Daily Respiratory Research Analysis
Analyzed 178 papers and selected 3 impactful papers.
Summary
Analyzed 178 papers and selected 3 impactful articles.
Selected Articles
1. GPR81 Activation by Lactate Delays Inflammation Resolution in Acute Lung Injury.
In LPS-induced acute lung injury, exogenous lactate increased neutrophil infiltration and inflammatory mediators, delaying inflammation resolution and worsening tissue damage. Using GPR81-deficient mice and primary alveolar macrophages, the study implicates GPR81-dependent lactate signaling as a driver of impaired resolution.
Impact: This mechanistic study links clinical hyperlactatemia to delayed resolution of lung inflammation via a defined receptor pathway (GPR81), providing a potential therapeutic target for ARDS.
Clinical Implications: Targeting lactate signaling or GPR81 may accelerate inflammation resolution in ARDS. Monitoring and managing lactate levels could have pathophysiologic relevance beyond perfusion status.
Key Findings
- Exogenous lactate delayed inflammation resolution and worsened lung injury in an LPS-induced ARDS model.
- Lactate exposure increased neutrophil infiltration and inflammatory factor levels.
- GPR81-deficient mice and in vitro studies with alveolar macrophages support a GPR81-dependent mechanism.
Methodological Strengths
- Use of both in vivo (WT vs GPR81-deficient mice) and in vitro primary alveolar macrophage systems.
- Multiple orthogonal readouts (flow cytometry, histology, inflammatory mediators) to assess resolution and injury.
Limitations
- Preclinical LPS-induced injury may not fully recapitulate heterogeneous human ARDS etiologies.
- Therapeutic window and safety of modulating GPR81 or lactate in humans are unknown.
Future Directions: Evaluate pharmacologic GPR81 antagonism or lactate-modulating strategies in additional lung injury models and early-phase clinical studies; delineate effects on efferocytosis and resolution pathways.
Acute respiratory distress syndrome (ARDS) involves impaired macrophage function in clearing apoptotic cells. The link between clinical hyperlactatemia in ARDS patients and poor outcomes prompted this study on the immunometabolic role of lactate in disease progression. In an LPS-induced ARDS mouse model, mice received either exogenous lactate or a lactate dehydrogenase inhibitor. Inflammatory cell infiltration was evaluated through flow cytometry and histological analysis with hematoxylin and eosin staining. Lactate signaling was confirmed in GPR81-deficient mice. In vitro, lactate metabolism during efferocytosis was studied using primary Alveolar Macrophages (AMs). Lactate accumulation, neutrophil infiltration, and elevated inflammatory factors were observed in this ARDS model. External lactate delayed inflammation resolution and worsened lung injury. GPR81
2. Efficacy of High-Flow Nasal Cannula Oxygen Therapy During Bronchoscopy: A Systematic Review and Meta-Analysis.
Across 11 RCTs (n=1714), HFNO versus conventional oxygen significantly reduced intraprocedural hypoxemia and procedure interruptions during bronchoscopy, while increasing nadir SpO2 without prolonging procedure time. The protocol was PROSPERO-registered, and benefits appear greatest in high-risk patients.
Impact: Provides high-certainty, procedure-focused evidence that can standardize periprocedural oxygenation strategies during bronchoscopy.
Clinical Implications: Adopt HFNO selectively for patients at high risk of hypoxemia during bronchoscopy to reduce desaturation and interruptions, while updating procedural protocols and resource planning.
Key Findings
- HFNO reduced intraprocedural hypoxemia versus COT (RR 0.39, 95% CI 0.26–0.59).
- HFNO reduced bronchoscopy interruptions (RR 0.39, 95% CI 0.27–0.55).
- HFNO increased nadir SpO2 by 4.5% (95% CI 3.02–5.99) without prolonging total procedure time.
Methodological Strengths
- Systematic review and meta-analysis of 11 RCTs with 1714 participants
- PROSPERO-registered protocol (CRD420251071548) and predefined outcomes
Limitations
- Heterogeneity in patient risk profiles, sedation techniques, and procedural contexts across trials
- Limited data on long-term outcomes or cost-effectiveness of routine HFNO use
Future Directions: Head-to-head RCTs in predefined high-risk subgroups and implementation studies evaluating workflow, cost-effectiveness, and oxygen resource utilization.
