Paediatr Respir Rev. 2025 Apr 5:S1526-0542(25)00033-8. doi: 10.1016/j.prrv.2025.04.002. Online ahead of print.

ABSTRACT

It is a challenge to select the "best" recent publications in a field. This is especially so when faced with a feast of outstanding manuscripts across a broad range of topics. I therefore reached out to a Who's Who of friends and colleagues in pediatric pulmonary and sleep medicine for suggestions, and I was delighted and overwhelmed by the response - please see the Acknowledgements for those who contributed ideas. Overwhelmed, by having to read 77 publications suggested by one or more colleagues and having to winnow the list down to a somewhat reasonable number. I chose to include all papers mentioned by two or more of my colleagues and I then selected the remainder to cover the broad range of our field, based upon my belief that a manuscript represented an important contribution to our understanding and clinical care. What follows are the chosen papers organized by topic area. Given the number of papers that made the final cut, I have briefly summarized each of these manuscripts. I hope that you will find something new and exciting in these publications and that you will have as much fun in reading them as I did.

PMID:40268602 | DOI:10.1016/j.prrv.2025.04.002

Eur Respir J. 2025 Apr 23:2402490. doi: 10.1183/13993003.02490-2024. Online ahead of print.

NO ABSTRACT

PMID:40268505 | DOI:10.1183/13993003.02490-2024

Chest. 2025 Apr 22:S0012-3692(25)00518-5. doi: 10.1016/j.chest.2025.04.017. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammation that is responsible for remodeling the bronchovascular bundles, which may lead to poor quality of life. Quantitative computed tomography (QCT) textures of the lung can capture local disease patterns of inflammation and related respiratory morbidity.

RESEARCH QUESTION: Are bronchovascular bundle textures, obtained from the adaptive multiple feature method (AMFM), associated with systemic inflammation, morbidity, and mortality in COPD?

STUDY DESIGN AND METHODS: We analyzed data from the SPIROMICS (n = 2,981) and COPDGene (n = 10,305) studies. The predictors included two QCT biomarkers, the bronchovascular bundles (BVB) and CT density gradient (CTDG) textures, age, sex, BMI, race, smoking status, smoking pack-years, CT emphysema, and Pi10 (airway wall thickness). Outcomes included plasma biomarker concentrations from Meso Scale Discovery proteomics assays and complete blood counts, both as markers of inflammation, along with FEV1, FEV1/FVC ratio, SGRQ, 6MWD, and mMRC dyspnea scale. Associations of these QCT textures with FEV1 decline and all-cause mortality were also investigated.

RESULTS: Increased BVB texture was significantly associated with elevated neutrophil and monocyte counts, and the neutrophil-to-lymphocyte ratio (NLR), independent of clinical covariates, CT emphysema, and Pi10. Elevated CTDG was associated with increased neutrophil count, NLR, and tumor necrosis factor (TNF)-α. Increased CTDG and BVB textures were also associated with a lower FEV1 and six-minute walk distance. CTDG at baseline was also associated with decline in FEV1 at five-year follow-up in COPDGene. We observed a significant association of both BVB (HRSPIROMICS=1.084, 95% CI: 1.035, 1.135, P<0.001; HRCOPDGene=1.106, 95% CI: 1.080, 1.131, P<0.001) and CTDG (HRSPIROMICS=1.033, 95% CI: 1.003, 1.064, P=0.03; HRCOPDGene=1.079, 95% CI: 1.061, 1.096, P<0.001) textures with all-cause mortality independent of CT emphysema and Pi10.

INTERPRETATION: QCT textures may provide imaging evidence of the spatial heterogeneity of lung inflammation and overall disease burden in COPD.

PMID:40268239 | DOI:10.1016/j.chest.2025.04.017

N Engl J Med. 2025 Apr 24;392(16):1569-1581. doi: 10.1056/NEJMoa2411664.

ABSTRACT

BACKGROUND: In bronchiectasis, neutrophilic inflammation is associated with an increased risk of exacerbations and disease progression. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), targets neutrophil serine proteases, key mediators of neutrophilic inflammation.

