Daily Respiratory Research Analysis

OBJECTIVE: To test the hypothesis that non-invasive high frequency oscillatory ventilation (NHFOV) is more efficacious than nasal continuous positive airway pressure (NCPAP) in reducing invasive mechanical ventilation as primary respiratory support for extremely preterm infants with respiratory distress syndrome. DESIGN: A multicentre, randomised controlled trial. SETTING: Twenty tertiary neonatal intensive care units in China. PARTICIPANTS: 342 extremely preterm infants (gestational age between 24 weeks +0 day and 28 weeks +6 days) with respiratory distress syndrome were enrolled in the study between August 2022 and August 2024. INTERVENTIONS: Participants were randomly allocated to receive NCPAP or NHFOV as primary respiratory support for respiratory distress syndrome. MAIN OUTCOME MEASURES: The primary outcome was treatment failure, defined as the need for invasive mechanical ventilation within 72 hours after birth. RESULTS: Treatment failure within 72 hours occurred in 27 of` 170 infants (15.9%) in the NHFOV group and 48 of 172 infants (27.9%) in the NCPAP group (risk difference -12.0 percentage points, 95% confidence interval -20.7 to -3.4; P=0.007). Treatment failure within seven days was also lower in the NHFOV group (-12.5 percentage points, 95% confidence interval -21.9 to -3.2; P=0.008) compared with the NCPAP group. All observed associations remained significant after sensitivity analysis including study sites and antenatal steroid use. No significant differences were found in any other secondary outcomes between the two groups. CONCLUSIONS: NHFOV appeared superior to NCPAP in reducing the need for intubation when used as a primary respiratory support strategy in extremely preterm infants. Both techniques did not show significant differences in neonatal adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT05141435.

RATIONALE: Early-life lung function trajectories predict long-term respiratory health, including COPD risk. Club Cell protein 16 (CC16) is a key determinant of lung health, with low levels associated with impaired lung development, reduced lung function, and COPD. Cigarette smoking lowers CC16, but it is unknown whether maternal smoking leads to persistent CC16 deficiency from early life, thereby disrupting lung development and predisposing to COPD risk and progression Methods: CC16 expression was analyzed across 4 human cohorts, in plasma samples (COPDGene [n=1,062] and ECLIPSE [n=2,164]), nasal brushings (ALLIANCE [n=63]), and peripheral lung sections (LTRC [n=44]) from participants with and without a history of maternal smoking exposure. Lung histology and respiratory mechanics were assessed in WT and RESULTS: Maternal smoking was linked to reduced circulating and airway CC16 in COPD patients, controls, and a preclinical murine COPD model. In human adults, lower CC16 correlated with accelerated lung function decline and emphysema progression, while in children it was associated with obstructive physiology and early small airway impairment. In both mice and humans, maternal smoking-induced CC16 reduction was accompanied by greater epithelial injury (fibrosis, inflammation, apoptosis, oxidative stress). In murine explants, smoking impaired lung branching, whereas rhCC16 restored branching via α2-integrin binding Conclusions: Maternal smoking reduces CC16 levels, disrupting lung development in ways that predispose to lifelong impairment of lung function and worse COPD outcomes. Defining the mechanisms by which CC16 regulates lung maturation is essential for establishing reliable outcome measures and designing trials aimed at preventing early COPD. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND: The triglyceride-glucose index (TyG) and C-reactive protein (CRP) are key biomarkers on clinical diagnosis, each related to lung dysfunction. However, the relationship of both indexes with the risk of chronic obstructive pulmonary disease (COPD) is still unclear. This study purposes to focus on the individual and joint associations of TyG and CRP levels with COPD risk. METHODS: This cohort study utilized baseline TyG and CRP data from the UK Biobank. Hazard ratios (HRs) and 95% confidence intervals (CIs) for COPD risk associated with TyG and CRP levels were calculated through Cox regression models. Receiver operating characteristic (ROC) curves were conducted to determine the optimal cut-off values for TyG and CRP, which were combined into a joint variable. Kaplan-Meier (KM) method was utilized to analyze cumulative hazard, while joint analysis was employed for evaluating the joint risk. Stratified and sensitivity analyses were also performed to assess the associations within subgroups, and mediation effect of TyG on COPD risk via CRP levels was assessed. RESULTS: This study enrolled 385,523 individuals, with 10,515 COPD cases were recorded in follow-up. Compared to the lowest quintile, individuals with higher TyG and CRP had increased risk of COPD (all HRs > 1.00). The optimal cut-off values of TyG and CRP were 7.14 and 1.88 mg/L, and we found that the simultaneous elevation of both TyG and CRP significantly increased the risk of COPD. Moreover, the joint effect was stronger in participants younger than 60 years old, males, smokers or passive smokers, those with body mass index (BMI) < 25.0 kg/m CONCLUSIONS: These results underscored the individual and joint effects of TyG and CRP upon COPD risk, indicating their usefulness as biomarkers for early risk assessment.