Daily Respiratory Research Analysis
Analyzed 145 papers and selected 3 impactful papers.
Summary
Analyzed 145 papers and selected 3 impactful articles.
Selected Articles
1. Aumolertinib as adjuvant therapy in resected EGFR-mutated non-small-cell lung cancer (ARTS): a double-blind, multicentre, randomised, controlled, phase 3 trial.
In 214 randomized patients (mITT n=210), adjuvant aumolertinib significantly improved disease-free survival versus placebo (HR 0.17); median DFS was not reached vs 19.42 months. Safety was manageable with few grade ≥3 events and no treatment-related deaths.
Impact: A rigorously conducted phase 3 RCT demonstrates a substantial DFS benefit in a high‑risk resected EGFR-mutated NSCLC population, informing adjuvant therapy choices beyond existing agents.
Clinical Implications: Clinicians may consider aumolertinib as an adjuvant option for resected stage II–IIIB EGFR-mutated NSCLC where available, with attention to monitoring for CPK elevation and QT prolongation. OS and CNS outcomes warrant ongoing assessment.
Key Findings
- BICR-assessed DFS significantly favored aumolertinib (HR 0.17; median not reached vs 19.42 months).
- 95% of patients had received prior adjuvant chemotherapy; benefit persisted in this context.
- Grade 3–4 AEs were infrequent (e.g., CPK increase 7%, QT prolongation 3%); no treatment-related deaths.
Methodological Strengths
- Double-blind, randomized, placebo-controlled, multicentre design with BICR of DFS.
- Stratification by mutation type and stage; adequate median follow-up (~27.6 months).
Limitations
- Overall survival not yet mature; study population limited to Chinese centers.
- Head-to-head comparisons with other third-generation EGFR-TKIs (e.g., osimertinib) are lacking.
Future Directions: Assess OS, CNS recurrence, MRD-guided therapy, and comparative effectiveness versus osimertinib; evaluate quality of life and long-term safety.
BACKGROUND: Patients with resectable non-small-cell lung cancer (NSCLC), particularly those with EGFR mutations, face a high risk of recurrence and mortality post-surgery. Aumolertinib, a third-generation EGFR tyrosine-kinase inhibitor, is approved in China for adjuvant treatment in patients with NSCLC harbouring EGFR with an exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation. The ARTS study aimed to evaluate the efficacy and safety of adjuvant therapy with aumolertinib in patients with stage II-IIIB EGFR-mutated NSCLC. METHODS: This double-blind, multicentre, randomised, controlled, phase 3 trial enrolled patients from 48 hospitals in mainland China. Eligible patients were 18 years or older with stage II-IIIB NSCLC, had undergone a complete resection followed by standard adjuvant therapy, and had an EGFR ex19del or Leu858Arg mutation and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were stratified by EGFR mutation status and tumour stage and were randomly assigned (1:1) to receive aumolertinib 110 mg or placebo orally, once daily for 3 years or until disease recurrence or other discontinuation criteria were met. Patients were randomly allocated to groups using an interactive web response system; the double‑dummy technique masked patients, investigators, and assessors. The primary endpoint was disease-free survival in the modified intention-to treat (mITT) population (ie, all patients with stage II-IIIB NSCLC harbouring EGFR mutations who had undergone complete tumour resection and standard adjuvant therapy), assessed by blinded independent central review (BICR). Safety was assessed in all patients who received at least one dose of study treatment. Although the study is ongoing, with some patients remaining in follow-up, this analysis represents the protocol-specified primary analysis. This study is registered with ClinicalTrials.gov (NCT04687241).
2. Impact of universal nirsevimab prophylaxis in infants on hospital and primary care outcomes across two respiratory syncytial virus seasons in Galicia, Spain (NIRSE-GAL): a population-based prospective observational study.
Among 12,492 eligible infants (94.4% vaccinated), RSV-LRTI hospitalizations declined by 85.9% in the first season and 55.3% in the second; first LRTI admissions fell by 59.8% (first season) and 48.1% (to 18 months). Outpatient visits for bronchitis/bronchiolitis, LRTI, and wheezing/asthma also decreased substantially.
Impact: This population-scale, seasonally adjusted evaluation demonstrates real-world effectiveness and persistence of benefit from universal infant RSV immunoprophylaxis across inpatient and outpatient settings.
Clinical Implications: Findings support universal nirsevimab programs to reduce RSV burden, with benefits extending into the second season. Data inform health policy, resource planning, and cost‑effectiveness modeling.
Key Findings
- 94.4% coverage; RSV-LRTI hospitalizations reduced by 85.9% (first season) and 55.3% (second season).
- First LRTI hospitalizations dropped 59.8% (first season) and 48.1% (to 18 months).
- Outpatient bronchitis/bronchiolitis visits fell 30.8%; LRTI 33.4%; wheezing/asthma 27.7% in the first season.
- Estimated number needed to immunize to prevent a second-season RSV-LRTI admission: 123.
Methodological Strengths
- Population-based, prospective design with linkage across hospital and primary care.
- Seasonality-adjusted Poisson models using multi-year historical comparators; multiple inpatient and outpatient endpoints.