METHODS: In a phase 3, double-blind trial, we randomly assigned patients with bronchiectasis (in a 1:1:1 ratio for adults and a 2:2:1 ratio for adolescents) to receive brensocatib (10 mg or 25 mg once per day) or placebo. The primary end point was the annualized rate of adjudicated pulmonary exacerbations over a 52-week period. The secondary end points, listed in hierarchical testing order, were the time to the first exacerbation during the 52-week period; the percentage of patients remaining exacerbation-free at week 52; the change in forced expiratory volume in 1 second (FEV1); the annualized rate of severe exacerbations; and change in quality of life.

RESULTS: A total of 1721 patients (1680 adults and 41 adolescents) underwent randomization and received brensocatib or placebo. The annualized rate of pulmonary exacerbations was 1.02 in the 10-mg brensocatib group, 1.04 in the 25-mg brensocatib group, and 1.29 in the placebo group (rate ratio, brensocatib vs. placebo, 0.79 [95% confidence interval {CI}, 0.68 to 0.92; adjusted P = 0.004] with the 10-mg dose and 0.81 [95% CI, 0.69 to 0.94; adjusted P = 0.005] with the 25-mg dose). The hazard ratio for the time to the first exacerbation was 0.81 (95% CI, 0.70 to 0.95; adjusted P = 0.02) with the 10-mg dose and 0.83 (95% CI, 0.70 to 0.97; adjusted P = 0.04) with the 25-mg dose. In each brensocatib group, 48.5% of patients remained exacerbation-free at week 52, as compared with 40.3% in the placebo group (rate ratio, 1.20 [95% CI, 1.06 to 1.37; adjusted P = 0.02] with the 10-mg dose and 1.18 [95% CI, 1.04 to 1.34; adjusted P = 0.04] with the 25-mg dose). At week 52, FEV1 had declined by 50 ml with the 10-mg dose, 24 ml with the 25-mg dose, and 62 ml with placebo (least-squares mean difference vs. placebo, 11 ml [95% CI, -14 to 37; adjusted P = 0.38] with the 10-mg dose and 38 ml [95% CI, 11 to 65; adjusted P = 0.04] with the 25-mg dose). The incidence of adverse events was similar across groups, except for a higher incidence of hyperkeratosis with brensocatib.

CONCLUSIONS: Among patients with bronchiectasis, once-daily treatment with brensocatib (10 mg or 25 mg) led to a lower annualized rate of pulmonary exacerbations than placebo, and the decline in FEV1 was less with the 25-mg dose of brensocatib than with placebo. (Funded by Insmed; ASPEN ClinicalTrials.gov number, NCT04594369; EudraCT number, 2020-003688-25.).

PMID:40267423 | DOI:10.1056/NEJMoa2411664

Pediatr Pulmonol. 2025 Apr;60(4):e71097. doi: 10.1002/ppul.71097.

ABSTRACT

BACKGROUND: New 2023 CF liver disease (CFLD) guidelines advocate for additional screening in people with cystic fibrosis (PwCF), including biennial abdominal ultrasound. As a first step towards effective and equitable guidelines implementation, we examined our current practice of CFLD screening and hepatobiliary involvement (HBI) evaluation. We identified characteristics of PwCF at-risk for incomplete screening and factors affecting evaluation.

METHODS: We retrospectively reviewed medical records of PwCF aged 0-21 years, with native liver and ≥ 2 outpatient CF clinic visits 2017-2023. Logistic regression was used to identify characteristics associated with incomplete screening and with HBI.

RESULTS: Amongst 112 PwCF at our center: 37% (n = 42) self-reported as mixed race, 27% (n = 30) as Hispanic; 53% (n = 59) had public insurance. Incomplete lab screening was identified in 19% of our cohort. GGT was the most frequently missed component (14%, n = 16). Hispanics and publicly insured people were more likely to have incomplete screening. Of the 112, 45 met criteria for HBI. Demographics did not predict HBI. Five with CF and HBI had the full hepatitis workup recommended by the new guidelines. Those with HBI documented (42%, n = 19) were more likely to receive additional workup. PwCF who were seen by a gastroenterologist were more likely to have additional diagnostic work-up for HBI.

CONCLUSION: One in five PwCF at our center were incompletely screened for CFLD, with Hispanics and publicly insured at higher risk. Accurate diagnosis and adequate documentation are the first steps to identifying HBI in PwCF. A dedicated CF gastroenterologist is key to completing CFLD screening and liver diagnosis.

