Daily Respiratory Research Analysis

BACKGROUND: Approximately 60 % of lung cancer cases occur in Asia, indicating an epidemiological disparity and need for effective therapies. Amivantamab-lazertinib is approved for first-line EGFR-mutated advanced non-small cell lung cancer (NSCLC) in many countries. In the protocol-specified final overall survival (OS) analysis of MARIPOSA (NCT04487080), amivantamab-lazertinib showed a statistically significant and clinically meaningful improvement in OS versus osimertinib (HR, 0.75; P = 0.005) among all participants. We evaluated OS for amivantamab-lazertinib versus osimertinib in Asian participants. PATIENTS AND METHODS: Participants with previously untreated EGFR-mutated, locally advanced/metastatic NSCLC were randomized 2:2:1 to receive amivantamab-lazertinib, osimertinib, or lazertinib (for evaluating contribution of components). Self-identified Asian race was a stratification factor. OS was a key secondary endpoint. RESULTS: Of 1074 randomized participants, 629 self-identified as Asian (amivantamab-lazertinib:250; osimertinib:251; lazertinib:128). At a median follow-up of 38.7 months, amivantamab-lazertinib significantly prolonged OS versus osimertinib among Asian participants. Median OS was not reached (NR; 95 % CI, NR-NR) for amivantamab-lazertinib versus 38.4 months (95 % CI, 35.1-NR) for osimertinib (HR, 0.74; 95 % CI, 0.56-0.97; nominal P = 0.026). Assuming exponential distribution of OS in both arms, amivantamab-lazertinib is projected to prolong median OS among Asian participants by > 12 months versus osimertinib. At 36 months, 61 % and 53 % were alive in the amivantamab-lazertinib and osimertinib arms. Safety profile was consistent with the overall population. CONCLUSIONS: Consistent with the overall population, amivantamab-lazertinib significantly improved OS versus osimertinib among Asian participants with previously untreated EGFR-mutated advanced NSCLC, making it the first regimen to improve survival among Asian patients.

BACKGROUND: Previous research identifies residual pulmonary vascular obstruction (RPVO) as an independent risk factor for venous thromboembolism (VTE) recurrence and a predictor of poor outcomes, yet its risk factors and prognostic impact remain unclear. PURPOSE: This study developed predictive models combining clinical and metabolic biomarkers to identify high-risk RPVO patients, offering clinically actionable guidance for optimizing anticoagulation therapy. PATIENTS AND METHODS: This retrospective study analyzed 363 acute pulmonary embolism (APE) patients (2018.1-2024.12) with ≥3-month follow-up. We developed comprehensive and simplified RPVO predictive models by identifying risk factors and assessing long-term outcomes. The models, incorporating metabolomic biomarkers from baseline blood samples, were validated in a prospective APE cohort (2024.12-2025.2). RESULTS: Multivariable analysis identified five independent RPVO predictors: 1) affected lobes on V/Q scan, 2) sPESI score, 3) pulmonary artery pressure, 4) recent surgery/immobilization, and 5) active cancer. Both the comprehensive and simplified predictive models showed excellent discrimination (kappa > 0.6) in training, validation, and prospective cohorts. Metabolomic analysis revealed azelaic acid and L-3-phenyl lactate as key differentiating metabolites, whose inclusion enhanced model performance. Notably, RPVO presence and extensive lung involvement (≥6 lobes) independently predicted adverse outcomes (recurrent VTE, cardiopulmonary failure, or mortality). CONCLUSION: We developed comprehensive and simplified RPVO prediction models incorporating five clinical predictors and two metabolic biomarkers (azelaic acid and L-3-phenyl lactic acid), significantly improving model performance. RPVO independently predicted adverse outcomes, highlighting the clinical value of combined clinical and molecular profiling.

BACKGROUND: Persistent tachypnea of infancy (PTI), also known as neuroendocrine cell hyperplasia of infancy (NEHI), represents one of the most common childhood interstitial lung diseases. Despite its frequency, standardized management protocol is lacking, and long-term outcome data remain limited. RESEARCH QUESTION: What treatment is used for patients with PTI/NEHI, how does clinical management vary across European countries, and what are the long-term outcomes in affected patients? STUDY DESIGN AND METHODS: This was a European, multicenter, retrospective, observational study. Clinical characteristics, therapeutic interventions, and long-term follow-up data were collected and analyzed. Treatment strategies were compared among countries that contributed at least 10 patients. RESULTS: A total of 378 children (63.5% male, 240/378) from 73 centers across 17 countries were enrolled, with a median age at diagnosis of 9 months (IQR, 6-13 months). Therapeutic interventions included oxygen supplementation (75.9%, 287/378), inhaled bronchodilators and/or inhaled glucocorticoids (62.4%, 236/378), systemic glucocorticoids (37.0%, 140/378), and nutritional support (33.8%, 128/378). Of the children who received oxygen therapy, 53.6% (154/287) were reported to have been weaned off, with a median age at weaning of 24 months (IQR, 16-36 months). Marked variability in treatment practices was observed across participating countries (p<0.05). Longitudinal data were available for 48.9% of patients (185/378) with a median follow-up of 19 months (IQR, 16-57 months). The proportion of symptomatic children declined over time, with the most marked improvement observed at 4 years of age. Resolution of imaging and pulmonary function abnormalities was also reported; however, a subset of patients continued to demonstrate persistent hypoxemia, crackles, exercise intolerance, as well as abnormal imaging and pulmonary function into adolescence. INTERPRETATION: Significant differences in treatment strategies for PTI/NEHI were observed across European countries, highlighting the need for evidence-based guidelines. While long-term prognosis is generally favorable, residual symptoms remain in some patients, warranting continued follow-up.