating alternative therapies such as doxycycline is warranted.

METHODS: A multicenter retrospective cohort study was conducted in adult and pediatric PwCF who received greater than 48 hours of either vancomycin or doxycycline to treat MRSA-associated APEs between May 1, 2014, and August 31, 2021. The primary outcome was the number of PwCF with a return to ≥90% of baseline forced expiratory volume in the first second (FEV1).

RESULTS: There were 229 PwCF encounters screened, of which 89 met inclusion criteria (n = 26, vancomycin; n = 63, doxycycline). There were no differences between vancomycin and doxycycline for the primary outcome: 18/26 (69.2%) in the vancomycin group vs 51/63 (81.0%) in the doxycycline group (P = 0.23). Secondary outcomes were similar between groups, including no difference in incidence of acute kidney injury (AKI), although a significantly higher incidence of adverse events occurred in the vancomycin arm.

CONCLUSION AND RELEVANCE: The findings of this study suggest doxycycline may be a reasonable alternative to vancomycin for MRSA-associated APEs, particularly in PwCF who may not tolerate vancomycin or who require concomitant nephrotoxins such as intravenous (IV) aminoglycosides.

PMID:39780358 | DOI:10.1177/10600280241310595

NPJ Biofilms Microbiomes. 2025 Jan 8;11(1):8. doi: 10.1038/s41522-024-00637-y.

ABSTRACT

Chronic infections represent a significant global health and economic challenge. Biofilms, which are bacterial communities encased in an extracellular polysaccharide matrix, contribute to approximately 80% of these infections. In particular, pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus are frequently co-isolated from the sputum of patients with cystic fibrosis and are commonly found in chronic wound infections. Within biofilms, bacteria demonstrate a remarkable increase in resistance and tolerance to antimicrobial treatment. We investigated the efficacy of combining the last-line antibiotic colistin with a membrane- and stringent stress response-targeting anti-biofilm peptide DJK-5 against co-biofilms comprised of multidrug-resistant P. aeruginosa and methicillin-resistant S. aureus (MRSA). Colistin lacks canonical activity against S. aureus. However, our study revealed that under co-biofilm conditions, the antibiofilm peptide DJK-5 synergized with colistin against S. aureus. Similar enhancement was observed when daptomycin, a cyclic lipopeptide against Gram-positive bacteria, was combined with DJK-5, resulting in increased activity against P. aeruginosa. The combinatorial treatment induced morphological changes in both P. aeruginosa and S. aureus cell shape and size within co-biofilms. Importantly, our findings also demonstrate synergistic activity against both P. aeruginosa and S. aureus in a murine subcutaneous biofilm-like abscess model. In conclusion, combinatorial treatments with colistin or daptomycin and the anti-biofilm peptide DJK-5 show significant potential for targeting co-biofilm infections. These findings offer promising avenues for developing new therapeutic approaches to combat complex chronic infections.

PMID:39779734 | DOI:10.1038/s41522-024-00637-y

J Cyst Fibros. 2025 Jan 7:S1569-1993(24)01860-5. doi: 10.1016/j.jcf.2024.12.009. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is caused by variants in a gene that encodes a protein essential for water and ion transport in the epithelial cells of exocrine organs. Given the possible relationship of this protein and conjunctival and corneal epithelium, the aim of this study was to evaluate ophthalmologic alterations in people with CF.

METHODS: Forty-five people with CF underwent pulmonary evaluation including inflammatory score (IS). These people along with 98 sex-matched controls underwent ophthalmologic evaluation including dry eye disease (DED) testing, corneal topography using Pentacam™ and macular and peripapillary retinal nerve fiber layer (pRNFL) thickness with optical coherence tomography (OCT).

RESULTS: The CF group presented a higher percentage of pathologic tear break-up time (T-BUT) (55.6 % vs 25 %, p = 0.001) and Schirmer's test 1 (40 % versus 19.4 %, p = 0.009) than the control group. In the CF group, an inverse correlation was observed between T-BUT and IS (r=- 0.373, p = 0.012), as well as T-BUT and peripheral eosinophilia (r=-0.338; p = 0.023). People with CF presented lower values of central corneal thickness (p = 0.009), thinnest point (p = 0.006), anterior chamber volume (p = 0.034), and anterior chamber angle (p = 0.011) than the control group and lower pRNLF thickness in the superior temporal sector (p = 0.002).

CONCLUSIONS: Our findings indicate a higher prevalence of dry eye disease (DED) among people with CF compared to controls. The severity of the condition increases with higher systemic inflammation. Additionally, CF may affect the anterior segment of the eye, leading to a reduction in the nerve fiber layer and early signs of glaucoma.

PMID:39779380 | DOI:10.1016/j.jcf.2024.12.009

J Clin Pathol. 2025 Jan 8:jcp-2024-209899. doi: 10.1136/jcp-2024-209899. Online ahead of print.

ABSTRACT

AIMS: In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD.

METHODS: A retrospective, single-centre observational study of cystic fibrosis LTRs between 2002 and 2021 was performed. Data from biopsy slides, pulmonary function testing and bronchoalveolar lavage fluid microbiology tests were collected. The primary outcome was bronchiolitis obliterans syndrome (BOS) or death after transplant, with an 8-year follow-up period.

