Abstract
The histological counterpart of idiopathic pulmonary fibrosis is usual interstitial pneumonia, in which areas of fibrosis of various ages are interspersed with normal lung. This pattern could be explained by repeated episodes of lung injury followed by abnormal wound healing responses. The cause of the initiating alveolar epithelial injury is unknown, but postulated mechanisms include immunological, microbial, or chemical injury, including aspirated gastric refluxate. Reflux is promoted by low basal pressure in the lower oesophageal sphincter and frequent relaxations, potentiated by hiatus hernia or oesophageal dysmotility. In susceptible individuals, repeated microaspiration of gastric refluxate may contribute to the pathogenesis of IPF. Microaspiration of nonacid or gaseous refluxate is poorly detected by current tests for gastroesophageal reflux which were developed for investigating oesophageal symptoms. Further studies using pharyngeal pH probes, high-resolution impedance manometry, and measurement of pepsin in the lung should clarify the impact of reflux and microaspiration in the pathogenesis of IPF.
Highlights
Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and carries a prognosis worse than many cancers
Classical hypotheses regarding the pathogenesis of IPF focused on a chronic inflammatory model leading to fibrosis, but the resulting treatment strategies focusing on anti-inflammatory agents have proven largely ineffective in altering the disease course and mortality [1,2,3]
Short telomeres and telomerase mutations, which may compromise cell renewal capacity in tissues, have been demonstrated in peripheral blood leukocytes in some IPF families and in a subset of sporadic IPF cases [11]. These findings suggest that IPF may be a disorder of lung regeneration, and none of these factors have been found to be either necessary or sufficient to cause the disease in isolation, pulmonary fibrosis may ensue only in response to certain stimuli
Summary
Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and carries a prognosis worse than many cancers. Our understanding of this condition has moved away from the inflammatory model towards a hypothesis focusing on alveolar epithelial injury followed by abnormal tissue repair and aberrant wound healing [4] This model proposes that failure of normal re-epithelialisation following loss of alveolar-capillary basement membrane secondary to lung injury results in cytokine-mediated fibroblast proliferation and subsequent fibrosis. Short telomeres and telomerase mutations, which may compromise cell renewal capacity in tissues, have been demonstrated in peripheral blood leukocytes in some IPF families and in a subset of sporadic IPF cases [11] These findings suggest that IPF may be a disorder of lung regeneration, and none of these factors have been found to be either necessary or sufficient to cause the disease in isolation, pulmonary fibrosis may ensue only in response to certain stimuli. Viruses [12, 13], autoantibodies [14], and chemicals including the reflux and aspiration of acid or nonacid material from the gastrointestinal tract (Figure 1)
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