Daily Respiratory Research Analysis
Analyzed 165 papers and selected 3 impactful papers.
Summary
Three high-impact studies refine respiratory care. A multicenter, blinded RCT found that endotracheal surfactant does not shorten ventilation in infants with critical bronchiolitis, arguing against its routine use. A large, pragmatic randomized trial showed that AI worklist prioritization of primary-care chest X-rays did not accelerate CT or lung cancer diagnosis, while a neonatal RCT demonstrated non-invasive high-frequency oscillation ventilation is non-inferior to CPAP as primary support in preterm RDS.
Research Themes
- Practice-changing neutral randomized trials in respiratory care
- Real-world randomized evaluation of AI in diagnostic pathways
- Optimization of non-invasive ventilatory strategies in neonatology
Selected Articles
1. AI-based chest X-ray prioritization in the lung cancer diagnostic pathway: the LungIMPACT randomized controlled trial.
In a pragmatic, multicentre randomized trial of 93,326 primary-care CXRs, AI-based worklist prioritization did not reduce time to CT or time to lung cancer diagnosis. No differences were observed in urgent referral timing, treatment timing, or stage at diagnosis; discordance between AI and radiologist reports occurred in 30% of CXRs.
Impact: This large, randomized evaluation sets realistic expectations for AI deployment by showing no measurable acceleration of the lung cancer diagnostic pathway through CXR prioritization, guiding resource allocation and implementation strategies.
Clinical Implications: Health systems should avoid relying on AI worklist prioritization of CXRs to speed lung cancer diagnosis and instead focus on end-to-end pathway optimization, including rapid-access CT and structured reporting. AI may still add value for quality assurance or detection, but not for prioritization alone.
Key Findings
- AI prioritization did not reduce time to CT (median 53 vs 53 days; ratio of geometric means 0.97, 95% CI 0.93-1.02).
- No reduction in time to lung cancer diagnosis (median 44 vs 46 days; ratio of geometric means 0.98, 95% CI 0.83-1.16).
- No differences in urgent referral timing, time to treatment, or stage at diagnosis.
- AI–radiologist discordance occurred in 30.3% of CXRs; expert review identified actionable findings in 23.9% of discordant cases.
Methodological Strengths
- Prospective, multicentre randomized controlled design with pragmatic deployment
- Very large sample with real-world primary-care CXR requests and prespecified outcomes
Limitations
- Randomization by day (worklist-level) rather than individual may introduce temporal clustering effects
- Exclusion of 4,405 CXRs due to compliance/randomization failures; results apply to primary-care CXR context only
Future Directions: Evaluate AI contributions beyond prioritization (e.g., structured reporting, quality control, triage to CT) and test pathway-level interventions with randomized or stepped-wedge designs.
Prioritizing artificial intelligence (AI)-detected imaging findings may reduce the time to diagnosis of lung cancer. This prospective, multicentre, randomized controlled trial tested whether immediate AI prioritization of primary care-requested chest X-rays (CXR) influenced time to computed tomography (CT) and lung cancer diagnosis, the primary outcomes. Secondary outcomes included the number of urgent suspected lung cancer referrals, incidence and stage of lung cancer, times to urgent referral and treatment, concordance between AI and radiology reports, and algorithm accuracy. AI was available in both study arms, with AI prioritization randomized by day. Of 97,731 participant CXRs, 4,405 were excluded due to data compliance issues or failure of randomization, resulting in 93,326 CXRs analyzed (45,987 and 47,339 in the prioritization 'on' or 'off' arms, respectively). A total of 13,347 CTs were identified, with 2,766 performed within 14 days of CXR. Median (interquartile range) times to CT were 53 days (17-145) and 53 days (19-141), with and without AI prioritization, corresponding to a ratio of geometric means of 0.97 (95% confidence interval (CI) = 0.93-1.02; P = 0.31). When restricted to CTs performed within 14 days of CXR, the median time to CT was 8 days (5-11) in both groups.
2. Endotracheal surfactant for infants with life-threatening bronchiolitis (BESS): a randomised, blinded, sham-controlled, phase 2 trial.
Among 232 randomized infants, endotracheal poractant alfa did not reduce the duration of invasive mechanical ventilation compared with sham (median ~63 vs 62 hours; GMR 1.02). Safety was acceptable with no treatment-related deaths. Findings do not support routine surfactant use for infant bronchiolitis requiring IMV.
Impact: A rigorous blinded, sham-controlled multicentre RCT provides definitive evidence against routine surfactant use in this context, curbing low-value interventions and redirecting care pathways.
Clinical Implications: Avoid routine endotracheal surfactant in ventilated infant bronchiolitis; focus on evidence-based supportive care and ventilatory strategies. Surfactant might be reserved only for research settings or clearly defined phenotypes pending new data.
Key Findings
- No reduction in duration of invasive mechanical ventilation with poractant alfa versus sham (geometric mean ratio 1.02; p=0.86).
