Asthma is a leading cause of paediatric mortality. This study aims to elucidate trends in paediatric mortality over time. Using US Centers for Disease Control (CDC) WONDER data, we conducted a cross-sectional analysis of...Asthma is a leading cause of paediatric mortality. This study aims to elucidate trends in paediatric mortality over time. Using US Centers for Disease Control (CDC) WONDER data, we conducted a cross-sectional analysis of paediatric asthma-related mortality between 1999 and 2023, overall and stratified by year, age, sex, race and region. Negative binomial regression was used to test the linear temporal trend and conduct group comparisons in asthma-related mortality rates. Over the study period, there were 5357 asthma deaths. The mortality rate was 3 per 1 000 000 children and rates remained stable over this period. Asthma mortality was higher in males, children 10-19 years (compared to children 5-9 years) and black (relative to white) children. Advances in the treatment of paediatric asthma should be aimed at reducing mortality and addressing differential health outcomes among black children.
Muiser S, Müllerová H, Belton L
… +13 more, Rusibamayila N, Erhard C, Agusti A, Faner R, Pavord I, Couillard S, Inoue H, Price DB, Olaguibel JM, Kerstjens HAM, van den Berge M, NOVELTY Scientific Community, NOVELTY study investigators
BACKGROUND: Blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO) are potential biomarkers for disease progression and treatment response in asthma and chronic obstructive pulmonary disease (COPD). We invest...BACKGROUND: Blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO) are potential biomarkers for disease progression and treatment response in asthma and chronic obstructive pulmonary disease (COPD). We investigated their association with exacerbations in asthma, COPD and asthma+COPD. METHODS: NOVEL observational longiTudinal studY is a multicountry prospective study of patients with physician-assigned asthma, COPD and asthma+COPD. Negative binomial and logistic regression analyses were performed for baseline EOS/FeNO (separately and combined), by diagnosis, and for different exacerbation subtypes (all, antibiotics-only, oral corticosteroids (OCS)-only). RESULTS: Higher baseline EOS was significantly associated with increased risk of all exacerbations in asthma (incidence rate ratio (IRR) 1.09, 95% CI 1.01 to 1.18, p=0.033), with a trend increase with COPD (IRR 1.09, 95% CI 1.00 to 1.19, p=0.069) but not asthma+COPD. Higher baseline FeNO was significantly associated with decreased risk of all exacerbations in COPD (IRR 0.91, 95% CI 0.84 to 0.99, p=0.025) and increased risk of OCS-only exacerbations in asthma (OR 1.16, 95% CI 1.04 to 1.29, p=0.006) and asthma+COPD (OR 1.55, 95% CI 1.22 to 1.97, p<0.001). In exacerbation risk in asthma (IRR 1.14, 95% CI 1.05 to 1.24, p=0.003), while in COPD, both higher EOS (IRR 1.12, 95% CI 1.02 to 1.24, p=0.033) and lower FeNO (IRR 0.87, 95% CI 0.78 to 0.96, p=0.009) were independently associated with exacerbation risk. CONCLUSIONS: Higher EOS predicted exacerbations in asthma and COPD, while FeNO showed heterogeneous associations, particularly for OCS-only treated exacerbations. Assessment of exacerbation subtype might improve personalised management. Interpretation is limited by physician-assigned diagnoses, potential ICS confounding and recall bias.
