BACKGROUND:Bronchiolitis obliterans syndrome (BOS) is the most common non-infectious complication of allogenic hematopoietic stem cell transplantation (HSCT) and is associated with poor outcomes. Hyperpolarized 129Xe MRI (Xe-MRI) holds promise for sensitive and non-ionizing imaging of lung ventilation in children and has been explored in the post-HSCT population. However, previous work was weighted towards children without BOS. In this pilot cross-sectional study, we hypothesize that ventilation abnormalities measured with Xe-MRI are increased in pediatric post-HSCT participants with BOS compared to those without. METHODS:Two groups of pediatric post-HSCT participants were recruited: those with a diagnosis or clinical findings consistent with BOS and those without. Xe-MRI was performed to calculate the ventilation defect percentage (VDP) and ventilation heterogeneity index (VHI) in all subjects. Group-wise differences were tested with Mann-Whitney U-test. Xe-MRI was compared to same-day spirometry and nitrogen multiple breath washout (MBW). RESULTS:Twelve (6 non-BOS and 6 BOS) participants aged 9-17 years (median 12.5 years) were recruited. VDP (median [range]) was elevated (p < 0.05) in participants with BOS (11.8 [4.3, 20.8]%) compared to those without BOS (4.0 [3.1, 4.9]%). A similar elevation (p < 0.01) in VHI was observed in those with BOS (12.1 [8.3, 16.3])%) compared to those without (7.4 [7.4, 8.1]%). Both VDP and VHI were correlated with forced expiratory volume in 1-second (FEV1) and the lung clearance index (LCI), while VDP also correlated with FEV1 over forced vital capacity ratio (FEV1/FVC). CONCLUSION:Xe-MRI ventilation measures were elevated in pediatric post-HSCT participants within the BOS group compared to those without BOS and correlated with same-day spirometry and MBW.
INTRODUCTION:Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to relevant clinical advances in people with cystic fibrosis (pwCF). However, its effects on aerobic fitness are unclear. OBJECTIVE:To evaluate the effects of CFTR modulator therapy on aerobic fitness in pwCF through a systematic review and meta-analysis. METHODS:This systematic review (CRD420251066602) was conducted by searching major databases without date or language restrictions. Analytical studies evaluating cardiopulmonary exercise testing outcomes before and after CFTR modulator therapy were included. The primary outcome was peak oxygen uptake (peak VO2). Secondary outcomes included peak VO2 (% predicted), VO2 at the first ventilatory threshold (VT1), breathing reserve, workload, forced expiratory volume in one second (FEV1), and body mass index. Meta-analyses were performed using a random-effects model with heterogeneity assessed by the I2 statistic, and sensitivity analyses conducted. RESULTS:Thirteen studies (n = 578 participants) were included, of which 11 were eligible for meta-analysis. The meta-analysis did not identify a significant improvement in peak VO2 (mL·kg-1·min-1) after CFTR modulator use (MD = -0.22; 95% CI: -2.10 to 1.65; p = 0.82). For submaximal outcomes, after sensitivity analysis, VO2 at VT1 was significantly lower in the post-intervention period (MD = -1.85; 95% CI: -2.61 to -1.10; p < 0.00001). Breathing reserve increased significantly (MD = 7.94; 95% CI: 2.15 to 13.73; p = 0.007), and workload also increased significantly (MD = 15.39; 95% CI: 2.20 to 28.58; p = 0.02). CONCLUSION:CFTR modulator therapy is not consistently associated with improvements in aerobic fitness, as assessed by peak VO2, although it appears to variably influence outcomes related to ventilatory response and exercise performance.
