Daily Respiratory Research Analysis
Risk-based selection improved the efficiency of lung cancer screening in a large German cohort, while an international randomized trial found no benefit of pirfenidone for bronchiolitis obliterans syndrome after lung transplantation. Real-world data from three European countries showed high effectiveness of nirsevimab against RSV hospitalization in infants, with evidence of waning over time.
Summary
Risk-based selection improved the efficiency of lung cancer screening in a large German cohort, while an international randomized trial found no benefit of pirfenidone for bronchiolitis obliterans syndrome after lung transplantation. Real-world data from three European countries showed high effectiveness of nirsevimab against RSV hospitalization in infants, with evidence of waning over time.
Research Themes
- Risk-based lung cancer screening improves detection efficiency
- Antifibrotic therapy (pirfenidone) ineffective for BOS after lung transplantation
- Real-world effectiveness and waning of RSV long-acting monoclonal antibody (nirsevimab)
Selected Articles
1. Effectiveness of NELSON versus PLCOm2012 lung cancer screening eligibility criteria in Germany (HANSE): a prospective cohort study.
In a prospective cohort of 5,191 high-risk participants, eligibility based on PLCOm2012 ≥1.58% yielded a higher positive predictive value for lung cancer (2.59%) and a lower number needed to screen than NELSON criteria. Two screening rounds identified 111 cancers with standardized low-dose CT protocols.
Impact: This study provides high-quality, real-world evidence that a risk-model approach improves screening efficiency, directly informing national program design.
Clinical Implications: Adopting a PLCOm2012 risk threshold (≥1.58% over 6 years) can improve screening yield and resource efficiency. Programs should consider transitioning from categorical criteria to risk-based eligibility.
Key Findings
- Among 5,191 participants, 111 lung cancers were detected over two rounds of low-dose CT screening.
- PLCOm2012-selected group had a higher PPV (2.59%) vs NELSON (2.17%), p=0.0016.
- Number needed to screen was lower with PLCOm2012 (38.6) vs NELSON (46.1).
Methodological Strengths
- Prospective, multicenter design with predefined PLCOm2012 threshold
- Standardized low-dose CT protocol and registered study
Limitations
- Limited to two screening rounds; no mortality outcomes
- Conducted in three German centers; generalizability may vary
Future Directions: Evaluate long-term outcomes (mortality, cost-effectiveness), refine risk thresholds across diverse populations, and integrate biomarkers to further optimize eligibility.
BACKGROUND: Low-dose chest CT screening can reduce lung cancer mortality through early diagnosis. Several studies suggest that risk prediction models are more efficient than categorical age and smoking criteria for participant selection, but there are still reservations from policy makers about their implementation. We aimed to compare the effectiveness of a predefined PLCOm2012 model threshold with the categorical NELSON risk criteria. METHODS: In this ongoing prospective cohort study, current or former smokers aged 55-79 years who met either NELSON risk criteria or had a PLCOm2012 6-year risk of at least 1·58% were recruited from three certified German lung cancer centres in Großhansdorf, Hannover, and Lübeck, and received low-dose CT at baseline and 1-year follow-up screening rounds, including all downstream follow-up procedures. The PLCOm2012 cutoff point of at least 1·58% was predefined and estimated to result in an equal group size as with the NELSON inclusion criteria. The primary outcome was the comparison of the positive predictive values for lung cancers detected in PLCOm2012-selected versus NELSON-selected groups. Here, we report the final results of the primary analysis. This study is registered with ClinicalTrials.gov, NCT04913155. FINDINGS: Between July 23, 2021, and Aug 19, 2022 (end of recruitment), 5191 participants (2208 [43·5%] female, 2983 [57·5%] male, and 5076 [97·8%] of European White ethnicity) who met either one or both high-risk criteria were enrolled (4167 PLCOm2012-selected vs 3916 NELSON-selected participants) and underwent the baseline low-dose CT scan. In the observation period between the two low-dose CT screening rounds (mean volume CT dose index 1·15 mGy [SD 0·15]) with a median time interval of 1·05 years (IQR 0·95-1·08), 111 lung cancers were detected. The positive predictive value (lung cancer detection rate) in the PLCOm2012-selected group was 108 of 4167 participants (2·59% [95% CI 2·13-3·12]) compared with 85 of 3916 participants (2·17% [1·74-2·68]) in the NELSON-selected group (p=0·0016), resulting in a lower number needed to screen (38·6 [32·1-46·9] vs 46·1 [37·3-57·5]). INTERPRETATION: Participant selection using the PLCOm2012 risk prediction model with a 6-year risk of at least 1·58% cutoff is more efficient and effective in detecting lung cancer than the NELSON criteria and should therefore be implemented in lung cancer screening programmes. FUNDING: Federal Ministry of Education and Research (German Center for Lung Research) and AstraZeneca.
