Daily Respiratory Research Analysis
A large NEJM randomized trial found that neither hypertonic saline nor carbocisteine reduced exacerbations in bronchiectasis over 52 weeks, informing deimplementation of commonly used mucoactive therapies. A Cochrane systematic review showed strong efficacy of RSV prefusion vaccines in older adults and maternal vaccination reducing severe infant RSV disease. The new ERS guideline provides GRADE-based, global recommendations for adult bronchiectasis management, including strong support for airway
Summary
A large NEJM randomized trial found that neither hypertonic saline nor carbocisteine reduced exacerbations in bronchiectasis over 52 weeks, informing deimplementation of commonly used mucoactive therapies. A Cochrane systematic review showed strong efficacy of RSV prefusion vaccines in older adults and maternal vaccination reducing severe infant RSV disease. The new ERS guideline provides GRADE-based, global recommendations for adult bronchiectasis management, including strong support for airway clearance, pulmonary rehabilitation, macrolides for frequent exacerbators, and long-term inhaled antibiotics for chronic infection.
Research Themes
- Bronchiectasis management and deimplementation of mucoactive agents
- RSV vaccination efficacy across populations
- Evidence-based guideline development in respiratory care
Selected Articles
1. Hypertonic Saline or Carbocisteine in Bronchiectasis.
In a 20-center, open-label, factorial RCT (n=288), neither hypertonic saline nor carbocisteine significantly reduced fully adjudicated pulmonary exacerbations over 52 weeks compared with standard care. Secondary outcomes and adverse events were similar across groups.
Impact: This definitive randomized trial challenges routine use of mucoactive agents in bronchiectasis, guiding deimplementation and resource allocation. Negative results in NEJM carry immediate practice implications.
Clinical Implications: Clinicians should avoid routine prescription of hypertonic saline or carbocisteine to prevent exacerbations in non-CF bronchiectasis and focus on proven strategies (airway clearance, macrolides for frequent exacerbators, inhaled antibiotics for chronic infection).
Key Findings
- Neither hypertonic saline nor carbocisteine reduced adjudicated exacerbations over 52 weeks versus no use.
- No significant differences in quality-of-life scores, time to next exacerbation, or safety outcomes.
- Open-label, two-by-two factorial design across 20 UK sites with 288 randomized participants.
Methodological Strengths
- Multicenter randomized factorial design with adjudicated outcomes
- Clear exclusion of current smokers and recent mucoactive use to reduce confounding
Limitations
- Open-label design may introduce performance bias
- Absolute exacerbation rates were relatively low, possibly limiting power for small effects
Future Directions: Evaluate patient subgroups (e.g., specific sputum rheology phenotypes) or combination strategies with airway clearance; prioritize trials of therapies targeting infection and inflammation.
2. Efficacy and safety of respiratory syncytial virus vaccines.
This Cochrane review of 14 RCTs found that RSV prefusion vaccines markedly reduce RSV-associated lower respiratory tract illness (VE ~77%) and acute respiratory illness (VE ~67%) in older adults, and maternal vaccination reduces medically attended and severe RSV lower respiratory tract illness and hospitalizations in infants. Safety signals were not increased for vaccine-related serious adverse events; evidence for live-attenuated vaccines in infants remains very uncertain.
Impact: Provides high-certainty, population-specific evidence to support deployment of RSV prefusion vaccines in older adults and maternal immunization programs for infant protection.
Clinical Implications: Support offering RSV prefusion vaccines to older adults and maternal RSV vaccination to reduce severe infant disease; live-attenuated infant vaccines require further data. Monitor for rare adverse events but current data suggest acceptable safety.
Key Findings
- Older adults: RSV prefusion vaccines reduced RSV-associated LRTI (VE 77%) and ARI (VE 67%) with high-certainty evidence.
- Maternal vaccination: reduced medically attended and severe RSV LRTI and hospitalizations in infants.
- Safety: No clear increase in vaccine-related serious adverse events; evidence for live-attenuated infant vaccines remains very uncertain.
Methodological Strengths
- Cochrane-standard systematic review with comprehensive search and RoB 2 assessment
- Population-stratified efficacy estimates and vaccine-type comparisons
Limitations
- Heterogeneity across trials and vaccine platforms; some outcomes with low event rates
- Very limited certainty for live-attenuated infant vaccines and neurologic adverse events
Future Directions: Head-to-head comparisons of RSV platforms, longer-term safety surveillance (e.g., GBS), and data in immunocompromised groups and LMIC settings.
3. European Respiratory Society Clinical Practice Guideline for the Management of Adult Bronchiectasis.
ERS issued GRADE-based, international guidelines emphasizing airway clearance and pulmonary rehabilitation, long-term macrolides for frequent exacerbators, and long-term inhaled antibiotics for chronic infection in adult bronchiectasis. The guideline standardizes heterogeneous practices and sets a benchmark for care quality.
Impact: Authoritative, globally applicable recommendations will harmonize care and directly influence clinical pathways, research priorities, and policy.
Clinical Implications: Adopt structured airway clearance for most patients, refer for pulmonary rehabilitation when exercise capacity is impaired, use long-term macrolides in frequent exacerbators after screening for contraindications, and apply long-term inhaled antibiotics for chronic infection (e.g., Pseudomonas).
Key Findings
- Strong recommendations for airway clearance and pulmonary rehabilitation in adult bronchiectasis.
- Strong recommendation for long-term macrolides in high-risk exacerbators.
- Strong recommendation for long-term inhaled antibiotics in chronic infection.
Methodological Strengths
- GRADE-based process with systematic searches, evidence tables, and evidence-to-decision framework
- Multidisciplinary task force with patient representation
Limitations
- Evidence gaps in specific subpopulations and interventions; heterogeneity of underlying studies
- Implementation may vary across health systems and resource settings
Future Directions: Address evidence gaps with pragmatic trials (e.g., inhaled antibiotic strategies across pathogens), refine phenotyping to personalize therapy, and develop implementation tools for diverse settings.