Daily Respiratory Research Analysis
Three studies advance respiratory prevention and treatment: a nationwide randomized implementation trial showed electronic, behaviorally framed letters markedly increased influenza vaccination among high‑risk adults; a multicentre randomized phase 2 trial found pirfenidone improved gas transfer in grade 2–3 radiation‑induced lung injury when added to glucocorticoids; and a pooled individual‑level analysis of two randomized trials showed high‑dose influenza vaccine reduced serious cardio‑respirat
Summary
Three studies advance respiratory prevention and treatment: a nationwide randomized implementation trial showed electronic, behaviorally framed letters markedly increased influenza vaccination among high‑risk adults; a multicentre randomized phase 2 trial found pirfenidone improved gas transfer in grade 2–3 radiation‑induced lung injury when added to glucocorticoids; and a pooled individual‑level analysis of two randomized trials showed high‑dose influenza vaccine reduced serious cardio‑respiratory outcomes in older adults.
Research Themes
- Behavioral nudges to increase respiratory vaccination uptake
- Antifibrotic therapy for radiation-induced lung injury
- Optimizing influenza vaccine dosing to prevent cardio-respiratory events in older adults
Selected Articles
1. Digital Nudges to Increase Influenza Vaccination in Patients with Chronic Diseases.
In a nationwide randomized implementation trial of 308,978 Danish adults with chronic conditions, behaviorally informed electronic letters increased influenza vaccination by 12.4 percentage points versus usual care, with the strongest effect from a repeated cardiovascular‑framed message (15.0 percentage points). Effects were consistent across subgroups and in a second consecutive season.
Impact: This trial demonstrates a scalable, low-cost strategy that substantially increases influenza vaccination uptake in high-risk adults, a cornerstone of respiratory disease prevention.
Clinical Implications: Health systems can deploy repeated, cardiovascular‑framed electronic letters via national patient portals to raise vaccination coverage in chronic disease populations, likely reducing influenza morbidity and downstream cardio‑respiratory complications.
Key Findings
- Any electronic letter increased influenza vaccination vs usual care (36.5% vs 24.1%; difference 12.4 percentage points; 99.29% CI 11.9–12.9; P<0.001).
- The repeated cardiovascular‑focused letter achieved the largest effect (39.1% vs 24.1%; difference 15.0 percentage points; 99.29% CI 14.2–15.7).
- Effects were consistent across subgroups and among individuals who had received a similar letter in the prior season.
Methodological Strengths
- Nationwide randomized implementation design with registry-based ascertainment
- Large sample size with multiple behaviorally informed intervention arms and stringent co-primary error control (99.29% CIs)
Limitations
- Conducted in a single country (Denmark), potentially limiting generalizability to other health systems
- Outcome was vaccine uptake rather than clinical endpoints (e.g., hospitalizations)
Future Directions: Evaluate message tailoring and frequency across diverse health systems, link to clinical outcomes (e.g., influenza hospitalizations), and test integration with multimodal outreach (SMS/app notifications).
2. Pirfenidone for grade 2 and grade 3 radiation-induced lung injury: a multicentre, open-label, randomised, phase 2 trial.
In a multicentre randomized phase 2 trial (n=134), adding pirfenidone to glucocorticoids improved DLCO% at 24 weeks by a least‑squares mean difference of 10.4% versus steroids alone, with similar serious adverse event rates and no treatment‑related deaths. This supports antifibrotic therapy for grade 2–3 radiation‑induced lung injury.
Impact: Provides randomized evidence that an antifibrotic agent improves gas transfer in symptomatic radiation‑induced lung injury beyond glucocorticoids, addressing an unmet need in thoracic oncology.
Clinical Implications: For grade 2–3 radiation‑induced lung injury, consider adding pirfenidone to standard glucocorticoids to improve pulmonary diffusing capacity, with ongoing monitoring for rash and infections; phase 3 confirmation is warranted.
Key Findings
- DLCO% improved at week 24 with pirfenidone add‑on vs glucocorticoids alone (LS mean difference 10.4%; 95% CI 4.3–16.5; p=0.0010).
- Serious adverse events were comparable (18% vs 16%); no treatment‑related deaths.
- Grade ≥3 pneumonia occurred less often with pirfenidone (6% vs 12%); rash grade ≥3 in 3% vs 0%.
Methodological Strengths
- Randomized, multicentre design with prespecified physiological primary endpoint (DLCO%)
- Standardized dosing over 24 weeks with safety monitoring
Limitations
- Open‑label phase 2 design with modest sample size
- Primary endpoint is physiological (DLCO%) rather than hard clinical outcomes
Future Directions: Conduct phase 3, placebo‑controlled trials powered for clinical endpoints (symptoms, exacerbations, steroid‑sparing, imaging fibrosis) and explore biomarkers predicting response.
3. High-Dose vs. Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: The FLUNITY-HD Prespecified Pooled Analysis.
Across 466,320 randomized older adults in two harmonized pragmatic trials, high‑dose influenza vaccine reduced hospitalizations for influenza or pneumonia, cardiorespiratory disease, laboratory‑confirmed influenza, and all‑cause admissions versus standard‑dose, with consistent benefits regardless of pre‑existing CVD. Protection was particularly strong against hospitalization for heart failure.
Impact: Strengthens evidence that dosing strategy for influenza vaccination in older adults affects not only respiratory but also cardiovascular outcomes, supporting preferential use of high‑dose formulations.
Clinical Implications: For adults ≥65 years, preferentially administer high‑dose inactivated influenza vaccine to reduce serious respiratory and cardiovascular hospitalizations, particularly heart failure admissions.
Key Findings
- In pooled individual-level data (n=466,320), HD-IIV reduced hospitalizations for influenza/pneumonia, cardiorespiratory disease, laboratory‑confirmed influenza, and any cause vs SD-IIV.
- Benefits were consistent irrespective of pre‑existing cardiovascular disease.
- Among CV outcomes, the strongest relative benefit was observed for hospitalization for heart failure.
Methodological Strengths
- Prespecified secondary analysis of individual-level data from two harmonized pragmatic randomized trials
- Very large sample with routine database follow-up through season end
Limitations
- Secondary analysis; detailed absolute effect sizes and some p-values not fully specified in abstract
- Findings derived from Denmark and Spain may vary with strain circulation and healthcare systems
Future Directions: Quantify absolute risk reductions across seasons and comorbidity strata, evaluate cost‑effectiveness, and assess integration with RSV and pneumococcal vaccination strategies.