BACKGROUND: Bronchoscopy frequently precipitates intraprocedural hypoxemia. Although several recent randomized controlled trials suggest that high-flow nasal cannula oxygen (HFNO) reduces intraprocedural hypoxemia during bronchoscopy, the overall certainty of this evidence remains insufficient. Hence, we performed a systematic review and meta-analysis to compare the efficacy of HFNO with that of conventional low-flow oxygen therapy (COT) during adult bronchoscopy. METHODS: MEDLINE, Embase, and trial registries were searched for randomized controlled trials (RCTs) involving adults (18 y or older) undergoing bronchoscopy that compared HFNO with COT. The primary outcome was the incidence of hypoxemia during the procedure. The key secondary outcomes were total procedure time, bronchoscopy interruption, and lowest intraprocedural peripheral oxygen saturation. The pooled risk ratios (RRs) or mean differences (MDs) were calculated, and the certainty of evidence was assessed. The protocol was registered with PROSPERO (CRD420251071548). RESULTS: Eleven RCTs (12 study arms) comprising 1714 participants met the inclusion criteria. HFNO was found to significantly reduce the incidence of hypoxemic events compared with COT (RR: 0.39, 95% CI: 0.26-0.59) and lowered the likelihood of procedure interruption (RR: 0.39, 95% CI: 0.27-0.55). HFNO also maintained a higher nadir SpO2 (MD=4.5%, 95% CI: 3.02-5.99). No statistically significant difference was observed in the total procedure time (MD: -0.87 min, 95% CI: -1.99 to 0.25). CONCLUSION: This meta-analysis showed HFNO reduces the incidence of intraprocedural hypoxemia and interruptions during bronchoscopy. Our findings support a selective approach, suggesting the benefits of HFNO are greater in high-risk patients.
3. Geographical and racial and/or ethnic disparities in pediatric ARDS mortality in the USA, 2016-2022: a triennial national database retrospective cohort analysis.
Using the Kids’ Inpatient Database across 2016, 2019, and 2022, pediatric algorithm-defined ARDS affected ~42,000 hospitalizations annually with mortality ~13% and increasing prevalence over time. Adjusted models show persistent and clinically significant regional and racial/ethnic mortality disparities, especially among Black children in the South and West.
Impact: This national analysis quantifies contemporary disparities in PARDS mortality, providing actionable targets for equity-focused quality improvement and policy.
Clinical Implications: Health systems should anticipate higher risk among specific regional and racial/ethnic groups and deploy targeted resources, standardized ARDS care bundles, and access initiatives.
Key Findings
- Algorithm-defined pediatric ARDS prevalence rose from 0.68% (2016) to 0.75% (2022) nationally.
- Overall in-hospital mortality remained high (~13%) and increased from 2019 to 2022.
- Adjusted mortality was higher for Black children in the South (ARD 3.27%) and West (ARD 3.69%), and for some Hispanic and Other groups by region.
Methodological Strengths
- Large, nationally representative database with mixed-effects modeling and adjustment for illness severity and chronic conditions.
- Joint modeling of geography and race/ethnicity to estimate adjusted mortality and risk differences.
Limitations
- Algorithm-defined ARDS is a surrogate and may misclassify PARDS using administrative codes.
- Observational design limits causal inference; potential residual confounding and coding bias.
Future Directions: Link clinical registries with administrative datasets to refine case definitions; develop and test equity-focused care bundles and access pathways in high-risk regions.
BACKGROUND: Disparities in pediatric critical care outcomes are recognized, but national data describing Pediatric Acute Respiratory Distress Syndrome (PARDS) prevalence, mortality and temporal trends are limited. We described prevalence, and regional and racial/ethnic mortality disparities for algorithm-defined ARDS, a surrogate for PARDS in US children from 2016 to 2022. METHODS: We performed a retrospective cohort study using the 2016, 2019, and 2022 Kids' Inpatient Database (KID). Algorithm-defined ARDS was identified with an ICD-10 approach requiring acute respiratory failure from pulmonary, sepsis, or shock etiologies requiring invasive mechanical ventilation ≥24 h. The primary outcome was in-hospital mortality. Exposures were US region and Race/Ethnicity, modeled individually and jointly. Mixed-effect logistic regression models, adjusting for income quartile, APR-DRG severity of illness, hospital type, and complex chronic conditions, estimated adjusted mortalities and risk differences. FINDINGS: Algorithm-defined ARDS occurred in about 42,000 hospitalizations per year, with prevalence increasing from 0.68% (95% CI 0.67-0.69) in 2016 to 0.75% (0.74-0.75) in 2022. Overall mortality was 12.9% (12.5-13.3) in 2016, 12.5% (12.1-12.9) in 2019, and 13.7% (13.3-14.1) in 2022. In the joint model, relative to Northeastern White children (predicted 10.9%, 95% CI 9.72-12.1), risks were higher for Black children in the South (predicted 14.2%, ARD 3.27%, 1.74-4.79) and West (14.6%, ARD 3.69%, 1.39-6.00); Hispanic children in the West (12.6%, ARD 1.70%, 0.09-3.31), and children of Other race/ethnicity in the South (16.5%, ARD 5.57%, 3.14-7.99) and West (14.0%, ARD 3.11%, 0.96-5.25). Disparities did not meaningfully change from 2016 to 2019, while mortality increased from 2019 to 2022. INTERPRETATION: Algorithm-defined ARDS among hospitalized US children remains common and highly fatal. Persistent regional and racial/ethnic disparities highlight systemic drivers of inequity and the need for targeted interventions. FUNDING: This work was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health (Award K23HL177271, PI: Keim).