Daily Respiratory Research Analysis
Analyzed 47 papers and selected 3 impactful papers.
Summary
A mechanistic single-cell multi-omics study identified an endothelial mechanosensitive PIEZO1–CAPN2–STAT3–IL-33 axis that drives pulmonary fibrosis, offering a promising therapeutic target. A controlled human influenza infection study directly quantified infectious virus expelled into air, revealing striking inter-individual heterogeneity linked to symptoms and viral loads. A multicenter genomic-epidemiologic investigation of KPC–NDM co-producing carbapenem-resistant Klebsiella pneumoniae highlighted high mortality, clonal spread (ST11/ST307), and preserved susceptibility to cefiderocol and aztreonam–avibactam, informing stewardship and therapy.
Research Themes
- Endothelial mechanotransduction in pulmonary fibrosis
- Respiratory virus transmission biology and infectious aerosol heterogeneity
- Antimicrobial resistance dynamics in severe respiratory infections
Selected Articles
1. Controlled human influenza infection reveals heterogeneous expulsion of infectious virus into air.
Using a novel sampling tunnel, investigators directly captured and quantified infectious influenza virus expelled into air from experimentally infected humans. Expelled infectious loads varied by orders of magnitude across individuals and correlated with infectious viral loads in saliva/nasopharynx and with symptoms, with expelled aerosols maintaining viral diversity.
Impact: This study provides rare, direct measurements of infectious virus in exhaled particles during human infection and links emission magnitude to clinical and virologic markers, refining transmission models.
Clinical Implications: Infection control may need to account for high-emitters and symptom-linked peaks, supporting targeted masking, ventilation, and testing strategies during periods of high contagiousness.
Key Findings
- A modular influenza sampling tunnel enabled culture-based quantification and sequencing of infectious virus from exhaled particles.
- Expelled infectious virus loads varied over three orders of magnitude among individuals.
- Emission magnitude correlated with infectious viral loads in saliva and nasopharyngeal swabs and with clinical symptoms.
- Expelled aerosols preserved viral diversity similar to that detected in clinical samples.
Methodological Strengths
- Controlled human infection with direct culture-based detection of infectious aerosols.
- Integrated particle size quantification with concurrent virological genotyping.
Limitations
- Generalizability from controlled challenge settings to community transmission is uncertain.
- Detailed sample size and demographic breadth were not provided in the abstract.
Future Directions: Identify host and behavioral determinants of high emission, assess intervention impact (masking, ventilation) on infectious emissions across strains and populations.
Influenza virus is transmitted via respiratory expulsions, but detecting infectious virus in expulsions is challenging. Here, we describe quantification and genotyping of infectious virus in respiratory particles using a modular influenza sampling tunnel (MIST). The particles deposit on cell monolayers, enabling culture, quantification, and sequencing of viruses. Concomitantly, water-sensitive paper and fine particle samplers yield respiratory particle counts over a broad size range. Using the MIST, we captured infectious virus from humans experimentally infected with the influenza virus on multiple days post-inoculation. The recovered respiratory particles varied in quantity over three orders of magnitude and contained viral variants also detected in samples from infected individuals. Expulsion of infectious virus was associated with infectious viral load in saliva and nasopharyngeal swabs and with clinical symptoms. These data reveal maintenance of viral diversity in expelled aerosols and suggest heterogeneity among individuals in the magnitude of infectious expulsions, impacting forward transmission potential.
2. Single-cell multiomics uncovers an endothelial mechanosensitive PIEZO1-IL-33 axis driving pulmonary fibrosis.
Integrated single-cell multi-omics of human pulmonary fibrosis and experimental models revealed endothelial PIEZO1 upregulation as a hallmark of fibrotic progression. Endothelial-specific Piezo1 deletion attenuated bleomycin-induced fibrosis, and mechanistic studies linked PIEZO1 to a CAPN2–STAT3–IL-33 pathway, nominating this endothelial axis as a therapeutic target.
Impact: This work mechanistically connects endothelial mechanotransduction to profibrotic IL-33 signaling, providing a concrete, targetable pathway in pulmonary fibrosis.
Clinical Implications: Therapeutic strategies aimed at PIEZO1 activation cascades or IL-33 signaling in endothelium may modulate fibrotic remodeling in interstitial lung diseases.
Key Findings
- Endothelial PIEZO1 is upregulated in human pulmonary fibrosis and in bleomycin/silica models.
- Endothelial-specific Piezo1 knockout significantly reduces bleomycin-induced fibrotic remodeling in male mice.
- PIEZO1 drives a CAPN2-mediated STAT3 phosphorylation pathway that may regulate IL-33 secretion, defining a PIEZO1–CAPN2–STAT3–IL-33 axis.
Methodological Strengths
- Integrated single-cell multi-omics with human specimens and complementary in vivo models.
- Genetic endothelial cell–specific loss-of-function establishing causal involvement.
Limitations
- Murine experiments were performed in male mice; sex-specific effects remain to be tested.
- Translational validation with pharmacologic inhibitors or clinical cohorts is needed.
