Pediatric Pulmonology

Bronchopulmonary dysplasia (BPD) in infancy is a risk factor for obstructive lung disease in adults. We hypothesized that adults born preterm and diagnosed with BPD have an altered lung architecture which is correlated to lung function impairment. Individuals from the LUNAPRE cohort (clinicaltrials.gov/ct2/show/NCT02923648) were included: preterm born (gestational week <32) with (n=24) or without (n=23) a previous diagnosis of BPD, full term born with allergic asthma (n=22) and healthy volunteers (n=24). Inspiratory and expiratory HRCT scans were performed and interpreted by two expert reviewers in a blinded manner. Structural changes were scored and quantitative density measurements were analysed automatically using a dedicated post-processing workstation. The HRCT scores were significantly higher in the BPD group compared to the other groups (p<0.001) and had highest numbers in subjects diagnosed with severe BPD. Most common HRCT changes were small peripheral opacities. Hypoattenuation during inspiration was only observed in the BPD group. Architectural distortion was observed in 6/24 BPD and 2/23 premature without BPD. HRCT scores correlated to FEV1 in a negative manner for preterm (p<0.001) and BPD (p<0.05) groups. Oxygen supplementation during the neonatal period correlated with HRCT score in a positive manner for preterm group (p<0.001). No differences in lung density were observed between the groups. Young adults previously diagnosed with BPD have structural changes on CT which correlate with airway obstruction. Severity of BPD at the diagnosis was associated with CT abnormalities in adulthood. HRCT changes in adults with BPD were correlated with spirometry findings.

BackgroundRecent guidelines differ in how fractional exhaled nitric oxide (FeNO) is used to diagnose school-age asthma, either as one of several tests with a cut-off at 25 ppb or as a single rule-in test at 35 ppb. Evidence on its diagnostic performance and clinical utility in subgroups remain limited. MethodsWe analysed data from 1,979 school-age children in the Swiss Paediatric Airway Cohort referred for suspected asthma. We investigated FeNO performance with diagnosis by paediatric pulmonologists as reference standard using receiver operating characteristics curves, selected cut-offs and simulated predictive values across different prevalence. Subgroup analyses considered allergic sensitisation with allergic rhinitis and current inhaled corticosteroid (ICS) use. ResultsIn the overall cohort (asthma diagnosis 70%), FeNO showed poor discrimination for asthma (AUC 0.66; 95% CI 0.64-0.68) with an optimal cut-off at 22 ppb. At 25 and 35 ppb, sensitivity was low (43%, 95% CI 40-46; 31%, 95% CI 29-34) and specificity moderate to high (84%, 95% CI 77-84; 90%, 95% CI 87-92). Positive predictive value at 35 ppb was 88% and was 57% when simulated at a prevalence of 30%. FeNO had no diagnostic value in non-sensitised children and lower performance in sensitised children with allergic rhinitis than in those without (AUC 0.59 vs 0.68). Current ICS use did not influence performance. ConclusionFeNO has limited diagnostic performance as a stand-alone test for school-age asthma, and underlying asthma prevalence and allergic characteristics should be considered in the interpretation.

Objective: Upper respiratory infections (URI) are the major trigger of asthma exacerbations in children with asthma and are more likely to be reported by Black and Mexican American children compared to White children in the US. We aimed to evaluate the extent to which obesity, nicotine exposure, household size, and socioeconomic status (SES) explained this excess URI risk among all children and among children with asthma. Study Design: Data collected on children aged 6-17 years from the National Health and Nutritional Examination Survey (2007-2012) were analyzed using survey weights and a mediation approach. Household SES was analyzed as a cumulative score reflecting income poverty ratio, education, and rental housing. URI was defined as cough, cold, phlegm, runny nose, or other respiratory illness (excluding hay fever and allergies) in the past 7 days. Results: Obesity and serum cotinine, a marker of nicotine exposure, explained little to none of the excess risk of URI while SES explained 36.4% (95% CI=34.1, 38.6) in Black and 28.5% (95% CI=26.7, 30.5) in Mexican American children. Living in rental housing and income poverty ratio<2, explained half (49.6%, 95% CI=46.9-52.3) and 20% (19.7%, 95% CI=18.9-20.5) of the excess URI risk among Black children, respectively. In Mexican American children, rental housing and low educational attainment each explained approximately 15-17% of the excess URI risk. Results were comparable among children with asthma. Conclusions: Markers of poverty, such as rental housing, contributed substantially to the excess risk of URI among Black and Mexican American children, including among those with asthma.