BACKGROUND:Congenital chylothorax is a rare pulmonary developmental disorder with high associated morbidity and mortality. A limited number of cases have been described, and clinical manifestations and outcomes vary. METHODS:This study aims to delineate the neonatal and long-term outcome of patients with congenital chylothorax by retrospective and prospective data collection at Ghent University Hospital in Belgium between 1992 and 2022. RESULTS:Eighteen patients with congenital chylothorax were included, seven of whom had a pathology-confirmed diagnosis of congenital pulmonary lymphangiectasia. Of 16 patients with prenatal diagnosis, four underwent an intra-uterine intervention. Thirteen patients were born prematurely. The most common comorbidities were hydrops (8/18), pulmonary hypertension (3/18), and reflux disease (6/18). One patient was diagnosed with Noonan syndrome. The majority of patients (14/18) required mechanical ventilation. Treatment included pleural drainage (15/18), total parenteral nutrition (14/18), medium-chain triglyceride diet (11/18), somatostatin (8/18), and surgical intervention (3/18), with a median hospital stay of 59 days. Three patients died during or after the neonatal period. Follow-up ranged from 6 months to 30 years, with most patients reporting good general health but variable respiratory complaints. Five out of eight respiratory function tests showed mild abnormalities. Follow-up chest CT showed persistent changes in all but two patients up to a maximum age of 16 years. Health-related quality of life was similar to healthy controls. CONCLUSION:Congenital chylothorax demonstrates a variable neonatal course. Long-term outcomes are generally favorable in patients without comorbidities, although mild pulmonary function and chest CT abnormalities persist in the majority of patients.
INTRODUCTION:Individuals born preterm (before 37 weeks' gestation) have an increased risk of developing lung disease compared with those born at term. However, life-long lung function trajectories and the factors influencing them remain insufficiently understood in this population, reflecting an unfortunate scarcity of data, substantial heterogeneity in findings, and variability across centers. The Prematurity's Effect on the Lungs in Children and Adults Network (PELICAN) was established in 2020 as a Clinical Research Collaboration of the European Respiratory Society, with a key aim to develop the first harmonized global repository of demographic, clinic and lung function data from existing datasets on individuals born preterm. METHODS:Eligible datasets for inclusion were identified through three systematic literature reviews. A scientific steering committee was convened and organized into sub-groups, which undertook a consensus-based variable selection and data harmonization exercise. Data contributors uploaded data to a secure online portal, where further harmonization was applied. RESULTS:As of June 2026, the PELICAN data repository includes 20 datasets representing 14 countries and 3,388 individuals born preterm. PELICAN collects 142 variables, of which 96 have been fully harmonized across all contributing datasets, and 42 partially harmonized. Four variables could not be harmonized. CONCLUSIONS:In this paper, we describe the PELICAN collaboration, outline key challenges and successes encountered during data harmonization, and report data availability to date. This work represents an important step towards understanding the respiratory consequences of preterm birth and could inform the development of a Core Outcome Set for future data collected in this area.
BACKGROUND:Heated, humidified, high-flow nasal cannula (HFNC) before intubation has been associated with increased mortality in children with immunocompromising conditions (ICC). OBJECTIVES:We sought to describe HFNC failure (intubation) rate and aimed to develop a novel score associated with HFNC failure. METHODS:This is a single center, retrospective cohort. Patients (aged 0-26 years) with ICCs who used HFNC between 2021 and 2023 were included. RESULTS:Forty-four (47.3%) of 93 included subjects failed HFNC. PICU mortality was 14% (n = 13). The median duration of HFNC was 18.7 h (IQR: 6.0, 40.4). We developed the novel FLOX ((flow in Liters/minute)/weight (kg)*FiO2) score. Median FLOX score was higher with HFNC failure at initiation (p = 0.04), 2 h (p = 0.03), 4 h (p = 0.05), and 6 h (p = 0.05). Adjusting for acuity, the odds of HFNC failure with a FLOX score (≥0.20) were as follows: Initiation OR = 2.5 (95%CI: 1.03, 5.9), p = 0.042); 2 h of HFNC, OR = 4.3 ((95%CI: 1.7, 10.9), p = 0.002); 4 h of HFNC, OR = 6.5 (95%CI: 2.5, 16.8), (p < 0.001); and 6 h of HFNC, OR = 4.9 (95%CI: 1.9, 12.7), (p = 0.001). CONCLUSION:In children with ICCs, almost half fail HFNC. Mortality was high in those who fail HFNC. The FLOX score, specifically a FLOX ≥ 0.20 is associated with increased odds of failing HFNC in our ICC cohort.
