Crosstalk between lung and extrapulmonary organs in sepsis-related acute lung injury/acute respiratory distress syndrome

Sepsis-related acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is associated with considerable morbidity and mortality, yet the efficacy of current treatments is limited. Previous studies have predominantly focused on the lung itself as an isolated organ, whereas the role of organ crosstalk in the pathogenesis of sepsis-related ALI/ARDS cannot be overlooked. Meanwhile, neglecting the discussion of heterogeneity in sepsis caused by different sources of infection may be another important obstacle to translating previous studies into clinical efficacy. In this review, we initially delineated the distinctions in pathogenesis between pulmonary and extrapulmonary sepsis-related ALI/ARDS in microbial species, pathogenesis, host response, and clinical manifestations. Additionally, systemic organ crosstalk mechanisms are summarized, including the commonality and specificity of systemic inflammation, lung and gut microbiome, as well as cascade cell injury and death in distant organs. Subsequently, organ crosstalk between lung and extrapulmonary in pulmonary sepsis and extrapulmonary sepsis-related ALI/ARDS are discussed by organs, including immunity, neuroendocrine, metabolism, and so forth. Furthermore, extracellular vesicles represent a promising avenue of research as potential players and targets in organ-lung crosstalk in sepsis. While the complexity of multi-organ interactions and the heterogeneity of septic patients present significant challenges, these issues are expected to be addressed by the emergence of organ-on-a-chip platforms, 3D organoid cultures, and multi-omics techniques.