BACKGROUND: Preterm birth is associated with lifelong respiratory sequelae, yet our understanding of lung function trajectories across the lifespan remains limited. We aimed to identify patterns of spirometry development...BACKGROUND: Preterm birth is associated with lifelong respiratory sequelae, yet our understanding of lung function trajectories across the lifespan remains limited. We aimed to identify patterns of spirometry development from childhood to early adulthood in survivors of very preterm birth using novel data-driven methods. METHODS: In this longitudinal study, 116 individuals born ≤32 weeks' gestation and 39 term-born controls underwent spirometry testing at up to four timepoints between 4-23 years of age. Patterns (trajectories) of forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and FEV/FVC z-scores were derived using group-based trajectory modelling. Risk factors for declining trajectories were assessed using regression analysis. RESULTS: Preterm participants followed distinct trajectories including low-declining FEV and very-low-declining FEV/FVC patterns. Term controls remained stable. Trajectory prevalence estimates require caution due to non-random attrition. Higher gestational age (OR 0.70, 95% CI 0.54 to 0.89) and early-childhood FEV (OR 0.03, 95% CI 0.00 to 0.17) protected against low-declining FEV, while asthma diagnosis (OR 5.55, 95% CI 1.51 to 27.4) and chest CT abnormalities increased risk. For FEV/FVC decline, higher early-childhood FEV was protective (OR 0.39, 95% CI 0.19 to 0.68), while bronchodilator responsiveness (OR 7.65, 95% CI 2.58 to 26.7), asthma diagnosis (OR 2.59, 95% CI 1.02 to 6.96) and CT abnormalities increased risk. CONCLUSIONS: A substantial proportion of very preterm survivors demonstrate progressive airway obstruction between early childhood and young adulthood, highlighting preterm birth as a significant risk factor for early onset chronic obstructive pulmonary disease. Early lung function screening and identifying modifiable risk factors may provide opportunities for intervention before clinically significant airway obstruction develops.
INTRODUCTION: Lung cancer remains the leading cause of cancer mortality worldwide despite advances in treatment. Patient-related factors beyond tumour characteristics may influence prognosis but are seldom integrated int...INTRODUCTION: Lung cancer remains the leading cause of cancer mortality worldwide despite advances in treatment. Patient-related factors beyond tumour characteristics may influence prognosis but are seldom integrated into staging or risk stratification. METHODS: We analysed data from 59 101 patients with resectable non-small cell lung cancer (NSCLC) in the French nationwide Epithor database. Using an unsupervised machine learning approach, we applied principal component analysis followed by means clustering on 13 patient-specific clinical variables excluding tumour or treatment features, to identify distinct patient phenotypes. Survival differences were evaluated with Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: Five distinct patient phenotypes emerged, reflecting differing distributions of sex, age, pulmonary function, comorbidity and performance status. These phenotypes also showed varied distributions of pathological stage and histology, confirming their clinical relevance. Survival outcomes differed significantly between clusters, with 5-year overall survival ranging from 76.6% (95% CI 75.8% to 77.3%) to 53.8% (95% CI 52.9% to 54.6%). Using the lowest-risk cluster (Cluster 0) as reference, crude HRs for mortality were significantly different between clusters: Cluster 1 (HR 1.48 (95% CI 1.42 to 1.54)), Cluster 2 (HR 1.94 (95% CI 1.84 to 2.03)), Cluster 3 (HR 2.45 (95% CI 2.36 to 2.55)) and Cluster 4 (HR 1.95 (95% CI 1.87 to 2.04)). Cluster assignment remained an independent predictor of survival after adjustment for usual confounders (p<0.001). CONCLUSIONS: Phenotype-based clustering of non-tumour patient characteristics identifies clinically meaningful subgroups with distinct survival patterns after NSCLC surgery. Incorporating these phenotypes into preoperative evaluation may enhance risk stratification and support personalised treatment strategies alongside traditional tumour staging.
