Daily Respiratory Research Analysis
Analyzed 231 papers and selected 3 impactful papers.
Summary
Analyzed 231 papers and selected 3 impactful articles.
Selected Articles
1. mRNA delivery of a class 1/4 SARS-CoV-2 neutralizing antibody protects against diverse sarbecoviruses in a lethal mouse challenge model.
Broadly neutralizing RBD-targeting antibodies, particularly class 1/4 bNAbs with long HCDR3 loops, were isolated from a SARS-CoV-2–exposed individual. Five bNAbs neutralized a panel of 18 sarbecoviruses, and Ab401 conferred robust prophylaxis in mice both as a recombinant protein and when delivered via lipid nanoparticle–encapsulated mRNAs.
Impact: Demonstrates a feasible mRNA-based platform for rapid deployment of broadly neutralizing antibodies with cross-variant and cross-species efficacy, directly relevant to respiratory pandemic preparedness.
Clinical Implications: While preclinical, the mRNA delivery of bNAbs suggests a rapid, adaptable prophylaxis/therapeutic strategy for immunocompromised patients and during outbreaks with immune-evasive variants, complementing vaccines and antivirals.
Key Findings
- Isolated 20 RBD-directed bNAb lineages; 13 targeted conserved class 1/4 or class 4 epitopes with long HCDR3 loops (IGHD3-22 usage).
- Five bNAbs potently neutralized all 18 viruses tested, including SARS-CoV-2 XBB.1.5, JN.1, and diverse non–SARS-CoV-2 sarbecoviruses.
- Ab401 provided robust prophylactic protection in mice as recombinant protein and via lipid nanoparticle–encapsulated mRNAs.
Methodological Strengths
- Breadth of neutralization tested against 18 diverse sarbecoviruses including recent variants.
- In vivo protection demonstrated with both recombinant protein and mRNA-LNP delivery; structural analyses corroborated epitope class.
Limitations
- Preclinical mouse models may not predict human pharmacokinetics, safety, or durability.
- Antibody lineages derived from a single individual may limit generalizability.
Future Directions: Advance to phase 1 studies of mRNA-delivered bNAbs, explore Fc-engineering for half-life and effector modulation, and evaluate cocktail strategies against antigenic drift.
The unyielding antigenic drift of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the threat of future zoonotic sarbecovirus spillovers, has prompted the search for broadly neutralizing antibodies (bNAbs) to inform rational therapeutic and vaccine design. Here, we isolated and characterized 20 receptor binding domain (RBD)-directed bNAb lineages from a serially sampled SARS-CoV-2 patient who was infected and vaccinated during the early months of the pandemic. Thirteen of these targeted the highly conserved, cryptic class 1/4 or class 4 RBD epitopes and had long (18 to 26 amino acid) heavy chain complementarity determining region 3 loops that utilized the IGHD3-22 gene segment. Five bNAbs potently neutralized all 18 viruses in a panel containing SARS-CoV-2 variants up to the recently emerged XBB.1.5 and JN.1 strains as well as diverse sarbecoviruses from other clades. Structural analyses of the Ab401 and Ab568 bNAbs complexed with RBD and Spike trimer, respectively, revealed recognition features in common with other class 1/4 bNAbs. Prophylactic administration of Ab401 as a recombinant protein afforded robust protection against infectious challenge with either SARS-CoV-2_WA1 or a related bat sarbecovirus with zoonotic potential. A similar level of protection was achieved when the heavy and light chains of Ab401 were delivered as lipid nanoparticle-encapsulated mRNAs. These data expand the arsenal of SARS-CoV-2 bNAbs for clinical development and identify mRNA-based antibody delivery as a promising platform for both pandemic preparedness and protection of immunocompromised patients against emerging sarbecovirus variants.
2. International evidence-based recommendations for point-of-care lung ultrasound : 2025 focused update of the 2012 recommendations.
Using a Delphi process and structured review of 1,775 publications since 2012, 21 experts achieved consensus on 83 statements covering PoCUS signs, technique, monitoring, and clinical applications. The update defines when PoCUS can be used as a standalone tool and clarifies integration needs with other imaging and diagnostics.
Impact: Provides contemporary, consensus-based guidance likely to standardize and expand high-value PoCUS use across acute and critical care settings.
Clinical Implications: Offers actionable recommendations for PoCUS acquisition, interpretation, and monitoring, informing protocols for dyspnea, pneumonia, pleural disease, and ventilator management, while highlighting limitations and research gaps.
Key Findings
- Delphi consensus among 21 experts reviewed 1,775 publications (2012–2025) and finalized 83 PoCUS statements.
- Recommendations span ultrasound signs, technical execution, monitoring strategies, and clinical applications as a standalone tool.
- Clarifies the role of PoCUS and its integration with other organ ultrasound and diagnostic modalities, adhering to ACCORD standards.
Methodological Strengths
- Structured Delphi with predefined agreement threshold and ACCORD adherence.
- Comprehensive literature synthesis including original studies, meta-analyses, and guidelines.
Limitations
- Consensus statements may outpace definitive trial evidence in some domains.
- Standalone focus may underrepresent multimodal pathways pending future integration frameworks.
Future Directions: Prospective validation of PoCUS-guided protocols, standardization of training/competency, and trials integrating PoCUS with other imaging and AI decision support.
