Daily Respiratory Research Analysis
Three impactful respiratory studies stand out today: a Nature Communications re-analysis shows lung cancer screening effectiveness varies markedly by smoking history, sex, and, critically, tumor histology. Two large pragmatic randomized trials from Europe report that high-dose influenza vaccination consistently outperforms standard-dose across cardiovascular subgroups, and that an RSV prefusion F vaccine has similar effectiveness in older adults with or without atherosclerotic cardiovascular dis
Summary
Three impactful respiratory studies stand out today: a Nature Communications re-analysis shows lung cancer screening effectiveness varies markedly by smoking history, sex, and, critically, tumor histology. Two large pragmatic randomized trials from Europe report that high-dose influenza vaccination consistently outperforms standard-dose across cardiovascular subgroups, and that an RSV prefusion F vaccine has similar effectiveness in older adults with or without atherosclerotic cardiovascular disease.
Research Themes
- Heterogeneity in lung cancer screening effectiveness driven by histology
- Optimization of respiratory virus vaccination strategies in older adults
- Cardiovascular–respiratory interface in vaccine outcomes
Selected Articles
1. High-dose vs. standard-dose inactivated influenza vaccine and cardiovascular outcomes in persons with or without pre-existing atherosclerotic cardiovascular disease: the DANFLU-2 trial.
In a large pragmatic randomized trial across three influenza seasons, high-dose inactivated influenza vaccine reduced influenza-related hospitalizations compared with standard-dose with consistent relative effectiveness in patients with and without ASCVD. Cardiovascular outcomes (MACE) showed no significant heterogeneity by ASCVD status.
Impact: This head-to-head randomized evidence supports preferential use of high-dose influenza vaccine in older adults regardless of ASCVD, informing vaccination policy for respiratory infection prevention and potential cardioprotection.
Clinical Implications: For adults ≥65 years, high-dose influenza vaccine can be favored over standard-dose to reduce influenza-related hospitalizations irrespective of ASCVD status, simplifying vaccine selection in primary and cardiovascular care settings.
Key Findings
- High-dose IIV showed substantially higher effectiveness for influenza hospitalization than standard-dose in both ASCVD and non-ASCVD groups.
- No significant interaction by ASCVD status for respiratory or cardiovascular outcomes (all Pinteraction ≥ .05).
- MACE relative vaccine effectiveness estimates were small and similar regardless of ASCVD (no statistically significant difference).
Methodological Strengths
- Pragmatic, individually randomized design with nationwide registry ascertainment across three seasons
- Large sample size enabling robust subgroup analyses by ASCVD status
Limitations
- Open-label design may introduce behavior or ascertainment bias
- Exploratory prespecified analysis; primary endpoints not powered specifically for ASCVD interaction
Future Directions: Assess cost-effectiveness and implementation strategies for scaling high-dose influenza vaccination in multimorbid older adults, and explore additive benefits with RSV vaccination.
2. A comparative analysis of heterogeneity in lung cancer screening effectiveness in two randomised controlled trials.
Using individual-level data from NLST and NELSON, the authors show that lung cancer screening mortality reduction varies substantially by pack-years, smoking status, sex, and, most critically, by histology. The heterogeneity across subgroups is largely explained by differing distributions of histologic subtypes with more favorable screening responsiveness.
Impact: This study reframes eligibility and evaluation for lung cancer screening by demonstrating histology-driven effectiveness, informing tailored screening policies beyond simple smoking thresholds.
Clinical Implications: Screening programs should consider histology-driven benefits when refining eligibility (e.g., relaxing smoking criteria) and when communicating expected benefit by patient subgroup, potentially improving population effectiveness.
Key Findings
- Mortality reduction varied by pack-years, smoking status, and sex across NLST and NELSON.
- Histology was the dominant driver: adenocarcinoma and non-squamous subtypes showed greater benefit; small-cell and, in NLST, squamous-cell carcinoma showed limited/negative benefit.
- Subgroup heterogeneity was largely attributable to differences in histologic distributions within those subgroups.
Methodological Strengths
- Individual participant data from two landmark randomized screening trials
- Multiple analytic approaches including traditional subgrouping, predictive modeling, and machine learning
Limitations
- Post hoc comparative analyses may be sensitive to model assumptions and confounding in cross-trial comparisons
- Histology-based inferences depend on accurate classification and may not capture intra-tumor heterogeneity
Future Directions: Prospective evaluation of histology-informed eligibility and decision tools; assess program-level impact of relaxing smoking criteria while safeguarding harms.
3. Effectiveness of bivalent respiratory syncytial virus prefusion F protein-based vaccine in individuals with or without atherosclerotic cardiovascular disease: the DAN-RSV trial.
In this prespecified secondary analysis of a large randomized registry-based trial, RSVpreF vaccination markedly reduced RSV-related respiratory hospitalizations with similar effectiveness in older adults regardless of ASCVD status. Major cardiovascular event reduction was small and did not differ by ASCVD.
Impact: Supports broad RSV vaccination of older adults including those with ASCVD, simplifying prioritization without compromising benefit in high-risk cardiovascular populations.
Clinical Implications: Clinicians can recommend RSVpreF broadly to ≥60-year-olds irrespective of ASCVD; counseling should note strong respiratory protection and uncertain/limited MACE impact.
Key Findings
- RSVpreF markedly reduced RSV-related respiratory tract hospitalization; VE was similar with and without ASCVD.
- No significant interaction by ASCVD for respiratory or cardiovascular outcomes.
- Effect on major adverse cardiovascular events was modest and not statistically significant in either subgroup.
Methodological Strengths
- Randomized allocation with nationwide registry ascertainment and prespecified subgroup analysis
- Very large sample enabling precise estimation across ASCVD strata
Limitations
- Secondary analysis; some VE estimates have wide confidence intervals (especially in ASCVD subgroup)
- Open-label vaccination strategy may introduce residual confounding in healthcare-seeking behaviors
Future Directions: Evaluate durability across multiple RSV seasons and potential additive value when co-administered with influenza vaccines in high-risk multimorbid elders.