Respiratory Research Analysis
September’s respiratory literature emphasized prevention and mechanistic insights with immediate clinical relevance. A nationwide registry-linked randomized trial demonstrated that an RSV prefusion F vaccine substantially reduced RSV-related hospitalizations in adults ≥60. In parallel, a translational study in AERD connected alcohol-triggered symptoms to type-2 cytokine suppression of epithelial ALDH2 and showed therapeutic reversibility with dupilumab. Pediatric prevention advanced with a live-
Summary
September’s respiratory literature emphasized prevention and mechanistic insights with immediate clinical relevance. A nationwide registry-linked randomized trial demonstrated that an RSV prefusion F vaccine substantially reduced RSV-related hospitalizations in adults ≥60. In parallel, a translational study in AERD connected alcohol-triggered symptoms to type-2 cytokine suppression of epithelial ALDH2 and showed therapeutic reversibility with dupilumab. Pediatric prevention advanced with a live-attenuated intranasal RSV vaccine showing strong immunogenicity and acceptable early safety in RSV-naïve infants, supporting progression to phase III.
Selected Articles
1. RSV Prefusion F Vaccine for Prevention of Hospitalization in Older Adults.
A pragmatic nationwide randomized trial in Denmark (n=131,276; ≥60 years) found that a bivalent RSV prefusion F vaccine reduced RSV-related respiratory hospitalizations by 83.3% and lower respiratory tract hospitalizations by 91.7% versus no vaccine, with similar serious adverse event rates and modest reductions in all-cause respiratory hospitalizations.
Impact: Provides large-scale randomized evidence of substantial hospitalization reduction in older adults, directly informing seasonal RSV immunization policy.
Clinical Implications: Supports offering RSVpreF vaccine to adults ≥60 as part of seasonal prevention to reduce hospital burden; counseling should note strong protection and comparable safety.
Key Findings
- RSV-related respiratory hospitalization: 0.11 vs 0.66 events/1000 PY; effectiveness 83.3% (95% CI 42.9–96.9).
- RSV-related lower respiratory tract hospitalization: 1 vs 12 events; effectiveness 91.7% (95% CI 43.7–99.8).
- All-cause respiratory hospitalization reduced by 15.2% (95% CI 0.5–27.9); serious adverse events similar between groups.
2. Reduced aldehyde dehydrogenase 2 in respiratory tract associates with dysregulated alcohol metabolism and respiratory reactions in aspirin-exacerbated respiratory disease.
In a 600-patient AERD cohort integrated with tissue and in vitro data, alcohol-induced respiratory symptoms were common and linked to worse control and higher eicosanoids; epithelial ALDH2 was reduced by IL-4/IL-13 and increased after IL-4Rα blockade (dupilumab), with clinical improvement in alcohol-induced symptoms.
Impact: Links a prevalent clinical trigger to a reversible molecular pathway and an available biologic, offering near-term translational impact.
Clinical Implications: Counsel AERD patients on alcohol triggers; consider IL-4/IL-13 blockade for severe alcohol-induced reactions; explore nasal ALDH2 as a biomarker for risk stratification and biologic response prediction.
Key Findings
- Alcohol-induced upper (79.6%) and lower (45.1%) respiratory symptoms common, associated with worse disease control and higher urinary eicosanoids.
- ALDH2 lower in AERD nasal tissues/epithelium than aspirin-tolerant controls.
- IL-4/IL-13 reduced epithelial ALDH2; dupilumab increased nasal ALDH2 transcripts and improved alcohol-induced symptoms.
3. Live-Attenuated Intranasal RSV Vaccine in Infants and Toddlers.
A multicenter phase I/II randomized trial in 6–18 month-olds (n=180; 115 RSV-naïve) showed that both low and high doses of a live-attenuated intranasal RSV vaccine elicited substantially higher neutralizing titers than placebo with acceptable reactogenicity and no immediate unsolicited systemic adverse events.
Impact: Addresses a major unmet need in pediatric RSV prevention with a mucosal platform, demonstrating target-population immunogenicity and early safety to justify phase III.
Clinical Implications: If efficacy and durability are confirmed, intranasal live-attenuated RSV vaccination could simplify infant immunization and reduce RSV hospitalization burden.
Key Findings
- RSV-naïve infants: higher neutralizing GMTs versus placebo after each dose (e.g., post-dose2 LD 142.0 / HD 107.0 vs placebo 26.3).
- No unsolicited systemic adverse events within 30 minutes; solicited reactions common but acceptable.
- Consistent immunogenicity across doses and countries.