Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.

Microbiology and Outcomes of Institutionalized Patients With Stroke-Associated Pneumonia: An Observational Cohort Study.

Background: The attributable mortality and microbial etiology of stroke-associated pneumonia (SAP) vary among different studies and were inconsistent. Purpose: To determine the microbiology and outcomes of SAP in the lower respiratory tract (LRT) for patients with invasive mechanical ventilation (MV). Methods: In this observational study, included patients were divided into SAP and non-SAP based on a comprehensive analysis of symptom, imaging, and laboratory results. Baseline characteristics, clinical characteristics, microbiology, and outcomes were recorded and evaluated. Results: Of 200 patients, 42.5% developed SAP after the onset of stroke, and they had a lower proportion of non-smokers (p = 0.002), lower GCS score (p < 0.001), higher serum CRP (p < 0.001) at ICU admission, and a higher proportion of males (p < 0.001) and hypertension (p = 0.039) than patients with non-SAP. Gram-negative aerobic bacilli were the predominant organisms isolated (78.8%), followed by Gram-positive aerobic cocci (29.4%). The main pathogens included K. pneumoniae, S. aureus, H. influenzae, A. baumannii, P. aeruginosa, E. aerogenes, Serratia marcescens, and Burkholderia cepacia. SAP prolonged length of MV (p < 0.001), duration of ICU stay (p < 0.001) and hospital stay (p = 0.027), shortened MV-free days by 28 (p < 0.001), and caused elevated vasopressor application (p = 0.001) and 60-day mortality (p = 0.001). Logistic regression analysis suggested that patients with coma (p < 0.001) have a higher risk of developing SAP. Conclusion: The microbiology of SAP is similar to early phase of HAP and VAP. SAP prolongs the duration of MV and length of ICU and hospital stays, but also markedly increases 60-day mortality.