INTRODUCTION:Advancements in the care of people with cystic fibrosis (PwCF) have made discussions about reproductive health increasingly important. Rising rates of both intended and unintended pregnancies highlight the need for effective contraception counseling. Understanding current contraception use patterns and identifying priorities for contraception education amongst PwCF are therefore essential. METHODS:A web-based survey was developed in partnership with Community Voice, a virtual community of PwCF and their family members supported by the Cystic Fibrosis Foundation. The survey was distributed over a 5-week period (June-July 2025) to participants from Community Voice and Elevate. Females with cystic fibrosis aged 18 years and older were eligible to participate. RESULTS:Ninety-seven PwCF completed the survey, representing 27 U.S. states and four Canadian provinces. Among individuals currently using contraception, the most common methods were intrauterine devices (34%), combined oral contraceptives (28.3%), and condoms/barrier methods (24.5%). Although 90% of PwCF were not actively trying to conceive, only 55% reported using a form of birth control. Knowledge-based questions revealed persistent misconceptions about the impact of common antibiotics on contraceptive effectiveness. While most PwCF (68.1%) wanted contraception information from their CF care team, only 28.9% reported receiving such education. Side effects were a major factor in decision-making: 78.9% selected contraceptive methods based on side-effect profiles (valued more than efficacy), 68.6% reported experiencing side effects, and side effects were the leading reason for contraception discontinuation. CONCLUSION:CF care teams can play a critical role in initiating and supporting conversations about contraception. Team members, including pharmacists, can provide medication counseling and help PwCF select contraceptive methods that align with their individual goals and needs.
BACKGROUND:Parapneumonic pleural effusion (PPE) is a frequent complication of pediatric pneumonia. Some cases progress to complicated PPE (cPPE), which is associated with greater morbidity, longer treatment, and a higher likelihood of need for pleural drainage. Early identification of children at risk of progression remains difficult at presentation, and pediatric evidence on early predictors is scarce and inconsistent. METHODS:We conducted a retrospective observational study including children aged <18 years admitted with PPE between 2015 and 2025. cPPE was defined through standard laboratory and/or imaging criteria. Twenty clinical, laboratory, and radiological candidate predictors available at initial evaluation were assessed. After univariate screening, variables with statistical association and clinical relevance were entered into a multivariate logistic regression model. After model assessment, a simplified score was derived from the original model for bedside use. RESULTS:A total of 122 children were included, 77 (63%) with cPPE and 45 (37%) with uncomplicated PPE. In univariate analyses, younger age, dyspnea, chest wall retractions, reduced lung sounds, C-reactive protein, lower hemoglobin, pleural effusion thickness, and mediastinal shift were associated with cPPE. In the final multivariate model, five variables remained independently associated: age (OR 0.73, 95% CI 0.63-0.84), retractions (OR 3.23, 95% CI 1.16-8.95), C-reactive protein ≥176.5 mg/L (OR 2.83, 95% CI 1.02-7.82), pleural effusion thickness (OR 2.16, 95% CI 1.27-3.70), and mediastinal shift (OR 10.75, 95% CI 2.24-51.64). The model showed good discriminatory performance, with an AUC of 0.883 (95% CI 0.817-0.948). The optimal probability threshold was 0.49, yielding a sensitivity of 92.2% and a specificity of 71.1%. A simplified additive clinical score derived from the model demonstrated similar performance, allowing stratification into four risk groups with progressively increasing observed rates of cPPE. CONCLUSIONS:Early risk stratification of pediatric PPE is feasible using a small set of readily available clinical, laboratory, and radiological variables. The proposed model and the adapted clinical score showed good discriminatory ability and may help identify children at increased risk of progression to cPPE who could benefit from closer monitoring and early optimized management. External validation is needed before routine clinical implementation.
Functional lung imaging enables pulmonary parameters, including ventilation, perfusion, gas exchange, and biomechanics, to be mapped and quantified noninvasively throughout the lungs. Pulmonary function testing is generally more difficult to perform in a child in comparison to an adult, and so pulmonary functional imaging has the potential to significantly benefit pediatric cohorts, giving clinicians an additional tool in assessing and managing pediatric lung disease. This scoping review aims to (1) identify current and emerging functional lung imaging techniques that have been investigated in pediatric cohorts and (2) describe how they have been compared to pulmonary function tests. PubMed, EMBASE, and CINAHL were searched for studies comparing pulmonary functional imaging techniques with pulmonary function testing in pediatric cohorts ≤ 18 years old. A total of 54 studies were included. Techniques were grouped into magnetic resonance imaging (MRI), computed tomography (CT), electrical impedance tomography (EIT), X-ray, and nuclear medicine methods. Most studies compared spirometry, multiple breath nitrogen washout, or both. At present, hyperpolarized gas MRI studies are the most widely investigated modality in children. However, despite the multiple different modalities investigated, there are no methods that have entered standard clinical pediatric use. Further research into functional lung imaging in pediatrics is required to provide validation, standardization, and establishment of normal values prior to implementation of these modalities into routine clinical care.
