Daily Respiratory Research Analysis
A phase 2 randomized trial showed that the DPP-1 inhibitor HSK31858 significantly reduced exacerbations in bronchiectasis without new safety signals. A large-scale lung cancer screening program (SUMMIT) demonstrated high sensitivity and specificity for low-dose CT in a diverse urban population with mostly early-stage detection and low surgical mortality. Precision phenotyping in central sleep apnea identified patients with high event-related heart rate surges who derive greater left ventricular
Summary
A phase 2 randomized trial showed that the DPP-1 inhibitor HSK31858 significantly reduced exacerbations in bronchiectasis without new safety signals. A large-scale lung cancer screening program (SUMMIT) demonstrated high sensitivity and specificity for low-dose CT in a diverse urban population with mostly early-stage detection and low surgical mortality. Precision phenotyping in central sleep apnea identified patients with high event-related heart rate surges who derive greater left ventricular ejection fraction benefit from transvenous phrenic nerve stimulation.
Research Themes
- Targeting neutrophil protease activation in bronchiectasis
- Implementation effectiveness of low-dose CT lung cancer screening
- Precision phenotyping to optimize therapy in central sleep apnea
Selected Articles
1. Effects of the DPP-1 inhibitor HSK31858 in adults with bronchiectasis in China (SAVE-BE): a phase 2, multicentre, double-blind, randomised, placebo-controlled trial.
In a multicenter phase 2 RCT (n=224), HSK31858 (20 mg or 40 mg daily for 24 weeks) significantly reduced annualized exacerbation frequency versus placebo (IRR 0.52 and 0.41, respectively) in adults with bronchiectasis. Safety profiles were similar across groups without increases in adverse events of special interest.
Impact: This trial provides the first robust randomized evidence that DPP-1 inhibition can reduce exacerbations in bronchiectasis, a condition with few disease-modifying therapies. It validates neutrophil protease activation as a tractable therapeutic axis.
Clinical Implications: If confirmed in phase 3, HSK31858 or similar DPP-1 inhibitors could be added to standard care to reduce exacerbations in bronchiectasis, especially in frequent exacerbators, without apparent new safety concerns.
Key Findings
- Annualized exacerbation frequency reduced versus placebo (IRR 0.52 at 20 mg; IRR 0.41 at 40 mg; both statistically significant).
- Consistent safety with no increase in adverse events of special interest (e.g., hyperkeratosis, gingivitis, life-threatening infections).
- Effect observed over 24 weeks across a multicenter Chinese cohort with stratification by prior exacerbation frequency.
Methodological Strengths
- Randomized, double-blind, placebo-controlled design with stratified randomization.
- Clear, clinically meaningful primary endpoint (annualized exacerbation frequency) with prespecified analysis in a full analysis set.
Limitations
- Phase 2 duration (24 weeks) limits long-term efficacy and safety assessment.
- Single-country (China) study may limit generalizability to other populations and etiologies of bronchiectasis.
Future Directions: Conduct phase 3 multinational trials with longer follow-up, explore biomarkers of neutrophil activity to enrich responders, and assess effects on quality of life, lung function, and microbiology.
2. Low-dose CT for lung cancer screening in a high-risk population (SUMMIT): a prospective, longitudinal cohort study.
Among 12,773 high-risk participants, low-dose CT screening achieved 97.0% episode sensitivity and 95.2% specificity with a 4.8% false-positive rate at 12 months. Most screen-detected lung cancers were stage I–II (79.3%), with surgery as the primary treatment (77.0%) and low 90-day surgical mortality (0.4%).
Impact: Demonstrates real-world performance and safety of large-scale lung cancer screening in an ethnically and socioeconomically diverse urban setting, informing program design and policy.
Clinical Implications: Health systems can deploy low-dose CT screening with high sensitivity and manageable false positives, anticipating predominantly early-stage detection and low perioperative mortality when surgical management is pursued.
Key Findings
- Episode sensitivity 97.0% and specificity 95.2% at 12 months; false-positive rate 4.8%.
- 79.3% of screen-detected lung cancers were stage I–II; surgery was primary treatment in 77.0%.
- Low 90-day postoperative mortality (0.4%) and benign resection rate of 11.6% among resections.
Methodological Strengths
- Large prospective cohort with standardized low-dose CT protocol and defined performance metrics.
- Inclusive recruitment across 329 primary care practices in a diverse metropolitan area.
Limitations
- Baseline round analysis; long-term mortality impact not assessed here.
- Benign resection rate (11.6%) indicates potential for further optimization of nodule management algorithms.
Future Directions: Evaluate longitudinal outcomes (mortality, overdiagnosis), refine risk models and nodule management to reduce benign resections, and assess equity and adherence in program scale-up.
3. Determinants of transvenous phrenic nerve stimulation-induced improvements in left ventricular function in central sleep apnea and heart failure.
Secondary analyses of the remedē pivotal trial identified that patients with high respiratory event-related heart rate surges (>14.6 bpm) experienced greater LVEF improvement with TPNS versus control (interaction estimate +7.8%). Benefits in LVEF persisted through 12 months in the high-∆HR subgroup but were absent in the low-∆HR subgroup.
Impact: Introduces a practical, physiology-based biomarker (∆HR) to identify heart failure patients with CSA who may derive cardiac functional benefit from TPNS, enabling precision therapy.
Clinical Implications: Measuring event-related ∆HR on baseline polysomnography may guide selection for TPNS in HF with CSA, prioritizing patients likely to improve LVEF and potentially clinical outcomes.
Key Findings
- High ∆HR subgroup (>14.6 bpm) showed greater LVEF improvement with TPNS vs control (interaction estimate +7.8%, 95% CI 0.37–15.2; pinteraction=0.04).
- Sustained LVEF gains at 6, 9, and 12 months in high-∆HR subgroup; no improvements in low-∆HR subgroup.
- Supports ∆HR as a marker of sympathetic overactivity that may mediate TPNS cardiac benefits.
Methodological Strengths
- Predefined physiologic metric (∆HR) quantified from polysomnography with echocardiographic LVEF endpoints.
- Longitudinal assessment demonstrating durability of effect up to 12 months.
Limitations
- Secondary analysis with subgroup interaction; limited sample size and sex imbalance (74 men, 5 women).
- Not powered for hard clinical outcomes; generalizability to broader CSA-HF populations requires validation.
Future Directions: Prospective trials stratifying by ∆HR to confirm predictive enrichment, explore mechanisms linking sympathetic surges to TPNS response, and assess impacts on clinical outcomes.