Daily Respiratory Research Analysis
Three impactful respiratory studies stood out: an interpretable dual-phase CT AI (NeoPred) that predicts pathological response to neoadjuvant chemo-immunotherapy in resectable NSCLC; a multi-trait genetic analysis identifying 31 new asthma loci in East Asians and implicating a CD36 missense variant; and a large cohort linking pulmonary arterial pressure trajectories before/after kidney transplant to mortality, spotlighting post-transplant pulmonary hypertension risk.
Summary
Three impactful respiratory studies stood out: an interpretable dual-phase CT AI (NeoPred) that predicts pathological response to neoadjuvant chemo-immunotherapy in resectable NSCLC; a multi-trait genetic analysis identifying 31 new asthma loci in East Asians and implicating a CD36 missense variant; and a large cohort linking pulmonary arterial pressure trajectories before/after kidney transplant to mortality, spotlighting post-transplant pulmonary hypertension risk.
Research Themes
- AI-driven imaging biomarkers for thoracic oncology
- Population-specific asthma genetics and immune mechanisms
- Hemodynamic trajectories of pulmonary hypertension and transplant outcomes
Selected Articles
1. NeoPred: dual-phase CT AI forecasts pathologic response to neoadjuvant chemo-immunotherapy in NSCLC.
In multi-center cohorts (retrospective n=509; prospective n=50), a dual-phase CT 3D-CNN (NeoPred) predicted major/pathologic complete response to neoadjuvant chemo-immunotherapy in resectable NSCLC, outperforming unaided radiologists and improving their performance when used as assistance. External validation AUC reached 0.772 (0.787 with clinical variables) and prospective AUC 0.760; expert AUC improved to 0.829 with model assistance.
Impact: Provides an interpretable, non-invasive biomarker to guide surgical timing and escalation/de-escalation after neoadjuvant chemo-immunotherapy in NSCLC, surpassing expert assessment and generalizing across centers.
Clinical Implications: May enable personalized surgical decision-making, triage for additional cycles vs early surgery, and stratification for trials; facilitates resource allocation in radiology and pathology by anticipating response.
Key Findings
- Dual-phase CT 3D-CNN (NeoPred) achieved AUC 0.772 in external validation, rising to 0.787 with clinical variables.
- Prospective cohort performance was AUC 0.760, exceeding the mean expert AUC of 0.720.
- Model assistance improved pooled expert AUC to 0.829 and accuracy to 0.820.
- Robust performance persisted in radiologic stable-disease subgroups (AUC up to 0.833).
Methodological Strengths
- Multi-center cohorts with external and prospective validation
- Head-to-head comparison with nine board-certified radiologists and interpretable analysis (SHAP)
Limitations
- Retrospective development on Chinese cohorts may limit global generalizability
- No randomized clinical utility assessment or impact on outcomes
Future Directions: Prospective, multinational impact trials to assess decision-change and outcomes; integration with PET/biopsy and circulating biomarkers to form multi-modal predictors.
BACKGROUND: Accurate preoperative prediction of major pathological response or pathological complete response after neoadjuvant chemo-immunotherapy remains a critical unmet need in resectable non-small-cell lung cancer (NSCLC). Conventional size-based imaging criteria offer limited reliability, while biopsy confirmation is available only post-surgery. METHODS: We retrospectively assembled 509 consecutive NSCLC cases from four Chinese thoracic-oncology centers (March 2018 to March 2023) and prospectively enrolled 50 additional patients. Three 3-dimen
2. Multi-trait genetic analysis of asthma and eosinophils uncovers pleiotropic loci in East Asians.
In East Asians, multi-trait GWAS linked asthma to eosinophil counts (LDSC and MR) and identified 52 loci, including 31 previously unreported. A missense variant in CD36 (rs75326924) showed higher expression in lymphocytes and ILC2-enriched cells in asthma and associated proteomic changes (downregulated IL-7, Oncostatin M, VEGFA), suggesting CD36-related immune pathways as population-specific targets.
