Daily Respiratory Research Analysis
A multicenter randomized trial in Thorax showed a novel liquid nitrogen airway balloon cryoablation system achieved higher 6-week airway patency and shorter procedure times versus a standard cryoprobe in malignant central airway obstruction. In Science Translational Medicine, an mRNA cocktail encoding 10 interferon-stimulated genes provided broad-spectrum antiviral prophylaxis, including protection against lethal SARS-CoV-2 in hamsters. A prospective study in Open Forum Infectious Diseases demon
Summary
A multicenter randomized trial in Thorax showed a novel liquid nitrogen airway balloon cryoablation system achieved higher 6-week airway patency and shorter procedure times versus a standard cryoprobe in malignant central airway obstruction. In Science Translational Medicine, an mRNA cocktail encoding 10 interferon-stimulated genes provided broad-spectrum antiviral prophylaxis, including protection against lethal SARS-CoV-2 in hamsters. A prospective study in Open Forum Infectious Diseases demonstrated stool-based qPCR tracks tuberculosis treatment response faster than sputum culture and flags risk of persistent culture positivity.
Research Themes
- Interventional bronchoscopy innovation for malignant central airway obstruction
- Broad-spectrum antiviral prophylaxis via multi-ISG mRNA delivery
- Accessible tuberculosis treatment monitoring using stool-based qPCR
Selected Articles
1. Efficacy and safety of novel airway balloon cryoablation system for malignant central airway obstruction: a prospective, multicentre, randomised, non-inferiority study.
In a 15-center randomized non-inferiority trial (n=198), liquid nitrogen airway balloon cryoablation achieved higher 6-week airway patency (78.5% vs 60.9%) and markedly shorter ablation time versus a standard CO2 cryoprobe, with similar bleeding rates and no life-threatening events. Dyspnea (mMRC) and performance (KPS) improved in both arms.
Impact: This is a rigorous multicenter RCT showing a device-based innovation that improves short-term airway outcomes with procedural efficiency in malignant central airway obstruction.
Clinical Implications: Interventional pulmonologists can consider liquid nitrogen balloon cryoablation as an alternative to standard cryoprobes to enhance 6-week airway patency and shorten ablation time without compromising safety.
Key Findings
- 6-week airway patency was higher with ABC vs EC cryoprobe (78.49% vs 60.92%; difference 17.58%, 95% CI 4.35–30.80).
- Ablation duration was significantly shorter with ABC (mean 378 s) than EC (mean 625 s), p<0.001.
- Bleeding rates were similar between groups and no life-threatening events occurred; mMRC and KPS improved in both arms.
Methodological Strengths
- Prospective, multicenter randomized controlled non-inferiority design with defined margin
- Clinically relevant primary endpoint (airway patency at 6 weeks) and standardized secondary outcomes
Limitations
- Short follow-up (6 weeks) for the primary endpoint; no long-term local control or survival data
- Allowing multimodality debulking pre-cryoablation may introduce procedural heterogeneity; blinding not feasible
Future Directions: Head-to-head trials with longer follow-up assessing local control, symptom durability, quality of life, and cost-effectiveness; evaluation in specific tumor subtypes and integration with systemic therapies.
2. An mRNA-based broad-spectrum antiviral inspired by ISG15 deficiency protects against viral infections in vitro and in vivo.
A 10-ISG mRNA cocktail, modeled on the antiviral state of ISG15 deficiency, conferred resistance to Zika virus, VSV, and SARS-CoV-2 in cells and protected animals when delivered prophylactically. Protection required the combination—individual ISG mRNAs were ineffective—with lipid nanoparticle delivery reducing influenza A plaque size in infected mouse samples and preventing lethal SARS-CoV-2 in hamsters.
Impact: Introduces a mechanistically grounded, multi-ISG mRNA prophylactic platform with broad antiviral potential, including respiratory pathogens, representing a paradigm shift from single-target antivirals.
Clinical Implications: While preclinical, the approach suggests a rapid-deployable prophylactic for high-risk exposures and outbreak containment, complementing vaccines and antivirals, pending human safety and dosing studies.
Key Findings
- A curated set of 10 ISGs reproduced broad antiviral protection typical of IFN-I responses in an IFN-nonresponsive cell line against Zika, VSV, and SARS-CoV-2.
- LNP-encapsulated 10-ISG mRNA reduced influenza A plaque size in samples from infected mice when administered prophylactically.
- Prophylactic delivery of the collective 10-ISG mRNAs protected hamsters from lethal SARS-CoV-2 challenge; individual ISG mRNAs lacked efficacy.
Methodological Strengths
- Mechanistic rationale leveraging human ISG15-deficiency phenotype and combinatorial ISG selection
- In vitro and in vivo validation across multiple viruses and species with LNP mRNA delivery
Limitations
- Preclinical models only; human safety, immunogenicity, and dosing are unknown
- Prophylactic efficacy demonstrated; therapeutic window and durability require evaluation
Future Directions: Phase 1 trials to assess safety/immunostimulation; optimization of ISG composition and dosing; evaluation of therapeutic versus prophylactic use and synergy with vaccines/antivirals.
3. Stool-Based Molecular Tuberculosis Treatment Monitoring: A Faster Means for Detecting Persistent Mycobacteria Compared to Phenotypic Culture.
Across three African countries (n=231), stool qPCR closely tracked bacillary burden versus sputum culture at baseline, delivered faster results, and identified patients at risk for persistent 2-month culture positivity and drug resistance. However, no single quantitative bacillary measure predicted symptom resolution or death.
Impact: Provides a practical, accessible biomarker strategy for TB treatment monitoring, especially where sputum collection is difficult, potentially accelerating clinical decision-making.
Clinical Implications: TB programs can incorporate stool qPCR to monitor early treatment response and flag likely non-responders or resistance, enabling earlier regimen adjustments while acknowledging limitations for predicting symptoms or mortality.
Key Findings
- Stool qPCR quantitative bacillary burden strongly correlated with sputum culture at baseline.
- Stool qPCR returned faster results and used an accessible specimen, improving feasibility across ages.
- Identified patients at risk for persistent 2-month culture positivity and drug resistance; quantitative tests did not predict symptom resolution or death.
Methodological Strengths
- Prospective, multicountry cohort including all ages with microbiologically confirmed TB
- Head-to-head comparison with sputum culture and linkage to WHO outcomes and resistance
Limitations
- Abstracted results do not provide sensitivity/specificity thresholds or longitudinal kinetics beyond baseline and 2 months
- Quantitative measures did not predict symptoms or death, limiting prognostic scope
Future Directions: Define actionable thresholds and sampling schedules; evaluate performance in pediatric paucibacillary disease; integrate with molecular resistance assays and digital adherence tools.