BACKGROUND:People with cystic fibrosis (pwCF) have complex treatment regimens with cystic fibrosis transmembrane conductance regulator (CFTR) modulators and supportive therapies. Evidence on adherence across cystic fibrosis (CF) therapies using different assessment methods and the added value of medication reviews remains limited. OBJECTIVE(S):This study compared adherence across CF therapies using three assessment methods and evaluated the contribution of medication reviews. METHODS:This cross-sectional study (February to April 2025) included pediatric and adult pwCF at Maastricht University Medical Centre+. Adherence to CFTR modulators and supportive therapies (vitamin supplements, pancreatic enzymes, inhalers, and nebulizers) was assessed with pharmacy refill data (medication possession ratio, MPR); self-reported adherence (Medication Adherence Report Scale-5, MARS-5), and structured medication reviews. The primary outcome was the proportion of pwCF adherent to CF medication per assessment method. Secondary outcomes were the within-patient differences in adherence between CFTR and supportive therapies (McNemar's exact test) based on MPR and the number and acceptance of DRP-interventions in the medication review. RESULTS:Forty-three pwCF (17 children, 26 adults; 39.5% female) were included. For CFTR modulators, adherence was 91.7% (MPR), 91.2% (MARS-5), and 72.2% (medication review). For supportive therapies, adherence was 56.3%, 77.7%, and 77.4%, respectively. Four nonadherent pwCF were identified exclusively through medication review. Within-patients, adherence was higher for CFTR modulators than for supportive therapies (p < 0.001). Medication reviews identified 51 DRPs in 41 pwCF (including nonadherence in 12 pwCF), all proposed interventions were accepted by the treating physician. CONCLUSION:Adherence varied by medication class and assessment method. Medication reviews provided clinically relevant information in addition to refill-based and self-reported measures.
BACKGROUND:Pediatric mild asthma is considered a benign condition, yet it accounts for a substantial proportion of morbidity. Characterization and management of children or adolescents with mild asthma are less explored than in adults, particularly due to its heterogeneous nature and variable course. Current definitions of mild asthma in pediatric populations vary across international guidelines or reports, limiting standardization. Although knowledge of asthma phenotypes and endotypes, and risk biomarkers has progressed notably, it is incomplete in the different pediatric age groups exhibiting mild or intermittent symptoms. Moreover, differing treatment recommendations may lead to uncertainty in clinical practice on whether using short-acting β2-agonist monotherapy or intermittent or daily inhaled corticosteroids or the regimen with inhaled corticosteroids plus bronchodilators combined in single-inhalers. METHODS:In this narrative review, we integrated evidence and recommendations from major asthma guidelines and reports complemented by selected insights from recent literature not addressed in these sources. RESULTS:We summarized the current knowledge of pediatric mild asthma, risk factors for exacerbation, treatment recommendations, and highlighted gaps in clinical practice or questions still unanswered. CONCLUSIONS:In children and adolescents, asthma may seem only apparently mild, mainly due to overlooked or poorly controlled exacerbations. A more unified approach would improve clinical outcomes and reduce its global burden. Priorities include a standardized definition of the mild asthma phenotype in children and adolescents, a detailed examination of risk factors as early predictors of poor outcomes and of the limited access to medications and healthcare resources in low-income countries. Incorporating a broader global health perspective would provide a more comprehensive understanding of the factors influencing the care of children with mild asthma worldwide.
