Pediatric Pulmonology

BackgroundAsthma is a frequent comorbidity in children with sickle cell disease and has been associated with an increased risk of acute complications, particularly vaso-occlusive crises and acute chest syndrome. However, determinants of clinical severity among children with sickle cell disease and confirmed asthma remain poorly characterized, especially in tropical settings. This study aimed to identify factors associated with clinical severity in this population. MethodsWe conducted an observational study among children with sickle cell disease followed in French Guiana. The analysis was restricted to children with confirmed asthma. Clinical severity was defined as the occurrence of at least two hospitalizations during the 12 months preceding evaluation for vaso-occlusive crises and/or acute chest syndrome. Factors associated with severity were assessed using univariate and multivariate logistic regression analyses. ResultsA total of 138 children with sickle cell disease and confirmed asthma were included, of whom 49 (35.5%) presented a severe clinical form. In multivariate analysis, no variable was independently associated with clinical severity. However, a trend toward an increased risk of severe disease was observed among children living in rural areas (adjusted OR = 1.94; 95% CI: 0.77-4.86), while a trend toward a protective effect was observed for Strongyloides stercoralis infection (adjusted OR = 0.18; 95% CI: 0.02-1.51). Allergic sensitization, although frequent (64.5%), was not associated with clinical severity after adjustment (adjusted OR = 0.66; 95% CI: 0.31-1.44). ConclusionAmong children with sickle cell disease and confirmed asthma, more than one third experience severe clinical disease. Severity does not appear to be driven by allergy but may be influenced by environmental and contextual factors specific to tropical settings. These findings support a stratified approach to sickle cell-associated asthma to identify high-risk children and prevent avoidable acute complications.

Background Recent 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. Methods We 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. Results In 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. Conclusion FeNO 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.

The genetic relationship between asthma and lung function may be dependent on age-at-onset (AAO) of asthma. We investigated whether the shared genetics between asthma AAO and lung function is dependent on AAO. Asthma cases from UK Biobank were subset according to their AAO and genetic correlation was used to obtain genetically homogeneous groups, i.e., [≤]20 (LT20), 20-40, and >40 (GT40) years. Association analysis and fine-mapping were performed to identify shared genetics between AAO groups and lung function. Mediation and quantitative trait locus (QTL) analyses were performed to identify mechanisms underlying shared genetic associations. Chr5, chr6, chr12, and chr17 each had one region that displayed a cross-phenotype replicated association with at least one AAO group and lung function. Overlapping credible sets obtained from fine-mapping were observed on chr5 and chr6. Mediation analyses demonstrated that for each region the proportion mediated through asthma on lung function was larger for asthma LT20 compared to 20-40 and GT40 suggesting that their effects on lung function were more strongly driven by this association. Tissue-specific QTL analysis revealed shared etiology on chr5 may be acting through SLC22A5 and C5orf56 which might play an important role in decreased lung function among individuals with earlier-onset 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.

Pediatric asthma exacerbations are a frequent cause of emergency department (ED) visits and hospitalizations, yet accurate risk prediction remains limited and no consensus risk scores exist. Using UF Health electronic health records (EHRs) from 2011-2023, we evaluated two computable phenotypes (i.e., CAPriCORN and COMPAC) to predict exacerbations over 6-, 12-, and 24-month horizons. Exacerbations were defined using a validated composite of diagnosis codes from ED, inpatient, or outpatient encounters combined with systemic corticosteroids prescriptions. Several commonly used machine learning (ML) models were trained with stratified five-fold cross-validation, Bayesian hyperparameter optimization, and Youdens J thresholding. XGBoost achieved the best performance, with SHapley Additive exPlanations (SHAP) highlighting note-derived symptom terms and rescue-medication use as dominant predictors. Future work will focus on external validation and assessment of generalizability. This interpretable, text-integrated framework may support child-specific risk stratification and inform EHR-based decision support for timely pediatric asthma management.

