Daily Respiratory Research Analysis
Analyzed 129 papers and selected 3 impactful papers.
Summary
Analyzed 129 papers and selected 3 impactful articles.
Selected Articles
1. Osimertinib with or without savolitinib as first-line treatment for MET-aberrant, EGFR-mutant NSCLC: randomized phase 2 trial (FLOWERS).
In treatment-naïve, EGFR-mutant NSCLC with de novo MET aberrations, osimertinib plus savolitinib yielded a confirmed ORR of 90.5% versus 60.9% with osimertinib alone, with high disease control in both groups. Grade ≥3 treatment-related adverse events were more frequent with the combination (57.1% vs 8.7%), but overall safety was manageable.
Impact: This randomized phase 2 study provides compelling early evidence that co-targeting EGFR and MET upfront may substantially improve tumor responses in a molecularly defined subgroup with high unmet need.
Clinical Implications: For EGFR-mutant NSCLC with de novo MET amplification/overexpression, combining osimertinib with a MET inhibitor may be considered in clinical trials or selected settings, with careful toxicity monitoring, pending confirmatory phase 3 outcomes.
Key Findings
- Confirmed ORR: 90.5% (combination) vs 60.9% (osimertinib alone).
- Disease control rate: 95.2% (combination) vs 87% (monotherapy).
- Grade ≥3 treatment-related AEs: 57.1% (combination) vs 8.7% (monotherapy).
- Multicenter, randomized, open-label phase 2 design targeting EGFR-mutant with de novo MET aberrations.
Methodological Strengths
- Randomized, multicenter comparative design with an active standard-of-care control.
- Clear molecular inclusion (EGFR mutation with de novo MET aberrations) enabling precision targeting.
Limitations
- Open-label phase 2 with a small sample size (n=44), limiting definitive conclusions.
- Short-term endpoints (ORR/DCR) without mature survival outcomes yet.
Future Directions: Confirmatory phase 3 trials should assess progression-free and overall survival, quality of life, resistance mechanisms, and optimal toxicity management for the combination strategy.
To investigate the efficacy and safety of osimertinib plus savolitinib for patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations and de novo MET aberrations, we conducted a randomized, multicenter, open-label, phase 2 study (ClinicalTrials.gov identifier: NCT05163249). Treatment-naïve patients with locally advanced or metastatic NSCLC harboring de novo MET amplification or overexpression and EGFR mutations were randomized to receive osim
2. High flow nasal cannula versus conventional oxygen therapy during bronchoscopy: A systematic review and individual participant data meta-analysis.
Across 17 RCTs (3,116 patients), HFNC significantly reduced desaturation, procedure interruptions, respiratory support escalation, and airway interventions compared with COT. IPD analysis (1,344 patients) identified greater relative benefit at lower BMI and lower baseline respiratory/heart rates, and flows ≥45 L/min further reduced desaturation risk.
Impact: High-quality aggregated and IPD evidence confirms HFNC improves safety during bronchoscopy and identifies practical flow thresholds and patient modifiers to tailor care.
Clinical Implications: Adopt HFNC as preferred oxygenation during bronchoscopy, especially at flows ≥45 L/min. Consider greater benefit in patients with lower BMI and lower baseline respiratory/heart rates, and anticipate fewer interruptions and escalations.
Key Findings
- Desaturation reduced vs COT: OR 0.23 (95% CI 0.15–0.34).
- Procedure interruption reduced: OR 0.36 (95% CI 0.20–0.67).
- Escalation of respiratory support reduced: OR 0.25 (95% CI 0.11–0.55).
- Airway intervention reduced: OR 0.19 (95% CI 0.10–0.36).
- HFNC flows ≥45 L/min associated with lower desaturation risk (OR 0.28, 95% CI 0.12–0.65).
- Treatment effect modified by BMI and baseline respiratory/heart rates (greater benefit at lower values).
Methodological Strengths
- Comprehensive RCT synthesis plus IPD one-stage regression enabling treatment-modifier analysis.
- Pre-registered IPD-MA with multiple clinically relevant outcomes.
Limitations
- IPD available from only 6 of 17 trials; heterogeneity across studies and patient selection.
- Exploratory nature of interaction analyses requires cautious interpretation.
Future Directions: Prospective trials should define optimal HFNC flow strategies across risk strata and evaluate cost-effectiveness and workflow integration during diverse bronchoscopic procedures.
BACKGROUND: High-flow nasal cannula (HFNC) is superior to conventional oxygen therapy (COT) in preventing hypoxaemia during bronchoscopy. However, factors associated with HFNC effectiveness remain unclear. We performed an individual participant data meta-analysis (IPD-MA) to identify treatment modifiers for HFNC during bronchoscopy. METHODS: We systematically reviewed randomised controlled trials (RCTs) comparing HFNC and COT during bronchoscopy in adults (January 2000-September 2025) and requested IPD from correspond
3. Predicting age of respiratory syncytial virus infection from birth timing.
Using birthdate, demographics, and public RSV circulation data, the model estimates the probability of first RSV infection from birth to 12 months. It explained ~37% of the variance in age at first infection and generalized across four U.S. datasets, accurately predicting age at first infection in two independent cohorts.
Impact: This interpretable, externally validated model enables targeting of infant RSV prophylaxis (e.g., maternal vaccination or nirsevimab) to the highest-risk age windows without intensive surveillance.
Clinical Implications: Health systems can use birth-cohort timing and circulation data to prioritize and schedule RSV preventive strategies in infancy, optimize trial enrichment, and better estimate exposure timing in observational studies.
Key Findings
- Probability model uses infant birthdate, demographics, and public RSV circulation to estimate age of first infection (0–12 months).
- Explains ~37% of variance in age at first infection across datasets.
- Generalizes across four independent U.S. datasets; accurate prediction in two independent cohorts.
- Model is interpretable and reduces need for costly active surveillance to infer infection timing.
Methodological Strengths
- External validation across multiple independent cohorts with generalization.
- Interpretable modeling framework leveraging routinely available public surveillance data.
Limitations
- Observational modeling may be influenced by unmeasured confounders and regional reporting biases.
- Model trained and validated on U.S. datasets; performance in other geographies and healthcare systems needs testing.
Future Directions: Prospective policy simulations and implementation studies should evaluate integration into maternal-infant RSV prophylaxis programs and assess impact on hospitalization and cost-effectiveness across regions.
Respiratory syncytial virus (RSV) infects nearly all children by age 2 to 3 years, and early-life infection-defined using active and passive surveillance with quantitative polymerase chain reaction- and serology-identified infection-has been implicated as a causal factor in childhood asthma. As such, identifying infants that are likely to be infected with RSV during this critical susceptibility window has important implications for identifying individuals at risk for chronic respiratory sequelae. Ho