Daily Respiratory Research Analysis
A multicenter randomized trial shows a 16‑week clofazimine-based regimen is non-inferior to the standard 24‑week course for drug‑susceptible pulmonary tuberculosis, suggesting a pathway to shorter treatment. In thoracic oncology, a randomized trial found sacituzumab tirumotecan significantly improves objective response, progression-free survival, and overall survival versus docetaxel in previously treated NSCLC. Multi-omic spatial profiling of COVID‑19 lungs identifies an immunosuppressive micro
Summary
A multicenter randomized trial shows a 16‑week clofazimine-based regimen is non-inferior to the standard 24‑week course for drug‑susceptible pulmonary tuberculosis, suggesting a pathway to shorter treatment. In thoracic oncology, a randomized trial found sacituzumab tirumotecan significantly improves objective response, progression-free survival, and overall survival versus docetaxel in previously treated NSCLC. Multi-omic spatial profiling of COVID‑19 lungs identifies an immunosuppressive microenvironment and early extracellular matrix remodeling with collagen VI, with circulating ECM biomarkers showing prognostic utility.
Research Themes
- Shortening tuberculosis treatment duration with clofazimine
- Antibody–drug conjugates improving outcomes in NSCLC
- Extracellular matrix biomarkers and lung microenvironment in COVID-19
Selected Articles
1. Four-month clofazimine regimen for susceptible pulmonary TB: a randomized clinical trial.
In a multicenter non-inferiority RCT (n=322), a 16‑week clofazimine-based regimen for drug-susceptible pulmonary TB achieved relapse, sputum conversion, and bacteriologic cure rates comparable to the standard 24‑week regimen. Safety was acceptable, supporting the feasibility of shortening first-line TB therapy pending confirmatory implementation studies.
Impact: Shortening TB treatment from 24 to 16 weeks without compromising outcomes could improve adherence, reduce toxicity and costs, and accelerate TB control globally.
Clinical Implications: If adopted, a 4‑month clofazimine-containing regimen could become a new standard for drug-susceptible pulmonary TB, particularly in settings where adherence to 6‑month therapy is challenging; programs will need to monitor safety and resistance.
Key Findings
- A 16-week clofazimine-based regimen was non-inferior to a 24-week standard regimen for relapse at 3 months post-treatment (3.2% vs 1.9%, within non-inferiority margin).
- Relapse at 1 year did not differ significantly between groups (RR 1.31; 95% CI 0.58–2.95).
- Sputum smear negativity and bacteriological cure at end of treatment were similar across arms, with an acceptable safety profile.
Methodological Strengths
- Multicenter, randomized, investigator-initiated non-inferiority design with trial registration (CTRI/2019/03/018102).
- Predefined primary and secondary endpoints with adequate sample size across 11 centers.
Limitations
- Open-label design and follow-up limited to 1 year for relapse outcomes.
- Generalizability beyond participating regions and in special populations (e.g., PLHIV, extrapulmonary TB) remains to be established.
Future Directions: Confirmatory pragmatic trials, pharmacovigilance for clofazimine-related adverse effects, resistance surveillance, and cost-effectiveness analyses across diverse settings are warranted.
BACKGROUND: Clofazimine, an antimycobacterial agent, has demonstrated efficacy in reducing the treatment duration for MDR TB. OBJECTIVES: To determine whether a 16 week clofazimine-based regimen is non-inferior to the standard 24 week regimen for drug-susceptible pulmonary TB. METHODS: CORTAIL was a multicentric, investigator-initiated, randomized controlled trial designed to assess the non-inferiority of a 16 week clofazimine-based regimen compared with the standard 24 week regimen for drug-susceptible pulmonary TB (Clinical Trials Registry of India no. CTRI/2019/03/018102). In the intervention arm, clofazimine replaced ethambutol during both the intensive and continuation phases of treatment. The primary outcome was relapse at the end of 3 month follow-up after treatment completion. RESULTS: Across 11 centres, a total of 161 patients were randomized to the standard regimen and 161 patients received the shorter regimen. Relapse was observed in 1.9% patients in the standard group and 3.2% in the shorter regimen, the difference lying within the predefined non-inferiority margin [relative risk (RR) 1.65; 95% CI 0.444-6.19; P = 0.723; adjusted risk (AR) 1.2%; 95% CI -3.3% to 6.1%]. Key secondary outcome of relapse at 1 year was also not significantly different between the two groups (RR 1.31; 95% CI 0.58-2.95; P = 0.652; AR 1.8%; 95% CI -4.5% to 8.2%). The proportion of patients achieving sputum smear negativity (RR 1.59; 95% CI 0.69-3; P = 0.36; AR 3.1%; 95% CI -3.2% to 9.5%) and bacteriological cure (RR 1.03; 95% CI 0.57-1.88; P = 0.99; AR 0.4%; 95% CI -7.4% to 8.2%) by the end of treatment was similar between the two treatment arms. CONCLUSIONS: A clofazimine-based 16 week regimen was found to be safe and non-inferior to the currently available 24 week regimen.
2. Sacituzumab tirumotecan versus docetaxel for previously treated
In a multicenter open-label RCT (n=137), sacituzumab tirumotecan achieved a significantly higher blinded ORR (45%) and improved PFS and OS versus docetaxel in previously treated advanced NSCLC, with manageable toxicity. These results support sac‑TMT as a superior second‑line option to docetaxel.
Impact: Head-to-head randomized data show an ADC outperforming docetaxel on hard endpoints, which can shift standard second‑line therapy in previously treated NSCLC.