PMID:40265529 | DOI:10.1002/ppul.71097

Int J Neonatal Screen. 2025 Apr 17;11(2):27. doi: 10.3390/ijns11020027.

ABSTRACT

Because a delayed diagnosis of cystic fibrosis (CF) is detrimental and may be fatal, screening at birth has become routine in the Western world and has proven beneficial for many reasons, in addition to enabling prompt specialized care. Newborn screening (NBS) programs have elucidated the true incidence of CF in a variety of populations and enabled rapid genotype identification through the analysis of the cystic fibrosis transmembrane regulator (CFTR) gene. NBS studies also have revealed regional and population differences in CFTR variants and refuted the dogma that CF is a "white person's disease". But some regions have not yet implemented CF NBS, particularly in Asia where the disease prevalence has been uncertain. While the needs of a few low-and-middle-income countries are being addressed sequentially, one of the regions of greatest current interest is the Indian subcontinent because of recent data suggesting a higher incidence than that previously assumed, and clinical observations indicating tragic outcomes due to delayed diagnoses or failure to diagnose the disorder in young children. Thus, we conclude that the opportunities for research combined with service in the Indian subcontinent are urgent and potentially very impactful. Consequently, India is the last and best frontier for CF NBS, as we argue herein.

PMID:40265448 | DOI:10.3390/ijns11020027

Int J Neonatal Screen. 2025 Apr 2;11(2):24. doi: 10.3390/ijns11020024.

ABSTRACT

Newborn screening for cystic fibrosis (CF) has been universal in the US since 2010; however, there is significant variation among newborn screening algorithms. Systematic reviews were used to develop seven recommendations for newborn screening program practices to improve timeliness, sensitivity, and equity in diagnosing infants with CF: (1) The CF Foundation recommends the use of a floating immunoreactive trypsinogen (IRT) cutoff over a fixed IRT cutoff; (2) The CF Foundation recommends using a very high IRT referral strategy in CF newborn screening programs whose variant panel does not include all CF-causing variants in CFTR2 or does not have a variant panel that achieves at least 95% sensitivity in all ancestral groups within the state; (3) The CF Foundation recommends that CF newborn screening algorithms should not limit CFTR variant detection to the F508del variant or variants included in the American College of Medical Genetics-23 panel; (4) The CF Foundation recommends that CF newborn screening programs screen for all CF-causing CFTR variants in CFTR2; (5) The CF Foundation recommends conducting CFTR variant screening twice weekly or more frequently as resources allow; (6) The CF Foundation recommends the inclusion of a CFTR sequencing tier following IRT and CFTR variant panel testing to improve the specificity and positive predictive value of CF newborn screening; (7) The CF Foundation recommends that both the primary care provider and the CF specialist be notified of abnormal newborn screening results. Through implementation, it is anticipated that these recommendations will result in improved sensitivity, equity, and timeliness of CF newborn screening, leading to improved health outcomes for all individuals diagnosed with CF following newborn screening and a decreased burden on families.

PMID:40265445 | DOI:10.3390/ijns11020024

J Pediatr Gastroenterol Nutr. 2025 Apr 23. doi: 10.1002/jpn3.70050. Online ahead of print.

ABSTRACT

OBJECTIVES: Cystic fibrosis hepato-biliary involvement (CFHBI) is a common comorbidity in patients with CF and is associated with increased morbidity and mortality. The effect of the new and highly potent CF transmembrane conductance regulator modulator therapy, elexacaftor-tezacaftor-ivacaftor (ETI), on CFHBI, is still unclear. This study aimed to investigate the impact of ETI on liver stiffness in children with CF, as measured using two-dimensional (2D) shear wave elastography (SWE).

METHODS: Twenty-one children with CF were included in this retrospective study at the CF centre, Skåne University Hospital, Lund, Sweden. Twelve children of our cohort had CFHBI; none had advanced CF liver disease. 2D SWE data from annual assessments, clinical data and liver enzymes were analysed.

