Daily Respiratory Research Analysis
Three impactful studies advance respiratory science and practice: a cross-species single-cell and regulatory analysis clarifies the evolutionary origins of vertebrate lungs; a clinical PET study shows data-driven respiratory gating can reliably replace device-based gating in routine oncology imaging; and a German prospective analysis quantifies high RSV hospitalization burden in older adults, supporting vaccination strategies.
Summary
Three impactful studies advance respiratory science and practice: a cross-species single-cell and regulatory analysis clarifies the evolutionary origins of vertebrate lungs; a clinical PET study shows data-driven respiratory gating can reliably replace device-based gating in routine oncology imaging; and a German prospective analysis quantifies high RSV hospitalization burden in older adults, supporting vaccination strategies.
Research Themes
- Evolutionary and developmental genomics of the lung
- Data-driven diagnostic methodology in respiratory motion management
- Respiratory virus epidemiology and vaccination policy
Selected Articles
1. Origin and stepwise evolution of vertebrate lungs.
Cross-species single-cell and regulatory analyses show that much of the genetic program for lungs existed before the emergence of bony fish, with later acquisition of lung-specific enhancers and mammal-specific alveolar innovations. Alveolar type 1 cells are mammal-specific, and sfta2 deletion causes severe respiratory defects in mice, establishing function for a new lung gene.
Impact: This work reframes the origin of lung developmental programs and identifies a mammal-specific alveolar cell type and essential gene, providing a unifying evolutionary and mechanistic blueprint for lung biology.
Clinical Implications: While not immediately clinical, defining mammal-specific alveolar programs and essential genes (e.g., sfta2) may inform congenital lung disease mechanisms and regenerative strategies targeting alveolar cell types.
Key Findings
- Single-cell analyses across vertebrates reveal conserved lung cell programs and trajectories despite organ absence in cartilaginous fishes.
- Many lung enhancers and lung-related gene coexpression patterns are present in cartilaginous fishes, indicating an ancestral regulatory foundation.
- Alveolar type 1 cells are mammal-specific, with mammal-specific genes (e.g., ager, sfta2) highly expressed in lungs.
- Functional deletion of sfta2 in mice causes severe respiratory defects, demonstrating essential gene function in mammalian lung.
Methodological Strengths
- Cross-species single-cell RNA-seq of adult and developing lungs with enhancer mapping
- Functional validation via mouse knockout (sfta2) establishing causality
Limitations
- Exact species numbers and developmental stages per species are not detailed in the abstract
- Regulatory inferences from enhancer conservation require further causal testing across taxa
Future Directions: Dissect regulatory enhancer function across non-mammalian models; map lineage trajectories with spatial multi-omics; translate mammal-specific alveolar programs to inform lung regeneration and disease.
2. Incidence of RSV-related hospitalizations for ARIs, including CAP: Data from the German prospective ThEpiCAP study.
Active surveillance with adjustment for underdetection shows high RSV-related ARI and CAP hospitalization rates in older adults (≥60 years: ~402 per 100,000 ARI hospitalizations), with substantial 30-day mortality and cardiovascular events. Findings support prioritizing RSV vaccination and resource planning for older populations.
Impact: Provides robust, adjusted incidence estimates that better reflect true RSV burden in older adults, directly informing vaccination policy and health system preparedness.
Clinical Implications: Supports offering RSV vaccination to older adults and integrating RSV testing/diagnosis into ARI/CAP pathways during RSV seasons; enables more accurate burden and cost-effectiveness modeling.
Key Findings
- Among 1,040 radiologically confirmed CAP cases, RSV positivity was 3.7% by swab, increasing to 7.8% after underdetection adjustment.
- Adjusted RSV-related ARI hospitalization rates per 100,000 were 19.8 (18–59 years) and 401.6 (≥60 years).
- Thirty-day mortality after RSV-related CAP admission was 18.2% in patients ≥65 years; cardiovascular events occurred in 11.1% (18–64) and 36.4% (≥65).
Methodological Strengths
- Prospective active surveillance with radiologically confirmed CAP and age-stratified adjustment for underdetection
- Use of external multispecimen data to extrapolate ARI rates beyond CAP
Limitations
- RSV detection based primarily on nasopharyngeal/nasal swabs may miss lower airway infections
- Extrapolation from CAP to broader ARI introduces model assumptions; single-country data (Germany)
Future Directions: Validate with multispecimen sampling (e.g., sputum, saliva) and multi-country cohorts; integrate vaccine effectiveness to refine burden and cost-effectiveness estimates.
3. Quantification in respiratory-gated PET acquisition: can data-driven methods replace device-based systems?-a comparative and retrospective study.
In 196 oncology patients (536 lesions), data-driven respiratory gating (OncoFreeze AI) showed negligible quantitative differences versus belt-based gating: mean absolute bias 3.8% (SUVmax) and 2.1% (SUVpeak), with minimal PERCIST-impacting discrepancies. Findings support data-driven gating as a reliable alternative in routine [18F]FDG PET/CT.
Impact: Demonstrates practice-ready equivalence of data-driven gating to device-based gating, reducing setup burden and failure risk while maintaining quantitative integrity.
Clinical Implications: Centers can adopt data-driven respiratory gating to simplify workflow, reduce hardware dependence, and standardize quantification, with minimal impact on PERCIST-based response assessment.
Key Findings
- Across 536 lesions, mean absolute bias was 3.8% for SUVmax and 2.1% for SUVpeak comparing data-driven vs belt-based gating.
- Only 2% (SUVmax) and 0.5% (SUVpeak) of patients showed PERCIST-impacting discrepancies.
- Lesion size and anatomical site did not produce clinically significant differences between gating methods.
Methodological Strengths
- Within-patient, same-scanner comparison with standardized acquisition (Siemens Biograph 64 Vision 600)
- Quantitative assessment across up to five lesions per patient with confidence intervals and subgroup analyses (PERCIST)
Limitations
- Single-center, retrospective design may limit generalizability and causal inference
- Specific to one vendor and data-driven solution (OncoFreeze AI) without clinical outcome correlation
Future Directions: Prospective multi-center trials linking gating choice to clinical outcomes and therapy response; evaluate generalization across vendors and tracers.