Daily Respiratory Research Analysis
A large international RCT (PROTHOR) found that higher PEEP with recruitment during one-lung ventilation did not reduce postoperative pulmonary complications and increased intraoperative hypotension and arrhythmias. A comprehensive network meta-analysis delineated inhaled corticosteroid adverse events by molecule and dose while confirming fewer exacerbations in asthma and COPD. In cystic fibrosis, structural and xenon MRI ventilation metrics predicted future exacerbations better than spirometry-b
Summary
A large international RCT (PROTHOR) found that higher PEEP with recruitment during one-lung ventilation did not reduce postoperative pulmonary complications and increased intraoperative hypotension and arrhythmias. A comprehensive network meta-analysis delineated inhaled corticosteroid adverse events by molecule and dose while confirming fewer exacerbations in asthma and COPD. In cystic fibrosis, structural and xenon MRI ventilation metrics predicted future exacerbations better than spirometry-based models.
Research Themes
- Perioperative ventilation strategies
- Precision safety profiling of inhaled corticosteroids
- Imaging biomarkers predicting respiratory exacerbations
Selected Articles
1. Effects of intraoperative higher versus lower positive end-expiratory pressure during one-lung ventilation for thoracic surgery on postoperative pulmonary complications (PROTHOR): a multicentre, international, randomised, controlled, phase 3 trial.
In a 74-center international phase 3 RCT of 2200 thoracic surgery patients, a high-PEEP lung expansion strategy during one-lung ventilation did not reduce postoperative pulmonary complications compared with low PEEP. High PEEP increased intraoperative hypotension and new arrhythmias, while hypoxemia rescue maneuvers were more frequent with low PEEP.
Impact: This definitive randomized trial informs global perioperative ventilation practice by showing no benefit and potential harm from higher PEEP strategies during one-lung ventilation.
Clinical Implications: Avoid routine high PEEP with recruitment during one-lung ventilation in patients with BMI <35; consider lower PEEP strategies to minimize hypotension and arrhythmias while preparing for potential hypoxemia rescue.
Key Findings
- Primary outcome (postoperative pulmonary complications) was similar: 53.6% (high PEEP) vs 56.4% (low PEEP); absolute risk difference −2.68 percentage points (95% CI −6.36 to 1.01; p=0.155).
- Intraoperative complications were higher with high PEEP: 49.8% vs 31.3%; notably hypotension 37.3% vs 14.3% and new arrhythmias 9.9% vs 3.9%.
- Hypoxemia rescue maneuvers were more frequent with low PEEP: 8.8% vs 3.3%.
- Extrapulmonary postoperative complications and overall adverse event counts did not differ between groups.
Methodological Strengths
- Large, multicentre, international phase 3 randomized controlled trial
- Modified intention-to-treat analysis with prespecified outcomes and balanced randomization
Limitations
- BMI <35 kg/m² population may limit generalizability to obese patients
- Blinding of intraoperative ventilation strategy is inherently difficult, potentially influencing management
Future Directions: Evaluate physiologically individualized PEEP during one-lung ventilation and explore protective strategies that balance oxygenation with hemodynamic stability across broader BMI ranges.
2. Adverse events of inhaled corticosteroids in adult patients with asthma or chronic obstructive pulmonary disease: pairwise, network and dose-response meta-analyses.
Across 129 trials involving 120,900 adults, ICS use increased pneumonia, oral candidiasis, and URTI risks but reduced asthma and COPD exacerbations. Risks differed by agent and dose: fluticasone and beclomethasone increased pneumonia, mometasone carried the highest oral candidiasis risk, whereas ciclesonide showed lower risks across comparisons; dose–response relationships were identified for several AEs.
Impact: This meta-analysis provides nuanced, agent- and dose-specific safety profiles to personalize ICS selection while balancing exacerbation prevention with adverse event risks.
Clinical Implications: Prefer agents with lower AE profiles (e.g., ciclesonide) when risks of pneumonia, oral candidiasis, or URTI are a concern; consider dose minimization strategies, especially with fluticasone (pneumonia/URTI) and budesonide (cataract) when clinically feasible.
Key Findings
- ICS increased pneumonia (RR 1.49), oral candidiasis (RR 2.29), and URTI (RR 1.17) versus control.
- ICS reduced asthma exacerbations (RR 0.30) and COPD exacerbations (RR 0.90) versus control.
- Agent differences: beclomethasone and fluticasone increased pneumonia (absolute risk up to +2.3%); fluticasone > budesonide for pneumonia risk.
- Ciclesonide showed consistently lower risks (e.g., up to −4.5% oral candidiasis versus other ICSs).
- Dose–response: fluticasone dose linked to pneumonia and URTI; multiple ICSs linked to oral candidiasis; budesonide dose linked to cataract.
Methodological Strengths
- Comprehensive pairwise and network meta-analysis with 129 trials and 120,900 participants
- Pre-registered (PROSPERO), PRISMA-compliant, GRADE certainty assessments, and Emax dose–response modeling
Limitations
- Heterogeneity across included trials and mixed asthma/COPD populations
- Trial-level (not patient-level) meta-analysis may limit granular risk stratification
Future Directions: Prospective head-to-head comparisons and patient-level meta-analyses to refine agent and dose selection; integrate AE risk models into individualized ICS benefit–risk calculators.
3. Structural and Functional Pulmonary MRI to Predict Pulmonary Exacerbations in Cystic Fibrosis.
In 106 individuals with cystic fibrosis, xenon MRI ventilation defect percent (VDP) and severe structural UTE MRI abnormalities predicted higher future exacerbation rates. Abnormal VDP (>3%) conferred nearly a threefold increase in exacerbation incidence, and imaging-based models outperformed clinical-only models.
Impact: Introduces robust imaging biomarkers that directly reflect structure-function abnormalities and improve prediction of exacerbations beyond spirometry and clinical history.
Clinical Implications: Imaging-derived metrics (VDP and structural MRI scores) can refine risk stratification and may guide proactive therapy, monitoring frequency, and trial enrichment strategies in CF care.
Key Findings
- Abnormal xenon MRI VDP (>3%) was associated with a 2.80-fold (95% CI 1.6–4.56) higher exacerbation incidence.
- Severe UTE MRI features (fourth quartile) for consolidation, wall thickening, and bronchiectasis were linked to increased exacerbations.
- Imaging-inclusive multivariable models outperformed clinical-only models; VDP remained significant even after controlling for prior exacerbations, whereas spirometry did not.
Methodological Strengths
- Combined structural (UTE) and functional (xenon MRI) assessments in the same cohort
- Multivariable modeling demonstrating incremental predictive value over clinical variables
Limitations
- Retrospective, single-cohort design with potential residual confounding
- Limited external validation and potential availability constraints of xenon MRI
Future Directions: Prospective multicenter validation and interventional studies testing imaging-guided care pathways; assess cost-effectiveness and integration into routine CF management.