Daily Respiratory Research Analysis
A phase 3 randomized trial in NEJM showed that amivantamab-lazertinib significantly improved overall survival versus osimertinib in previously untreated patients, albeit with higher grade ≥3 adverse events. A 25-year cohort study found that baseline emphysema on low-dose CT in lung cancer screening predicts long-term mortality from COPD and cardiovascular disease. A minimally invasive, percutaneous hypoglossal nerve stimulation approach acutely restored airflow and improved airway collapsibility
Summary
A phase 3 randomized trial in NEJM showed that amivantamab-lazertinib significantly improved overall survival versus osimertinib in previously untreated patients, albeit with higher grade ≥3 adverse events. A 25-year cohort study found that baseline emphysema on low-dose CT in lung cancer screening predicts long-term mortality from COPD and cardiovascular disease. A minimally invasive, percutaneous hypoglossal nerve stimulation approach acutely restored airflow and improved airway collapsibility in OSA, suggesting a less invasive bioelectronic therapy path.
Research Themes
- Targeted first-line therapy in lung cancer
- Imaging-based risk stratification for long-term respiratory and cardiovascular outcomes
- Minimally invasive bioelectronic therapies for obstructive sleep apnea
Selected Articles
1. Overall Survival with Amivantamab-Lazertinib in
In this phase 3 randomized trial, amivantamab-lazertinib significantly improved overall survival versus osimertinib (HR 0.75; 95% CI 0.61–0.92) with 3-year OS 60% vs 51%. Grade ≥3 adverse events were more frequent with amivantamab-lazertinib (80% vs 52%), notably skin events, venous thromboembolism, and infusion reactions.
Impact: Demonstrates an overall survival advantage of a novel combination targeted regimen over the current standard comparator in previously untreated patients, representing a potential change in first-line therapy.
Clinical Implications: If adopted, therapy selection may shift toward amivantamab-lazertinib in the first-line setting, with proactive monitoring and management of skin toxicity, venous thromboembolism, and infusion reactions.
Key Findings
- Overall survival was significantly longer with amivantamab-lazertinib versus osimertinib (HR 0.75; P=0.005).
- Three-year overall survival: 60% vs 51% (amivantamab-lazertinib vs osimertinib).
- Grade ≥3 adverse events were more frequent with amivantamab-lazertinib (80% vs 52%), especially skin-related events, venous thromboembolism, and infusion reactions.
- At data cutoff, ongoing treatment rates were 38% vs 28% (amivantamab-lazertinib vs osimertinib).
Methodological Strengths
- Phase 3 randomized design with a large sample (n≈858) and long median follow-up (37.8 months).
- Clinically meaningful primary endpoint (overall survival) with statistically robust results.
Limitations
- Higher toxicity with amivantamab-lazertinib may limit tolerability for some patients.
- Abstract lacks detail on subgroup biomarker stratification and quality-of-life outcomes.
Future Directions: Define biomarker-driven subgroups benefiting most from amivantamab-lazertinib, optimize toxicity mitigation strategies, and assess quality-of-life and cost-effectiveness.
BACKGROUND: Previous results from this phase 3 trial showed that progression-free survival among participants with previously untreated METHODS: We randomly assigned, in a 2:2:1 ratio, participants with previously untreated RESULTS: A total of 429 participants each were assigned to receive amivantamab-lazertinib or osimertinib. Over a median follow-up of 37.8 months, amivantamab-lazertinib led to significantly longer overall survival than osimertinib (hazard ratio for death, 0.75; 95% confidence interval, 0.61 to 0.92; P = 0.005); 3-year overall survival was 60% and 51%, respectively. At the clinical cutoff date, 38% of participants in the amivantamab-lazertinib group and 28% in the osimertinib group were still receiving the assigned treatment. Adverse events of grade 3 or higher were more common with amivantamab-lazertinib (in 80% of participants) than with osimertinib (in 52%), particularly skin-related events, venous thromboembolism, and infusion-related events; these findings were consistent with the established safety profile of each treatment. No new safety signals were observed with additional follow-up. CONCLUSIONS: Amivantamab-lazertinib led to significantly longer overall survival among participants with previously untreated
2. Emphysema at Baseline Low-Dose CT Lung Cancer Screening Predicts Death from Chronic Obstructive Pulmonary Disease and Cardiovascular Disease Up to 25 Years Later.
In a 9047-participant lung cancer screening cohort with median 23.3 years follow-up, baseline visual emphysema (29.1% prevalence) independently predicted mortality. Visual emphysema scoring was associated with increased all-cause mortality (HR 1.29; 95% CI 1.21–1.38) and, per the title, predicted COPD and CVD deaths over up to 25 years.
Impact: Provides long-term prognostic validation that a simple visual emphysema score at baseline LDCT predicts not only COPD but also cardiovascular mortality, enabling integrated risk stratification in screening populations.
Clinical Implications: Radiologists' emphysema scoring during LDCT screening can flag patients for aggressive COPD prevention and cardiometabolic risk management alongside lung cancer surveillance.
Key Findings
- Among 9047 screened adults, 29.1% had emphysema (mild 21.1%, moderate 5.7%, severe 2.4%).
- Median follow-up was 23.3 years, enabling evaluation of up to 25-year mortality.
- Baseline visual emphysema independently predicted all-cause mortality (HR 1.29; 95% CI 1.21–1.38) and, per study scope, COPD and CVD deaths using competing-risks models.
