Daily Respiratory Research Analysis
A multicountry precision-medicine RCT (ImmunoSep) showed that immunophenotype-guided therapy (anakinra or interferon-γ) improved early organ dysfunction in sepsis. A phase 3 trial in The Lancet Respiratory Medicine (ASTRUM-002) found serplulimab plus chemotherapy prolonged PFS in non-squamous NSCLC, while adding bevacizumab did not. A nationwide Danish cohort linked adult RSV infection to a sustained one-year excess risk of cardiovascular events, underscoring prevention needs.
Summary
A multicountry precision-medicine RCT (ImmunoSep) showed that immunophenotype-guided therapy (anakinra or interferon-γ) improved early organ dysfunction in sepsis. A phase 3 trial in The Lancet Respiratory Medicine (ASTRUM-002) found serplulimab plus chemotherapy prolonged PFS in non-squamous NSCLC, while adding bevacizumab did not. A nationwide Danish cohort linked adult RSV infection to a sustained one-year excess risk of cardiovascular events, underscoring prevention needs.
Research Themes
- Precision immunotherapy in sepsis
- First-line PD-1 inhibitor strategy in non-squamous NSCLC
- Long-term cardiovascular risk after RSV infection
Selected Articles
1. Precision Immunotherapy to Improve Sepsis Outcomes: The ImmunoSep Randomized Clinical Trial.
In a multicountry double-blind RCT, immunophenotype-guided therapy with IV anakinra for macrophage activation-like syndrome or SC interferon-γ for immunoparalysis increased the proportion achieving a ≥1.4-point SOFA reduction by day 9 versus placebo (35.1% vs 17.9%). No significant 28-day mortality difference was observed, and safety signals included more anemia with anakinra and bleeding with interferon-γ.
Impact: This is among the first rigorous trials operationalizing immune endotypes to tailor sepsis therapy, demonstrating early organ support benefits and opening a precision-immunotherapy pathway in a traditionally heterogeneous syndrome.
Clinical Implications: Consider feasible bedside immunophenotyping (ferritin thresholds and monocyte HLA-DR) to identify candidates for anakinra or interferon-γ in sepsis to improve early organ dysfunction, while monitoring for anemia and bleeding. Mortality benefit remains unproven.
Key Findings
- Primary endpoint achieved more often with precision immunotherapy: 35.1% vs 17.9% (difference 17.2%, 95% CI 6.8–27.2; P=.002)
- No statistically significant difference in 28-day mortality between groups
- Safety signals: higher anemia with anakinra; higher hemorrhage with interferon-γ
Methodological Strengths
- Randomized, double-blind, double-dummy, placebo-controlled, multicountry design
- Biologically driven stratification using ferritin and monocyte HLA-DR to target therapies
Limitations
- Primary endpoint focuses on day-9 organ dysfunction; no mortality benefit at 28 days
- Potential generalizability constraints of immunophenotyping thresholds and operational logistics
Future Directions: Larger trials powered for mortality and patient-centered outcomes; refine immunophenotyping cutoffs; evaluate combination or sequential strategies and cost-effectiveness.
2. First-line serplulimab plus chemotherapy with or without HLX04 versus chemotherapy in locally advanced or metastatic non-squamous non-small-cell lung cancer (ASTRUM-002): a randomised, double-blind, multicentre phase 3 trial.
Serplulimab plus chemotherapy significantly prolonged PFS versus chemotherapy alone in first-line non-squamous NSCLC (HR 0.55). Adding bevacizumab biosimilar HLX04 to serplulimab plus chemotherapy did not further improve PFS. Serious treatment-related adverse events were more frequent with immunotherapy-containing regimens.
Impact: A large, double-blind phase 3 trial establishes serplulimab plus chemotherapy as an effective first-line option and clarifies that bevacizumab addition offers no incremental benefit, informing regimen selection and resource allocation.
Clinical Implications: For EGFR/ALK/ROS1–negative non-squamous NSCLC, serplulimab plus pemetrexed-carboplatin is a viable first-line option; routine addition of bevacizumab is not supported. Monitor for higher rates of serious treatment-related adverse events.
Key Findings
- Serplulimab + chemotherapy improved PFS vs chemotherapy alone (HR 0.55, 95% CI 0.43–0.69; p<0.0001)
- Adding HLX04 to serplulimab + chemotherapy did not significantly improve PFS (HR 0.86; p=0.25)
- Serious treatment-related adverse events: 39% (A), 37% (B), 24% (C); grade ≥3 TRAEs: 71% (A), 66% (B), 57% (C)
Methodological Strengths
- Randomised, double-blind, three-arm, multicentre phase 3 design
- Blinded independent central review of PFS per RECIST v1.1
Limitations
- Population enrolled exclusively in China; generalizability beyond this setting requires caution
- Overall survival and biomarker analyses not detailed in abstract
Future Directions: Report OS, quality-of-life, and biomarker-defined subgroups; compare against established PD-1/PD-L1 regimens and evaluate real-world safety.
3. Cardiovascular Events 1 Year After Respiratory Syncytial Virus Infection in Adults.
In a nationwide matched cohort of adults ≥45 years, laboratory-confirmed RSV infection was associated with a 4.69 percentage-point absolute excess risk of any cardiovascular event over 1 year. Excess risk was highest among hospitalized patients, the very old, and those with baseline CVD or diabetes, and was comparable to that seen after influenza.
Impact: Quantifies long-term CVD risk after RSV, informing prioritization of adult RSV vaccination and post-infection cardiovascular surveillance strategies.
Clinical Implications: RSV prevention (vaccination) and targeted post-infection monitoring for CVD should be considered, especially in hospitalized, older, and comorbid patients.
Key Findings
- Absolute excess risk of any cardiovascular event at 1 year: 4.69 percentage points (95% CI 4.02–5.36)
- Greatest excess risk in hospitalized patients (6.61 pp), ages 85–94 (7.93 pp), and those with preexisting CVD (11.95 pp) or diabetes (7.50 pp)
- Cardiovascular risk after RSV infection was similar in magnitude to that after influenza
Methodological Strengths
- Nationwide registry-based matched cohort with large sample size and 1:1 matching
- Use of Aalen-Johansen estimator and multiple comparator cohorts (influenza, hip fracture, UTI)
Limitations
- Observational design susceptible to residual confounding and misclassification
- Findings from Denmark may not fully generalize to other health systems
Future Directions: Assess RSV vaccination impact on post-infection CVD, elucidate mechanisms linking RSV to CVD, and develop risk stratification tools.