BACKGROUND: Sex-based differences in immune response are well established, but whether men and women derive comparable benefit from immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) remai...BACKGROUND: Sex-based differences in immune response are well established, but whether men and women derive comparable benefit from immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) remains uncertain. This systematic review and meta-analysis aimed to investigate sex-related differences in effectiveness of ICI for the treatment of advanced NSCLC. METHODS: A systematic review and meta-analysis of randomised controlled trials (RCTs) was conducted to compare overall survival (OS) and progression-free survival (PFS) between men and women treated with ICIs versus chemotherapy for stage III-IV NSCLC. Eligible studies compared programmed cell death protein 1/programmed cell death ligand 1 (PD-L1) inhibitors with chemotherapy and reported sex-specific OS and/or PFS outcomes. HRs were pooled using random-effects models, and secondary analyses incorporated updated follow-up data where available. RESULTS: 55 RCTs comprising 28 550 adults (71.6% men; 28.4% women) were included. ICIs significantly improved OS in both men (HR=0.75, 95% CI 0.72 to 0.78) and women (HR=0.81, 95% CI 0.76 to 0.86; p=0.17 for difference). However, PFS benefits favoured men (HR=0.62, 95% CI 0.59 to 0.65) compared with women (HR=0.76, 95% CI 0.70 to 0.81; p=0.005). In analyses using the most recent follow-up data, women showed lower ICI effectiveness for both OS (p=0.043) and PFS (p=0.003). CONCLUSIONS: ICIs confer similar OS benefits in men and women with advanced NSCLC, but women show shorter PFS, particularly in PD-L1-positive and monotherapy settings. Further research should clarify the biological and clinical factors underlying these differences and ensure balanced representation and equitable evaluation in future trials. PROSPERO REGISTRATION NUMBER: CRD42024451670.
BACKGROUND: A regional trial indicated that implementing at-risk asthma registers in primary care could reduce hospital admissions. This national study assessed whether the intervention lowered asthma crisis events. METH...BACKGROUND: A regional trial indicated that implementing at-risk asthma registers in primary care could reduce hospital admissions. This national study assessed whether the intervention lowered asthma crisis events. METHODS: This cluster randomised trial involved 275 UK primary care practices. The intervention included identifying at-risk patients, staff training, a clinical decision support system alerting practice staff to patients' at-risk status to facilitate prompt and opportunistic care, and ongoing support. Control practices continued with standard care. Patients (n=10 945) were included if identified as at-risk, unless they declined data sharing. Routine data linked across care settings captured asthma-related crisis events (hospitalisations, accident and emergency visits or death), asthma care indicators and healthcare costs over 12 months. RESULTS: Complete data were available from 185 practices (6207 patients), with exclusions mainly due to record linkage issues. Crisis events occurred in 7.2% of control versus 6.3% of intervention patients (OR 0.82, 95% CI 0.66 to 1.03, p=0.09). Individual components of the composite outcome showed similar, non-significant reductions. The use of systemic corticosteroids for asthma attacks had an OR of 1.18 (95% CI 0.99 to 1.41, p=0.07); personalised asthma action plans, OR 1.05 (95% CI 0.78 to 1.42, p=0.74); inhaler technique assessments, OR 1.13 (95% CI 0.93 to 1.38, p=0.23). Economic analysis estimated the intervention was cost-effective, with average annual National Health Service costs £306 lower in the intervention group. CONCLUSION: This trial did not provide sufficient evidence to show that the establishment and integration of at-risk registers for asthma in primary care reduces asthma-related crisis events for people with at-risk asthma, but there was some indication of benefit. TRIAL REGISTRATION NUMBER: ISRCTN95472706.
