Daily Respiratory Research Analysis
Analyzed 191 papers and selected 3 impactful papers.
Summary
Triple fixed-dose inhaled therapy with budesonide–glycopyrronium–formoterol reduced severe exacerbations and improved lung function in patients with asthma insufficiently controlled on ICS–LABA. Point-of-care lung ultrasound scores in critically ill children correlated with oxygenation indices and predicted patient-centered outcomes. Large-scale breathomics using PTR-TOF MS plus machine learning accurately distinguished lung cancer, including early-stage disease, from controls and benign nodules.
Research Themes
- Asthma therapy escalation with fixed-dose triple inhalers
- Point-of-care imaging for pediatric respiratory failure
- AI-enabled noninvasive diagnostics (breathomics) for lung cancer
Selected Articles
1. Budesonide-glycopyrronium-formoterol fumarate dihydrate in uncontrolled asthma (KALOS and LOGOS): twin multicentre, double-blind, double-dummy, parallel-group, randomised, phase 3 trials.
In two parallel phase 3 RCTs, fixed-dose budesonide–glycopyrronium–formoterol improved lung function and reduced severe exacerbations versus dual therapy in patients inadequately controlled on medium/high-dose ICS–LABA. Benefits were observed irrespective of recent exacerbation history, supporting earlier escalation to triple inhaler therapy.
Impact: This large, rigorously designed RCT provides practice-changing evidence that fixed-dose triple therapy can benefit a broad asthma population beyond current step-up triggers.
Clinical Implications: Consider escalation to budesonide–glycopyrronium–formoterol in patients with persistent symptoms or risk despite medium/high-dose ICS–LABA, even without a very recent exacerbation, while monitoring individual response and safety.
Key Findings
- BGF improved lung function and reduced severe exacerbations versus ICS–LABA (dual therapy).
- Efficacy was consistent regardless of recent exacerbation history.
- Findings applied across a broad 12–80-year-old asthma population inadequately controlled on medium/high-dose ICS–LABA.
Methodological Strengths
- Multicentre, double-blind, double-dummy, randomized phase 3 design
- Large sample across 20 and 15 countries with parallel twin trials
Limitations
- Abstract does not provide numerical effect sizes by subgroup or dose
- Comparisons to alternative add-on strategies (e.g., tiotropium add-on) were not detailed
Future Directions: Head-to-head trials versus other step-up strategies and longer-term safety/effectiveness studies across diverse phenotypes will refine patient selection for triple therapy.
BACKGROUND: Long-acting muscarinic antagonists (LAMA) can be added to inhaled corticosteroid- (ICS)-long-acting β METHODS: Two multicentre, randomised, double-blind, double-dummy, phase 3 studies (KALOS and LOGOS) recruited participants aged 12-80 years with inadequately-controlled asthma despite daily medium-dose or high-dose ICS-LABA use from across 378 sites in 20 countries (KALOS), and 324 sites in 15 countries (LOGOS). Participants were randomly assigned (1:1:1:1) to BGF 320 μg, 28·8 μg, 10 μg (BGF 28·8); BGF 320 μg, 14·4 μg, 10 μg (BGF 14·4); BFF FINDINGS: Between Dec 15, 2020, and March 21, 2025 (KALOS), and between March 1, 2021, and March 20, 2025 (LOGOS), 8820 participants were recruited and 4311 received treatment (1179 received BGF 28·8, 726 received BGF 14·4, 1210 received BFF INTERPRETATION: These findings show that BGF improves lung function and reduces severe exacerbation rates in a broad population with asthma inadequately controlled despite medium-dose or high-dose ICS-LABA use. Given that these findings were observed regardless of recent exacerbation history, BGF could benefit individuals with inadequately controlled asthma without requiring a recent episode of acute deterioration on ICS-LABA before escalation. FUNDING: AstraZeneca.
2. Validation of Lung Ultrasound Score for Disease Severity and Outcomes in Pediatric Acute Respiratory Failure.
In a two-center prospective study (n=76), global lung ultrasound scores differentiated ARDS and LRTI from controls within 24 hours, correlated with oxygenation and ventilatory parameters, and predicted fewer ventilator- and ICU-free days at 28 days. LUS remained stable over the first 24 hours, supporting its role as an objective severity index.
Impact: Provides prospective validation that bedside lung ultrasound quantifies disease severity and is associated with meaningful patient-centered outcomes in pediatric acute respiratory failure.
Clinical Implications: Integrate early LUS scoring within 24 hours to stratify severity, guide ventilatory management, and track response in pediatric ARDS and LRTI; invest in training to standardize acquisition and scoring.
Key Findings
- Median global LUS scores differed markedly among ARDS (19), LRTI (8), and controls (2) within 24 hours (p<0.001).
- LUS correlated with oxygenation index (r=0.67), SpO2/FiO2 (r=-0.63), mean airway pressure (r=0.63), and dynamic compliance (r=-0.43).
- Higher LUS predicted fewer ventilator-free, positive-pressure ventilation–free, and ICU-free days at 28 days (all p<0.001).
Methodological Strengths
- Prospective, two-center design with predefined time points
- Objective correlations with multiple physiologic indices and patient-centered outcomes
Limitations
- Modest sample size and limited generalizability beyond two centers
- Blinding and inter-operator variability not fully detailed
Future Directions: Multicenter validation with standardized training, assessment of responsiveness to therapy, and integration into decision-support algorithms could extend LUS utility.
