Daily Respiratory Research Analysis
Three impactful respiratory studies stood out today. Real-world test-negative analyses show strong effectiveness of nirsevimab against RSV hospital encounters in U.S. infants and superiority of cell-based over egg-based influenza vaccines in 2023–2024. A multinational cohort (ATLANTIS) identifies small airway dysfunction by impulse oscillometry as an independent risk biomarker for future exacerbations even in well-controlled asthma.
Summary
Three impactful respiratory studies stood out today. Real-world test-negative analyses show strong effectiveness of nirsevimab against RSV hospital encounters in U.S. infants and superiority of cell-based over egg-based influenza vaccines in 2023–2024. A multinational cohort (ATLANTIS) identifies small airway dysfunction by impulse oscillometry as an independent risk biomarker for future exacerbations even in well-controlled asthma.
Research Themes
- RSV prophylaxis effectiveness in infants
- Small airway dysfunction as risk biomarker in asthma
- Superiority of cell-based influenza vaccines over egg-based
Selected Articles
1. Effectiveness of nirsevimab among infants in their first RSV season in the United States, October 2023-March 2024: a test-negative design analysis.
In a six-system, test-negative EHR analysis of U.S. infants in their first RSV season, nirsevimab was 77% effective against RSV-related ED encounters and 98% effective against RSV-related hospitalization. Protection estimates reflect a median 7–8 weeks since administration, underscoring the need to monitor durability over time.
Impact: This is the first large, multisystem real-world effectiveness evaluation of universal infant nirsevimab in the U.S., demonstrating strong protection against clinically meaningful outcomes. It directly informs immunization policy and hospital preparedness during RSV seasons.
Clinical Implications: Supports broad implementation of nirsevimab for infants entering their first RSV season, with expectation of substantial reductions in ED visits and hospitalizations. Systems should plan for timely administration and track effectiveness as time since dose increases.
Key Findings
- Effectiveness against RSV-associated ED encounters: 77% (95% CI 69–83%)
- Effectiveness against RSV-associated hospitalization: 98% (95% CI 95–99%)
- Median time since dose at encounter: 52 days (ED) and 48 days (hospitalization)
Methodological Strengths
- Test-negative design across six healthcare systems with adjustment for key confounders
- Exclusion of infants with maternal RSV vaccination reduces exposure misclassification
Limitations
- Short time since dose may overestimate near-term effectiveness; durability not fully assessed
- Observational design with potential residual confounding and EHR misclassification
Future Directions: Prospective follow-up to quantify waning over the season, effectiveness in high-risk subgroups, and combined program impact with maternal vaccination.
2. Assessment of the role of small airway dysfunction in relation to exacerbation risk in patients with well controlled asthma (ATLANTIS): an observational study.
Across nine countries, small airway dysfunction measured by impulse oscillometry was common in well-controlled asthma and independently predicted future exacerbations. Metrics such as elevated R5–R20 and AX or reduced X5 identified patients at higher risk despite good symptom control.
Impact: Establishes small airway dysfunction as a clinically actionable risk biomarker in ostensibly well-controlled asthma, supporting routine use of impulse oscillometry where available to refine risk stratification and management.
Clinical Implications: Consider incorporating impulse oscillometry to detect small airway dysfunction in well-controlled asthma to guide therapy optimization (e.g., extra-fine particle inhaled corticosteroids, targeting peripheral inflammation) and follow-up intensity.
Key Findings
- Small airway dysfunction present in 26–36% of well-controlled asthma across IOS metrics
- R5–R20-defined dysfunction independently associated with future exacerbation risk after multivariable adjustment
- Findings consistent across multiple IOS parameters (R5–R20, AX, X5)
Methodological Strengths
- Multinational, multi-setting cohort with standardized IOS definitions using Z-scores
- Predefined well-controlled asthma subgroup and multivariable adjustment for key confounders
Limitations
- Observational design cannot establish causality or treatment effect of targeting small airways
- Generalizability depends on IOS availability and expertise; partial IOS data across metrics
Future Directions: Interventional trials testing strategies that target small airway inflammation in IOS-defined high-risk patients; implementation studies on integrating IOS into routine asthma care.
3. Superior Effectiveness and Estimated Public Health Impact of Cell- Versus Egg-Based Influenza Vaccines in Children and Adults During the US 2023-2024 Season.
In a large test-negative study spanning the 2023–2024 U.S. season, cell-based QIVc outperformed egg-based QIVe with a relative vaccine effectiveness of 19.8% overall and consistent superiority in both pediatric and adult subgroups. Modeling suggests that replacing QIVe with QIVc could avert ~2.4 million symptomatic illnesses and thousands of healthcare encounters.
Impact: Provides robust, real-world evidence that addresses egg-adaptation limitations, with immediate implications for seasonal vaccine selection and procurement, including the first demonstration of superiority in children from 6 months.
Clinical Implications: Health systems and payers should consider preferential use of cell-based vaccines to improve population-level influenza prevention, especially in pediatric programs, while ensuring equitable access.
Key Findings
- Relative vaccine effectiveness of QIVc vs QIVe: 19.8% overall (95% CI 15.7–23.8%)
- Consistent superiority in children 6 months–17 years (rVE 19.6%) and adults 18–64 years (rVE 18.5%)
- Modeled public health impact: ~2.38 million symptomatic illnesses, 1.1 million outpatient visits, 14,940 hospitalizations, and 574 deaths prevented if QIVc replaced QIVe
Methodological Strengths
- Large linked real-world dataset with test-negative design and doubly robust logistic regression
- Extensive subgroup and sensitivity analyses across care settings and influenza types
Limitations
- Observational design with potential residual confounding and vaccine selection biases
- Vaccine exposure and outcome ascertainment depend on routine data and testing behavior
Future Directions: Head-to-head evaluations across multiple seasons and age groups, cost-effectiveness analyses, and integration with variant-specific vaccine updates.