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.
BACKGROUND: Bronchiectasis guidelines are inconsistent with regard to the effectiveness of mucoactive agents, and their use varies geographically. Large trials are needed to assess safety and effectiveness. METHODS: For this open-label, randomized, two-by-two factorial trial at 20 sites in the United Kingdom, we enrolled participants with non-cystic fibrosis bronchiectasis who had frequent pulmonary exacerbations and daily sputum production. Current smokers and persons who had recently received mucoactive treatments were excluded. All participants received standard care and were also assigned either to one of three mucoactive-drug groups - hypertonic saline (the hypertonic-saline group), hypertonic saline and carbocisteine (the combination group), or carbocisteine (the carbocisteine group) - or to standard care alone. The comparisons were between hypertonic saline and no hypertonic saline and between carbocisteine and no carbocisteine, with each category consisting of two groups. The primary outcome was the number of pulmonary exacerbations over a 52-week period. Key secondary outcomes were scores on disease-specific health-related quality-of-life assessments, time to next pulmonary exacerbation, and safety. RESULTS: A total of 288 participants underwent randomization. No treatment interactions were found. The mean number of adjudicated fully qualifying pulmonary exacerbations over the 52-week period was...
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.
RATIONALE: Respiratory syncytial virus (RSV) is a highly transmissible pathogen that causes varying degrees of respiratory illness across all age groups. The safety and efficacy profiles of available RSV vaccines, a critical consideration for their integration into public health strategies and clinical practice, remain uncertain. OBJECTIVES: To assess the benefits and harms of RSV vaccines compared to placebo, no intervention, vaccines for other respiratory infections, other RSV vaccines, or monoclonal antibodies (mAbs) across all human populations. SEARCH METHODS: We conducted a comprehensive literature search of CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the WHO ICTRP following standard systematic review methodology from 2000 to April 2024. ELIGIBILITY CRITERIA: We included both randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) involving all human populations comparing RSV vaccines with placebo, no intervention, vaccines for other respiratory infections, other RSV vaccines, or mAbs. We excluded studies focused on dose-finding schedules and immunogenicity assessment. OUTCOMES: Benefits included frequency of RSV illness (both lower and upper respiratory illness) confirmed by laboratory tests (RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness); hospitalisation due to RSV disease (both lower and upper respiratory illness) confirmed by laboratory tests; mortality from illness caused by RSV (confirmed by laboratory test); all-cause mortality; and admission to an intensive care unit. Harms included serious adverse events (SAEs) related to vaccination, including neurological disorders such as Guillain-Barré syndrome. RISK OF BIAS: We assessed risk of bias in RCTs using Cochrane's RoB 2 tool....
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.
BACKGROUND: Bronchiectasis is a common lung condition associated with wide range of infectious, immunological, autoimmune, allergic and genetic conditions. Exacerbations and daily symptoms have the largest impact on patients and healthcare systems, and they are the key focus of treatments. Current practice is heterogeneous globally, and bronchiectasis has historically been a neglected disease. Here, we present evidence-based international guidelines for the management of adults with bronchiectasis. METHODS: A European Respiratory Society (ERS) Task Force, comprising global experts, a methodologist, and patient representatives, developed clinical practice guidelines in accordance with ERS methodology and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. Systematic literature searches, data extraction, and meta-analysis were performed to generate evidence tables, and recommendations were formulated using the evidence-to-decision framework. A total of 8 PICO (Patient, Intervention, Comparator, Outcomes) questions and 3 narrative questions were developed. RECOMMENDATIONS: The Task Force recommendations include strong recommendations in favour of airway clearance techniques for most patients with bronchiectasis and pulmonary rehabilitation for those with impaired exercise capacity. We issue a strong recommendation for the use of long-term macrolide treatment for patients at high risk of exacerbations and a strong recommendation in favour of long-term inhaled antibiotics in patients with chronic CONCLUSION: The ERS bronchiectasis guidelines provide an evidence-based framework for optimal management of adults with bronchiectasis and serve as a benchmark for evaluating the quality of care....