Transient tachypnea of the newborn (TTN) commonly affects near- and full-term infants and often requires respiratory support. The use of nebulized salbutamol to improve respiratory outcomes has been of interest, though its clinical efficacy remains controversial. This systematic review and meta-analysis aimed to evaluate whether nebulized salbutamol improves clinical outcomes in affected infants. We searched PubMed, Scopus, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating the efficacy of nebulized salbutamol in infants with TTN. We used a random-effects model to calculate mean differences (MDs) with 95% confidence intervals (CIs). Twenty-five studies were included in the systematic review, comprising seventeen RCTs for meta-analysis involving 1,317 infants. The analysis showed that salbutamol significantly decreased the duration of respiratory support (MD: -14.85 hours; 95% CI [-25.05, -4.65]; p = 0.004), duration of continuous positive airway pressure (MD: -18.19 hours; 95% CI [-30.03, -6.35]; p = 0.003), duration of oxygen requirement (MD: -24.57 hours; 95% CI [-35.03, -14.10]; p < 0.001), and length of hospitalization (MD: -1.17 days; 95% CI [-1.69, -0.65]; p < 0.001). However, there was no significant decrease in duration of tachypnea (MD: -9.93 hours; 95% CI [-25.42, 5.56]; p = 0.21) or duration of neonatal intensive care unit stay (MD: -0.84 days; 95% CI [-2.62, 0.94]; p = 0.36). Subgroup analysis for respiratory support duration showed no significant effect in infants with clinical score of TTN < 5 (MD: -10.88 hours; 95% CI [-24.48, 2.73]; p = 0.12), while the certainty of evidence for all outcomes was low to very low. Nebulized salbutamol may improve clinical outcomes relevant to the evolution of the disease in TTN infants, with potential benefits in certain subgroups such as those with greater disease severity, though the available evidence is of low to very low certainty. Therefore, our confidence in its efficacy in treating TTN remains limited.

Background: The alveolar epithelial glycocalyx is a layer of glycosaminoglycans (GAGs) and proteoglycans (e.g., syndecan-1) that is located between the apical alveolar epithelium and the surfactant layer. It is degraded in murine models of lung injury and in patients with ARDS. Targeted degradation of the epithelial glycocalyx impairs surfactant function in mice. We sought to determine the relationship between epithelial glycocalyx degradation, pulmonary physiology, and clinical outcomes in patients with ARDS. Methods: We first analyzed the relationship between the concentration of syndecan-1 (a marker of glycocalyx shedding) in directly aspirated pulmonary edema fluid and both lung injury severity and patient outcomes in a retrospective cohort of patients with ARDS or hydrostatic pulmonary edema. Subsequently, we prospectively collected heat-moisture-exchange (HME) filter fluid, a noninvasive approach to distal airspace sampling, at two additional centers and determined the relationships between syndecan-1, respiratory mechanics, patient outcomes, and other established ARDS biomarkers. Results: Airspace fluid syndecan-1 was associated with impaired lung mechanics (static respiratory system compliance and driving pressure), more severe hypoxemia, prolonged mechanical ventilation, and increased mortality. Other airspace biomarkers of lung injury were not associated with lung mechanics. These findings were observed similarly across multiple cohorts, using either directly aspirated pulmonary edema fluid or noninvasively collected HME fluid. Conclusions: Airspace fluid syndecan-1 is associated with the severity of hypoxemia, impaired lung mechanics, and worse clinical outcomes in ARDS patients. These results support further research into therapeutics to restore the integrity of the epithelial glycocalyx in ARDS.

The endothelial glycocalyx depends on Exostosin-1 (Ext1)-mediated heparan sulfate synthesis; however, its endothelial cell-autonomous role in acute inflammation remains unclear. Therefore, we examined the role of Ext1 during acute inflammation. In this study, endothelial-specific Ext1-deficient mice (Ext1flox/flox and VE-cadherin-Cre) were generated, and their response to endotoxin challenge was investigated using transcriptomics and imaging. Transcriptomic profiling revealed downregulation of heparan sulfate- and glycocalyx-related genes, with upregulation of genes associated with immune activation. Fluorescence imaging demonstrated lectin- and heparan sulfate-defined glycocalyx depletion; dextran extravasation confirmed impaired barrier integrity. Ultrastructural analyses demonstrated a near-complete absence of the luminal glycocalyx at baseline in Ext1-deficient lungs. Following lipopolysaccharide administration, Ext1-deficient mice exhibited altered cytokine kinetics, delayed clearance of neutrophils and CD11b+ myeloid cells, increased late-phase macrophage accumulation, and prolonged pulmonary edema, indicating impaired resolution of inflammation. Gene set enrichment analysis revealed upregulated leukocyte transendothelial migration, chemokine signaling, and vascular endothelial growth factor pathways, consistent with a persistently activated endothelial phenotype. Endothelial Ext1 is indispensable for heparan sulfate biosynthesis, endothelial glycocalyx integrity, and timely inflammation resolution. Loss of Ext1 leads to an intrinsically pro-inflammatory endothelial state characterized by impaired heparan sulfate-dependent signaling and dysregulated leukocyte-endothelial interactions, heightened vascular permeability, and prolonged tissue injury. Our findings support glycocalyx-targeted therapy in sepsis, acute respiratory distress syndrome, diabetes-associated inflammation, and other conditions of endothelial vulnerability.

A recent study associated early proliferative or fibrotic diffuse alveolar damage with mortality in acute respiratory distress syndrome. We highlight four interpretive concerns: phenotype status was assigned at biopsy after follow-up began, creating potential immortal-time bias; a single biopsy cannot measure pathological velocity; sparse and imbalanced phase-by-timing cells limit component-specific inference; and concurrent physiological measurements complicate causal interpretation. Until delayed-entry survival and phase-specific sensitivity analyses are reported, the phenotype is better viewed as early advanced-phase histology than evidence of accelerated pathology.