Methods: Using Global Burden of Disease (GBD) data, we analyzed prevalence, incidence, mortality, and disability-adjusted life years (DALYs) rates across global and 21 GBD regions from 1990-2023. Joinpoint regression identified temporal trends, age-period-cohort models analyzed effect contributions, Das Gupta decomposition quantified demographic and epidemiological impacts, inequality indices assessed health equity, and Bayesian models projected 2024-2038 trends. Results: In 2023, the global number of children and adolescents with asthma reached 131 million, with an age-standardized prevalence rate (ASPR) of 1,789.9 per 100,000. From 1990 to 2023, the global ASPR and age-standardized incidence rate (ASIR) of asthma in children and adolescents showed an upward trend, while the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years (DALYs) rate (ASDR) exhibited a downward trend. Among the 0-14 age group, the disease burden was greater in males than in females, whereas in the 15-19 age group, males had a lower disease burden than females. Projections indicate that over the next 15 years, the overall disease burden will continue to decline; however, female mortality rates and DALYs rates are projected to show an upward trend. Conclusions: The increasing prevalence and incidence rates, coupled with declining mortality and DALYs rates of asthma among children and adolescents globally, underscore the necessity for targeted public health interventions. These findings provide crucial insights for early diagnosis, treatment optimization, and global health policy formulation.

BackgroundTBX4 variants are a recognised cause of paediatric pulmonary hypertension (PH), often associated with interstitial lung disease (ILD). Evidence for ILD-directed therapy in this group is lacking. MethodsWe conducted a retrospective study of children ([&le;]18 years) with TBX4-associated PH at a national centre (2001-2025). ILD was defined using ChILD-EU criteria. Patients treated with pulsed intravenous methylprednisolone were assessed for response using ChILD-EU categories. Secondary outcomes included respiratory severity score (RSS), functional class (FC), echocardiographic measures, and NT-proBNP. ResultsOf 21 children, 11 (52%) had ILD; 9 received corticosteroids. Median age at treatment was 0.8 years. A clear or best response occurred in 7/9 (78%). RSS improved in 6/9 (p=0.02), with all children on respiratory support showing partial or complete weaning. Functional class improved in all with FC III/IV at baseline (p=0.02). Right ventricular function improved (TAPSE z-score +1.65, p=0.04), and elevated NT-proBNP normalised. Key clinical milestones included ECMO weaning, transplant delisting, and discontinuation of prostacyclin therapy. No significant adverse effects were observed. Untreated children showed no early improvement. ConclusionsCorticosteroids were associated with meaningful improvements in respiratory and PH outcomes in TBX4-associated PH with ILD. Prospective evaluation is warranted.

ObjectiveTo test whether machine learning (ML) models trained on tidal breathing flow time series can discriminate between individuals with and without respiratory disease and predict lung function indices obtained from conventional pulmonary function testing. BackgroundAccurate assessment of respiratory function in infants and young children is challenging because conventional pulmonary function testing requires sophisticated equipment and/or active patient cooperation. Tidal breathing measurements, in contrast, can be obtained non-invasively with little or no patient cooperation and at low cost, yet their clinical utility has been limited. We hypothesized that sufficiently long tidal breathing flow time series contain clinically relevant information that can be extracted using a recurrent neural network known as a long short-term memory (LSTM) network. ApproachWe evaluated LSTM models in two scenarios within the Basel-Bern Infant Lung Development cohort. First, we assessed the ability of a model trained on flow and derived volume time series to detect bronchopulmonary dysplasia (BPD) in 329 infants. Second, we examined whether a model trained on tidal breathing flow alone could predict forced expiratory volume in one second (FEV1) in 135 school-age children. Signals were filtered and normalized prior to model training, and performance was evaluated on held-out test datasets. Main resultsFor BPD detection, the model achieved 97.0% accuracy, 100% specificity, 91.7% sensitivity, 100% precision, and an F1-score of 95.7%. For FEV1 prediction, Bland-Altman analysis showed a mean bias of -0.009 L (95% CI -0.091 to 0.074), with limits of agreement of -0.416 L and 0.399 L. The mean relative prediction error was 13.7%. SignificanceThese findings demonstrate that temporal patterns in tidal breathing flow signals contain diagnostically and functionally relevant information. ML applied to tidal breathing measurements may provide a low-burden, minimal-cooperation approach for early respiratory disease detection and functional assessment across early life stages.

