Daily Respiratory Research Analysis
Analyzed 197 papers and selected 3 impactful papers.
Summary
Three studies stand out today: an exploratory analysis of the phase 3 CheckMate 77T trial shows perioperative nivolumab plus chemotherapy benefits stage III N2 resectable NSCLC; a prospective multicenter cohort identifies admission eosinopenia (≤30/µL) as a robust predictor of respiratory failure in CAP; and an independent, pre-EUA testing program (ITAP) accelerated validation of SARS-CoV-2/Influenza LFAs, linking bench LODs to field performance. Together they advance perioperative oncology, acute pneumonia triage, and diagnostic readiness.
Research Themes
- Perioperative immunotherapy in resectable lung cancer
- Biomarker-based risk stratification in community-acquired pneumonia
- Independent validation pathways for point-of-care respiratory diagnostics
Selected Articles
1. Clinical outcomes with perioperative nivolumab by nodal status in patients with stage III resectable NSCLC: phase 3 CheckMate 77T exploratory analysis.
In an exploratory analysis of CheckMate 77T, perioperative nivolumab plus chemotherapy improved event-free survival and pathological complete response in stage III N2 resectable NSCLC, including multistation N2 disease, without new safety signals. Nodal downstaging was frequent, suggesting N2 may not portend poor prognosis under perioperative immunotherapy.
Impact: The analysis extends perioperative immunotherapy evidence to the highest-risk resectable subgroup (N2), potentially reshaping surgical oncology decision-making and multidisciplinary planning.
Clinical Implications: Supports perioperative nivolumab plus chemotherapy for stage III N2 resectable NSCLC, informing patient selection and counseling; MDTs may favor immunochemotherapy even in multistation N2 with an expectation of downstaging and higher pCR.
Key Findings
- In N2 disease, 1-year EFS was 70% with nivolumab vs 45% with placebo (HR 0.46, 95% CI 0.30–0.70).
- Pathological complete response: 22.0% (nivolumab) vs 5.6% (placebo).
- Multistation N2: 1-year EFS 71% vs 46% (HR 0.43), pCR 29.0% vs 2.7%.
- High rates of nodal downstaging after surgery (57% vs 44% to node-negative).
- No new safety signals identified.
Methodological Strengths
- Randomized phase 3 backbone with predefined perioperative regimen and robust endpoints (EFS, pCR).
- Clinically meaningful subgroup analysis including multistation N2 with consistent benefit signals.
Limitations
- Exploratory subgroup analysis; not powered specifically for N2 strata.
- Limited granular toxicity details in the abstract and no biomarker-stratified outcomes reported.
Future Directions: Prospective stratification by nodal status and tumor immune features to validate benefit and optimize perioperative regimens; integration with surgical planning and adjuvant strategies.
Individuals with non-small-cell lung cancer (NSCLC) with metastases to the ipsilateral mediastinum or subcarinal lymph nodes (N2 disease) have poor long-term survival. This exploratory analysis from the randomized phase 3 CheckMate 77T study assessed clinical outcomes by nodal status in individuals with stage III NSCLC who received neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab (nivolumab) versus neoadjuvant chemotherapy followed by surgery and adjuvant placebo (placebo). Here we show that among patients with N2 disease, nivolumab versus placebo improved event-free survival (1-year rate, 70% versus 45%; hazard ratio, 0.46 (95% confidence interval, 0.30-0.70)) and pathological complete response rate (22.0% versus 5.6%); 77% versus 73% had definitive surgery, of whom 84% versus 74% received a simple lobectomy. Furthermore, nivolumab improved outcomes versus placebo in patients with multistation N2 NSCLC (1-year event-free survival rate: 71% versus 46%; hazard ratio, 0.43 (0.21-0.88); pathological complete response rate, 29.0% versus 2.7%). In the N2 subgroup with definitive surgery, 67% and 59% of patients had nodal downstaging after surgery (57% versus 44% downstaged to node-negative disease). Median EFS in randomized patients with stage III non-N2 NSCLC was not reached with nivolumab and 17.0 months with placebo (1-year EFS rate, 74% versus 62%; hazard ratio, 0.60 (0.33-1.08)). No new safety signals were identified. These findings support perioperative nivolumab plus neoadjuvant chemotherapy as an efficacious treatment for stage III N2 disease and suggest that N2 status may not predict poor prognosis in resectable NSCLC treated with perioperative immunotherapy. ClinicalTrials.gov identifier: NCT04025879 .
2. Blood eosinopenia (≤30/µL) as an early predictor of respiratory failure in community-acquired pneumonia: A prospective multicentre study.
In a prospective multicenter cohort, an admission eosinophil threshold of ≤30/µL optimally predicted the need for mechanical ventilation in CAP, even after adjusting for corticosteroid exposure. This simple lab value can enhance early risk stratification and escalation decisions.
Impact: Defines a practical, actionable eosinophil threshold for predicting respiratory failure in CAP, enabling rapid triage without specialized testing.
Clinical Implications: Incorporate admission eosinophil count ≤30/µL into CAP triage algorithms to prioritize monitoring, early ICU consults, and escalation (e.g., HFNC/NIV readiness). Consider steroid confounding but retain predictive utility after adjustment.
Key Findings
- Optimal admission eosinophil threshold for predicting mechanical ventilation was ≤30/µL (derived via ROC/Youden index).