- No treatment-related deaths; safety profile acceptable across up to three endotracheal doses.
- Multicentre, blinded, sham-controlled design resolves prior uncertainty from small, unblinded studies.
Methodological Strengths
- Blinded, sham-controlled, multicentre randomized design
- Mechanistic exploratory analyses alongside clinical endpoints
Limitations
- Phase 2 sample size may miss small effects on ventilation duration
- Heterogeneity in timing before randomization (<24 vs ≥24 h IMV) may influence trajectories
Future Directions: Phenotype-specific trials (e.g., surfactant deficiency markers) or alternative delivery strategies could be explored; prioritize trials of ventilatory strategies and adjuncts with stronger mechanistic rationale.
BACKGROUND: Bronchiolitis is a common viral respiratory disease of infants, with severity ranging from mild symptoms, such as coryza and feeding difficulties, to fulminant respiratory failure. Endotracheal administration of exogenous surfactant has been shown in small studies to improve gas exchange in critically ill infants with bronchiolitis. We aimed to investigate the safety and efficacy of endotracheal poractant alfa for treating critical bronchiolitis compared with a sham procedure. METHODS: BESS was a multicentre, blinded, randomised, sham-controlled, parallel-group, phase 2, superiority trial with exploratory mechanism evaluation studies. The trial was done in 15 paediatric intensive care units in the devolved National Health Service (NHS) of England, Scotland, and Northern Ireland. Preterm and term-born infants younger than 26 weeks of gestationally corrected age admitted to hospitals with bronchiolitis requiring invasive mechanical ventilation (IMV) were randomly assigned (1:1) to receive up to three doses of endotracheal poractant alfa (Curosurf) or sham intervention, allocated through web-based randomisation.
3. Non-invasive high-frequency oscillation ventilation versus nasal CPAP as primary respiratory support in preterm neonates ≥ 30 weeks with RDS: a non-inferiority randomized controlled trial.
In preterm neonates ≥30 weeks with RDS, NHFOV was non-inferior to CPAP for treatment failure and IMV requirement, while reducing the duration of primary noninvasive support and increasing ventilator-free days. The trial standardized pressure and interface, addressing prior methodological gaps.
Impact: Provides randomized evidence supporting NHFOV as a viable initial support option in preterm RDS, potentially expanding noninvasive strategies where resources vary.
Clinical Implications: NHFOV can be considered as primary NRS for preterm neonates ≥30 weeks with RDS, with attention to standardized pressures and interfaces; referral centers should integrate NHFOV protocols and training while monitoring for generalizability to younger gestational ages.
Key Findings
- NHFOV was non-inferior to CPAP for treatment failure (both 4.2%; RD 0.00, 90% CI -0.06 to +0.06).
- No difference in IMV requirement (RD -0.01, 90% CI -0.04 to 0.01).
- Shorter duration of primary noninvasive support (median 7 hours less; p=0.03) and more ventilator-free days (MD 0.30 days; p=0.02) with NHFOV.
Methodological Strengths
- Randomized non-inferiority design with prespecified margin and equivalent pressure settings
- Standardized nasal mask interface and lung recruitment protocol
Limitations
- Open-label, single-centre design limits blinding and generalizability
- Non-inferiority margin (20%) is relatively wide; not powered for superiority outcomes
Future Directions: Multicentre trials including <30-week gestations, standardized NHFOV parameterization, and longer-term respiratory/neurodevelopmental outcomes are needed.
UNLABELLED: The purpose of this study is to evaluate if non-invasive high-frequency oscillation ventilation (NHFOV) is non-inferior to nasal continuous positive airway pressure (CPAP) as primary non-invasive respiratory support (NRS) in preterm neonates of ≥ 30 weeks' gestation with respiratory distress syndrome (RDS). In this open-label randomized controlled trial (RCT) with a non-inferiority design conducted in a lower middle-income country, 142 preterm neonates were randomized to receive NHFOV (n = 71) or CPAP (n = 71) at equivalent pressures after lung recruitment with nasal mask (NM) interface. A non-inferiority margin of 20% was pre-specified and a two-sided 90% confidence interval (CI) standardly used in non-inferiority trials was chosen. For the outcome treatment failure (requirement of an alternate NRS as rescue), the event rate was 4.2% in both groups, risk difference (RD) with 90% CI being 0.00 (- 0.06 to + 0.06), and that for IMV requirement was - 0.01 (- 0.04 to 0.01). Since upper limits of CIs for both primary outcomes were well below the non-inferiority margin, NHFOV was proven to be non-inferior compared to CPAP. Duration of primary NRS was significantly lesser (median difference (MD) (95% CI), 7 h lesser (- 14 to 0); p = 0.03) and ventilator-free days for primary NRS were significantly higher (MD (95% CI), 0.30 days (0.00 to 0.60); p = 0.02) in the NHFOV group.