Despite advances in medical care, respiratory tract infections continue to be a leading cause of morbidity and mortality in children worldwide. In addition to posing a healthcare burden, infections acquired early in life are associated with long-term detrimental effects on lung and immune function. This narrative review examines evidence on how environmental factors, such as air pollution and microbes, can affect children's susceptibility to upper and lower airway infections. Epidemiological studies correlate elevated concentrations of ambient and indoor air pollution with a higher frequency of acute upper and lower respiratory tract infections in pediatric populations. Experimental investigations of individual criteria air pollutants such as PM2.5 demonstrate compromised lung epithelial barrier integrity, oxidative stress and inflammation, and impaired innate and adaptive immune cell function with exposure, all of which may contribute to enhanced infection rates. Concomitantly, the developing respiratory microbiome plays a central role in shaping mucosal immunity; balanced communities provide colonization resistance and support immune education, while dysbiosis driven by antibiotic exposures, air pollution, or other perturbations can predispose to infection and chronic respiratory disease such as asthma. Exposure to diverse environmental microbes, including certain fungi, may also be protective against respiratory illness, and specific microbial signals can confer antiviral benefits. Collectively, the interplay between environmental exposures and infection risk is complex and likely influenced by developmental factors. Policies aimed at improving air quality and strategies to support a healthy microbiome in early life can mitigate the risk of respiratory infections and promote lifelong lung health.
OBJECTIVE:To compare the effectiveness of various surfactant administration methods. METHODS:We conducted an umbrella review of meta-analyses conducted on randomized controlled trials. The search was conducted in March 2024 in four databases. Two authors screened the results and extracted the data. Review quality was assessed according to AMSTAR-2. Traffic-light plots were used to summarize the effectiveness of different administration methods. RESULTS:Nineteen meta-analyses comprising 247 comparisons were included. The most evaluated method was less invasive surfactant administration (LISA), across 16 comparisons versus InSurE and intubation. LISA significantly reduced risks of bronchopulmonary dysplasia (BPD), BPD or death combined, mechanical ventilation, pneumothorax/air leaks, and intraventricular hemorrhage (IVH) versus intubation; it also lowered mortality versus InSurE and intubation. No IVH difference was seen between LISA and InSurE. Five comparisons (17 outcomes) assessed laryngeal mask airway (LMA) against intubation and InSurE. LMA reduced subsequent intubation or mechanical ventilation versus intubation. Findings on post-surfactant FiO2 were inconsistent. No differences were observed in mortality, BPD (or death), IVH, additional surfactant needs, pneumothorax, patent ductus arteriosus, desaturation, reflux, procedure failure, bradycardia, or home oxygen use between LMA and intubation, nor in BPD outcomes versus InSurE. CONCLUSION:Based on recent meta-analyses, LISA appears to be the most effective and extensively evaluated surfactant administration method in head-to-head comparisons. Future research should clarify LMA's role and establish a definitive method hierarchy; currently, LISA remains the preferred choice when feasible.
Primary ciliary dyskinesia (PCD) is a rare, hereditary disorder characterized by impaired motile ciliary function, resulting in abnormal mucociliary clearance (MCC). This leads to persistent infection and inflammation, progressive airway damage, and bronchiectasis. Physiotherapy, particularly airway clearance therapy (ACT), is considered a cornerstone of PCD management to compensate for the mechanical MCC deficit, aiming to reduce infection risk, prevent disease progression, and improve quality of life (QOL). However, evidence supporting specific physiotherapy regimens in PCD remains limited. Current practice varies widely across centers and countries, with no standardized guidelines. Common ACT methods include positive expiratory pressure (PEP) with or without oscillation, autogenic and postural drainage, active cycle of breathing technique (ACBT), intrapulmonary percussive ventilation (IPV), and high-frequency chest wall oscillation (HFCWO). Comparative studies show no clear superiority among techniques. Evidence for mucolytic therapy, such as hypertonic saline or rhDNAse, is weak or controversial. Scarce data demonstrate potential benefits of exercise interventions in improving ventilatory capacity and QOL. Age-specific considerations are crucial: ACT should be started early, be adapted to developmental stages, and be combined with strategies to enhance adherence. Despite physiotherapy being standard care, randomized controlled trials are challenging due to ethical constraints, potentially reducing a therapy that is already believed to be helpful. Future priorities include developing international guidelines and conducting high-quality studies to optimize treatment strategies. In conclusion, physiotherapy plays a crucial role in PCD management, but current recommendations rely largely on expert opinion and extrapolation from related conditions like cystic fibrosis (CF) and non-CF bronchiectasis (BRECT), underscoring the need for robust evidence.