RESULTS: We found a significant reduction in liver stiffness after starting treatment with ETI in the total cohort. This reduction in liver stiffness could even be seen in children with CFHBI. Liver enzymes were within the normal range in both pre- and post-ETI therapy in the total cohort. In children with CFHBI, a decline in aspartate aminotransferase activity was observed after ETI was initiated. Lung function and lung clearance index improved significantly after ETI treatment commenced.

CONCLUSION: ETI treatment could positively affect CFHBI in children with CF, as demonstrated by reduced liver stiffness during treatment.

PMID:40264362 | DOI:10.1002/jpn3.70050

Biomater Sci. 2025 Apr 23. doi: 10.1039/d5bm00322a. Online ahead of print.

ABSTRACT

The rapid advancement of mRNA therapeutics, exemplified by COVID-19 vaccines, underscores the transformative potential of non-viral delivery systems. However, achieving efficient and targeted mRNA delivery to the lungs remains a critical challenge due to biological barriers such as pulmonary mucus, nanoparticle instability, and off-target accumulation particularly in the liver. Addressing these challenges is crucial for advancing treatments for respiratory diseases, including cystic fibrosis, primary ciliary dyskinesia, and lung cancers. This review highlights emerging strategies to enhance lung-targeted mRNA delivery, focusing on lipid nanoparticles, polymeric nanoparticles, lipid-polymer hybrids, and peptide/protein conjugates. By discussing advances in bioinspired design and nanoparticle reformulation, this review provides a roadmap for overcoming current delivery limitations and accelerating the clinical translation of lung-targeted mRNA therapies.

PMID:40264303 | DOI:10.1039/d5bm00322a

BMJ. 2025 Apr 22;389:r699. doi: 10.1136/bmj.r699.

NO ABSTRACT

PMID:40262835 | DOI:10.1136/bmj.r699

Proc Natl Acad Sci U S A. 2025 Apr 29;122(17):e2418407122. doi: 10.1073/pnas.2418407122. Epub 2025 Apr 22.

ABSTRACT

Cystic fibrosis (CF) is a lethal genetic disorder caused by variants in CF transmembrane conductance regulator (CFTR). Many variants are treatable with correctors, which enhance the folding and trafficking of CFTR. However, approximately 3% of persons with CF harbor poorly responsive variants. Here, we used affinity purification mass spectrometry proteomics to profile the protein homeostasis (proteostasis) changes of CFTR variants during correction to assess modulated interactions with protein folding and maturation pathways. Responsive variant interactions converged on similar proteostasis pathways during correction. In contrast, poorly responsive variants subtly diverged, revealing a partial restoration of protein quality control surveillance and partial correction. Computational structural modeling showed that corrector VX-445 failed to confer enough NBD1 stability to poor responders. NBD1 secondary stabilizing mutations rescued poorly responsive variants, revealing structural vulnerabilities in NBD1 required for treating poor responders. Our study provides a framework for discerning the underlying protein quality control and structural defects of CFTR variants not reached with existing drugs to expand therapeutics to all susceptible CFTR variants.

PMID:40261935 | DOI:10.1073/pnas.2418407122

PLoS Pathog. 2025 Apr 22;21(4):e1013067. doi: 10.1371/journal.ppat.1013067. eCollection 2025 Apr.

NO ABSTRACT

PMID:40261841 | DOI:10.1371/journal.ppat.1013067

JCI Insight. 2025 Apr 22:e188146. doi: 10.1172/jci.insight.188146. Online ahead of print.

ABSTRACT

Pf bacteriophages, lysogenic viruses that infect Pseudomonas aeruginosa (Pa), are implicated in the pathogenesis of chronic Pa infections; phage-infected (Pf+) strains are known to predominate in people with cystic fibrosis (pwCF) who are older and have more severe disease. However, the transmission patterns of Pf underlying the progressive dominance of Pf+ strains are unclear. In particular, it is unknown whether phage transmission commonly occurs horizontally between bacteria via viral particles within the airway or if Pf+ bacteria are mostly acquired via de novo Pseudomonas infections. Here, we studied Pa genomic sequences from 3 patient cohorts totaling 662 clinical isolates from 105 pwCF. We identified Pf+ isolates and analyzed transmission patterns of Pf within patients between genetically similar groups of bacteria called "clone types". We found that Pf was predominantly passed down vertically within Pa clone types and rarely via horizontal transfer between clone types within the airway. Conversely, we found extensive evidence of Pa de novo infection by a new, genetically distinct Pf+ Pa. Finally, we observed that clinical isolates showed reduced activity of the type IV pilus and reduced susceptibility to Pf in vitro. These results cast new light on the transmission of virulence-associated phages in the clinical setting.

