Daily Respiratory Research Analysis
Analyzed 86 papers and selected 3 impactful papers.
Summary
Analyzed 86 papers and selected 3 impactful articles.
Selected Articles
1. A modular three in one mucosal vaccine against three antigenic clusters of ACE2 using sarbecoviruses.
The authors mapped sarbecovirus RBD antigenicity into three clusters and created a single intranasal immunogen (3Rs-NC) carrying representatives of each. With a flagellin-derived mucosal adjuvant, the vaccine elicited robust systemic and mucosal immunity and protected mice against SARS‑CoV‑2 Omicron BA.1 and SARS-like viruses (WIV1, rRsSHC014S), with greater efficacy in females.
Impact: This study advances a modular, needle‑free, broad‑spectrum mucosal vaccine platform against current and emerging ACE2‑using sarbecoviruses, addressing a critical pandemic preparedness gap.
Clinical Implications: If safety and efficacy translate to humans, an intranasal, cross‑protective vaccine could complement or replace strain‑matched injectables, improve uptake, and provide upper airway sterilizing immunity for outbreak control.
Key Findings
- Antigenic mapping of sarbecovirus RBDs revealed three distinct clusters and enabled a single “three‑in‑one” immunogen design (3Rs‑NC).
- Intranasal 3Rs‑NC with a flagellin‑derived mucosal adjuvant induced strong serum IgG, mucosal IgA, and potent neutralization.
- KFD‑adjuvanted 3Rs‑NC protected mice in upper and lower airways against Omicron BA.1 and WIV1, and conferred survival against lethal rRsSHC014S challenge with better efficacy in females.
Methodological Strengths
- Rational immunogen design grounded in antigenic landscape mapping
- Robust in vivo efficacy across multiple heterologous viral challenges and compartments (upper/lower airways)
Limitations
- Preclinical mouse data; translatability to humans is unproven
- Manufacturing, stability, and sex‑based immune response differences require further investigation
Future Directions: Evaluate safety, dosing, durability, and breadth in non‑human primates; perform sex‑stratified immunogenicity; advance to GMP production and early‑phase clinical trials.
The recurrent emergence of ACE2‑using sarbecovirus underscores the need for a broadly protective vaccine. Here, we mapped the antigenic landscape of sarbecovirus receptor-binding domains (RBDs) and identified three distinct clusters. We then engineered a single "three‑in‑one" immunogen, 3Rs-NC, incorporating representative RBDs from each cluster into a single scaffold. Intranasal administration of 3Rs-NC with a flagellin-derived mucosal adjuvant (KFD), which possess excellent safety profile potential for clinica
2. Phosphoglycerate dehydrogenase-mediated serine reprogramming aggravates macrophage hyperinflammation in murine Pseudomonas aeruginosa pneumonia.
PHGDH fuels de novo serine synthesis to augment one‑carbon metabolism, which enhances H3K27me3–DUSP4 interaction and drives ERK1/2 phosphorylation, amplifying macrophage hyperinflammation in P. aeruginosa pneumonia. Myeloid PHGDH deletion and dietary L‑serine restriction improved survival, reduced lung injury, and lowered bacterial burden in mice.
Impact: This work uncovers a metabolism‑epigenetics axis linking serine/one‑carbon metabolism to MAPK signaling in bacterial pneumonia, revealing druggable targets (PHGDH, serine metabolism) for hyperinflammation.
Clinical Implications: Targeting PHGDH or modulating serine availability could complement antibiotics to dampen hyperinflammation in severe Gram‑negative pneumonia; translational studies and safety profiling are needed.
Key Findings
- PHGDH identified as a key mediator of macrophage hyperinflammation during P. aeruginosa infection.
- Pharmacologic/genetic PHGDH inhibition suppresses cytokine production; myeloid PHGDH deletion improves survival, reduces lung injury, and bacterial load in murine pneumonia.
- Serine/one‑carbon metabolism enhances H3K27me3–DUSP4 interaction, promoting ERK1/2 phosphorylation and inflammatory amplification; dietary L‑serine restriction improves outcomes.
Methodological Strengths
- Convergent pharmacologic, genetic, and dietary interventions with in vivo validation
- Mechanistic linkage from metabolism to epigenetics and MAPK signaling
Limitations
- Findings are preclinical and derived from murine models; human validation is lacking
- Potential off‑target or systemic effects of serine restriction and PHGDH inhibition require safety assessment
Future Directions: Assess PHGDH/serine‑pathway biomarkers in human pneumonia, test PHGDH inhibitors with antibiotics, and delineate cell‑specific effects and safety in higher mammals.
