Daily Respiratory Research Analysis
Analyzed 172 papers and selected 3 impactful papers.
Summary
Today’s top respiratory research spans preparedness, precision therapy, and diagnostics: a Cell study maps diverse SARS-CoV-2–related bat coronaviruses with human ACE2-binding potential but attenuated fitness; a JCI Insight paper demonstrates clinically meaningful CFTR rescue using CRISPR base editing delivered by polymeric nanoparticles; and a multicenter RCT shows AI-supported mandibular jaw movement monitoring accelerates obstructive sleep apnea diagnosis and treatment versus polysomnography.
Research Themes
- Zoonotic coronavirus evolution and spillover risk mapping
- Nonviral CRISPR base editing for cystic fibrosis airway epithelium
- AI-enabled home diagnostics to streamline OSA care pathways
Selected Articles
1. Virological characteristics of SARS-CoV-2-related coronaviruses dynamically circulating in Southeast Asia.
Two distinct clades of SARS-CoV-2–related coronaviruses co-circulate in Thai horseshoe bats. One clade binds human ACE2 yet shows reduced fusogenicity, replication, pathogenicity, and transmissibility versus SARS-CoV-2. Recombination and recent geographic movement shape their complex evolutionary dynamics, informing risk assessment and surveillance.
Impact: This study integrates structural, in vitro, in vivo, and phylogeographic analyses to functionally de-risk bat coronaviruses with human ACE2-binding capacity, providing an evidence-based framework for surveillance and pandemic preparedness.
Clinical Implications: Refines priority targets for genomic surveillance, helps calibrate spillover risk, and guides preemptive countermeasure development (e.g., broadly neutralizing antibodies, vaccines) against high-risk sarbecoviruses.
Key Findings
- Identified two SC2r-CoV clades co-circulating in the same bat population in Thailand.
- One clade binds human ACE2 but shows reduced fusogenicity, replication, pathogenicity, and transmissibility compared with SARS-CoV-2.
- Phylogeography and recombination analyses reveal extensive recent geographic movement and inter-lineage recombination shaping evolution.
Methodological Strengths
- Multimodal approach: cryo-EM, pseudovirus, live virus, and hamster transmission/pathogenicity assays.
- Integrated phylogeography and recombination analyses to contextualize evolutionary dynamics.
Limitations
- Findings derive from bat sampling in Thailand; generalizability to other regions and hosts remains uncertain.
- Reduced in vitro/in vivo fitness versus SARS-CoV-2 does not eliminate future adaptation potential.
Future Directions: Expand longitudinal, multi-country bat and intermediate-host surveillance with functional characterization; assess cross-neutralization by broadly neutralizing antibodies and pan-sarbecovirus vaccine candidates.
By sampling horseshoe bats-the reservoir hosts of SARS-CoV-2-related coronaviruses (SC2r-CoVs)-in Thailand, we present two clades of SC2r-CoVs co-circulating in the same bat population. Through a comprehensive set of experimental approaches, including cryo-electron microscopy (cryo-EM), pseudovirus and live virus assays, and hamster experiments, we characterize the virological properties of these new viruses. We show that one of the two clades discovered in this study is able to bind the human angiotensin converting enzyme 2 (ACE2) receptor; however, it exhibits reduced fusogenicity and replication in vitro and lower pathogenicity and transmissibility compared with SARS-CoV-2. Phylogeography and recombination analyses reveal a complex evolutionary history for these viruses characterized by extensive, recent geographic movement and recombination with co-circulating virus lineages. Our findings provide new insights into the diversity of SC2r-CoVs dynamically co-circulating in Southeast Asia as well as the virological characteristics of these viruses relative to SARS-CoV-2.
2. Time to diagnosis and treatment of obstructive sleep apnoea using mandibular jaw movement monitoring versus polysomnography: an open-label, multicentre, randomised, controlled trial.
In a multicentre RCT (n=849), AI-supported mandibular jaw movement monitoring was noninferior to PSG for improving daytime sleepiness at 3 months post-diagnosis and significantly reduced both time to diagnosis and treatment initiation, yielding earlier symptom improvement.
Impact: Demonstrates a scalable, home-based diagnostic pathway for OSA that preserves clinical effectiveness while markedly accelerating care timelines.
Clinical Implications: Health systems can deploy AI-supported MJM monitoring to reduce PSG bottlenecks, shorten time-to-treatment, and expand access—particularly where sleep lab capacity is limited.
Key Findings
- AI-supported MJM monitoring was noninferior to PSG for ESS improvement at 3 months post-diagnosis.
- Significantly shorter time to diagnosis and to treatment initiation with MJM versus PSG.
- Earlier improvement in daytime sleepiness attributable to accelerated diagnostic and treatment pathways.
Methodological Strengths
- Prospective, multicentre randomized controlled design with hierarchical endpoints.
- Pragmatic comparison of at-home MJM versus in-lab PSG in real-world diagnostic pathways.