2. A European multi-center, randomized controlled trial of Pirfenidone in bronchiolitis obliterans syndrome after bilateral lung transplantation.
In a double-blind, placebo-controlled phase II trial (n=90), pirfenidone did not reduce FEV1 decline nor improve secondary clinical outcomes in progressive BOS after bilateral lung transplantation. Safety profiles were comparable between groups.
Impact: A rigorous negative RCT de-implements an increasingly considered off-label antifibrotic strategy in BOS, avoiding ineffective therapy and focusing research on alternative CLAD treatments.
Clinical Implications: Pirfenidone should not be used for BOS after lung transplantation outside clinical trials. Management should prioritize established CLAD care pathways and clinical trial enrollment for novel interventions.
Key Findings
- No significant difference in FEV1 decline at 26 weeks between pirfenidone and placebo across ITT, imputed ITT, and PP analyses.
- Secondary endpoints (graft loss, death, re-transplantation) were similar between groups.
- Treatment-related serious adverse events occurred at similar frequency in both arms.
Methodological Strengths
- Randomized, double-blind, placebo-controlled multicenter design
- Clinically relevant endpoints with prespecified analyses
Limitations
- Modest sample size may limit power to detect small effects
- Follow-up limited to 26 weeks; heterogeneity of BOS phenotypes
Future Directions: Focus on alternative pathobiology-driven interventions for CLAD/BOS, including immune modulation, infection control, and airway-targeted therapies; consider longer follow-up and phenotype-stratified trials.
BACKGROUND: Chronic Lung Allograft Dysfunction (CLAD) is a major obstacle to improving outcomes after lung transplantation. Bronchiolitis Obliterans Syndrome (BOS), characterized by progressive decline in FEV1 due to fibrotic scarring of the small airways, accounts for most CLAD cases. Pirfenidone, an antifibrotic agent used for idiopathic pulmonary fibrosis (IPF), was assessed for treating progressive BOS. METHODS: An investigator initiated, international, multicenter, randomized, double-blind, placebo controlled phase II trial was conducted in 9 European Lung Transplant centers. Adults with bilateral lung transplants and progressive BOS were randomized (1:1) to receive Pirfenidone 2403 mg·day FINDINGS: From May 1, 2015, to December 1, 2019, 477 patients were screened, and 90 were randomized to Pirfenidone (n=48) or placebo (n=42). Both groups showed continued decline in FEV1 from baseline to week 26, with no significant difference in intention to treat (ITT), ITT with imputation, or per-protocol (PP) analyses. Secondary endpoints (graft loss, death, re-transplantation) were similar between groups. Treatment related serious adverse events were equally distributed. INTERPRETATION: Pirfenidone did not show superiority over placebo and standard care in this exploratory trial. It cannot be recommended for treating BOS. Further research is needed to explore other treatments for CLAD to improve long-term outcomes after lung transplantation.
3. Effectiveness of long-acting monoclonal antibodies against laboratory-confirmed RSV in children aged < 24 months and hospitalised for severe acute respiratory infection, European pilot study, 2024 to 2025.
In a three-country test-negative study of 2,201 hospitalized children <24 months, nirsevimab showed 79% effectiveness against laboratory-confirmed RSV, with attenuation from 85% (<30 days) to 69% (90–215 days) since immunization.
Impact: Provides real-world effectiveness estimates across Europe and characterizes time-dependent waning, informing immunization timing and programmatic decisions.
Clinical Implications: Supports implementation of nirsevimab for RSV prevention in infants with awareness of waning beyond 3 months. Programs should optimize timing before peak RSV circulation and monitor effectiveness seasonally.
Key Findings
- Overall effectiveness against lab-confirmed RSV was 79% (95% CI: 58–89) among 2,201 hospitalized children <24 months.
- Effectiveness declined with time since immunization: 85% (<30 days), 78% (30–89 days), 69% (90–215 days).
- Test-negative design across three European countries supports robust real-world estimates.
Methodological Strengths
- Test-negative case-control design reduces bias related to healthcare-seeking behavior
- Multi-country implementation enhances generalizability
Limitations
- Observational design susceptible to residual confounding
- One-season analysis; effectiveness may vary by season and circulation patterns
Future Directions: Evaluate duration of protection across multiple seasons, assess effectiveness in high-risk subgroups, and model optimal timing strategies relative to local RSV phenology.
We measured effectiveness of nirsevimab against laboratory-confirmed respiratory syncytial virus (RSV) infection in a test-negative case-control study among children aged < 24 months hospitalised for severe acute respiratory infection in three European countries. The overall effectiveness in the 2024/25 season among 2,201 children was 79% (95% CI: 58 to 89) and 85%, 78% and 69% at < 30, 30-89 and 90-215 days since immunisation. Immunisation was effective for preventing RSV-related hospitalisation in children, but effectiveness by time since immunisation needs monitoring in future seasons.