PMID:40261708 | DOI:10.1172/jci.insight.188146

JCI Insight. 2025 Apr 22:e187951. doi: 10.1172/jci.insight.187951. Online ahead of print.

ABSTRACT

Pharmacological rescue of F508del-CFTR by the triple combination CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) leads to unprecedented clinical benefits in patients with cystic fibrosis (CF), however, previous studies in CF primary human airway epithelial cultures demonstrated that chronic treatment with the potentiator ivacaftor can render the F508del protein unstable thus limiting restoration of CFTR chloride channel function. However, quantitative studies of this unwanted effect of ivacaftor on F508del channel function including dependency on cell culture conditions remain limited and the impact of chronic ivacaftor exposure on restoration of mucociliary clearance that is impaired in patients with CF has not been studied. In patient-derived primary nasal epithelial cultures, we found that different culture conditions (UNC-ALI medium vs. PneumaCult medium) have profound effects on ETI-mediated restoration of F508del-CFTR function. Chronic treatment with ivacaftor as part of ETI triple therapy limited the rescue of F508del-CFTR chloride channel function when CF nasal epithelial cultures were grown in UNC-ALI medium, but not in PneumaCult medium. In PneumaCult medium, both chronic and acute addition of ivacaftor as part of ETI treatment led to constitutive CFTR-mediated chloride secretion in the absence of exogenous cAMP-dependent stimulation. This constitutive CFTR-mediated chloride secretion was essential to improve viscoelastic properties of the mucus layer and to restore mucociliary transport on CF nasal epithelial cultures. Furthermore, nasal potential difference measurements in patients with CF showed that ETI restored constitutive F508del-CFTR activity in vivo. These results demonstrate that ivacaftor as a component of ETI therapy is essential to restore mucociliary clearance and suggest that this effect is facilitated by its constitutive activation of F508del channels following their folding-correction in patients with CF.

PMID:40261705 | DOI:10.1172/jci.insight.187951

Physiother Theory Pract. 2025 Apr 22:1-8. doi: 10.1080/09593985.2025.2494114. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize physiological responses to a 1-minute sit-to-stand test (STS) and assess correlations with cardiopulmonary exercise test (CPET) variables, nutritional status, pulmonary function, and quadriceps muscle strength in cystic fibrosis (CF) patients.

METHODS: Subjects aged 6-18 years with a genetic diagnosis of CF were enrolled in this cross-sectional study. After collecting demographic, anthropometric, and clinical data the following tests were performed: pulmonary function (spirometry), aerobic fitness (CPET), STS, and isometric quadriceps muscle strength (hand-held dynamometry). Data collection was performed on the same day.

RESULTS: The study sample comprised 17 children (9.8 ± 1.6 years) and adolescents (13.7 ± 1.5 years) with a mean forced expiratory volume in one second (FEV1) of - 0.80 ± 1.61 (z-score). In the CPET, peak exercise oxygen consumption (VO2peak) was 35.1 ± 4.2 mL.kg-1.min-1, while in the STS mean number of repetitions was 32.5 ± 6.2 and total work (repetitions × body mass) was 1326.9 ± 379.6. At peak exercise, CPET elicited higher heart rate (p = .001) and subjective sensation of dyspnea (p = .001) compared to STS, though no significant differences were observed in peripheral oxygen saturation. Moderate and significant correlations were identified between total workload (CPET) and repetitions adjusted for body weight (r = 0.684; p = .002) and between STS repetitions and muscle strength corrected for body weight (r = 0.531; p = .034). No significant correlations were found with nutritional status (BMI), pulmonary function (FEV1), or other aerobic fitness variables (VO2 at ventilatory threshold or VO2peak).

CONCLUSION: In children and adolescents with CF, compared to CPET, the STS test elicits a submaximal cardiorespiratory response that is mostly dependent on quadriceps muscle strength.