- Patients with eosinophils ≤30/µL had higher mechanical ventilation rates (15.5% vs 7.3%).
- Associations remained significant after adjustment for corticosteroid use; ICU admission and LOS were worse below the threshold.
Methodological Strengths
- Prospective multicenter design with predefined analytic approach (ROC/Youden).
- Multivariable adjustment including corticosteroid exposure to address confounding.
Limitations
- Abstract does not report exact cohort size or external validation.
- Threshold performance across diverse healthcare systems and outpatient settings remains to be confirmed.
Future Directions: External validation in varied populations, integration into CAP risk scores, and evaluation of impact on clinical outcomes via implementation studies.
INTRODUCTION AND OBJECTIVES: Lower blood eosinophil counts have been associated with increased mechanical ventilation rates in patients with community-acquired pneumonia (CAP). However, the optimal eosinophil count threshold for identifying CAP patients at high risk of respiratory failure remains undefined. This study aimed to establish an optimal admission eosinophil count as a prognostic biomarker for respiratory failure in CAP. METHODS: This prospective, multicentre cohort study (PROGRESS) enrolled adult patients (≥18 years) hospitalised with community-acquired pneumonia (CAP). A receiver operating characteristic curve analysis with Youden's index was applied to identify the optimal eosinophil threshold for predicting mechanical ventilation. Associations were adjusted for corticosteroid use using multivariable regression. Additional outcomes - ICU admission and hospital length of stay - were compared between patients above and below the optimal eosinophil count threshold. RESULTS: An eosinophil count threshold of ≤30/µL was optimal for predicting mechanical ventilation. Patients with eosinophil counts ≤30/µL experienced significantly higher mechanical ventilation rates (15.5% versus 7.3%; CONCLUSIONS: Admission eosinopenia (≤30 µL) is a robust, easily measured biomarker that predicts respiratory failure in hospitalised CAP. It supports early risk stratification and may guide timely escalation of care.
3. Independent Testing to Accelerate the Development of Lateral Flow Assays for Influenza A, Influenza B and SARS-COV-2.
The ITAP program independently quantified analytical LODs and real-world sensitivity/specificity for 14 LFAs (30 iterations) targeting SARS‑CoV‑2 and influenza, enabling iterative improvements and supporting 7 EUAs and 3 clearances. This framework links bench performance to field utility and regulatory readiness.
Impact: Establishes a reproducible, independent pathway to vet and iterate point-of-care respiratory diagnostics before formal trials, accelerating access during epidemics and informing manufacturer design decisions.
Clinical Implications: Clinicians and public health programs can select LFAs with validated performance; regulators gain high-quality standardized evidence; manufacturers can iterate based on independent feedback to improve real-world sensitivity.
Key Findings
- Bench LODs spanned ~5.3×10^4–1.39×10^6 GE/mL (SARS‑CoV‑2), 8.5×10^4–1.73×10^6 (Influenza A), and 1.17×10^4–2.96×10^6 (Influenza B).
- Field sensitivities: 0.57–1.00 (SARS‑CoV‑2) and 0.64–0.85 (Influenza A); specificities 0.91–1.00 across targets.
- 11/14 devices underwent ≥2 test iterations; 7 EUAs and 3 de novo/510(k) clearances followed ITAP assessments.
Methodological Strengths
- Independent benchmarking combining analytical LOD with field RT‑PCR-referenced performance.
- Iterative testing across multiple device generations to inform design and regulatory dossiers.
Limitations
- Some LFAs enrolled few influenza B positives, limiting precision.
- Field cohorts were moderate in size per device (≥50 typical), not population-representative.
Future Directions: Expand to RSV and multiplex targets, standardize quality metrics across sites, and link performance to clinical outcomes and cost-effectiveness.
BACKGROUND: As the test verification core for the Rapid Acceleration of Diagnostics (RADx) Independent Test Assessment Program (ITAP), we conducted independent bench- and field-based performance testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A&B lateral flow assays (LFAs) prior to formal clinical studies for Food and Drug Administration (FDA) submission. METHODS: During bench testing, the limit of detection (LOD) was approximated using serially diluted panels of laboratory-propagated virus. In field studies, LFA results were interpreted by study participants, and sensitivity and specificity were determined using reverse transcription polymerase chain reaction (RT-PCR) (Xpert CoV-2/Flu/RSV plus) from a concurrent nasal swab as the reference standard. RESULTS: Between February 2023 and February 2025, we tested 30 iterations of 14 LFAs. LODs were 53 277-1 393 314 genome equivalents (GE)/mL for SARS-CoV-2, 85 027-1 731 676 for influenza A, and 11 688-2 960 941 for influenza B. Field studies enrolled 27 to 126 participants per LFA with most enrolling at least 50 participants. When minimum 5 positive cases were enrolled, sensitivity ranged from 0.57-1.00 for SARS-CoV-2 and 0.64-0.85 for influenza A. Influenza B case enrollment was low. Specificity ranged from 0.91-1.00 across all targets. Eleven of 14 devices underwent at least two iterations of testing. Following ITAP assessment, 7 devices received FDA emergency use authorization, and 3 ultimately received de novo marketing approval or 510 (k) clearance. CONCLUSIONS: The ITAP enabled rapid feedback to federal agencies and manufacturers on the analytical and clinical performance of over-the-counter LFAs for SARS-CoV-2 and influenza, ultimately contributing to success in regulatory authorization or clearance.