Daily Respiratory Research Analysis
Three impactful respiratory-related studies span clinical and translational science: a double-blind RCT shows inhaled nitric oxide does not reduce AKI after prolonged cardiopulmonary bypass with endothelial dysfunction; a geometry-matched DNA nanostructure delivers multivalent ligands that broadly inhibit influenza across mouse and porcine models; and a T cell–only SARS-CoV-2 vaccine strategy gains durable protection when boosted intranasally, highlighting the value of mucosal resident memory T
Summary
Three impactful respiratory-related studies span clinical and translational science: a double-blind RCT shows inhaled nitric oxide does not reduce AKI after prolonged cardiopulmonary bypass with endothelial dysfunction; a geometry-matched DNA nanostructure delivers multivalent ligands that broadly inhibit influenza across mouse and porcine models; and a T cell–only SARS-CoV-2 vaccine strategy gains durable protection when boosted intranasally, highlighting the value of mucosal resident memory T cells.
Research Themes
- Negative randomized evidence guiding perioperative respiratory therapies (inhaled NO and AKI prevention)
- Geometry-matched multivalency via DNA nanostructures for broad-spectrum respiratory antivirals
- Mucosal T cell–focused vaccination to counter variant escape in respiratory viruses
Selected Articles
1. Nitric Oxide to Reduce Acute Kidney Injury in Patients with Pre-existing Endothelial Dysfunction Requiring Prolonged Cardiopulmonary Bypass: A Randomized Clinical Trial.
In a double-blind randomized trial of 250 adults undergoing prolonged CPB with pre-existing endothelial dysfunction, perioperative 80 ppm inhaled NO for 24 hours did not reduce AKI (44.0% vs 43.2%; adjusted OR 1.00) or renal replacement therapy up to 1 year. The results do not support routine NO use for AKI prevention in this population.
Impact: A high-quality negative RCT resolves uncertainty from prior subgroup signals and prevents unnecessary perioperative NO use for AKI prevention. It guides resource allocation and protocol refinement in cardiac anesthesia and perfusion practice.
Clinical Implications: Do not routinely administer inhaled NO to reduce AKI in prolonged CPB patients with endothelial dysfunction; focus on alternative nephroprotective strategies and risk stratification. Consider limiting NO to indications with proven benefit.
Key Findings
- AKI incidence was similar with NO vs control (44.0% vs 43.2%; adjusted OR 1.00, 95% CI 0.59–1.69).
- No differences in AKI severity (KDIGO stages 1–3) or renal replacement therapy during hospitalization and at 6 weeks, 90 days, and 1 year.
- Double-blind, placebo-controlled design with NO delivered via oxygenator and postoperatively via ventilator/facemask for a total of 24 hours.
Methodological Strengths
- Double-blind, randomized, placebo-controlled trial with prespecified KDIGO-defined AKI endpoint.
- Extended outcome assessment including renal replacement therapy up to 1 year.
Limitations
- Single-center study may limit generalizability across surgical programs and perfusion practices.
- Potential underpowering for modest effects in subgroups; biochemical characterization of endothelial dysfunction not detailed in the abstract.
Future Directions: Multicenter trials with biomarker-defined subgroups and alternative dosing/duration strategies may identify populations benefiting from NO. Explore complementary hemolysis-mitigation or endothelial-protective strategies during CPB.
2. DNA Nanostructure-Templated Multivalency Enables Broad-Spectrum Virus Inhibition.
A honeycomb DNA nanostructure presenting trimeric HA-targeting ligands achieved geometry-matched multivalency that dramatically enhanced influenza neutralization. The HC-Nanobody construct exceeded 99% entry inhibition and improved viability by 35–45% in murine H1N1/H3N2, and retained >97% inhibition with 30–55% viability gains in a porcine model, indicating cross-species translational promise.
Impact: Introduces a modular, geometry-guided antiviral platform with robust efficacy across species, providing a blueprint for rapidly evolving respiratory pathogens where antigenic drift undermines monomeric inhibitors.
Clinical Implications: Supports development of reprogrammable intranasal or inhaled antivirals leveraging multivalency to counter antigenic escape in influenza and potentially other respiratory viruses. Preclinical safety, delivery, durability, and immunogenicity require evaluation.
Key Findings
- Honeycomb DNA nanostructures (HC-DDN) displaying trimeric HA ligands matched native HA geometry and enhanced neutralization.
- HC-Nanobody achieved >99% inhibition of viral entry and 35–45% improved cell viability at nanomolar concentrations in murine H1N1/H3N2 models.
- In a porcine influenza model, HC-Nanobody maintained >97% inhibition and 30–55% higher viability versus free nanobodies, indicating cross-species efficacy.
Methodological Strengths
- Rational, geometry-matched multivalency design rigorously tested across in vitro, murine, and porcine systems.
- Direct comparison to monomeric counterparts demonstrates clear added value of multivalency.
Limitations
- In vivo testing focused on influenza A; breadth against other respiratory viruses remains to be demonstrated.
- Clinical translation challenges (formulation, delivery, stability, immunogenicity) not yet addressed.
Future Directions: Optimize intranasal delivery and pharmacokinetics, expand to other respiratory pathogens (e.g., RSV, SARS-CoV-2), and evaluate safety/efficacy in GLP toxicology and early-phase human studies.
3. Conserved CD8 T cell vaccines without B cell epitopes drive robust protection against SARS-CoV-2 that is enhanced by intranasal boost.
In mice, subcutaneous vaccines composed of conserved CD8 T cell epitopes reduced lung viral load and protected against low-dose SARS-CoV-2, while an intranasal boost (with or without adjuvant) enhanced lung resident memory T cells and conferred durable protection even against high-dose challenge. The work supports mucosal T cell–focused vaccination to broaden immunity against evolving respiratory viruses.
Impact: Highlights a T cell–only vaccine strategy augmented by mucosal boosting, addressing antibody escape and emphasizing conserved epitopes for durable, variant-resilient protection.
Clinical Implications: Supports the rationale for intranasal T cell–boosting strategies to complement or update current vaccines, potentially improving breadth and durability against variants and other respiratory viruses.
Key Findings
- Identified Omicron BA.1-specific and Wuhan-conserved CD8 T cell epitopes within spike and built carrier-fusion vaccines.
- Subcutaneous immunization with two CD8 epitope peptides lowered lung viral loads and protected against low-dose challenge but not high-dose.
- Intranasal boosting (± adjuvant) enhanced lung resident memory T cells and conferred potent, durable protection against high-dose infection.
Methodological Strengths
- Combines epitope discovery with functional in vivo vaccination and challenge models.
- Direct comparison of systemic versus mucosal boosting clarifies the role of resident memory T cells.
Limitations
- Mouse model findings may not fully translate to humans; safety of T cell–only vaccination requires clinical evaluation.
- Focus on spike epitopes; breadth across proteins and impact on transmission were not assessed.
Future Directions: Advance to human studies of intranasal T cell boosters, broaden epitope sets across conserved proteins, and evaluate efficacy against transmission and across variant landscapes.