Gastric Aspiration and Its Role in Airway Inflammation

Abstract

Gastro-Oesophageal Reflux (GOR) has been associated with chronic airway diseases while the passage of foreign matter into airways and lungs through aspiration has the potential to initiate a wide spectrum of pulmonary disorders. The clinical syndrome resulting from such aspiration will depend both on the quantity and nature of the aspirate as well as the individual host response. Aspiration of gastric fluids may cause damage to airway epithelium, not only because acidity is toxic to bronchial epithelial cells but also due to the effect of digestive enzymes such as pepsin and bile salts. Experimental models have shown that direct instillation of these factors to airways epithelia cause damage with a consequential inflammatory response. The pathophysiology of these responses is gradually being dissected, with better understanding of acute gastric aspiration injury, a major cause of acute lung injury, providing opportunities for therapeutic intervention and potentially, ultimately, improved understanding of the chronic airway response to aspiration. Ultimately, clarification of the inflammatory pathways which are related to micro-aspiration via pepsin and bile acid salts may eventually progress to pharmacological intervention and surgical studies to assess the clinical benefits of such therapies in driving symptom improvement or reducing disease progression.

Keywords: Cytokines; Epithelium; Inflammation; Lung Injury; Medicine; Reflux.

Fig. (1)

Gastric aspiration and the complex inflammatory cascade in airway epithelium and endothelium. Direct and indirect pathways when exposed to acid environment as well as the parallel pathways involving pepsin and bile salts, ultimately leading to endothelial damage, and acute and chronic lung injury. TNF- α (Tumour necrosis factor-α), IL-8 (Interleukin-8), MIP-2 (macrophage inflammatory protein), CINC2 (Cytokine-induced neutrophil chemoattractant), MCP (Monocyte chemotactic protein), CCL2 (chemokine (C-C motif) ligand), TGF-β (Transforming growth factor), NADPH (Nicotinamide adenine dinucleotide phosphate), and NFR-2 (Nuclear factor (erythroid-derived 2)-like 2).