Methodological Strengths
- Large prospective cohort with very long follow-up and adjudicated causes of death.
- Adjusted Cox and Fine-Gray models accounting for competing risks.
Limitations
- Visual scoring by one of four radiologists may introduce interobserver variability.
- Observational design cannot eliminate residual confounding or establish causality.
Future Directions: Validate automated or standardized emphysema quantification across centers and integrate with cardiopulmonary risk algorithms to guide preventive interventions.
Background The prognostic value of baseline visual emphysema scoring at low-dose CT (LDCT) in lung cancer screening cohorts is unknown. Purpose To determine whether a single visual emphysema score at LDCT is predictive of 25-year mortality from all causes, chronic obstructive pulmonary disease (COPD), and cardiovascular disease (CVD). Materials and Methods In this prospective cohort study, asymptomatic adults aged 40-85 years with a history of smoking underwent baseline LDCT screening for lung cancer between June 2000 and December 2008. Follow-up continued until death, loss to follow-up, or December 31, 2024. Emphysema was assessed at baseline LDCT and scored from 0 (none) to 3 (severe) by one of four experienced chest radiologists. Baseline smoking history and comorbidities were self-reported. Causes of death (International Classification of Diseases, 10th Revision) were obtained from the U.S. National Death Index, physicians, and family. Associations between emphysema and mortality were evaluated using adjusted Cox proportional hazards and adjusted Fine-Gray competing risks models. Results Among 9047 participants (4614 female; median age, 65 years [IQR, 61-69 years]; median pack-years of smoking, 43 [IQR, 28-64]), 2637 (29.1%) had emphysema (mild in 1908 [21.1%], moderate in 512 [5.7%], and severe in 217 [2.4%]). Median follow-up was 23.3 years. Emphysema was independently predictive of all-cause mortality (hazard ratio [HR], 1.29; 95% CI: 1.21, 1.38;
3. Effect of Novel Hypoglossal Stimulation on Airflow and Airway Collapsibility in OSA.
In 14 participants with moderate-severe OSA during drug-induced sleep endoscopy, percutaneous ultrasound-guided hypoglossal nerve stimulation restored peak inspiratory flow during transient CPAP reductions to levels comparable to therapeutic CPAP and improved airway collapsibility metrics.
Impact: Introduces a minimally invasive, percutaneous HNS approach that acutely achieves physiological efficacy similar to CPAP, addressing barriers of cost and invasiveness of implanted systems.
Clinical Implications: If validated in chronic use, percutaneous HNS could expand access to neuromodulation for OSA patients who cannot tolerate CPAP or invasive implants; patient selection and safety over time require study.
Key Findings
- Percutaneous, ultrasound-guided HNS increased airflow in 13 of 14 participants during induced obstruction.
- Peak inspiratory flow recovered from 0.10 L/s (obstruction) to 0.41 L/s with HNS, comparable to therapeutic CPAP (0.43 L/s), then fell after HNS cessation (P < .001).
- Airway collapsibility (active critical closing pressure) improved during HNS application.
Methodological Strengths
- Physiological endpoints with within-subject testing using epiglottic pressure, pneumotachography, and controlled CPAP manipulations.
- Systematic testing of stimulation amplitudes and electrode configurations.
Limitations
- Small sample size (n=14) and acute, drug-induced sleep setting limit generalizability.
- Durability, nighttime efficacy, and long-term safety are unknown.
Future Directions: Conduct chronic implantation or repeated-use studies in natural sleep, compare against implanted HNS and CPAP for efficacy, adherence, and safety, and define selection criteria.
BACKGROUND: Hypoglossal nerve stimulation (HNS) to treat OSA currently requires placement of a cuff or "saddle" electrode around or adjacent to the hypoglossal nerve or nerves. Limitations for this therapy include cost, invasiveness, and variable efficacy. RESEARCH QUESTION: Can HNS applied via percutaneous implantation of a linear, multipair electrode array restore airflow to airway narrowing, obstruction, or both and improve airway collapsibility in people with OSA? STUDY DESIGN AND METHODS: Participants with OSA undergoing drug-induced sleep endoscopy with propofol were instrumented with an epiglottic pressure catheter, nasal mask, and pneumotachograph. Ultrasound was used to identify the hypoglossal nerve and to guide percutaneous electrode array placement. Transient CPAP reductions induced airflow limitation or obstruction for ≥ 9 breaths/efforts with HNS applied during breaths 4 through 6. A range of HNS amplitudes (0.5-5 mA) and electrode array combinations were tested to determine optimal airflow responses. Time-permitting, active critical closing pressure (P RESULTS: Fourteen people with moderate to severe OSA (mean [SD] apnea-hypopnea index, 30 [16] events/h) were studied. HNS increased airflow in 13 participants. Mean (SD) peak inspiratory flow on therapeutic CPAP was 0.43 (0.09) L/s. During transient CPAP reductions, mean (SD) peak inspiratory flow reduced to 0.10 (0.07) L/s for breaths 1 through 3, increased to therapeutic CPAP levels with HNS for breaths 4 through 6 (0.41 (0.18) L/s), and returned to 0.14 (0.14) L/s for breaths 7 through 9 after HNS (P < .001). Mean (SD) active P INTERPRETATION: Our results show that acute HNS via a minimally invasive, percutaneous, ultrasound-guided approach increases airflow to levels equivalent to therapeutic CPAP and improves airway collapsibility in people with OSA.