BackgroundChildren with tracheostomies experience frequent and recurrent acute respiratory infections (ARIs). While cultured respiratory pathogens can inform ARI diagnosis, it is unknown if their presence in the airway affects future ARI risk. ObjectiveTo identify predictors of frequent (3+) ARIs within 36 months of tracheostomy. MethodsWe conducted a single-center, retrospective cohort study of children with tracheostomies placed between 2010-2016. Medical records were reviewed for each encounter in which a respiratory culture was obtained over the 3 years post-tracheostomy. ARIs were defined using encounter ICD-9/10 codes. Logistic and Poisson regression were used to model the association between clinical and microbiologic predictor variables with having frequent (3+) ARIs and the total number of ARIs per child. Mediation analysis using stepwise regression models further evaluated the role of P. aeruginosa. ResultsAmong 436 children, 631 diagnosed ARIs occurred within 36 months of tracheostomy; 20.2% of children had 3+ ARIs. Pseudomonas aeruginosa was isolated in 25% of children and was more common among those with 3+ ARIs compared with 0-2 ARIs (56.8% vs 20.7%, p<0.001). Those with early P. aeruginosa isolation were more likely to have 3+ ARIs (aOR 3.38, 95% CI 1.97-5.81), and this relationship persisted when analyzing ARIs and P. aeruginosa counts. Identification of P. aeruginosa partially mediated the relationship of ventilator dependence with ARI frequency. ConclusionIsolation of P. aeruginosa, particularly early and repeated isolation, is associated with frequent ARIs in the 3 years after tracheostomy and is an important partial mediator. Findings may inform risk stratification and targeted treatment strategies.

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.

BackgroundPediatric eczema is a highly prevalent condition that often causes substantial suffering among affected children and their families. Numerous modifiable lifestyle and environmental risk factors for the condition have been identified, although these risk factors and related interventions have generally been studied in isolation. The goal of this study was to evaluate the effects of an integrative program for parents of children with eczema that simultaneously addressed multiple lifestyle and environmental risk factors. MethodsChildren with eczema diagnosis who began the online eczema program and provided outcomes data from May 2024 to May 2025 were eligible. The primary outcome was the Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD), a validated measure of eczema symptoms and burden. Outcomes were assessed at baseline and at one month, two months, and six months after beginning the program. Changes in mean PO-SCORAD scores from baseline throughout the duration of the study were assessed with analysis of variance (ANOVA). Multivariate linear regression modeling of PO-SCORAD scores using population-averaged generalized estimating equations (GEE) were also constructed accounting for baseline PO-SCORAD scores and adjusting for age, sex, presence of any allergy, use of topical corticosteroids, and use of antihistamines. Results197 participants were included in the study. The mean baseline PO-SCORAD score was 51.4, which is considered severe eczema. PO-SCORAD scores improved over the course of the study (p<0.0001) and there were statistically significant and clinically meaningful improvements noted after one month (11.3 points, 22.0% improvement), two months (17.8 points, 34.6% improvement), and six months (27.2 points, 52.9% improvement) in the program (p<0.0001). After accounting for baseline PO-SCORAD scores and covariates in regression modeling, there was a 22.5-point (p<0.0001) improvement in PO-SCORAD scores from baseline to final assessment. There was a 31.4-point decrease in PO-SCORAD scores from baseline to final assessment (p<0.0001, 47.2% improvement) among the subgroup of participants with severe eczema symptoms at baseline. ConclusionsAn online program focusing on modifiable lifestyle and environmental modifications was associated with clinically meaningful symptom improvements among children with eczema. Symptoms improved relatively quickly and the greatest improvements were noted among children with severe symptoms at baseline.

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.

