Pulmonary histopathology in an experimental model of chronic aspiration is independent of acidity

Exp Biol Med (Maywood). 2008 Oct;233(10):1202-12. doi: 10.3181/0801-RM-17. Epub 2008 Jul 18.


Gastroesophageal reflux has become a major health concern in industrialized countries, with drugs aimed at blocking acid production being more frequently prescribed than any other drug. Damage to lung tissue as a result of chronic aspiration of gastric fluid is a primary health risk associated with gastro-esophageal reflux, with such aspiration being suspected in the induction or exacerbation of asthma and other lung diseases. In this study, a rodent model of chronic aspiration was used to characterize the pulmonary histopathology produced by repetitive aspiration events and to investigate the pathologic roles of individual gastric fluid components such as acid and particulate food matter. Rats exposed to chronic aspiration of whole gastric fluid developed a pathology distinct from that of acute lung injury, characterized by granulomatous interstitial pneumonitis with prominent formation of multinucleated giant cells. This pattern of injury could be reproduced with chronic aspiration of particulate food matter and with chronic aspiration of pH-neutralized gastric fluid, but not with chronic aspiration of hydrochloric acid. Thus, since acid-neutralizing therapy is currently the mainstay of treatment for patients with reflux-associated respiratory symptoms, these results strongly suggest that alternative therapeutic approaches aimed at preventing chronic-aspiration induced lung injury may be warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Chronic Disease
  • Cytokines / analysis
  • Disease Models, Animal
  • Gastric Acid / physiology*
  • Gastric Juice / physiology
  • Gastroesophageal Reflux / complications
  • Gastrointestinal Contents
  • Hydrogen-Ion Concentration
  • Lung / pathology*
  • Male
  • Pneumonia, Aspiration / etiology
  • Pneumonia, Aspiration / pathology*
  • Pneumonia, Aspiration / physiopathology
  • Rats
  • Rats, Inbred F344
  • Respiratory Aspiration / complications
  • Respiratory Aspiration / pathology*
  • Respiratory Aspiration / physiopathology


  • Cytokines