Limitations
- Observational design with historical comparators susceptible to residual confounding and secular trends.
- Generalizability limited to one region; vaccine price and uptake dynamics may differ elsewhere.
Future Directions: Assess durability beyond two seasons, interaction with maternal RSV vaccination and adult RSV vaccines, and comprehensive cost-effectiveness and equity analyses.
BACKGROUND: Real-world evidence on nirsevimab impact beyond the first season when given under universal immunisation programmes is emerging. We aimed to assess the medium-term impact of universal infant respiratory syncytial virus (RSV) prophylaxis with nirsevimab across inpatient and outpatient settings during two consecutive RSV seasons. METHODS: NIRSE-GAL is an ongoing, population-based, prospective, longitudinal study in Galicia, Spain. For this study, we included all infants eligible for nirsevimab in the 2023-24 RSV campaign in Galicia, followed up from their first RSV season (2023-24) until the end of their second RSV season (2024-25). The primary endpoint was RSV-related lower respiratory tract infection (LRTI) hospitalisation. Secondary endpoints were LRTI hospitalisation, acute bronchitis or bronchiolitis hospitalisation, pneumonia admissions, all-cause hospitalisations, and primary health-care outcomes (acute bronchitis or bronchiolitis, wheezing or asthma, LRTI, respiratory infections, acute otitis media, and all otitis diagnoses). The first recurrences of these endpoints were also assessed as secondary endpoints. Impact was estimated by Poisson regression models using weekly incidence rates of historical non-pandemic seasons (2017-18 to 2022-23) as comparators, adjusted for RSV seasonality, and evaluated across three follow-up periods: the first RSV season, the second RSV season, and up to 18 months. This study is registered with ClinicalTrials.gov, NCT06180993.
3. Gasdermin D-dependent macrophage pyroptosis mediates polystyrene microplastics-induced pulmonary fibrosis.
In a 56-day mouse model, chronic intranasal exposure to 5-μm polystyrene microplastics caused pulmonary fibrosis via GSDMD-dependent pyroptosis in alveolar macrophages. Gsdmd knockout attenuated fibrosis and improved lung function, while conditioned media from pyroptotic macrophages activated fibroblasts, nominating GSDMD as a therapeutic target for microplastic-associated lung disease.
Impact: This study mechanistically links a pervasive environmental pollutant to fibrotic lung disease and identifies GSDMD as a central, druggable node in the pathway.
Clinical Implications: While preclinical, the findings prioritize GSDMD/NLRP3/caspase-1 signaling as potential therapeutic targets and support monitoring environmental microplastic exposure as a respiratory health risk.
Key Findings
- Chronic intranasal exposure to 5-μm polystyrene microplastics induced collagen deposition, ECM remodeling, and lung function impairment.
- PS-MPs triggered NLRP3 activation, caspase-1 activation, and GSDMD-NT pore formation, indicating GSDMD-dependent macrophage pyroptosis.
- Gsdmd knockout reduced fibrosis, improved lung function, and lowered IL-1β; pyroptotic conditioned media activated fibroblasts and ECM production.
Methodological Strengths
- Chronic in vivo exposure model with genetic ablation (Gsdmd knockout) to establish causality.
- Multi-modal validation (ELISA, qPCR, Western blot, immunofluorescence) and functional assays including conditioned media on fibroblasts.
Limitations
- Preclinical murine model; human relevance and dose/exposure comparability remain to be established.
- Single particle size and polymer type (5-μm polystyrene) may limit generalizability across microplastic species and exposure routes.
Future Directions: Validate GSDMD pathway activation in human PF tissue with environmental microplastic exposure, and test pharmacologic GSDMD/NLRP3 inhibitors in translational models.
Exposure to microplastic (MPs) pollution may induce pulmonary fibrosis (PF). Macrophage pyroptosis has been directly implicated in the pathogenesis of PF. This study focused on the potential driving role of macrophage pyroptosis in polystyrene microplastics (PS-MPs) induced pulmonary fibrosis. Through a 56-day intranasal exposure model in mice, we demonstrate that chronic exposure to 5-μm PS-MPs induces significant pulmonary fibrosis characterized by collagen deposition, extracellular matrix remodeling, and substantial lung function impairment. PS-MPs specifically trigger GSDMD-dependent pyroptosis in alveolar macrophages, as evidenced by enhanced NLRP3 inflammasome assembly, caspase-1 activation, and GSDMD-NT pore formation. Genetic ablation of Gsdmd substantially attenuated fibrotic progression, improved pulmonary functional parameters, and reduced production of pro-fibrotic mediators including IL-1β. Crucially, we established a direct paracrine link between macrophage pyroptosis and fibrogenesis through conditioned medium experiments, demonstrating that GSDMD-dependent release of pyroptotic factors promotes fibroblast activation and extracellular matrix production. Our results delineate a complete pathogenic pathway wherein PS-MPs induce pulmonary fibrosis through macrophage pyroptosis, thereby positioning GSDMD as both a key mediator and promising therapeutic target for combating microplastic-associated lung disease. These findings provide crucial insights into the environmental health risks of microplastics and identify potential intervention strategies for plastic pollution-related respiratory disorders.