OBJECTIVES: The objective of this study was to investigate the validity of global lung ultrasound (LUS) scores among critically ill children with different etiologies and severities of acute respiratory failure as well as associations with outcomes. DESIGN: Prospective, observational study. SETTING: PICUs at two large children's hospitals. PATIENTS: Children receiving noninvasive or invasive mechanical ventilation and met criteria for acute respiratory distress syndrome (ARDS), lower respiratory tract infection (LRTI), or control group (no lung disease). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: LUS was performed and LUS scores calculated at two time points: 1) within 24 hours of respiratory failure for all groups (time 1) and 2) at 24 hours of time 1 for patients with ARDS and LRTI (time 2). A total of 76 patients (25 ARDS, 26 LRTI, and 25 control) were included. There was a significant difference in median time 1 global LUS scores between groups (ARDS, 19; interquartile range [IQR], 12-24; LRTI, 8 [IQR, 2-11]; and control, 2 [IQR, 0-6]; p < 0.001). Global LUS scores remained similar from time 1 to time 2 in both ARDS (19 to 17) and LRTI (8 to 7) groups. There were moderate correlations between LUS scores and oxygen saturation index (r = 0.67; p < 0.001), peripheral oxygen saturation/Fio2 ratio (r = -0.63; p < 0.001), mean airway pressure (r = 0.63; p < 0.001), positive end-expiratory pressure (r = 0.52; p < 0.001), and dynamic compliance (r = -0.43; p = 0.001). Higher LUS scores were associated with fewer ventilator-free days at 28 days (p < 0.001), fewer positive pressure ventilation-free days at 28 days (p < 0.001), and fewer ICU-free days at 28 days (p < 0.001). CONCLUSIONS: In critically ill children with acute respiratory failure, global LUS scores within 24 hours of admission differed by severity of parenchymal lung disease, correlated with oxygenation parameters, and were associated with patient-centered outcomes of duration of respiratory support and PICU length of stay.
3. Breathomics Analysis for Early Diagnosis of Lung Cancer Based on PTR-TOF MS: A Large Sample Size Cross-Sectional Study.
In a 4,515-participant cross-sectional study, PTR-TOF MS breathomics combined with LGBM achieved 95–98% sensitivity and specificity for lung cancer identification and 97–98% for distinguishing early-stage cancer from benign nodules. SHAP interpretability highlighted alpha-pinene and methyl methacrylate as key VOCs driving model performance.
Impact: Demonstrates scalable, interpretable, noninvasive diagnostics with high accuracy for early lung cancer, a major unmet need in respiratory oncology.
Clinical Implications: Breathomics may serve as an adjunct screening/triage tool to prioritize imaging and invasive diagnostics, particularly for indeterminate pulmonary nodules, pending external and prospective validation.
Key Findings
- LGBM achieved 95% sensitivity and 98% specificity for lung cancer vs healthy controls; 97%/98% for early-stage vs benign nodules.
- Alpha-pinene (m/z 137) and methyl methacrylate (m/z 101) were top SHAP-ranked VOCs.
- PTR-TOF MS enabled rapid, noninvasive breath profiling at scale (n=4515).
Methodological Strengths
- Very large sample with explicit ML model interpretability via SHAP
- Dual classification tasks including the clinically challenging early-stage vs benign nodule discrimination
Limitations
- Cross-sectional design without external prospective validation
- Potential confounding of VOCs by diet, smoking, medications, and comorbidities not fully controlled
Future Directions: Prospective, multicenter validation across histologies, assessment of confounders, and integration into clinical pathways for nodule triage and screening programs.
INTRODUCTION: Lung cancer remains a leading cause of cancer mortality globally, emphasising the critical need for non-invasive and cost-effective early screening methods. Breath analysis, detecting disease-specific volatile organic compounds (VOCs), presents a promising diagnostic avenue. METHODS: This cross-sectional study enrolled 4515 participants, including 4099 nonmalignant controls and 416 lung cancer patients. Exhaled breath samples were analysed using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF MS). Machine learning algorithms, particularly Light Gradient Boosting Machine (LGBM), were employed to construct classification models for distinguishing lung cancer from healthy controls and early-stage lung cancer from benign pulmonary nodules. Model interpretability was assessed using SHAP values. RESULTS: The LGBM model demonstrated superior performance, achieving 95% sensitivity, 98% specificity, and 98% accuracy for discriminating lung cancer from healthy controls. For the clinically challenging task of distinguishing early-stage lung cancer from benign nodules, LGBM achieved 97% sensitivity, 98% specificity, and 98% accuracy. SHAP analysis identified alpha-pinene (m/z 137) and methyl methacrylate (m/z 101) as the most significant VOCs. CONCLUSION: This large-scale study validates PTR-TOF MS based breath analysis combined with machine learning as a robust, non-invasive tool for early lung cancer detection. The LGBM model, supported by SHAP interpretability, offers high diagnostic accuracy in large cohorts. Future work will expand to diverse histological subtypes and multicenter validation. TRIAL REGISTRATION: ChiCTR2500101879.