BackgroundCystic Fibrosis (CF) is a lethal genetic condition affecting over 100,000 people worldwide, characterised by multi-organ dysfunction and a progressive lethal lung disease. The disease occurs due to faulty cystic fibrosis transmembrane conductance regulator (CFTR) ion channels effecting flow of chloride, bicarbonate and water out of cells. This causes thick mucus with repeated bacterial infections, systemic inflammation and a decrease in lung function. CFTR modulator therapies have shown variable improvements in lung function and reduction in exacerbation frequency. Basal cells within the lung act as a stem cell for repair following injury and can repopulate the epithelial layer. This process is dysfunctional in CF causing progressive damage. Spontaneous lung repair is well described but not well characterised. Nothing is known about the effects of CFTR modulator therapy on these cells, but this could be of major consequence for people with CF (pwCF). AimsTo determine the effects of CFTR modulator therapy on the activity of CF basal cells and relate this to progenitor function and to study the effects of CFTR modulators on systemic inflammation and clinical outcomes. MethodsClinical information, blood and nasal brushes were obtained from pwCF prior to commencing modulator therapy and at multiple time points up until 1 year of treatment. 10 pwCF were recruited to undertake thoracic CT scans pre-treatment and at 1 year of therapy. Nasal samples were used to isolate basal cells and serum to study systemic markers of inflammation. RNA sequencing of basal cells was undertaken by Ilumina Novoseq to a depth of 20 million read pairs and gene ontology analysis was performed. Functional assays of basal cell activity were carried out. Proteomic analysis and ELISAs were undertaken to determine changes in inflammatory cytokines within the serum across the first year of treatment. Quantitative results were generated by Lung Quantification (LungQ) analysis with qualitative reports from independent radiologists. Results were compared with clinical outcomes. Results110 pwCF were recruited in total who commenced a commercially available CFTR modulator therapy. Serum samples were collected from 77pwCF, nasal brushes obtained from 40 pwCF and 10 completed their CT scans following 1 year of highly effective CFTR modulator therapy. Systemic IL-6, CRP and calprotectin (a biomarker of CF exacerbation) were all significantly reduced with highly effective CFTR modulator treatment. Clinical results were in keeping with those seen in published CFTR modulator clinical trials with improvement in lung function, weight, and exacerbation frequency. Subjective improvements were seen in all 10 CT scans following 1 year of modulator therapy. Significant reductions were seen in airway wall thickening and reduction in thoracic lymphadenopathy were also observed. Basal cell RNA sequencing showed that the relative expression of 2570 genes were significantly different following treatment with CFTR modulators. Ontology analysis showed enrichment in multiple pathways including cilliagenesis and Notch signalling, a key pathway in lung tissue development and homeostasis. Functional assays exhibited a deficit in repair mechanisms of the CF basal cell compared to healthy controls, and reduction in progenitor function. ConclusionsAlthough CFTR modulators improve multiple clinical and radiological outcomes, they also have impacts on basal cell function. There are however, limited impacts on systemic inflammation and more work is needed in this area to understand the disease process.

IntroductionChildhood asthma remains a major public health challenge in low- and middle-income countries, where social and economic factors influence disease outcomes. This study examined the sociodemographic determinants of asthma exacerbation among children attending clinic at Thika Level 5 Hospital, Kenya. MethodsThis study employed a hospital-based cross-sectional study involving 108 caregivers- child dyads, each consisting of a child with confirmed asthma and their primary caregiver. The dyads were recruited from the pediatric asthma clinic from 31st March 2025 to 30th April 2025 then follow up was conducted for six months form 1st May to 31st October 2025. Data were collected using structured questionnaires and clinic records. Descriptive statistics summarized sociodemographic characteristics, while chi-square tests and logistic regression assessed associations between caregiver factors and asthma control. ResultsThe mean age of children was 8.1 years (range 3-17), with males comprising 57.4%. Most caregivers were mothers (88%), had secondary education (57.4%), and were in informal employment (75.9%). Household income was low for 59.3% of participants (<KES 30,000/month). Caregiver education (AOR=2.8; 95% CI:1.5-5.2; p=0.001) was the strongest predictor of asthma control, followed by medical insurance ({chi}2=10.41; p=0.001). Formal employment and higher income were significantly associated with controlled asthma ({chi}2=6.45; p=0.04 and {chi}2=9.72; p=0.02 respectively). Urban residence modified the positive effect of education on asthma management (interaction AOR=1.9; p=0.03). ConclusionCaregiver education level, employment, income, and medical insurance significantly influence asthma control among children. Enhancing health literacy and expanding insurance coverage under the Social Health Authority (SHA) can improve asthma outcomes in Kenyan children.