Impact: Expands asthma genetics in an underrepresented population and pinpoints a functionally supported CD36 variant with immunologic readouts, informing precision therapeutics for East Asians.
Clinical Implications: Supports development of population-tailored biomarkers and therapies (e.g., targeting CD36/ILC2 pathways) and refines risk prediction models for East Asians.
Key Findings
- LDSC and MR demonstrated significant genetic correlation between asthma and eosinophil count in East Asians.
- MTAG identified 52 genome-wide significant loci, including 31 novel loci specific to East Asians.
- A missense variant in CD36 (rs75326924) showed increased expression in lymphocytes and ILC2-enriched cells and was associated with downregulation of IL-7, Oncostatin M, and VEGFA.
- Findings highlight pleiotropy across asthma and WBC traits and nominate CD36-related pathways as therapeutic targets.
Methodological Strengths
- Integration of LDSC, Mendelian randomization, and MTAG across East Asian cohorts
- Functional validation via flow cytometry and proteomics
Limitations
- Population focus on East Asians may limit generalizability to other ancestries
- Observational genetic associations without interventional validation
Future Directions: Replication in multi-ancestry cohorts, mechanistic dissection of CD36-ILC2 signaling, and early-phase trials targeting implicated pathways.
Asthma is a prevalent respiratory condition with over 100 genetic loci identified through genome-wide association studies (GWAS). However, the genetic basis of asthma in East Asians remains underexplored. To address this, we performed a comprehensive analysis of shared genetic mechanisms between asthma and white blood cell (WBC) traits in East Asians, aiming to identify potential pleiotropic loci. Using linkage disequilibrium score regression (LDSC), we identified a significant genetic correlatio
3. Longitudinal Pulmonary Arterial Pressure Trajectories and Clinical Outcome in Kidney Transplantation Patients.
In 631 kidney transplant recipients with pre- and post-transplant echocardiographic PAPs, new-onset or persistent pulmonary hypertension after transplant independently increased mortality versus no PH, whereas resolved PH showed the most favorable survival. Each 10 mmHg increase in sPAP from pre- to post-KT raised mortality risk by 21%, and a 10 mmHg decrease reduced risk by 17%; findings were validated in an external cohort.
Impact: Establishes PAP trajectory as a dynamic biomarker for post-transplant risk stratification, highlighting modifiable hemodynamic targets that correlate with survival.
Clinical Implications: Supports integrating serial PAP assessment into KT evaluation and follow-up to identify high-risk patients (New/Persistent-PH) and prioritize PH management to improve survival.
Key Findings
- New-PH and Persistent-PH post-transplant increased mortality risk vs No-PH (HR 1.51 and 1.37, respectively).
- Resolved-PH had the most favorable survival; trend toward lower risk vs No-PH.
- Each 10 mmHg increase in sPAP from pre- to post-KT increased mortality by 21%; a 10 mmHg decrease reduced mortality by 17%.
- Results reproduced in a sex-balanced validation cohort using echo and right heart catheterization.
Methodological Strengths
- Large, real-world cohort with pre- and post-transplant measurements
- Independent validation cohort and consistent findings across modalities
Limitations
- Retrospective design with potential residual confounding
- Echocardiographic sPAP as a surrogate may misclassify PH severity
Future Directions: Prospective interventional studies to test PH optimization pre/post-KT and determine thresholds/targets for sPAP that improve survival.
BACKGROUND: Pulmonary hypertension (PH) is a high-risk finding in end-stage kidney disease (ESKD) and is independently associated with increased mortality. RESEARCH QUESTION: What is the relationship between pulmonary artery pressure (PAP) trajectories from before kidney transplantation (KT) to after KT, as well as the role of PH after KT? STUDY DESIGN AND METHODS: We retrospectively analyzed patients in the Veterans Affairs Healthcare System with PAP values both before KT and after KT using echoca