Weekly Respiratory Research Analysis
This week highlighted high-impact randomized trials and large-scale real-world syntheses that will change respiratory practice: a phase 3 trial showed sotatercept added early in pulmonary arterial hypertension dramatically reduced clinical worsening; a definitive NEJM RCT found no benefit from hypertonic saline or carbocisteine for bronchiectasis exacerbation prevention, informing deimplementation; and the first head-to-head biologic RCT in CRSwNP demonstrated dupilumab’s superiority over omaliz
Summary
This week highlighted high-impact randomized trials and large-scale real-world syntheses that will change respiratory practice: a phase 3 trial showed sotatercept added early in pulmonary arterial hypertension dramatically reduced clinical worsening; a definitive NEJM RCT found no benefit from hypertonic saline or carbocisteine for bronchiectasis exacerbation prevention, informing deimplementation; and the first head-to-head biologic RCT in CRSwNP demonstrated dupilumab’s superiority over omalizumab. Across the week, advances spanned disease-modifying therapies, vaccine policy-relevant evidence, and diagnostic/AI innovations that improve case-finding in primary care.
Selected Articles
1. Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis.
In a multicenter phase 3 randomized, placebo-controlled trial of 320 adults with PAH diagnosed within the prior year, add-on sotatercept on top of double/triple background therapy markedly reduced time to clinical worsening (HR 0.24) over a median follow-up of 13.2 months. Benefits were driven by fewer exercise-test deteriorations and PAH hospitalizations; common adverse events included epistaxis and telangiectasia.
Impact: High-quality phase 3 evidence of an early, substantial disease‑modifying effect in a high‑morbidity condition likely to alter guideline recommendations and clinical practice for recently diagnosed PAH patients.
Clinical Implications: Consider adding sotatercept to optimized background therapy for WHO FC II–III PAH diagnosed within one year in intermediate/high‑risk patients, with monitoring for epistaxis, telangiectasia, and hematologic effects; discuss early initiation benefits with patients.
Key Findings
- Primary endpoint events: 10.6% with sotatercept vs 36.9% with placebo (HR 0.24; 95% CI 0.14–0.41; P<0.001).
- Exercise-test deterioration and unplanned PAH hospitalizations were substantially reduced in the sotatercept group.
- Most common adverse events: epistaxis (31.9%) and telangiectasia (26.2%).
2. Hypertonic Saline or Carbocisteine in Bronchiectasis.
A 20-center, open-label, randomized two-by-two factorial NEJM trial (n=288) found that neither nebulized hypertonic saline nor oral carbocisteine reduced adjudicated pulmonary exacerbations over 52 weeks in non-CF bronchiectasis. Secondary outcomes and safety were similar across groups, challenging long-standing mucoactive practices.
Impact: A definitive randomized trial published in NEJM that provides strong negative evidence prompting deimplementation of widely used mucoactive agents in bronchiectasis.
Clinical Implications: Avoid routine prescription of hypertonic saline or carbocisteine for exacerbation prevention in non‑CF bronchiectasis; prioritize evidence‑based interventions (airway clearance techniques, macrolides for frequent exacerbators, inhaled antibiotics for chronic infection) per guidelines.
Key Findings
- No reduction in adjudicated pulmonary exacerbations over 52 weeks with hypertonic saline or carbocisteine.
- No significant differences in quality-of-life scores, time to next exacerbation, or safety outcomes across groups.
- Open-label, factorial design across 20 UK sites with prespecified adjudicated outcomes.
3. Dupilumab versus omalizumab in patients with chronic rhinosinusitis with nasal polyps and coexisting asthma (EVEREST): a multicentre, randomised, double-blind, head-to-head phase 4 trial.
EVEREST, the first head-to-head biologic trial in respiratory disease, randomized patients with severe CRSwNP and coexisting asthma to dupilumab or omalizumab for 24 weeks. Dupilumab was superior for reducing endoscopic nasal polyp scores and improving olfaction (UPSIT) with safety profiles consistent with known data.
Impact: First high‑quality head‑to‑head RCT between two approved biologics in airway disease; directly informs biologic selection and personalization of therapy in CRSwNP with asthma.
Clinical Implications: When choosing between biologics for severe CRSwNP with asthma, prioritize dupilumab given superior reductions in polyp burden and improved olfaction over 24 weeks, while considering patient‑specific factors and safety profiles.
Key Findings
- Dupilumab superior to omalizumab for endoscopic nasal polyp score reduction at 24 weeks.
- Greater improvement in olfaction (UPSIT) with dupilumab at 24 weeks; safety consistent with established profiles.