Daily Respiratory Research Analysis
Three studies advance respiratory medicine across diagnostics and oncology. A prospective study shows bronchial washing fluid supernatant (BWFS) is a high-yield liquid biopsy for genotyping advanced NSCLC, rivaling tissue and outperforming plasma. A large test-performance study demonstrates that nasal CXCL10 can triage respiratory viral infections, while CSF ctDNA profiling in EGFR-mutant NSCLC leptomeningeal metastasis (LM) reveals richer mutation landscapes than plasma and identifies prognosti
Summary
Three studies advance respiratory medicine across diagnostics and oncology. A prospective study shows bronchial washing fluid supernatant (BWFS) is a high-yield liquid biopsy for genotyping advanced NSCLC, rivaling tissue and outperforming plasma. A large test-performance study demonstrates that nasal CXCL10 can triage respiratory viral infections, while CSF ctDNA profiling in EGFR-mutant NSCLC leptomeningeal metastasis (LM) reveals richer mutation landscapes than plasma and identifies prognostic treatment factors after third-generation EGFR-TKI resistance.
Research Themes
- Liquid biopsy innovation for respiratory oncology
- Host-response biomarkers for viral respiratory infection triage
- CSF genomics to guide management after EGFR-TKI resistance
Selected Articles
1. Bronchial washing fluid supernatant serves as a novel liquid biopsy specimen for genome profiling in advanced non-small cell lung cancer.
In a prospective cohort of advanced NSCLC, BWFS provided genotyping performance comparable to tumor tissue and superior to plasma, including higher mutation detection and sensitivity. TMB estimates from BWFS strongly correlated with tissue, and BWFS better captured CNVs and fusions than plasma.
Impact: This study introduces BWFS as a practical, high-yield liquid biopsy when tissue is limited, directly informing targeted therapy selection in advanced lung cancer.
Clinical Implications: BWFS can be integrated into bronchoscopy workflows to obtain actionable genomic data when tissue is scant, improving detection of CNVs/fusions and reliable TMB estimation to guide targeted and immunotherapy decisions.
Key Findings
- BWFS showed a higher mutation detection rate than plasma (96.4% vs 85.7%) and matched tissue performance.
- Using tissue as reference, BWFS sensitivity exceeded plasma (78.22% vs 36%).
- TMB estimates from BWFS and tissue were highly correlated (Pearson r = 0.97).
- BWFS outperformed plasma for detecting CNVs and gene fusions.
Methodological Strengths
- Prospective enrollment with matched triad sampling (BWFS, tissue, plasma).
- Targeted NGS panels covering 168–520 cancer-related genes with concordance analyses.
Limitations
- Single-center, small sample size with only 28 complete triads.
- Clinical outcome impact and turnaround time were not assessed.
Future Directions: Multicenter validation of BWFS workflows, standardization of collection/processing, and prospective trials assessing clinical decision impact and cost-effectiveness.
2. Nasal biomarker testing to rule out viral respiratory infection and triage samples: a test performance study.
In 1088 nasopharyngeal samples, nasal CXCL10 achieved AUC 0.87 versus PCR, and modeling indicated substantial PCR reduction at low prevalence (NPV 0.975 at 5% prevalence). False negatives clustered among patients on specific chemotherapy and those with low viral loads.
Impact: A single host-response biomarker enabling pan-viral rule-out could streamline outbreak control and routine screening, mitigating resource constraints and assay fragmentation.
Clinical Implications: CXCL10 testing can triage likely negatives during low-prevalence periods, reducing PCR burden and turnaround time in EDs, long-term care, and pre-procedural settings, while PCR remains for confirmatory diagnosis.
Key Findings
- CXCL10 predicted respiratory virus positivity with AUC 0.87 (95% CI 0.85–0.90) against PCR.
- Modeling suggests at 5% prevalence, 92% of samples would screen negative with NPV 0.975, substantially reducing PCR testing.
- False negatives were associated with specific chemotherapeutic agents and low viral load.
Methodological Strengths
- Large, mixed-age sample size (n=1088) with direct comparison to multiplex PCR.
- Quantitative performance metrics (AUC) plus resource-use modeling and EMR-driven false-negative analysis.
Limitations
- Single biomarker approach may underperform in immunosuppressed hosts or very early infection.
- Study design appears cross-sectional; impact on clinical outcomes and prospective workflow integration not tested.
Future Directions: Prospective implementation trials across settings to define thresholds, cost-effectiveness, and integration with multiplex platforms; evaluation in immunocompromised populations.
3. Genomic profiling and prognostic factors of leptomeningeal metastasis in EGFR-mutant NSCLC after resistant to third-generation EGFR-tyrosine kinase inhibitors.
In EGFR-mutant NSCLC with LM after third-generation EGFR-TKI resistance, CSF ctDNA outperformed plasma for mutation detection and pathway mapping, with higher ctDNA abundance and richer CNVs. Prognosis was associated with ECOG PS 1–2, furmonertinib plus bevacizumab, and higher-dose pemetrexed for intraventricular chemotherapy.
Impact: By establishing CSF ctDNA as a superior substrate for genomic profiling in LM and identifying treatment combinations linked to improved outcomes, this study directly informs management strategies in a high-mortality setting.
Clinical Implications: Routine CSF ctDNA profiling should be considered in LM to uncover actionable alterations missed in plasma and to guide therapy, including potential use of furmonertinib plus bevacizumab and optimized pemetrexed dosing for IVC in suitable patients.
Key Findings
- CSF had higher ctDNA abundance than plasma (0.76 vs 0.21; P < 0.001) and higher detection of EGFR, TP53 and copy-number alterations.
- Pathways enriched in CSF included cell cycle (80% vs 23%), KRAS/RAF (27% vs 8%), and WNT (18% vs 4%).
- Median intracranial PFS and OS after LM were 6.60 and 14.42 months; ECOG PS 1–2, furmonertinib plus bevacizumab, and higher-dose pemetrexed for IVC predicted better survival.
Methodological Strengths
- Relatively large LM cohort (n=116) with paired CSF and plasma NGS.
- Multivariate survival analysis to identify independent prognostic factors.
Limitations
- Single-center, retrospective design with potential selection and treatment confounding.
- Therapeutic associations are not randomized and require prospective validation.
Future Directions: Prospective trials incorporating CSF ctDNA-guided therapy selection in LM, and randomized evaluation of furmonertinib plus bevacizumab and intraventricular pemetrexed dosing strategies.