Asthma is a chronic respiratory illness that causes mild to severe inflammation throughout narrowed airways. During allergic airways inflammation, autophagy prevents extensive lung tissue impairment while inducing a protective anti-pathogen response and macrophages in the lung to maintain homeostasis. Previous studies of autophagy genes and asthma have shown an association with variants in ATG5, but a comprehensive analysis of autophagy related genes and asthma has not been performed. Here we utilize summary statistic data generated from a two-stage genome-wide association study (GWAS) of asthma in the UK Biobank. We examined variants in 21 autophagy related genes and found statistically significant associations for 28 variants in two genes in the discovery dataset and nominally significant replication for 16 of these variants, all annotated to ATG4B. This is the first evidence of an association with variants in ATG4B with asthma which provides a novel potential for future drug development.

IntroductionAlthough temporal variation is the hallmark of asthma, recommended diagnostic approaches largely rely on single clinic-based measurements. Ambulatory monitoring captures diurnal and day-to-day variability and may therefore enhance diagnostic accuracy. We evaluated the clinical feasibility and potential utility of home spirometry and fractional exhaled nitric oxide (FeNO) monitoring in asthma diagnosis. MethodsSymptomatic, untreated adults with GP-suspected asthma underwent diagnostic tests including bronchodilator reversibility, in-clinic FeNO, blood eosinophil counts and bronchial challenge. Participants measured spirometry and FeNO four times daily over one week; during the second week spirometry were measured twice daily. The reference standard was provided (asthma/not-asthma) by an expert panel of at least two asthma specialists based on clinical history and the results of all in-clinic testing; home spirometry (except for peak expiratory flow) and FeNO measurements were blinded to the panel. ResultsOf 67 eligible participants, 51(76%) were recruited, and 38 had asthma confirmed or excluded by the panel. 1058 home spirometry measurements were obtained from 37(73%) participants; 848 home FeNO readings were obtained from 39(76%) participants. Among those completing at least one home measurement, median (IQR) adherence was 66.7(58.6-97.6)% for spirometry and 78.5(51.8-103.6)% for FeNO. Collection of health impact data for economic evaluation was feasible. In participants with a confirmed diagnostic outcome who completed home measurements (FeNO: n=32; spirometry: n=28), the putative home-testing metrics demonstrated high sensitivities at [&ge;]90% specificity, and outperformed peak expiratory flow diurnal variability. Incorporating home testing into the BTS/NICE/SIGN 2024 diagnostic pathway had the potential to reduce reliance on bronchial challenge testing by 57%. ConclusionsHome spirometry and FeNO testing and the prospective collection of health-economic data in the diagnostic setting were feasible. Home-based testing strategy showed early potential to improve asthma diagnosis and pathway efficiency. These findings support further evaluation through an adequately powered diagnostic accuracy study and health-economic assessment. Key messagesO_LIWhat is already known on this topic: Asthma can be difficult to diagnose, as objective tests may be normal when assessments are performed during periods of minimal or intermittent symptoms. C_LIO_LIWhat this study adds: Our data suggest that home spirometry and FeNO monitoring could be successfully implemented within a diagnostic accuracy trial. Participants were able to perform these tests reliably in the home environment. C_LIO_LIHow this study might affect research, practice or policy: The early findings suggest that home-based physiological monitoring may offer additive diagnostic value beyond standard clinic-based assessments and could reduce reliance on bronchial challenge testing. These results provide a clear rationale for larger diagnostic accuracy trials and for undertaking early health-economic modelling to assess the potential impact on clinical pathways and resource utilisation. C_LI