Introduction: Although 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. Methods: Symptomatic, 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. Results: Of 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%. Conclusions: Home 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.

Purpose: We evaluated healthcare resource utilization (HCRU) and costs in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Methods: Patients 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). Results: In 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. Conclusions: These 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.

BackgroundBronchiectasis in adults often goes undiagnosed following the routine assessment. Cystic Fibrosis (CF) is usually diagnosed during childhood, but some cases are identified in adulthood when disease is mild. High-resolution computed tomography (HRCT) of chest may offer structural information that can indicate CF as an underlying etiology. ObjectiveTo compare the HRCT features of adult patients with CF and non-CF bronchiectasis and to determine the radiologic features that may be suggestive of CF. MethodsThis retrospective, analytical, cross-sectional study was carried out in Bangladesh Medical University after IRB clearance. Total 130 adults (12 with CF and 118 with non-CF bronchiectasis) of both sexes, whose bronchiectasis was confirmed by chest HRCT were included. Imaging findings were assessed based on Reid morphological classification, anatomical distribution and extent of spread within the lungs, and their association was tested using chi-square test with statistical significance of p<0.05. ResultsCystic bronchiectasis was more common in CF than non-CF patients (83.3% vs 29.7; p<0.001). Mixed central-peripheral extension had been found a considerable associated with CF (66.7% vs. 42.4; p=0.034). There was no statistically significant difference in right lung lobar distribution (p=0.540) but combined upper and lower lobe involvement on the left side was more common in CF patients (54.5%) than non-CF patients (21.3) (p=0.054). ConclusionAdult CF had unique chest HRCT imaging characteristics when compared to non-CF bronchiectasis, especially cystic morphology and mixed extension. Identification of such features could help physician in the early diagnosis and selection of treatment strategy.

Mucociliary clearance is a key component of the pathophysiology of bronchiectasis but cilia function is poorly defined. This study aims to characterize nasal ciliary function in bronchiectasis and examine associations with disease severity, infection, inflammation and outcome. Adults with bronchiectasis and healthy volunteers were recruited to the international observational study EMBARC-BRIDGE. Individuals with a known diagnosis of Primary Ciliary Dyskinesia (PCD) were excluded. Nasal respiratory epithelium was sampled by brush biopsy. Ciliary function was assessed by high-speed video microscopy in primary samples and following re-differentiation in air-liquid interface (ALI) culture. Ciliary parameters (cilia length, angle, amplitude, clearance, frequency and ciliation) were quantified and compared with disease severity, microbiology, inflammation and future risk of exacerbations. 171 participants with bronchiectasis were recruited (54% female, age 68years (59-74)). Bronchiectasis nasal brushings showed greater epithelial disruption compared to healthy volunteers (p=0.0006). Six individuals with previously undiagnosed PCD were identified and excluded. In the remaining bronchiectasis cohort, ciliary beat frequency and length were similar to healthy controls. In contrast ciliary beat amplitude, angle, amplitude per second and clearance capacity, were significantly reduced (all p<0.001). These parameters were restored following ALI culture. Regenerated epithelia from bronchiectasis donors exhibited reduced ciliated area. Ciliary dysfunction was strongly associated with future risk of severe exacerbations. The upper airway epithelium is disrupted in bronchiectasis; ciliary movement is impaired and is associated with future risk of exacerbation. Ciliary dysmotility is reversible following ALI culture. This indicates that impaired ciliary function is secondary to the airway environment and therapeutically targetable.