BACKGROUND: Short-acting β2-agonist (SABA) overuse is associated with increased asthma exacerbations and mortality, yet its impact on cardiovascular disease remains unclear. We investigate the association between SABA ov...BACKGROUND: Short-acting β2-agonist (SABA) overuse is associated with increased asthma exacerbations and mortality, yet its impact on cardiovascular disease remains unclear. We investigate the association between SABA overuse and the risk of major adverse cardiovascular events (MACE) in patients with asthma. METHODS: Between 2011 and 2019, patients with asthma were identified from the Taiwan asthma pay-for-performance database. SABA overuse was defined as using ≥3 canisters annually, compared with acceptable use (0-2 canisters/year). Inverse probability of treatment weighting (IPTW) was applied to balance baseline covariates. The primary outcome was 1-year MACE. Secondary outcomes included MACE component (non-fatal myocardial infarction, haemorrhagic stroke, ischaemic stroke) and mortality. RESULTS: Among 231 970 patients, 28 500 had SABA overuse and 203 470 had acceptable use. In the IPTW-weighted cohort, 1-year MACE incidence was higher in the overuse group (2.82 vs 0.99 per 100 person-years; adjusted HR (aHR) 1.25, 95% CI 1.12 to 1.39). SABA overuse significantly increased the risk of non-fatal MI (aHR: 1.28, 95% CI 1.09 to 1.50), ischaemic stroke (aHR: 1.26, 95% CI 1.08 to 1.46) and mortality (aHR: 1.40, 95% CI 1.24 to 1.58). Haemorrhagic stroke risk was not significantly increased. A non-linear dose-response was observed, with MACE risk peaking at 6-8 canisters annually. CONCLUSION: SABA overuse (≥3 canisters/year) is associated with increased risks of MACE and mortality in patients with asthma. These findings emphasise the importance of monitoring SABA use and assessing cardiovascular risk in asthma management.
OBJECTIVE: To assess the impact of acute hypoxia-induced periodic breathing on respiratory efficiency in young healthy males. METHODS: 20 healthy male (median (IQR) age: 24 (22 to 25) years; body mass index: 22.5 (20.9 t...OBJECTIVE: To assess the impact of acute hypoxia-induced periodic breathing on respiratory efficiency in young healthy males. METHODS: 20 healthy male (median (IQR) age: 24 (22 to 25) years; body mass index: 22.5 (20.9 to 24.9) kg/m)-no sleep-disordered breathing in normoxia-underwent polysomnography in normobaric hypoxia simulating 3500 m altitude. Measurements included oesophageal pressure-time curve, airflow and exhaled fraction of carbon dioxide (CO). Inspiratory pressure-time product (iPTP, index of respiratory muscle effort) was calculated from oesophageal pressure. Physiological dead-space volume, ventilation ([Formula: see text]D) and alveolar ventilation ([Formula: see text]A) were calculated from exhaled fractions of CO (Bohr equation). Within-subject comparisons of periodic (PB) and regular breathing (RB) periods were made using the Wilcoxon signed-rank test. RESULTS: In hypoxia, 17 participants had sufficient (>3 min) breathing periods of both periodic and non-periodic breathing for analysis. The median (IQR) Apnoea-Hypopnoea Index was 76.9 (62.8 to 122.7)/hour and participants spent 40.8% (27.3% to 64.6%) of sleep in periodic breathing (n=17). Tidal volume was greater in periodic breathing (n=17, median (IQR), PB vs RB; 0.815 (0.636 to 0.928) L vs 0.633 (0.517 to 0.673) L, p<0.001). Physiological dead space was similar in both breathing patterns (n=17, PB vs RB, 0.172 (0.160 to 0.196) L vs 0.184 (0.162 to 0.205) L, p=0.782). Respiratory rate was lower in periodic breathing (n=17; PB vs RB; 10.6 (9.8 to 13.6)/min vs 16.8 (15.4 to 17.7)/min, p<0.001). [Formula: see text]D was lower in periodic breathing (n=17; PB vs RB; 1.9 (1.7 to 2.2) L/min vs 3.0 (2.6 to 3.4) L/min, p<0.001), while [Formula: see text]A remained similar (n=17, PB vs RB; 6.9 (6.3 to 7.4) L/min vs 7.3 (6.8 to 7.7) L/min, p=0.102). iPTP/min was lower in PB (n=14, PB vs RB; 185.4 (154.3 to 203.8) cm2O×s/min vs 221.5 (189.2 to 291.9) cm2O×s/min, p=0.002). CONCLUSIONS: Periodic breathing in acute normobaric hypoxia reduces inspiratory effort without impairing alveolar ventilation, suggesting an adaptive mechanism to optimise respiratory efficiency in young healthy males.