Future Directions: Evaluate pharmacologic modulation of PIEZO1 or IL-33 in preclinical models, assess sex differences, and validate endothelial glymphatic markers longitudinally in patients with fibrotic lung disease.
Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.
3. Clinical characteristics and molecular epidemiology of KPC-NDM co-producing carbapenem-resistant Klebsiella pneumoniae in China: a multicentre retrospective case-control study.
Among 3012 CRKP isolates, 71 (2.4%) were KPC–NDM co-producers, with pneumonia the most common infection. KN-CRKP infections had higher in-hospital mortality and were linked to prior ceftazidime–avibactam exposure; susceptibility remained high to colistin, cefiderocol, and aztreonam–avibactam. Dominant clones were ST11 and ST307, with global phylogeography indicating pandemic ST11 diversification.
Impact: Defines clinical risk, mortality, clonal dynamics, and actionable susceptibility for dual-carbapenemase CRKP, guiding stewardship and therapy in severe hospital-acquired respiratory infections.
Clinical Implications: For suspected KN-CRKP pneumonia, early consideration of cefiderocol or aztreonam–avibactam is warranted; stewardship should recognize that CZA exposure may select for KN-CRKP.
Key Findings
- Among 3012 CRKP isolates, 2.4% were KPC–NDM co-producers; hospital/ventilator-associated pneumonia was most common among infections (41%).
- KN-CRKP infections had higher in-hospital mortality (46.2% vs 25.6%) with risk factors including diabetes, prior CRO infection treated with CZA, and recent β-lactam/β-lactamase inhibitor use.
- All KN-CRKP were resistant to carbapenems and CZA but remained highly susceptible to colistin (98.6%), cefiderocol (94.4%), and aztreonam–avibactam (100%).
- Dominant clones were ST11 and ST307; global phylogeography showed pandemic ST11 diversification with emerging ST147/ST307 increases.
Methodological Strengths
- Large multicenter isolate collection with linked clinical case-control analysis.
- Comprehensive genomics (WGS, plasmid profiling) integrated with global phylogeography.
Limitations
- Retrospective design with potential residual confounding in outcomes.
- Clinical outcome analysis included a relatively small number of KN-CRKP cases (n=39), limiting power.
Future Directions: Prospective surveillance and interventional studies assessing cefiderocol and aztreonam–avibactam for KN-CRKP pneumonia; infection control targeting high-risk clones (ST11/ST307).
BACKGROUND: KPC and NDM co-producing carbapenem-resistant Klebsiella pneumoniae (KN-CRKP) is an escalating global health threat with limited treatment options. METHODS: Here, we conducted a multicentre retrospective case-control study on KN-CRKP in China (2020-2025), collecting 3012 non-duplicated CRKP isolates, of which 71 (2.4%) were KN-CRKP. For clinical analysis, 39 patients with KN-CRKP infections were identified from 71 isolates and matched in a 1:2 ratio with 78 patients infected by KPC-2-producing CRKP. For global analysis, we retrieved 100,141 genomes from GenBank, of which 662 non-redundant KN-CRKP sequences were combined with our 71 KN-CRKP isolates. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), plasmid transfer and stability, fitness cost, transcriptomics and Bayesian phylogeography were used to investigate evolution mechanisms and molecular epidemiology of KN-CRKP strains. FINDINGS: Among the infected patients, hospital-acquired or ventilator-associated pneumonia was the most common (41.0%, 16/39). Patients with KN-CRKP infections had a non-significantly higher 28-day mortality (38.5%, 15/39) than the KPC-CRKP control group (24.4%, 19/78; p = 0.133), but a significantly higher in-hospital mortality (46.2%, 18/39 vs. 25.6%, 20/78; p = 0.036). Independent risk factors included diabetes, a history of CRO (carbapenem-resistant gram-negative organism) infection treated with ceftazidime-avibactam (CZA) treatment, and recent use of β-lactam/β-lactamase inhibitor combinations. All KN-CRKP isolates were resistant to carbapenems and CZA, but exhibited highly susceptible to colistin (98.6%), cefiderocol (94.4%), and aztreonam-avibactam (100%). The predominant KN-CRKP clones were ST11 (73.2%) and ST307 (15.5%). Global surveillance of 733 global KN-CRKP identified ST11 as a pandemic lineage diverging into China/Brazil subclusters, with emerging clones ST147/ST307 showing post-pandemic increases. Plasmid profiling revealed bla INTERPRETATION: The high mortality and global prevalence of KN-CRKP emphasise the need for enhanced surveillance and infection control globally. FUNDING: National Natural Science Foundation of China (82472323 and 82172306), Zhejiang Province Natural Science Foundation of China (LQN26H200003, LR25H200001, LQN25H200002, MS25H190009), the "Pioneer" and "Leading Goose" R&D Program of Zhejiang Province (2025C02187), the Zhejiang Provincial Medical and Health Technology Project (2025HY0224) and Zhejiang Provincial Disease Prevention and Control Science and Technology Program (2025JK063). We appreciate the statistical support provided by Hui Liu (Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China).