Daily Respiratory Research Analysis
Three impactful studies advance respiratory medicine: a multicenter prospective PET/CT radiomics model accurately predicts invasiveness and high‑risk pathology in early lung adenocarcinoma; a nationwide cohort identifies modifiable risk predictors of mortality and hospitalized exacerbations in obstructive airway diseases; and a translational study uncovers α7 nicotinic acetylcholine receptor–driven vascular dysfunction in COPD, highlighting a new therapeutic target.
Summary
Three impactful studies advance respiratory medicine: a multicenter prospective PET/CT radiomics model accurately predicts invasiveness and high‑risk pathology in early lung adenocarcinoma; a nationwide cohort identifies modifiable risk predictors of mortality and hospitalized exacerbations in obstructive airway diseases; and a translational study uncovers α7 nicotinic acetylcholine receptor–driven vascular dysfunction in COPD, highlighting a new therapeutic target.
Research Themes
- AI-driven imaging biomarkers for surgical decision-making in early lung cancer
- Population-scale predictors of mortality and exacerbations in obstructive airway diseases
- Mechanistic vascular pathology and therapeutic targets in COPD
Selected Articles
1. Non-invasive prediction of invasive lung adenocarcinoma and high-risk histopathological characteristics in resectable early-stage adenocarcinoma by [18F]FDG PET/CT radiomics-based machine learning models: a prospective cohort Study.
A multicenter, prospectively validated PET/CT radiomics model distinguished invasive from preinvasive lung adenocarcinoma (AUC ~0.92–0.93) and predicted high-risk histopathology (AUC ~0.82–0.85). Decision-curve analysis showed greater net benefit than CT alone, and the model stratified survival, supporting surgical planning.
Impact: Provides externally validated, noninvasive biomarkers to tailor extent of resection and nodal management in early-stage lung adenocarcinoma.
Clinical Implications: Can inform limited versus anatomical resection decisions, prioritize nodal sampling, and triage patients for more extensive surgery when high-risk pathology is predicted.
Key Findings
- Hybrid [18F]FDG PET/CT radiomics + clinical model achieved AUC 0.93 (internal) and 0.92 (external) for IA vs AIS/MIA discrimination.
- High-risk histopathological features were predicted with AUC 0.82 (internal) and 0.85 (external).
- Decision curve analysis demonstrated higher net clinical benefit than CT-only models; the model stratified PFS (P=0.002) and OS (P=0.017).
Methodological Strengths
- Prospective internal and external multicenter validation
- Robust feature selection (mRMR, LASSO) and AutoML modeling with calibration and decision-curve analysis
Limitations
- Potential spectrum and center variability in imaging protocols may affect generalizability
- Thresholds and workflow integration for real-world surgical decision-making require prospective impact studies
Future Directions: Prospective clinical utility trials to test decision impact, integration with genomic/molecular markers, and harmonization across scanners and centers.
2. Uncovering a novel role of nAChRs in oxidative stress-mediated vascular dysfunction in COPD.
Using human cells, mouse models, and human pulmonary arteries, the study identifies α7 nicotinic acetylcholine receptor activation as a driver of oxidative stress–linked pulmonary vascular dysfunction in COPD. Pharmacologic antagonism or genetic deletion mitigated damage, and α7 expression correlated with COPD severity, nominating nAChRs as therapeutic targets.
Impact: Reveals a previously underappreciated receptor-mediated mechanism of COPD vascular pathology with immediate translational relevance for drug development.
Clinical Implications: Targets such as α7 nAChR could be explored to prevent or treat COPD-associated pulmonary vascular dysfunction and hypertension alongside standard care.
Key Findings
- Cigarette smoke–induced oxidative stress, Ca2+ dysregulation, and contractile disruption in hPASMCs were driven by nAChR activation.
- nAChR antagonists or genetic deletion of α7 nAChR protected pulmonary artery function in mouse models.
- α7 nAChR expression increased with COPD severity in human pulmonary arteries and inversely correlated with respiratory function.
Methodological Strengths
- Multi-system translational approach (in vitro human cells, in vivo mouse models, human vascular tissues)
- Mechanistic interrogation linking receptor activation to oxidative stress and vascular dysfunction with pharmacologic and genetic tools
Limitations
- No interventional clinical trial data to confirm therapeutic efficacy in patients
- Quantitative human sample sizes and longitudinal outcomes were not detailed
Future Directions: Early-phase clinical studies testing α7 nAChR antagonists in COPD-related pulmonary vascular dysfunction; biomarker-guided patient selection based on vascular α7 expression.
3. Predictors of mortality and hospitalised exacerbations in obstructive airway diseases.
In a nationwide cohort of 1,006,968 adults with obstructive airway disease prescriptions, heavy short-acting bronchodilator overuse, current smoking, frailty, and prior exacerbations independently predicted mortality and hospitalized exacerbations. Findings emphasize modifiable targets for prevention and disease control.
Impact: Defines high-risk, modifiable predictors at population scale, guiding interventions to reduce mortality and exacerbation burden in asthma/COPD.
Clinical Implications: Prioritize smoking cessation, reduce SABA overuse by optimizing controller therapy, and address frailty to lower risk of death and hospitalizations.
Key Findings
- Among 1,006,968 adults, 14.4% died and 3.9% had a hospitalized exacerbation during follow-up.
- Mortality predictors included frailty (aHR 2.09), heavy SABA overuse (≥6 packages/year; aHR 1.81), current smoking (aHR 1.64), and ≥2 outpatient exacerbations in the prior year (aHR 1.52).
- Hospitalized exacerbation risk was highest with recent hospitalization (aHR 5.67), current smoking (aHR 3.69), and heavy SABA overuse (aHR 3.15).
Methodological Strengths
- Nationwide, very large sample with standardized claims data
- Multivariable Cox modeling to adjust for comorbidity and socioeconomic status
Limitations
- Claims-based definitions may misclassify disease and medication use
- Residual confounding and lack of granular clinical measures (spirometry, biomarkers)
Future Directions: Prospective interventions to curb SABA overuse, integrate frailty screening in primary care, and validate risk models with clinical data.