Background: The chromosome 1q31 Th2 pathway-associated interval has been linked to asthma, but its phenotype specificity and cross-ancestry architecture remain unclear. Methods: We analyzed African (AFR) and European (EU) ancestry datasets, including 9,965 asthma cases and 37,391 controls of AFR, and 6,074 cases and 116,255 controls of EU ancestry. Imputed dosage-based association analyses were performed for asthma, steroid-dependent asthma (SDA), and non-steroid-dependent asthma, followed by QC-filtered SDA remapping, leave-one-batch-out analysis, cross-ancestry comparison, and functional enrichment. Results: Strong regional association was observed only for SDA. After quality-control (QC) filtering, the SDA signal remained significant in both ancestries, with 2,280 genome-wide significant variants in AFR and 859 in EU. Cross-ancestry comparison identified 3,129 significant variants: 10 shared, 2,270 AFR-specific, and 849 EU-specific. Shared variants showed concordant effects, whereas 237 variants showed nominal heterogeneity. AFR-specific signals included PTPRC variants with larger effects in AFR. Functional enrichment suggested different biological emphases within the same interval: immune and contractile airway-wall biology in AFR, and additional neuroaxonal components in EU. Conclusions: The 1q31 interval is strongly associated with SDA in both AFR and EU populations, and its fine-scale architecture differs by ancestry. These findings highlight population-specific effects within a shared SDA susceptibility interval, with potential implications for population-informed precision medicine in steroid responsiveness and asthma management.

PurposeWe evaluated healthcare resource utilization (HCRU) and costs in patients with eosinophilic granulomatosis with polyangiitis (EGPA). MethodsPatients with newly diagnosed EGPA (2017-2021), [&ge;]12 months pre-diagnosis health plan enrollment, and [&ge;]1 inpatient or [&ge;]2 outpatient claims with an EGPA diagnosis were included. Follow-up was from EGPA diagnosis until disenrollment or database end. HCRU and health insurer payment costs during follow-up were compared with those for matched cohorts of general insured patients without EGPA (comparison A) and without EGPA but with severe uncontrolled asthma (SUA; comparison B). ResultsIn comparison A, all-cause HCRU was higher in the EGPA cohort (n = 213) versus matched patients (n = 779) for all clinical encounters/pharmacy claim types; annualized, mean total all-cause costs were 16-fold higher ($117,563/patient) versus matched patients ($7,520/patient). In comparison B, all-cause HCRU was higher for the EGPA cohort (n = 182) versus the matched SUA cohort (n = 640) for all clinical encounters/pharmacy claim types, with 5-fold higher mean total all-cause costs ($118,127/patient vs $22,286/patient). In both EGPA cohorts, HCRU and associated costs increased between the baseline and follow-up periods. ConclusionsThese findings highlight the need for more effective treatments to reduce the clinical and economic burden of EGPA.