PMID:40260956 | DOI:10.1080/09593985.2025.2494114

Sci Rep. 2025 Apr 21;15(1):13767. doi: 10.1038/s41598-025-98900-5.

ABSTRACT

The prevalence of attention deficit-hyperactivity disorder (ADHD) symptoms among individuals with cystic fibrosis (CF) is significantly elevated compared to the general population. Given that the cystic fibrosis transmembrane conductance regulator (CFTR) is the causative gene for cystic fibrosis, this raises the possibility of CFTR playing a crucial role in ADHD. In our study, three heterozygous missense variants (p.E217G, p.F316L, and p.T1220I) were detected in the CFTR gene, which co-segregate with ADHD in two consanguineous families, impacting a total of six family members. Through the utilization of a zebrafish model, it was observed that the cftr knockout line exhibited behaviors akin to hyperactivity, impulsivity, and attention deficits, mirroring the symptoms seen in human ADHD patients. Single-cell RNA sequencing performed on 7 dpf larvae revealed clusters of neuron cells that exhibited sensitivity to cftr, particularly noting a reduction in the number of dopaminergic neuron cells within the cftr mutant fish. Additionally, bulk RNA sequencing and proteomic analysis conducted during the early gastrulation stage demonstrated abnormal expression levels of nervous system genes. Notably, we attempted to employ CFTR modulators Lumacaftor (VX-809) and Ivacaftor (VX-770) to ameliorate the ADHD zebrafish model (generated via per1b mutant), and it was found that enhanced CFTR activity could mitigate ADHD-like behaviors. In summary, our findings shed light on the potential involvement of CFTR in the pathogenesis of ADHD and pave the way for exploring novel diagnostic approaches and therapeutic strategies for ADHD by targeting CFTR.

PMID:40258939 | DOI:10.1038/s41598-025-98900-5

Mol Cell Pediatr. 2025 Apr 21;12(1):5. doi: 10.1186/s40348-025-00190-4.

ABSTRACT

BACKGROUND: Intercellular communication is a critical process that ensures cooperation between distinct cell types and maintains homeostasis. In the past decades, extracellular vesicles (EVs) have been recognized as key components in cell-to-cell communication. These EVs carry multiple factors such as active enzymes, metabolites, nucleic acids and surface molecules that can alter the behavior of recipient cells. Thus, the role of EVs in exacerbating disease pathology by transporting inflammatory mediators, and other molecular signals that contribute to chronic inflammation and immune dysregulation in various diseases including cystic fibrosis (CF) is well documented.

MAIN BODY: CF is a genetic disorder characterized by chronic inflammation and persistent infections, primarily affecting the respiratory system. This review explores the multifaceted roles of EVs in CF lung disease, focusing on their biogenesis, cargo, and contributions to disease progression. It is well known that CF results from mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, leading to defective ion transport, thick mucus secretion, and a propensity for bacterial infections. However, it has been observed that EVs derived from CF patients carry altered molecular cargo, including proteins, lipids, RNA, and DNA, which can exacerbate these conditions by promoting inflammation, and modulating immune responses. Beyond their pathogenic roles, EVs also hold significant therapeutic potential. Their natural ability to transfer bioactive molecules positions them as promising vectors for delivering therapeutic agents, such as gene therapy constructs and anti-inflammatory compounds. Accordingly, a study has shown that these EVs can act as a carrier molecule for transport of functional CFTR mRNA, helping to restore proper chloride ion channel function by correcting defective CFTR proteins in affected cells.

CONCLUSION: This review aims to summarize the role of EVs and their molecular cargo in pathogenesis of CF lung disease via modulation of intracellular signaling leading to persistent inflammation and increased disease severity. We also explored the mechanisms of EV biogenesis, cargo selection, and their effects on recipient cells which may provide novel insights into CF pathogenesis and open new avenues for EV-based therapies aimed at improving disease management.

PMID:40257719 | DOI:10.1186/s40348-025-00190-4

J Asthma. 2025 Apr 21:1-14. doi: 10.1080/02770903.2025.2494222. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma is a common condition among women of childbearing age, requiring careful management, particularly during pregnancy. Despite existing guidelines, significant gaps remain in asthma management during pregnancy, notably for women with moderate-to-severe asthma.