Clinical Implications: Sacituzumab tirumotecan should be considered over docetaxel after platinum-based therapy failure, with attention to ADC-specific toxicities and patient selection.
Key Findings
- Randomized 2:1 trial (n=137) showed sac-TMT had a blinded ORR of 45%, significantly higher than docetaxel.
- Progression-free survival and overall survival were improved with sac-TMT versus docetaxel at 12.2 months median follow-up.
- Safety profile was manageable, supporting clinical adoption pending broader access.
Methodological Strengths
- Randomized controlled design with blinded independent response assessment (BIRC).
- Clinically meaningful endpoints (ORR, PFS, OS) and multi-center enrollment.
Limitations
- Open-label design and modest sample size; detailed biomarker stratification not reported in the abstract.
- Conducted in a single country, which may affect generalizability until externally validated.
Future Directions: Further trials should refine biomarker selection, compare against other ADCs or targeted agents, and evaluate quality of life and cost-effectiveness.
OBJECTIVE: To compare the efficacy and safety of sacituzumab tirumotecan (sac-TMT) with docetaxel in patients with locally advanced or metastatic epidermal growth factor receptor ( DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 48 centres in China, 1 September 2023 to 31 December 2024. PARTICIPANTS: 137 adults (aged 18-75 years) with INTERVENTION: Patients were randomly assigned (2:1) to receive sac-TMT (5 mg/kg) on days 1 and 15 of each four week cycle, or docetaxel (75 mg/m MAIN OUTCOME MEASURES: The primary endpoint was objective response rate as assessed by a blinded independent review committee (BIRC). The secondary endpoints included objective response rate assessed by the investigator; disease control rate, progression-free survival, time to response, and duration of response assessed by BIRC and the investigator; overall survival; and safety. RESULTS: 137 patients were randomised to receive sac-TMT (n=91) or docetaxel (n=46). Median follow-up was 12.2 months at the data cut-off for efficacy (31 December 2024). BIRC assessed objective response rate was significantly higher in the sac-TMT group (45% (41/91)) CONCLUSIONS: Sac-TMT showed statistically significant and clinically meaningful improvements in objective response rate, progression-free survival, and overall survival compared with docetaxel, with a manageable safety profile in patients with TRIAL REGISTRATION: ClinicalTrials.gov NCT05631262.
3. Multi-omic spatial profiling reveals the unique SARS-CoV-2 lung microenvironment and collagen VI as a predictive biomarker in severe COVID-19.
Integrating bulk RNA-seq, spatial transcriptomics, and multiplex imaging of post-mortem lungs with serum biomarker analyses (n=215 COVID-19; 54 controls), the study shows SARS-CoV-2 localizes to pneumocytes and macrophages early, within an immunosuppressive PD‑L1-enriched niche. Early collagen VI–centric ECM remodeling was identified, and circulating ECM markers demonstrated prognostic relevance, highlighting collagen deposition as an early pathological event.
Impact: This work links spatial lung microenvironment features with circulating ECM biomarkers, nominating collagen VI as a potential predictor and refining COVID‑19 pathogenesis models.
Clinical Implications: Serum ECM biomarkers, including collagen VI turnover, may aid early risk stratification and monitoring in severe COVID‑19; therapeutic strategies targeting immunosuppressive niches or ECM remodeling warrant exploration.
Key Findings
- SARS-CoV-2 localization in early disease was restricted to pneumocytes and macrophages in post-mortem lung tissue.
- Spatial profiling revealed an immunosuppressive microenvironment enriched for PD‑L1 and distinct immune niches.
- Early extracellular matrix remodeling with collagen VI was identified; circulating ECM synthesis/breakdown markers in 215 patients showed prognostic relevance.
Methodological Strengths
- Integration of bulk RNA-seq, spatial transcriptomics, RNAscope, multiplex IF, and IHC on human lung tissue.
- Prospective measurement of serum ECM markers in a sizable cohort (215 patients, 54 controls).
Limitations
- Post-mortem cross-sectional tissue analysis limits temporal inference; exact tissue sample size not specified in abstract.
- Single-disease focus and potential variant-era effects may limit generalizability; external validation of serum biomarker cutoffs is needed.
Future Directions: Validate collagen VI–related biomarkers in prospective cohorts, define actionable thresholds, and test interventions modulating immunosuppressive niches or ECM remodeling.
BACKGROUND: While coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, few studies have characterised the immune response to COVID-19 in lung tissue. We sought to understand the pathogenic role of microenvironmental interactions and the extracellular matrix in post-mortem COVID-19 lung using an integrative multi-omic approach. METHODS: Post-mortem formalin-fixed paraffin-embedded lung tissue from fatal COVID-19 and nonrespiratory death control lung underwent multi-omic evaluation by Quantseq Bulk RNA sequencing, Nanostring GeoMx spatial transcriptomics, RNAscope, multiplex immunofluorescence and immunohistochemistry, to evaluate virus distribution, immune composition and the extracellular matrix. Markers of extracellular synthesis and breakdown were measured in the serum of 215 patients with COVID-19 and 54 healthy volunteer controls using ELISA. RESULTS: We found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was restricted to the pneumocytes and macrophages of early-stage disease. Spatial analyses revealed an immunosuppressive virus microenvironment, enriched for PDL1 CONCLUSIONS: Our data refine the current model of respiratory COVID-19 with regard to virus distribution, immune niches and the role of the noncellular microenvironment in pathogenesis and risk stratification in COVID-19. We show that collagen deposition is an early event in the course of the disease.