Bubble continuous positive airway pressure (bCPAP) is a low-cost respiratory support device that has demonstrated different outcomes for children with severe pneumonia in different settings. Some differences in outcomes may be attributable to implementation factors (e.g., patient monitoring and feeding practices). We aimed to characterize bCPAP reach, implementation fidelity, and safety outcomes for children with severe pneumonia in Pakistan. We conducted a prospective cohort study at Aga Khan University Hospital and Abbasi Shaheed Hospital from February through May 2025. We enrolled children 1-59 months who met WHO criteria for severe pneumonia within 24 hours of presentation to the emergency department. Participants were followed daily via chart review, caregiver survey, and physical exam through discharge, transfer, or death. We reported the proportion of children receiving bCPAP ("reach") and constructed a mixed-effects, multinomial logistic regression model with robust standard errors to report: fidelity (child location in a highly monitored area, continuous monitoring, avoidance of unplanned disruptions to bCPAP, and avoidance of oral feeding); safety (aspiration events and pneumothorax); bCPAP failure (death, respiratory support escalation, or leaving against medical advice); and in-hospital mortality. Of 165 children with severe pneumonia, 88 (53%) received bCPAP over 141 bCPAP days. The average predicted probabilities (95% CI) of our fidelity measures were: 85% (78-92%) for location in a highly monitored area; 56% (51-60%) for continuous monitoring; 66% (57-75%) for continuous bCPAP without disruptions; 46% (36-55%) for avoidance of oral feeding while on bCPAP. Among children receiving bCPAP, 9 (10%) experienced an aspiration event, 1 (2.2%) experienced a pneumothorax; 19 (22%) experienced bCPAP treatment failure. One child (1.1%) died; 6 (6.8%) required respiratory support escalation; 14 (16%) left against medical advice. We identified several gaps in bCPAP reach and fidelity. These may be modifiable by individual-and team-targeted strategies to reduce bCPAP-related complications and pneumonia-related child deaths.

Background: Apnoea of prematurity is common and may cause desaturation and/or bradycardia. There is marked variability in infants cardiorespiratory responses to apnoea, despite standardised clinical thresholds. Factors influencing apnoea-related cardiorespiratory instability and whether instability can be predicted warrant investigation. Methods: 181,511 apnoeas >5 seconds were identified from continuous physiological recordings from 146 preterm infants <37 weeks postmenstrual age. Cardiorespiratory instability was defined as bradycardia (>30% heart rate reduction) and/or oxygen desaturation (<85%). Mixed-effects models assessed clinical, demographic and dynamic modulators of the relationship between apnoea duration and cardiorespiratory instability. Machine learning (XGBoost) was used to train models to predict apnoea-related cardiorespiratory instability. Results: Longer duration apnoeas were associated with increased instability, although variability was substantial and 3.6% of apnoeas <10 seconds were associated with cardiorespiratory instability, while 61.2% of apnoeas [&ge;]20 seconds were not. Multiple clinical/demographic (postmenstrual and gestational age, sex, weight z-score, and ventilation mode) and dynamic (baseline heart rate, oxygen saturation, and recent apnoea clustering) factors were associated with increased instability risk. Apnoea-related cardiorespiratory instability could be predicted with a balanced test accuracy of 75.8% when incorporating all features, while a model using only clinical/demographic features achieved 66.0%. Conclusions: Multiple factors influence cardiorespiratory responses to apnoea. Predictive modelling may enable personalised apnoea definitions, improving individualised care.

Abstract Background: Pediatric respiratory infections are a leading cause of morbidity and mortality globally, representing a major health challenge in children. Research Gap: Despite extensive studies on epidemiology, clinical management, and specific pathogens, no bibliometric analysis has systematically evaluated the most influential research in this field. Objectives: This study aimed to evaluate the characteristics of the top 50 most-cited articles on pediatric respiratory infections and to identify emerging research trends. Methods: The Web of Science database was searched without publication year restrictions. Independent reviewers screened studies based on predefined inclusion and exclusion criteria. Data were extracted using a standardized form, including study details. Results: The 50 most-cited articles ranged from 34 to 384 citations and showed a right-skewed distribution with a sharp drop after the top ten. Publication years ranged from 1978 to 2021, with over half published in the 2010s. Articles appeared in 31 journals, with Pediatrics contributing five. Leading countries were the United States (18%), China (12%), and Canada (10%), with research largely concentrated in high-income regions and limited multicenter collaboration. Cohort studies dominated (66%), while randomized trials (12%) and reviews/meta-analyses (16%) were less common. Research clustered around three themes: clinical outcomes (e.g., pneumonia, bronchiolitis); viral etiology/diagnostics (e.g., RSV, SARS-CoV-2); and antimicrobial stewardship. Conclusion: Over the past decades, pediatric respiratory infection research has developed but remains unbalanced, relying heavily on observational evidence from high-income countries, with limited randomized trials, systematic reviews, multicenter collaborations, and LMIC-led studies. These findings provide insights that may direct researchers to identify potential focal points and guide future research in the field.