AIM: This study aimed to explore the awareness, limitations, and challenges of asthma management during childbearing age and pregnancy from both asthmatic women (AW) and physician perspectives in Italy. Additionally, it sought to identify unmet needs and collect real-life experiences from Italian centers specialized in severe asthma care.

METHODS: An anonymous online survey was disseminated through scientific networks and patient associations. Separate questionnaires were developed for doctors and AW by a task force of specialists.

RESULTS: 76 doctors and 54 AW completed the survey, with 70% of AW reporting moderate-to-severe asthma. While most physicians had experience managing asthma in pregnancy, 40% lacked systematic collaboration with gynecologists recognizing the need for integrated care. Despite guidelines supporting asthma medication continuity, 60% of doctors reported discontinuing treatments due to perceived risks. However, surveyed AW generally expressed greater confidence in medication safety. Physicians and AW highlighted the lack of pre-pregnancy counseling, with 55% of AW reporting they had never discussed pregnancy plans when starting asthma treatment. Both groups emphasized the need for improved interdisciplinary collaboration and structured asthma care pathways during pregnancy.

CONCLUSIONS: This study reveals significant gaps in asthma management for women of childbearing age and during pregnancy, especially those with moderate-to-severe asthma. Improving outcomes requires better education for patients and healthcare providers, along with a structured multidisciplinary network.

PMID:40257168 | DOI:10.1080/02770903.2025.2494222

Clin Pharmacokinet. 2025 Apr 21. doi: 10.1007/s40262-025-01505-4. Online ahead of print.

ABSTRACT

Pulmonary complications are the leading cause of morbidity and mortality in pediatric patients with cystic fibrosis. Altered pharmacokinetic parameters in this population, as well as high inter- and intra-individual variability, complicate the optimization of anti-infective treatments. In this review, we aim to summarize and describe all anti-infective population pharmacokinetic (popPK) models applied to pediatric populations with cystic fibrosis. Our objectives were to identify the most-reported structural models and retained covariates and to compare the dosing regimens used in clinical routine with those recommended in literature and guidelines. A literature search was done through the PubMed database from inception to August 2024. Studies were retained only if they complied with the inclusion and exclusion criteria. The review included 21 popPK models covering the pharmacokinetic profiles of eight different molecules. Among these, five are recommended antibiotics for treating pulmonary infections in patients with cystic fibrosis. All models incorporated body composition and/or renal function measures as covariates in their pharmacokinetic parameter equations. Standard dosing regimens in the studies were consistent with guidelines and literature recommendations. This is the first review summarizing and describing all anti-infective popPK models in pediatric patients with cystic fibrosis. Improved estimation of pharmacokinetic parameters and a clearer understanding of variability sources will enhance the optimization of antibiotic treatment in clinical practice. Finally, the impact of new targeted therapies on the management of this population will have to be closely monitored in the years ahead.

PMID:40254714 | DOI:10.1007/s40262-025-01505-4

J Cyst Fibros. 2025 Apr 19:S1569-1993(25)00772-6. doi: 10.1016/j.jcf.2025.04.006. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis related diabetes (CFRD) is the most common comorbidity of cystic fibrosis (CF) still, its pathogenesis is poorly understood. Recent studies have suggested that although pancreatic insufficiency is an important explanation for CFRD development, inherent pancreatic islet cell dysfunction may play a role. This study aimed to systematically compile current data regarding the impact of pancreatic islet cell dysfunction on the development of CFRD.

METHODS: A systematic search was conducted in PubMed and Embase. The resulting articles were screened for relevant experimental design and outcomes. Articles underwent data extraction and quality assessment before compilation and analysis of the results.

RESULTS: A total of 268 articles were initially screened and 19 studies conducted between 2006-2022 were finally included in this review. Half of the studies in human tissue and most of the studies in animal tissue could detect CFTR in the islets. Similarly, half of the publications in human islets and most studies in animal islets detect decreased insulin secretion with inhibition/mutation of CFTR.

CONCLUSIONS: The literature on the role of islet CFTR is contradictory. However, a pattern emerges where CFTR loss-of-function mutations have the potential to negatively affect islet cell function in a way that, together with previously described exocrine damage occurring in CF, could play a part in the development of CFRD.

PMID:40254519 | DOI:10.1016/j.jcf.2025.04.006