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.

Regeneration of severely damaged lungs using an interventional cross-circulation platform

“…Pepsin, a biomarker of gastric aspiration 49,50 , has recently been linked to allograft injury and bronchopulmonary dysplasia in transplant patients 51 . Pepsin-induced cytotoxicity and release of IL-6 and IL-8 peaks at pH 1.5–2.5 52 . After 12 h of cross-circulation and repeated bronchoalveolar lavage, pepsin concentrations in BAL fluid significantly decreased, pH of BAL fluid normalized to pH > 5, and IL-6 and IL-8 concentrations decreased significantly (Fig.…”

Laryngopharyngeal Reflux and Inflammatory Responses in Mucosal Barrier Dysfunction of the Upper Aerodigestive Tract

“…54 Other tissues of the UAT can also be affected by gaseous reflux due to the large scope of gas diffusion. 57 In recent clinical research, LPR has been correlated with chronic otitis media with effusion (OME), oral soft tissue disorders, chronic rhinosinusitis, and dacryostenosis, 6,[58][59][60] and patients with these diseases show non-specific laryngopharyngeal symptoms, positive results of MII-pH monitoring, or the detection of reflux agents in the secretions. 6,61,62 Although the control of LPR in some of these diseases was considered beneficial, how LPR is involved in the diseases remains uncertain.…”

“…Gastric-duodenal refluxate contains gastric acid, proteases, and bile acids 3,57 and has a pH ranging from 1.5 to 2.0, 3,12,76 which is damaging to the luminal environment of the UAT that normally has a pH of 6.8-7.0. 3,12 In healthy subjects, the amount of refluxate is usually small and can be cleared quickly by their innate defense mechanisms.…”

“…3,12 In healthy subjects, the amount of refluxate is usually small and can be cleared quickly by their innate defense mechanisms. 57 While LPR leads to adverse clinical consequences, the nature of this evolving disease depends on the contents of the gastric refluxate, the duration of exposure, and the activity of the local defense mechanisms of the UAT mucosa.…”

“…Large volumes of gastric acid result in chemical injury to the airway epithelium, while recurrent small-volume reflux may result in chronic injury. 57 Damage to the UAT epithelia by acid reflux might be due to the toxicity of its low pH. 3 Such caustic injury leads to disruption of the mucosal barrier, and the severity of such acid-induced damage depends on the level of exposure.…”