AimCystic fibrosis (CF) care has been transformed by CFTR modulator therapies, yet most efficacy data arise from clinical trials with restrictive eligibility criteria. Real-world registry data can capture treatment outcomes in broader, more diverse patient populations. We used the Cystic Fibrosis Foundation Patient Registry (CFFPR) data to evaluate longitudinal clinical outcomes, and care benchmarking at a single Adult CF Program Center over a decade. MethodsA retrospective, descriptive analysis of CFFPR data (2011-2022) was performed to assess trends in modulator use, lung function (ppFEV1), body mass index (BMI), respiratory microbiology, and pulmonary exacerbations (PEx). Comparative Effectiveness Research (CER) methods were applied to compare outcomes across peak modulator eras: pre-modulator (2011), ivacaftor (2015), mixed-modulator (2019), and elexacaftor/tezacaftor/ivacaftor (ELE/TEZ/IVA) (2021). Program-level outcomes were benchmarked against national network metrics to assess adherence to guideline-based care. ResultsOver ten years, median ppFEV1 improved from 63.4% (2011) to 78.8% (2021), and BMI increased from 22.3 to 24.8 kg/m2. The proportion of adults experiencing more than one PEx annually declined from 39.7% to 19.5%, while Pseudomonas aeruginosa (P.a.) culture positivity decreased from 79% to 47%. ELE/TEZ/IVA therapy was associated with greatest clinical improvements. Program-level performance remained comparable to national network benchmarks, reflecting high adherence to standard care metrics. ConclusionRegistry-based CER provides valuable real-world insights into CF care effectiveness and quality improvement. This decade-long analysis demonstrates significant clinical gains associated with modulator therapies and highlights the importance of patient registries in monitoring outcomes, benchmarking care, and informing global CF care models and standards for rare disease management. Key Messages{square} Real-world registry data enables decade-long evaluation of CFTR modulator effectiveness. {square}Elexacaftor/tezacaftor/ivacaftor demonstrates the greatest clinical benefit among modulator therapies. {square}Benchmarking Adult CF Program performance against the Network of Adult CF Programs facilitates quality improvement and standard care guideline adherence. {square}Patient registries provide insights for personalized care, program-level decision-making, and international standards for rare disease management.

BackgroundIn patients requiring respiratory support, clinicians rely on physical exam, radiologic, laboratory, and ventilator-derived measures for the provision of sufficient support while minimizing ventilator and "work of breathing" induced lung injury. Point of care lung ultrasound (LUS) is a widely available tool in hospital and clinic environments. To date, LUS has not been used to evaluate lung strain. MethodsWe collected LUS images in four anesthetized, neuromuscularly blocked, and mechanically ventilated pigs being used for another experiment. A feature tracking tool was developed which tracked echo-bright lung structures in ten second clips obtained in triplicate of the right and left, upper and lower lung fields using tidal volumes of 4, 6, 8, 10, and 12 mL/kg. Pleural lines were manually drawn and a program for quantifying lung strain developed with assistance from Anthropic Claude Artificial Intelligence tool. Structures were identified in inspiratory and expiratory frames and tracked bidirectionally with median strain per frame used for calculations. ResultsTriplicate measures of lung ultrasound images in four pigs had a median coefficients of variation of 35% (23-47% IQR) and linear modeling of strain with tidal volumes of 4-12 mL/kg showed positive correlation with R2 value ranging from 0.89 to 0.97. Strain measurements were similar after bronchial administration of 1.5M hydrochloric acid. ConclusionsRegional lung strain quantification using LUS is a viable and potentially useful tool for respiratory support management.

