Daily Respiratory Research Analysis

IMPORTANCE: Effective lung aeration is crucial for successful postnatal transition. Goal targets to achieve lung aeration during positive pressure ventilation have not been established for preterm neonates. OBJECTIVE: To identify respiratory parameters associated with successful lung aeration during delivery room resuscitation. DESIGN, SETTING, AND PARTICIPANTS: This multicenter prospective cohort study was conducted from March 2016 to April 2021. The primary population included preterm neonates from 3 centers of 22 weeks to 31 weeks 6 days' gestation with bradycardia who received positive pressure ventilation during resuscitation after birth. An independent population of preterm neonates (24 weeks to 27 weeks 6 days' gestation) in the multicenter Monitoring Neonatal Resuscitation randomized clinical trial served as a confirmatory dataset. Data were analyzed January 2022 to May 2025. EXPOSURES: Rolling means of pressure, inspiratory and expiratory tidal volumes (VTE), and mask leak, as measured with a respiratory function monitor (RFM). Counts of spontaneous breaths between inflations and mask removal instances. MAIN OUTCOMES AND MEASURES: The primary outcome was a sustained increase in heart rate to at least 100 beats per minute, indicating effective lung aeration, within the first 10 minutes of resuscitation. Associations between clinical covariates, respiratory parameters, and heart rate increase were examined using cause-specific Cox proportional hazards regression models. RESULTS: There were 132 neonates in the primary dataset (median [IQR] gestation, 26.6 [25.1-29.2] weeks; 67 [50.8%] male) and 115 in the confirmatory dataset (median [IQR] gestation, 26.7 [25.6-27.4] weeks; 65 [56.5%] male). Of 132 primary dataset participants, 125 (94.7%) achieved the primary outcome. Among the measured respiratory parameters, only VTE was associated with an increase in heart rate (adjusted hazard ratio [AHR], 1.10 [95% CI, 1.01-1.20]). The AHR was higher for increases in VTE up to 4 mL/kg (AHR, 1.55 [95% CI, 1.20-2.00]) than for VTEs higher than 4 mL/kg (AHR, 1.04 [95% CI, 0.98-1.10]). These results were consistent with those in the confirmatory dataset: an association for an increase in heart rate with VTE values up to 4 mL/kg (AHR, 1.31 [95% CI, 1.01-1.70]) but not higher than 4 mL/kg (AHR, 1.02 [95% CI, 0.96-1.08]). Other covariates associated with an increase in heart rate included birth weight (per 100 g) (AHR, 1.12 [95% CI, 1.05-1.20]) and mask removal count (AHR, 0.83 [95% CI, 0.70-0.98]). CONCLUSIONS AND RELEVANCE: This cohort study observed in one neonatal population and confirmed in another that a minimum VTE of 4 mL/kg was associated with successful lung aeration as assessed by an increase in heart rate to at least 100 beats per minute during preterm neonate resuscitation. These results may inform future studies to determine the clinical impact of incorporating data-based targets for delivery room resuscitation of preterm neonates.

BACKGROUND: Patients with asthma are at risk of airflow obstruction due to small-airway dysfunction (SAD), which responds poorly to current therapies. VESTIGE (NCT04400318) was a phase 4 study that evaluated the impact of dupilumab on airway inflammation using spirometry, airway oscillometry, and functional respiratory imaging. OBJECTIVE: We sought to evaluate the effect of dupilumab on SAD in moderate to severe asthma. METHODS: Patients with moderate to severe asthma and blood eosinophils greater than or equal to 300 cells/μL and fractional exhaled nitric oxide greater than or equal to 25 parts per billion at screening were randomized 2:1 to dupilumab 300 mg every 2 weeks or matched placebo for 24 weeks. SAD-related secondary and exploratory end points were change from baseline over time in prebronchodilator and postbronchodilator forced expiratory flow at 25% to 75% of forced vital capacity (FEF RESULTS: Of 109 patients, 72 received dupilumab and 37 received placebo. At week 24, dupilumab versus placebo nominally significantly improved prebronchodilator FEF CONCLUSIONS: Dupilumab improved SAD in patients with moderate to severe asthma.

Dendritic cells (DCs) play a critical role in the development of acute lung injury (ALI) / acute respiratory distress syndrome (ARDS), but the underlying mechanisms remain poorly understood, due to their heterogeneous phenotype and function. In this study, a novel DC subset is defined in mice, Ly6C⁺ cDC2, which corresponds to CD14⁺ cDC2 in humans. These subsets highly express C-X-C motif chemokine receptor 1 (Cxcr1) and exhibit pro-inflammatory effects during ALI. Ex vivo, Ly6C⁺ cDC2s release higher levels of Il-6 and Il-1β, thereby promoting naïve T cells to differentiate into Th17 cells. Notably, Cxcr1 deficiency reduced the release of Il-6 and Il-1β from Ly6C⁺ cDC2s and shifted naïve T cells toward Treg differentiation, resulting in a decreased Th17/Treg ratio. In vivo, adoptive transfer of Ly6C⁺ cDC2s increased the Th17/Treg ratio in the lungs and spleens of LPS-treated mice, exacerbating lung injury. Specific depletion of Cxcr1 in DCs significantly reduced the severity of ALI and mortality. Mechanistically, it is found that Cxcr1 regulates the expression of Il-6 and Il-1β in Ly6C⁺ cDC2s through the MEK1/ERK/NF-κB pathway. Collectively, pro-inflammatory Ly6C⁺ cDC2s are identified as key effector cells mediating the role of Cxcr1 signaling in modulating T cell differentiation, driving the progression of ALI.