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.
Lungs are essential respiratory organs in terrestrial vertebrates, present in most bony fishes but absent in cartilaginous fishes, making them an ideal model for studying organ evolution. Here we analysed single-cell RNA sequencing data from adult and developing lungs across vertebrate species, revealing significant similarities in cell composition, developmental trajectories and gene expression patterns. Surprisingly, a large proportion of lung-related genes, coexpression patterns and many lung enhancers are present in cartilaginous fishes despite their lack of lungs, suggesting that a substantial genetic foundation for lung development existed in the last common ancestor of jawed vertebrates. In addition, the 1,040 enhancers that emerged since the last common ancestor of bony fishes probably contain lung-specific elements that led to the development of lungs. We further identified alveolar type 1 cells as a mammal-specific alveolar cell type, along with several mammal-specific genes, including ager and sfta2, that are highly expressed in lungs. Functional validation showed that deletion of sfta2 in mice leads to severe respiratory defects, highlighting its critical role in mammalian lung features. Our study provides comprehensive insights into the evolution of vertebrate lungs, demonstrating how both regulatory network modifications and the emergence of new genes have shaped lung development and specialization across species.
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.
BACKGROUND: RSV is a leading cause of ARI, including CAP, in older adults. Data available often underestimate RSV-related ARI incidence. We estimated RSV-related ARI hospitalization incidence from a prospective CAP study, adjusting for undiagnosed RSV infections due to nasopharyngeal/nasal swab testing only. METHODS: Active surveillance of adult CAP hospitalizations in Germany was conducted between 2021-2023. Nasopharyngeal/nasal swabs were RSV-tested, and age-group specific proportions were applied to calculate RSV-related CAP incidence. This was divided by the CAP proportions among RSV-related ARI hospitalizations (from multispecimen study) to extrapolate RSV-related ARI rates. RESULTS: Among 1040 radiologically confirmed CAP cases, 3.7% tested RSV-positive via nasopharyngeal/nasal swab, corresponding to 7.8% after adjusting for underdetection. For 18-59 and ≥60 years, adjusted RSV-related CAP hospitalization rates (95% CI) were 4.9 (1.8-10.9) and 115.6 (78.8-163.6); adjusted RSV-related ARI hospitalization rates were 19.8 (6.8-50.1) and 401.6 (260.7-609.3) per 100,000, respectively. Within 30 days of an RSV-related CAP admission, 18.2% of those ≥65 years died, and 11.1% and 36.4% had cardiovascular events among those 18-64 and ≥65 years, respectively. CONCLUSIONS: Older adults in Germany experience a high burden of RSV-related ARI hospitalizations, including CAP, underscoring RSV vaccination's potential utility for this population.
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.
BACKGROUND: Device-based respiratory gating improves diagnostic and quantification accuracy in positron emission tomography (PET), but requires additional time to setup the device and the failure rate can be significant. Our aim was to internally validate the quantification performance of data-driven respiratory-gated PET imaging against the gold standard, the device-based method, in clinical oncological practice. We retrospectively analysed [18F]FDG PET/CT scans of patients from our centre with at least one measurable [18F]FDG-avid malignant lesion. All PET/CT acquisitions were performed on a Siemens Biograph 64 Vision 600 system with respiratory gating by belt and also by adding the data-driven gating with OncoFreeze AI™. We recorded the SUVmax and SUVpeak for up to a maximum of 5 lesions per patient. We computed the mean absolute bias between the two gating methods and the 95% confidence intervals (CI) at the cohort level and in subgroups. RESULTS: Of the 692 consecutive patients screened for inclusion, 196 patients were analysed, from whom 536 lesions were measured. The mean absolute biases in the SUVmax and SUVpeak of lesions in the whole cohort were 3.8% (CI 3.4-4.2) and 2.1% (CI 1.9-2.4), respectively. At patient-level, 21% of them had at least one lesion with a SUVmax bias above 10%, while for SUVpeak this proportion was 5%. In the subgroup analysis by PERCIST criteria, only 2% of patients had significant bias in the SUVmax, and 0.5% in SUVpeak. There was no clinically significant effect of lesion size or anatomical site on SUV measurements between the two respiratory gating methods. CONCLUSION: Quantitative comparison of data-driven and device-based respiratory-gated PET scans revealed negligible differences, proving that data-driven respiratory gating is a reliable and accurate alternative to the device-based gating method in routine [18F]FDG-PET/CT oncological evaluation.