BackgroundBronchiectasis is a debilitating respiratory condition characterized by chronic cough with expectoration of thick sputum. It accounts for significant morbidity and mortality, especially when associated with exacerbations. Assessing the health-related quality of life (HR-QoL) of patients with bronchiectasis is important to ascertain the impact of the disease on day-to-day life, as well as to gauge the effect of targeted interventions. Conventionally used methods for assessing HR-QoL such as the St. Georges Respiratory Questionnaire (SGRQ) are time-consuming and have limitations in day-to-day application. The Bronchiectasis Health Questionnaire (BHQ) is a novel, compact tool used for assessing the HR-QoL, and has been validated for use in Korean and Turkish populations. MethodsWe attempted to develop and validate the Hindi version of the Bronchiectasis Health Questionnaire (BHQ) in Indian adults with bronchiectasis. We assessed the correlation between the Hindi BHQ (H-BHQ) scores and other measures of lung health including the Hindi version of the COPD Assessment Tool (H-CAT), pulmonary function tests and the bronchiectasis severity index (BSI). In addition, we assessed the correlation between the H-BHQ scores and the number of exacerbations and hospital admissions in the previous year. ResultsA total of 145 subjects with bronchiectasis were included. The mean ({+/-} SD) H-BHQ total score was 49.10 {+/-} 10.3. The H-BHQ score correlated well with the H-CAT score (Correlation coefficient -0.6534, p value < 0.0001) and the mMRC scale (Correlation coefficient of -0.4459,p value < 0.0001). The H-BHQ score also had a moderate correlation with the number of exacerbations and low correlation with hospital admissions in the previous year, with correlation coefficients of -0.4193 (p < 0.0001) and -0.3030 (p < 0.0001), respectively. The correlation between the H-BHQ and the Bronchiectasis Severity Index (BSI) score was weak (Correlation coefficient of -0.3012, p value < 0.01). ConclusionThe H-BHQ offers a simple and convenient method to assess the HR-QoL in patients with bronchiectasis, and correlates well with other measures of respiratory health, including the H-CAT, the mMRC score and the number of exacerbations and hospital admissions in the previous year.

BackgroundImpulse oscillometry is a noninvasive pulmonary function test performed during quiet breathing and requires minimal patient cooperation. It is useful for detecting small airway disease and provides increased sensitivity for diagnosing asthma in younger children who may have difficulty completing standard spirometry. Bronchodilator testing, a standard assessment of airflow obstruction reversibility, is recommended in patients with suspected asthma who present obstructive airflow patterns. ObjectiveTo evaluate impulse oscillometry parameters before and after bronchodilator administration across different age groups and to examine the relationship between age and airway resistance in patients with clinician-diagnosed asthma. MethodsThis retrospective study included patients with clinician-diagnosed asthma who demonstrated obstructive airflow patterns and a positive bronchodilator response. Participants were grouped by age: younger than 6 years, 6 to 20 years, and older than 20 years. Key impulse oscillometry parameters--airway resistance at 5 Hz, airway resistance at 20 Hz, the difference between these values, and resonance frequency--were collected and compared across groups. A positive bronchodilator response was defined as a reduction in airway resistance of more than 30% in individuals younger than 18 years and more than 40% in adults. ResultsA total of 225 patients (123 males and 102 females) were included, with a median age of 6 years. At baseline, the median airway resistance at 5 Hz was 175.34% of the reference value (95% CI, 171.66-178.62), and airway resistance at 20 Hz was 121.68% (95% CI, 118.73-127.12). The median difference between these values was 52.32% (95% CI, 49.89-57.14), and the median resonance frequency was 5.11 Hz (95% CI, 4.62-5.35). After bronchodilator administration, airway resistance at 5 Hz decreased to 123.56% (95% CI, 119.07-126.77), corresponding to a median reduction of 52.8% (95% CI, 49.48-56.08; P < 0.0001). Age demonstrated a moderate positive correlation with airway resistance at 20 Hz (r = 0.51, P < 0.001). ConclusionsProximal airway resistance increases with age among patients with asthma, suggesting age-related differences in airway inflammation. Impulse oscillometry combined with bronchodilator assessment provides a practical approach for evaluating airflow reversibility and enhances diagnostic accuracy in suspected asthma.

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.