Daily Ards Research Analysis

IMPORTANCE: The impact of antenatal corticosteroids (ACS) on bronchopulmonary dysplasia (BPD) in very preterm infants remains controversial, with limited evidence on causal mediation pathways. OBJECTIVE: To evaluate the association between ACS and BPD in very preterm infants and assess whether respiratory distress syndrome (RDS) and invasive mechanical ventilation (IMV) have mediating roles. DESIGN, SETTING, AND PARTICIPANTS: This prospective multicenter cohort study included preterm infants from 28 tertiary centers in China between September 1, 2019, and December 31, 2020. Inclusion criteria were gestational age (GA) less than 30 weeks, admission to the neonatal intensive care unit with 24 hours of birth, and neonatal hospitalization for more than 2 weeks. Analysis was done from April 1 to May 1, 2025. EXPOSURE: Complete or incomplete ACS courses (vs no ACS). MAIN OUTCOMES AND MEASURES: The primary outcome was moderate-to-severe BPD (using National Institute of Child Health and Human Development 2001 criteria) assessed at corrected GA of 36 weeks. Secondary outcomes were severe RDS (grade 3-4) and IMV duration. Regression models adjusted for demographic, pregnancy, and birth characteristics. RESULTS: A total of 1097 preterm infants were enrolled, with median gestational age of 28.71 weeks (IQR, 27.71-29.29 weeks), median birth weight of 1150 g (IQR, 1000-1310 g), and median IMV duration of 2.0 days (IQR, 0.0-7.0 days). Of 1075 infants with available sex data, 599 (56%) were males. A total of 1069 infants had known ACS data; ACS were given in 832 cases (78%), with 518 (48%) receiving complete courses. Moderate-to-severe BPD occurred in 309 of 1097 infants (28%) and severe RDS in 237 of 1085 (22%). Complete ACS courses showed negative associations with risk of moderate-to-severe BPD (adjusted risk ratio [ARR], 0.68; 95% CI, 0.55-0.84), severe RDS (ARR, 0.67; 95% CI, 0.51-0.88), and IMV duration (β, -2.003; 95% CI, -3.391 to -0.614). Significant associations with lower BPD risk were observed in infants with GA of 28 weeks to 28 weeks 6 days (ARR, 0.47; 95% CI, 0.29-0.74), singletons (ARR, 0.67; 95% CI, 0.50-0.88), and vaginal deliveries (ARR, 0.62; 95% CI, 0.46-0.83). Mediation analysis suggested that ACS was associated with reduced risk of BPD (β, -0.050; 95% CI, -0.081 to -0.017) through direct (β, -0.031; 95% CI, -0.061 to -0.001) and indirect (β, -0.019; 95% CI, -0.032 to -0.007) effects, with the latter comprising both single and serial mediation pathways. CONCLUSIONS AND RELEVANCE: In this cohort study of preterm infants, complete ACS courses in high-risk pregnancies were associated with a reduction in neonatal BPD, potentially mediated through multifactorial pathways. Emphasizing the importance of timely ACS completion and postnatal airway management may help optimize neonatal pulmonary outcomes.

BACKGROUND: Neonatal Acute Respiratory Distress Syndrome (NARDS) is a critical contributor to neonatal morbidity and mortality, with a global health burden that varies significantly by region. The Montreux definition provides a unified diagnostic framework; however, a significant clinical paradox exists. A prospective cohort in China reported a NARDS mortality rate of 12.6%, which is notably lower than the 17%-24% reported in a large-scale international prospective study. The underlying reasons for this discrepancy remain to be elucidated, whether due to differences in etiology, clinical practice, or patient demographics. METHODS: The Shenzhen Neonatal ARDS Cohort Study (SZ-NARDS) is a prospective, multicenter observational cohort study spanning from 2025-2028, designed to address this knowledge gap. We will enroll more than 1,000 neonates who meet the Montreux criteria across nine tertiary neonatal intensive care units (NICUs) in Shenzhen, China. Longitudinal data collection includes granular clinical parameters, respiratory support metrics, and multi-modal biospecimens for deep phenotyping and multi-omics profiling. Survivors will undergo rigorous follow-up until 36 months' corrected age, with standardized neurodevelopmental, pulmonary, and growth assessments. RESULTS: The primary objective of this study is to characterize the epidemiology of NARDS in this regional population and to test the following hypotheses: (1) The true incidence, etiology, and mortality rates of NARDS in Shenzhen will differ from existing international and Chinese cohorts, and these differences can be systematically explained by specific clinical and demographic factors. A multi-modal predictive model that integrates early clinical variables with multi-omics biomarkers has the potential to accurately identify neonates at high risk for severe NARDS [oxygenation index (OI) ≥ 16] and long-term adverse outcomes [Area Under the Receiver Operating Characteristic Curve (AUROC) > 0.85]. CONCLUSIONS: The SZ-NARDS cohort is uniquely positioned to resolve a major clinical contradiction in NARDS epidemiology. By integrating deep phenotyping with a longitudinal biobank and advanced machine learning algorithms, this initiative will generate a comprehensive dataset. This dataset will serve to refine existing prognostic models, identify regional disparities in disease biology, and inform the development of precision medicine interventions for this vulnerable population. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier ChiCTR2400093854.

Alcohol use disorder (AUD) predisposes individuals to pneumonia, acute respiratory distress syndrome, and chronic obstructive pulmonary disease, yet the mechanisms underlying alcohol-related lung disease (ARLD) remain unclear. Alveolar type II (AT2) epithelial cells play a central role in ethanol (EtOH) metabolism, surfactant production, alveolar repair, and pulmonary innate immunity. To examine EtOH-mediated effects, immortalized human AT2 cells were treated with 22-130 mM EtOH for 6 h (concentration-dependent) and 65 mM EtOH for 6-72 h (time-dependent). Cytotoxicity, inflammation, surfactant lipid/protein dysregulation, fatty acid ethyl ester (FAEE) formation, cellular stress responses, AMP-activated protein kinase (AMPKα) signaling, and mitochondrial function were analyzed. EtOH disrupted surfactant homeostasis by reducing dipalmitoylphosphatidylcholine and surfactant protein C (SP-C). Importantly, EtOH inactivated AMPKα, downregulated CPT1A (involved in β-oxidation of fatty acids), and upregulated lipogenic proteins ACC1 and FAS, accompanied by increased ER stress markers (GRP78, p-eIF2α, and CHOP). Expression of carboxyl ester lipase (FAEE-synthesizing enzyme) and FAEE levels increased with EtOH exposure, further exacerbating oxidative and ER stress, impairing mitochondrial energetics, ATP production, and AT2 cell function. These findings suggest that EtOH-induced FAEE formation, dysregulation of AMPKα-CPT1A signaling, and surfactant contribute to AT2 cell dysfunction and play a critical role in the pathogenesis of ARLD.