Pathogenesis of influenza-induced acute respiratory distress syndrome

• Published in: The Lancet infectious diseases Vol. 14; no. 1; pp. 57 - 69
• Main Authors: Short, Kirsty R, PhD, Kroeze, Edwin J B Veldhuis, DVM, Fouchier, Ron A M, Prof, Kuiken, Thijs, Prof
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 2014; Lancet Publishing Group; Elsevier Limited
• Subjects: Biological and medical sciences; Endothelial Cells - pathology; Endothelial Cells - physiology; Epithelial Cells - pathology; Epithelial Cells - physiology; Epithelial Cells - virology; Human viral diseases; Humans; Immune System - physiology; Immune System - physiopathology; Infectious Disease; Infectious diseases; Influenza, Human - complications; Medical sciences; Nitric oxide; Pneumology; Respiratory Distress Syndrome, Adult - pathology; Respiratory Distress Syndrome, Adult - physiopathology; Respiratory system : syndromes and miscellaneous diseases; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Infection; Respiratory disease; Pathogenesis; Viral disease; Acute; Influenza; Respiratory distress
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(13)70286-X

Summary Acute respiratory distress syndrome (ARDS) is a fatal complication of influenza infection. In this Review we provide an integrated model for its pathogenesis. ARDS involves damage to the epithelial–endothelial barrier, fluid leakage into the alveolar lumen, and respiratory insufficiency. The most important part of the epithelial–endothelial barrier is the alveolar epithelium, strengthened by tight junctions. Influenza virus targets these epithelial cells, reducing sodium pump activity, damaging tight junctions, and killing infected cells. Infected epithelial cells produce cytokines that attract leucocytes—neutrophils and macrophages—and activate adjacent endothelial cells. Activated endothelial cells and infiltrated leucocytes stimulate further infiltration, and leucocytes induce production of reactive oxygen species and nitric oxide that damage the barrier. Activated macrophages also cause direct apoptosis of epithelial cells. This model for influenza-induced ARDS differs from the classic model, which is centred on endothelial damage, and provides a rationale for therapeutic intervention to moderate host response in influenza-induced ARDS.