Metabolic reprogramming in immune cells can determine the outcome of pathogen infection. For Pseudomonas aeruginosa, a clinically challenging pathogen, it remains unclear whether the host can exploit this strategy to combat bacterial invasion. Here, we identify phosphoglycerate dehydrogenase as a key mediator of macrophage inflammation during Pseudomonas aeruginosa infection. Pharmacological and genetic inhibition of phosphoglycerate dehydrogenase suppress macrophage hyperactivation and the producti
3. Effects of Inspiratory Muscle Training on Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.
Across 10 RCTs, inspiratory muscle training improved sleep quality, daytime sleepiness, inspiratory strength, oxygen nadir, FVC% predicted, systolic blood pressure, and BMI, but did not reduce AHI. IMT should be considered an adjunct to standard OSA therapies to improve patient‑centered outcomes.
Impact: Clarifies that IMT benefits key patient‑reported and physiological outcomes without altering event frequency, refining OSA management by identifying where IMT adds value.
Clinical Implications: IMT can be incorporated into sleep and cardiopulmonary rehabilitation programs for OSA to improve symptoms, fitness, and blood pressure, while CPAP/primary treatments remain necessary to control AHI.
Key Findings
- Significant improvements with IMT in PSQI (−3.15), ESS (−3.18), MIP (+25.54 cmH2O), LSaO2 (+2.86%), FVC% predicted (+17.20%), SBP (−6.63 mmHg), and BMI (−1.48 kg/m2).
- No significant change in AHI compared with controls, indicating limited impact on event frequency.
- Heterogeneity driven by protocol differences and baseline severity; sensitivity analyses supported robustness for several outcomes.
Methodological Strengths
- Focus on randomized controlled trials with comprehensive outcome set
- Assessment of heterogeneity and sensitivity analyses with credible intervals
Limitations
- Total sample size remains modest across small RCTs; adherence and protocol variability may influence effects
- Lack of AHI reduction limits IMT as a standalone OSA therapy
Future Directions: Standardize IMT protocols, identify responsive phenotypes, and test IMT as part of multimodal rehabilitation alongside CPAP with longer‑term outcomes.
RATIONALE: Inspiratory muscle training (IMT) is a relatively new intervention for obstructive sleep apnea (OSA) with the aim of improving respiratory muscle strength and mitigating OSA-related symptoms. However, its effects on key clinical endpoints remains unclear. OBJECTIVES: To evaluate the effects of IMT on OSA severity, sleep quality, respiratory function, and cardiovascular outcomes. METHODS: We systematically searched PubMed, EMBASE, CENTRAL, and Web of Science for randomized control trials (RCTs) assessing IMT in adults with OSA. Studies assessed IMT versus control/placebo with outcomes, including the apnea-hypopnea index (AHI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), maximal inspiratory pressure (MIP), lowest oxygen saturation (LSaO2), blood pressure (BP), and body mass index (BMI). RESULTS: Ten RCTs (166 IMT vs. 157 control participants) found significant improvements in OSA with IMT across multiple domains. The intergroup difference in mean BMI reduction (mean difference [MD], -1.48; 95% credible interval [CI], -2.39 to -0.57), mean PSQI gain (-3.15; -3.69 to -2.62), mean LSaO2 gain (2.86; 1.01 to 4.71), mean ESS reduction (-3.18; -4.50 to -1.87), mean MIP gain (25.54; 11.09 to 40.00), the percentage of predicted values for forced vital capacity (FVC) (FVC%) predicted gain (17.20; 9.53 to 24.87), and mean systolic blood pressure (SBP) reduction (-6.63; -13.26 to -0.00) indicated the benefit of IMT over the control therapy. However, there was no significant improvement in AHI (1.00; -2.57 to 4.56). Heterogeneity primarily stemmed from differences in intervention protocols and baseline disease severity among the patients. CONCLUSIONS: IMT resulted in clinically meaningful symptomatic benefits across OSA phenotypes by enhancing respiratory strength, sleep quality, and cardiovascular health. However, the lack of significant improvement in AHI suggests that IMT may not impact primary pathophysiological markers of OSA. Thus, IMT may be an adjunctive intervention, rather than a primary therapy, for reducing event frequency in OSA.