BackgroundPleuroparenchymal fibroelastosis (PPFE) is a rare, fibrotic lung disease with poor prognosis, usually affecting adults which most commonly occurs idiopathically. Biallelic pathogenic variants in DGUOK cause mitochondrial DNA (mtDNA) depletion syndrome, predominantly affecting infants with severe hepatic and neurological symptoms. Detailed description of pulmonary manifestations with late-onset presentation have not been reported. MethodsWe describe nine patients with PPFE and DGUOK-associated mitochondriopathy. Clinical, radiological, histopathological, and genetic data were systematically collected from all patients. Functional studies, single nucleus RNA sequencing (snRNAseq), immunofluorescence staining, transmission electron microscopy and respiratory chain enzyme activity assays were conducted on patient-derived fibroblasts, muscle or lung tissues. mtDNA content quantification was performed on whole genome sequencing (WGS) data. ResultsAll patients (ages 5-36) presented with progressive dyspnea, weight loss and some with spontaneous pneumothoraces. Chest computed tomography and lung biopsies showed features of PPFE. Biallelic pathogenic DGUOK variants were identified in all patients, seven of them carry an unreported intronic variant leading to mtDNA depletion. snRNAseq of lung tissue from four pediatric patients identified Aberrant Basaloid cells and intermediate cells as their precursor localized at the fibrotic edge. Mitochondrial alterations were identified by electron microscopy. ConclusionPPFE in children and young adults is associated with DGUOK-related mitochondriopathy. For the first time, we demonstrate Aberrant Basaloid cells in pediatric fibrotic lung tissue. Since pulmonary involvement may be underrecognized or misinterpreted and the clinical presentation may not always be typical of a mitochondriopathy, we recommend genetic testing in all patients with PPFE of unknown origin.

Asthma is the most common chronic respiratory disease of childhood and is strongly associated with genetic variants at the 17q21 locus that increase expression of ORMDL3, a negative regulator of serine palmitoyl-CoA transferase (SPT), the rate-limiting enzyme in de novo sphingolipid synthesis. Reduced sphingolipid production has been linked to airway hyperreactivity, a key physiological feature of asthma, but the mechanisms connecting altered sphingolipid metabolism to airway dysfunction remain unclear. We examined whether sphingolipid metabolites regulate airway smooth muscle reactivity. Circulating sphingolipids were quantified in children with asthma carrying 17q21 risk alleles and in mice with reduced SPT activity. Functional airway responses were assessed in precision-cut lung slices exposed to sphingosine-1-phosphate (S1P), sphinganine-1-phosphate (Sa1P), and S1P receptor antagonists. Homozygous carriers of the rs7216389 risk allele and SPT-deficient mice displayed an increased S1P-to-Sa1P ratio. In functional assays, Sa1P opposed S1P-induced airway contraction, and increasing Sa1P availability reduced airway hyperresponsiveness. These findings identify the S1P/Sa1P axis as a metabolic rheostat regulating airway smooth muscle tone and suggest that targeting sphingolipid metabolism may offer a therapeutic strategy to mitigate intrinsic airway hyperreactivity in asthma. One sentence summaryAn imbalance between sphingosine-1-phosphate and sphinganine-1-phosphate links the asthma risk locus 17q21 to airway hyperreactivity and reveals sphingolipid metabolism as a potential therapeutic target.

Co-designed research in paediatric HSCT is limited. We sought to determine research priorities which represent the shared priorities of patients, parents, carers, and healthcare professionals (HCP) within Australia, New Zealand, the Netherlands and United Kingdom. An international, multiphase priority-setting methodology was implemented in partnership with the James Lind Alliance and delivered over an 18-month period. Part 1: an international scoping survey asked respondents to submit their research uncertainties related to paediatric HSCT. Part 2: summarising and evidence-checking the submitted uncertainties. Part 3: interim prioritisation survey. Part 4: consensus workshop. In the first international scoping survey, 667 topic ideas were suggested (45% by consumers, 55% by HCP), which were categorized into 80 summary questions. After systematic literature review, 35 summary questions were judged to be true uncertainties (i.e. not answered by existing evidence). These 35 uncertainties were included in a second interim prioritisation survey, completed by 224 participants. From those, a shortlist of 19 questions was drawn. After a multistakeholder workshop, consensus was reached on the top 10 priorities. The PSP identified important research gaps in the management of paediatric HSCT. Priority areas included: implementing personalised medicine approaches, improving immune recovery and adjunct interventions such as exercise, nutrition and microbiome-directed strategies.

