American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2024
Randomized Controlled TrialImpact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.
Rationale: Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high-dose early active mobilization. Objectives: To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial. Methods: All TEAM trial patients were included. ⋯ In patients receiving high-dose early mobilization, the number of days alive and out of the hospital at Day 180 was 73.0 (0.0-144.5) in patients with diabetes and 146.5 (95.8-163.0) in patients without diabetes (P value for interaction = 0.108). However, in patients with diabetes, high-dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio, 3.47; 95% confidence interval, 1.67-7.61; P value for interaction = 0.001). Conclusions: In this secondary analysis of the TEAM trial, in patients with diabetes, a high-dose early mobilization strategy did not significantly decrease the number of days alive and out of the hospital at Day 180, but it increased 180-day mortality.
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Am. J. Respir. Crit. Care Med. · Sep 2024
Neuromedin-U Mediates Rapid Activation of Airway Group 2 Innate Lymphoid Cells in Mild Asthma.
Rationale: In asthma, sputum group 2 innate lymphoid cells (ILC2s) are activated within 7 hours after allergen challenge. Neuroimmune interactions mediate rapid host responses at mucosal interfaces. In murine models of asthma, lung ILC2s colocalize to sensory neuronal termini expressing the neuropeptide neuromedin U (NMU), which stimulates type 2 (T2) cytokine secretion by ILC2s, with additive effects to alarmins in vitro. ⋯ Coculturing with alarmins upregulated NMUR1 in ILC2s, which was attenuated by dexamethasone. NMU-stimulated T2 cytokine expression by ILC2s, maximal at 6 hours, was abrogated by dexamethasone or specific signaling inhibitors for mitogen-activated protein kinase 1/2 and phosphoinositol 3-kinase but not the IL-33 signaling moiety MyD88 in vitro. Conclusions: The NMU/NMUR1 axis stimulates rapid effects on ILC2s and may be an important early activator of these cells in eosinophilic inflammatory responses in asthma.
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Am. J. Respir. Crit. Care Med. · Sep 2024
Single-Cell RNA Sequencing Reveals Repair Features of Human Umbilical Cord Mesenchymal Stromal Cells.
Rationale: The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD. ⋯ Moreover, scRNA-seq identified major histocompatibility complex class I as a molecular marker of nontherapeutic cells and associated with decreased lung retention. Conclusions: UC-MSCs with a progenitor-like transcriptome, but not with a fibroblast-like transcriptome, provide lung protection in experimental BPD. High expression of major histocompatibility complex class I is associated with reduced therapeutic benefit. scRNA-seq may be useful to identify subsets of MSCs with superior repair capacity for clinical application.