PURPOSE: Since the publication of the previous consensus document on point-of-care lung ultrasound (PoCLUS) in 2012, new evidence has emerged. This consensus aims to update current recommendations by focusing on the clinical applications of PoCLUS as a standalone tool, while acknowledging that this focused approach represents a necessary preliminary step toward its effective integration with other organ-specific ultrasound examinations and complementary diagnostic modalities. METHODS: A Delphi-based consensus process was conducted under the supervision of a Steering Committee (five voting members) and a Delphi Committee (two non-voting members). Experts were selected according to strict predefined criteria based on highly impactful scientific output and were assigned to specific domains. A structured literature review covering publications from 2012 to 2025 was performed. Statements were drafted, discussed through multiple online rounds, and iteratively refined. Anonymous voting was conducted for each statement using a predefined agreement threshold (80% full agreement); abstentions were excluded from percentage calculations. The process adhered to ACCORD recommendations. RESULTS: Twenty-one experts participated in the entire process. A total of 1775 new publications were reviewed, including 892 original studies, 62 meta-analyses, 38 guidelines, 162 original studies discussed in the first consensus. New statements were developed across multiple domains addressing ultrasound signs, technical aspects, monitoring strategies, and clinical applications of PoCLUS. Consensus was achieved for 83 statements following iterative discussion and voting rounds. CONCLUSION: This updated consensus provides evidence-based recommendations on the use of PoCLUS in clinical practice, defining its strengths and limitations as a standalone tool and identifying areas requiring further investigation.
3. Joint modelling of wheeze and lung function from childhood to early adulthood: four population-based birth cohorts.
Across four population-based cohorts, six joint trajectories of wheeze and FEV1/FVC were identified, revealing a disconnect between symptoms and lung function. Persistent wheeze with reduced lung function (PEW-RLF) linked to perinatal factors and eosinophilic inflammation, while asymptomatic reduced lung function (NIFW-RLF) associated with tobacco exposures and adiposity without inflammatory signals.
Impact: Refines respiratory phenotyping by integrating symptoms and physiology, informing precision prevention and tailored interventions beyond symptom-driven approaches.
Clinical Implications: Supports targeted strategies: anti-inflammatory therapies for PEW-RLF versus environmental and lifestyle interventions for NIFW-RLF; underscores screening for low lung function even without symptoms.
Key Findings
- Identified six joint trajectories of wheeze and FEV1/FVC, including NIFW-RLF and PEW-RLF with distinct risk profiles.
- PEW-RLF associated with prematurity, low birth weight, in utero smoke exposure, high FeNO, bronchodilator reversibility, and atopic family history.
- NIFW-RLF showed similar lung function impairment without inflammatory biomarkers, linked to prenatal tobacco exposure, adolescent smoking, and higher adolescent body fat.
Methodological Strengths
- Large, unselected birth cohorts with longitudinal wheeze and spirometry data, plus replication in independent cohorts.
- Group-based multi-trajectory modeling jointly analyzing symptoms and lung function.
Limitations
- Spirometry measures (FEV1/FVC) may not capture small airway dysfunction or diffusion abnormalities.
- Residual confounding and cohort heterogeneity across eras and geographies.
Future Directions: Extend to biomarker-integrated trajectories (omics, imaging), evaluate intervention responsiveness by phenotype, and implement screening frameworks for asymptomatic low lung function.
BACKGROUND: Wheeze and lung function (LF) during childhood are key indicators of respiratory health, yet their trajectories are usually examined separately. We aimed to identify joint developmental patterns of wheeze and LF. METHODS: We used data from four unselected birth cohorts established between 1989 and 1996 with repeated assessments of wheeze from infancy and spirometry from early school-age to early adulthood. We used group-based multi-trajectory modelling to derive trajectories based on joint modelling of current wheeze and forced expiratory volume in 1 s/forced vital capacity ratio (FEV FINDINGS: In the discovery analysis (n = 4645), we identified 6 trajectories: (1) Never/infrequent wheeze with normal LF (NIFW-NLF, 2925/4645 [62.97%]); (2) Never/infrequent wheeze with reduced LF (NIFW-RLF, 475/4645 [10.22%]); (3) Early-transient wheeze with normal LF (ETW-NLF, 559/4645 [12.03%]); (4) Late-onset wheeze with NLF (LOW-NLF, 335/4645 [7.21%]); (5) Persistent wheeze with NLF (PEW-NLF, 202/4645 [4.34%]); and (6) PEW with RLF (PEW-RLF, 149/4645 [3.21%]). Risk profiles of two trajectories characterised by persistent wheeze but differentiated by normal or reduced LF differed significantly. Elevated fractional exhaled nitric oxide (FeNO) and allergic sensitisation were highly prevalent in both, but only PEW-RLF was significantly associated with perinatal and early-life factors/exposures (prematurity; lower gestational age: RRRs [95% CI] 2.21 [1.49-3.28], low birth weight: 2.60 [1.47-4.60]: and exposure to smoking during gestation: 2.00 [1.49-2.63]). Two low lung function trajectories (with and without symptoms; PEW-RLF and NIFW-RLF) had similar LF impairment, but divergent clinical and risk factor profiles. PEW-RLF was associated with high rates of asthma diagnosis, high FeNO, bronchodilator reversibility, and family history of atopy. In contrast, those in NIFW-RLF trajectory had no elevation in inflammatory biomarkers and low prevalence of airway hyperreactivity, and were characterised by much higher rates of prenatal tobacco smoke exposure, and greater active adolescent smoking (2.06 [1.41-3.01]), and higher body fat mass in adolescence (1.02 [1.01-1.03], p = 0.01) with no difference in birth weight or preterm birth. Replication analyses in independent cohorts (n = 3388) were consistent with the discovery. INTERPRETATION: The disconnect between symptoms and lung function, along with the differences in risk profiles, has important implications for respiratory health intervention strategies. FUNDING: UK MRC grant MR/S025340/1.