INTRODUCTION:Dysregulated protease activity contributes to airway inflammation and tissue remodeling in cystic fibrosis (CF); however, the role of the lysosomal cysteine protease Cathepsin B (CTSB) remains incompletely defined. This cross-sectional study investigates relationships between pro-CTSB and mature CTSB activity with CF-specific pathogens and airway inflammation in children with and without CF. METHODS:Bronchoalveolar lavage fluid (BALF) was collected from clinically indicated bronchoscopies in children (N = 52 CF, N = 161 non-CF). CTSB was interrogated using ELISA, fluorogenic activity assay, and Western blot analysis to distinguish pro- and mature CTSB. Total bacterial and total fungal load (TFL) were quantified by quantitative polymerase chain reaction, and community composition was determined by 16S bacterial and 18S fungal sequencing. Concentrations of proinflammatory cytokines and neutrophil elastase (NE) were measured via Luminex multiplatform and a spectrophotometric assay, respectively. Analyses included Spearman's rank correlations and Wilcoxon rank-based tests. RESULTS:Pro-CTSB and CTSB activity were significantly (p < 0.01) elevated in CF BALF and in samples with a positive Staphylococcus aureus airway culture. Pro-CTSB concentrations correlated with staphylococcal relative abundance (RA, ρ = 0.25, p < 0.02) and reduced bacterial diversity ( ρ = -0.41, p < 0.01). Mature CTSB activity correlated with TFL ( ρ = 0.50, p < 0.05) and Aspergillus spp. RA ( ρ = 0.36, p < 0.04). Western blot analysis confirmed pro-CTSB expression and mature CTSB in BALF with measurable activity. Both CTSB measures correlated strongly with NE and proinflammatory cytokines ( ρ ≥ 0.47, p < 0.001). Pro-CTSB concentrations negatively correlated with FEV1/FVC measurements in CF ( ρ = -0.32, p = 0.05). CONCLUSIONS:BALF CTSB concentration may serve as a CF-specific biomarker of infection-related inflammation and obstructive lung disease driven by specific pathogen interactions.
BACKGROUND:Advances in genetic analysis techniques and strategies have enabled the identification of rare novel genetic entities in children's interstitial lung disease (chILD). AIMS:To describe an extensive array of demographic, clinical, radiological, and laboratory data from a national registry of children with diffuse lung disease caused by rare and novel genetic variants. STUDY DESIGN:Retrospective cohort study. METHODS:This study used data from the chILD Türkiye (chILD-TR) registry to analyze rare genetic chILD subtypes, excluding surfactant protein gene variants, ABCA3, and NKX2-1, between November 2021 and January 2024. Of 671 patients in chILD-TR, 182 underwent genetic analysis excluding surfactant protein-related variants, resulting in 37 patients identified with rare genetic variants included in the study. RESULTS:Among the 37 patients with rare genetic variants, 19 (51.4%) were male, and the median age at diagnosis was 40.5 months (IQR 15.5-115.5). Genetic analysis conducted on 15 patients identified COPA, STAT3, STING1, ADA, ZNFX1, PIK3CD, PLCG2, OAS1, CCR2, RNF168 and ATM gene variants, which are associated with immunodeficiency/dysregulation and autoinflammation; 15 NPC1, SMPD1, GBA1, SLC7A7, MARS1, FARSB, and PEPD genes, variants linked to inherent metabolic errors. Seven patients were found with TBX4, SLC34A2, PLG, and SMAD4 gene variants. All patients were born at term, and five (13.5%) of them were small for gestational age. Two patients (5.4%) had previously been on a mechanical ventilator in the neonatal intensive care unit, 25(67.6%) had familial consanguinity, and 23 (62.1%) had comorbid systemic disease. Thirteen patients (35.1%) required oxygen support. All patients underwent chest computed tomography scans at initial assessment, showing ground-glass opacities in 29 (78.3%), infiltrations in 27 (72.9%), and interlobular septal thickening in 20 (54%). Eight patients (21.6%) received oral steroids, and six (16.2%) received pulse steroids in addition to their primary treatments for systemic diseases. CONCLUSIONS:Interstitial lung disease rarely occurs in children, but increased awareness and genetic testing may enable earlier diagnosis. Recognizing that diffuse parenchymal lung disease can occur in rare systemic diseases may improve diagnoses and treatment.