Introduction Obstructive lung diseases (OLDs) are responsible for high rates of illness and death worldwide. Inflammation, chronic airflow limitation, and bronchial remodeling occur in OLD and eventually result in the unique respiratory sounds. Despite its subjective and having low reproducibility, still traditional auscultation using a manual stethoscope is the main method used to identify the lung sounds. Nevertheless, the combination of recent advancements in digital stethoscopes and AI (Artificial Intelligence) has permitted the objective measurement of lung sounds. Nevertheless, there is a lack of standardized, region-specific databases for AI training and validation. Even though lung sound classification is an emerging aspect in research and telerehabilitation the lobar wise acoustic pattern is still novel due to lack of prevailing database to train AI models. Identifying this gap this study aims to develop an acoustic repository and analyze the data using segmental lung sounds from patients with OLDs and healthy controls through an electronic stethoscope. Methods and analysis This is a cross sectional observational study involving 120 participants (60 OLD patients and 60 healthy controls). Lobar wise acoustic signals will be captured using an electronic stethoscope in healthy and diseases population. The data will be analyzed using Audacity software for annotations and then it will be used for feature extraction and statistical analysis. The acoustic features extracted through Audacity, will include frequency, intensity, pitch, and root mean square (RMS) energy. Repeated measures ANOVA will be applied to compare mean sound intensities across lung segments while Pearson correlation will be used to assess associations with body composition parameters. The data will then be standardized for AI-based diagnostic applications. Ethics and dissemination The study is being reviewed from the Ethics Review Committee, Faculty of Medicine, University of Peradeniya (2025/EC/87) will be sought. Informed consent will be obtained in writing. The dissemination of results will take place through peer-reviewed publications and the creation of a public database containing lung sounds from the region.

BackgroundPatent ductus arteriosus (PDA) is a common and potentially serious cardiovascular condition in preterm infants, particularly those with low gestational age and birth weight. Its management remains controversial due to variability in screening, diagnostic criteria, and treatment strategies. This study aimed to evaluate risk factors, outcomes, and management strategies for PDA in preterm infants, and to identify predictors of clinical and echocardiographic response to therapy. MethodsWe conducted a retrospective cohort study over a 4-year period (2016-2019) in the neonatal intensive care unit (NICU) of a tertiary care center. All consecutive preterm infants admitted during the study period were eligible. Infants with echocardiographically confirmed PDA who received pharmacological treatment with intravenous paracetamol or ibuprofen were included in the analysis. Missing data were minimal and handled using available-case analysis. Statistical analyses included descriptive statistics, Pearsons chi-square test, and multivariable logistic regression. ResultsAmong 2154 preterm infants admitted to the NICU, 60 were diagnosed with PDA (incidence : 2.8%). The mean gestational age was 29 {+/-} 2.6 weeks, and the median birth weight was 1200 g. Respiratory distress occurred in 95% of cases, mainly due to hyaline membrane disease (86.7%). PDA was symptomatic in 80% of infants. First-line treatment resulted in clinical improvement in 77% and ductal closure in 83.3% of cases, most within 3 days. Predictors of successful closure included gestational age [&ge;] 28 weeks (OR = 5.9; 95% CI : 1.7-20.2) and antenatal corticosteroid exposure (OR = 1.2; 95% CI : 1.0-1.6). Overall mortality was 35% and was significantly higher in infants < 28 weeks (OR = 5.0; 95% CI : 2.4-10.3). Clinical improvement (OR = 3.7) and echocardiographic closure (OR = 4.5) after first-line treatment were associated with reduced mortality. ConclusionsPDA in preterm infants is associated with substantial morbidity and mortality, particularly in those born before 28 weeks of gestation. Early diagnosis, antenatal corticosteroid exposure, and timely pharmacological treatment may improve outcomes. Systematic echocardiographic screening in high-risk neonates should be considered.