Limitations
- Open-label design may introduce performance and expectation biases.
- Conducted in France; generalizability and payer adoption may vary by health system.
Future Directions: Health-economic evaluations, stratified efficacy by OSA severity, and integration with telemedicine and PAP adherence optimization.
BACKGROUND: Obstructive sleep apnoea (OSA) is often underdiagnosed, highlighting the need for scalable diagnostic alternatives. The SUNSAS study compared a new device for at-home diagnosis of OSA (artificial intelligence [AI]-supported analysis of mandibular jaw movements [MJM]) with polysomnography (PSG) for time to diagnosis and treatment, and patient-reported outcomes. METHODS: This prospective, multicentre, randomised, controlled, open-label study was conducted in France (October 2021-October 2024). Adults aged 18-80 years with suspected OSA were randomised (1:1) to undergo diagnostic testing using MJM monitoring (Sunrise) or PSG. Primary endpoints were assessed using hierarchical testing: 1. daytime sleepiness (Epworth Sleepiness Scale [ESS] score) at 3 months post-diagnosis and time to diagnosis; 2. time to treatment; and 3. daytime sleepiness at 3 months post-randomisation. Secondary endpoints included quality of life (Short Form-36, Quebec Sleep Questionnaire), work productivity (Work Productivity and Activity Impairment questionnaire), and positive airway pressure therapy adherence at 3 months after treatment initiation. FINDINGS: Of 849 participants randomised (58·7% male, median age 50 years, body mass index 28·0 kg/m INTERPRETATION: OSA diagnosis based on MJM monitoring with AI-supported analysis is noninferior to PSG in reducing daytime sleepiness at 3 months after diagnosis, while significantly accelerating time to diagnosis and treatment initiation, resulting in earlier improvement in daytime sleepiness. FUNDING: Sunrise, with support from the French Ministry of Health through the
3. Base editing and nanoparticle transfection of airway cell types essential for treatment of cystic fibrosis.
CRISPR base editor RNAs corrected a prevalent CFTR splice-site variant (3120+1G>A) in primary airway cells, with scRNA-seq showing broad CFTR transcript recovery and enrichment of ionocytes and goblet cells. Polymeric nanoparticles delivered base editors and achieved clinically meaningful CFTR functional rescue, supporting a scalable nonviral platform.
Impact: Offers a viable nonviral gene-correction strategy for CF patients unresponsive to modulators, bridging mechanistic editing with functional rescue in primary human airway cells.
Clinical Implications: Provides a translational path to in vivo base editing for CF, potentially benefiting the ~10% of patients not eligible for or unresponsive to CFTR modulators.
Key Findings
- Base editor RNAs corrected CFTR 3120+1G>A in primary CF airway cells; scRNA-seq showed increased CFTR transcripts across epithelial cell types with enrichment of ionocytes and goblet cells.
- Polymeric nanoparticles delivered base editors, restoring CFTR function to clinically meaningful levels in immortalized and primary airway cells.
- PNPs delivered GFP RNA to progenitor cells in differentiated airway cultures; vitronectin formed a protein corona in vivo, but preincubation did not enhance delivery.
Methodological Strengths
- Use of primary human CF airway cells with variant-specific correction and single-cell transcriptomic validation.
- Demonstration of functional CFTR rescue using clinically scalable, nonviral polymeric nanoparticles.
Limitations
- Preclinical study without in vivo genome editing efficacy and durability data in humans.
- Off-target editing and long-term safety require comprehensive assessment.
Future Directions: Advance to large-animal and early-phase human studies, optimize PNP tropism and dosing, and perform genome-wide off-target and durability assessments.
Cystic fibrosis (CF) is a life-limiting genetic disorder caused by deleterious variants in the CFTR gene that results in altered mucus impairing the airway epithelia. Durable correction of these variants in airway cells remains a therapeutic challenge for about 10% of individuals unresponsive to CFTR modulators. A common disease-causing CFTR splice site variant, 3120+1G>A, was corrected in primary CF airway cells using base editor RNAs. Single-cell RNA sequencing revealed a remarkable increase in detectable CFTR transcript in most CF airway epithelial cell types resulting in notable enrichment of CFTR-expressing ionocytes and secretory goblet cells. Progenitor basal cell subtypes were edited, but they decreased as a fraction of total cells and CFTR-expressing cells compared with unedited cells. CRISPR base editors delivered by polymeric nanoparticles (PNPs) facilitated functional rescue of CFTR to clinically meaningful levels in immortalized and primary airway cells. PNPs delivered GFP-encoding RNA to progenitor airway cells in fully differentiated airway cultures. Vitronectin was a major component of the PNP corona that formed in vivo, but preincubation with vitronectin did not enhance delivery. Together, these findings validate a scalable, nonviral platform with compelling translational promise for treating CF and other respiratory diseases involving respiratory epithelial cell dysfunction.