RESULTS: 40 patients were identified with an average age of 35.3 at first transplantation, including 5 redo lung transplants. Fungal infections were correlated with higher rejection scores (p<0.01) and survival status (p=0.027). Fungal and bacterial infection rates were reduced in later transplants (2014-2021) compared with earlier (2002-2014). Fungal infections were associated with significantly worsened outcomes (p≤0.001). Eosinophils in large airways was associated with worse BOS-free survival (p=0.03).

CONCLUSIONS: Subcategorisation of the inflammatory milieu (particularly noting eosinophils) in surveillance biopsies may help detect CLAD earlier and improve long-term outcomes in cystic fibrosis LTRs.

PMID:39779317 | DOI:10.1136/jcp-2024-209899

Eur Respir Rev. 2025 Jan 8;34(175):240131. doi: 10.1183/16000617.0131-2024. Print 2025 Jan.

ABSTRACT

The systemic use of corticosteroids for patients with severe community-acquired pneumonia (sCAP) remains controversial in clinical practice, particularly in terms of the safety profile of these drugs. This narrative review aims to analyse the available literature data concerning the safety of short-term steroid use in the treatment of sCAP, while also highlighting potential future research directions. Several trials and meta-analyses have evaluated corticosteroid therapy as an adjuvant treatment for sCAP, yielding heterogeneous results regarding its efficacy and safety. Despite the wide variability in results, it is generally accepted that steroids are not associated with a significant risk of healthcare-associated infections, gastrointestinal bleeding or acute kidney injury in patients with sCAP in the short term. Nevertheless, such drugs are linked to hyperglycaemia, necessitating regular monitoring and appropriate management. The influence of steroids on long-term outcomes and their potential risks in viral sCAP still needs to be investigated.

PMID:39778921 | DOI:10.1183/16000617.0131-2024

Int Forum Allergy Rhinol. 2025 Jan 8. doi: 10.1002/alr.23524. Online ahead of print.

ABSTRACT

BACKGROUND: Steroid rinses and steroid-eluting stents are both options for preventing postoperative stenosis after frontal sinus surgery. This study aimed to assess whether steroid-eluting stents offer added benefit over steroid rinses alone in postoperative healing and long-term frontal sinus patency.

METHODS: A randomized controlled trial enrolled patients with CRS with nasal polyps (CRSwNP) who underwent surgery for bilateral and equal frontal sinusitis after failing prior medical therapy. Each patient served as their own control, with each patient randomized to stent placement in either right or left frontal sinuses. Exclusion criteria included unequal frontal sinusitis, aspirin exacerbated respiratory disease, cystic fibrosis, primary ciliary dyskinesia, and immunocompromise. All patients used steroid rinses postoperatively. Scarring, edema, patency, and the need for additional treatments were assessed at 1, 3, 12, and 24 weeks postoperatively. Univariate and multivariate analyses were performed.

RESULTS: Sixty-two patients were enrolled. Postoperatively, scarring, edema, patency, and the need for further treatment were similar in both groups at 24 weeks (p = 0.878, 0.688, 0.817, 1.00, and 1.00, respectively). Multivariable regression analysis identified time as an independent risk factor for scarring (OR = 1.32, [1.03‒1.71]) and patency (OR = 1.39, [1.10‒1.82]), while it was an independent protective factor for edema (OR = 0.40, [0.32‒0.49]). The steroid-eluting stent did not significantly affect this.

CONCLUSION: For CRSwNP, with or without asthma, without other underlying systemic disease factors, steroid-eluting stents may not add benefit over steroid rinses in reducing postoperative scarring and edema, improving long-term frontal sinus patency, or reducing the need for additional treatments, as long as patients continue topical therapy and know how to rinse effectively.

PMID:39778085 | DOI:10.1002/alr.23524

Pediatr Pulmonol. 2025 Jan 7:e27471. doi: 10.1002/ppul.27471. Online ahead of print.

ABSTRACT

INTRODUCTION: While the diagnosis of cystic fibrosis (CF) is often straightforward and reliant on correlation between genetic testing and clinical signs and symptoms, there is a subset where the distinction is not nearly as clearcut. This has previously been reported in patients identified through newborn screening but not meeting full CF diagnostic criteria, earning the label of CF Screen Positive, Inconclusive Diagnosis (CFSPID) instead. A homologous diagnostic category in adults is named CF Transmembrane Conductance Regulator-Related Disorder (CFTR-RD).

METHODS: Through a retrospective chart review, this study reports on a relatively large adult cohort (n = 23) that presented to pulmonology clinic at a single center with intermediate or positive sweat chloride tests but non-diagnostic full CFTR gene analysis.

RESULTS: Median sweat chloride result was 48 mmol/L, and a majority of the cohort had chronic lung disease with atypical pathogens on sputum culture, including Pseudomonas aeruginosa, non-tuberculous Mycobacteria, Acinetobacter species, amongst others.

CONCLUSIONS: This clinical picture suggests CFTR dysfunction or similar mechanism in the absence of an identified genetic cause. Alternate chloride channels and their respective genes or candidates of genetic modifiers to the CF-phenotype could be targets of further research in this cohort or similar patients. Such genetic modifiers include loci that have been implicated in inflammation, the CFTR interactome, and/or co-/post-translational modification of CFTR.

PMID:39778078 | DOI:10.1002/ppul.27471