The role of gastroesophageal reflux in idiopathic pulmonary fibrosis

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Abstract

Fibroblast foci are indicative of idiopathic pulmonary fibrosis and appear to be a cellular attempt to repair the damaged alveolus. Although this progressive, often fatal, clinical syndrome is thought to be dependent on alveolar injury of unknown origin, significant clinical and preclinical evidence points to gastric acid as a causative harmful agent. Graded instillation of various forms of acid in several animal models resulted in aspiration-induced lung injury, including pulmonary fibrosis in pigs. Moreover, compelling clinical data suggest that a high percentage of patients with idiopathic pulmonary fibrosis also experience abnormal esophageal acid exposure, without necessarily experiencing the typical symptoms of gastroesophageal reflux disease (GERD). Aggressive, long-term therapeutic trials of patients with GERD and evaluation of the therapeutic effects on pulmonary disease will allow determination of the real influences of abnormal esophageal acid exposure in the development of idiopathic pulmonary fibrosis.

Section snippets

Histology

Histologic features of idiopathic pulmonary fibrosis include the presence of patchy, nonuniform, and variably distributed interstitial changes at low magnification, as demonstrated by Katzenstein and Myers3 (Figure 1). Histologic variation, with alternating sections of interstitial fibrosis, inflammation, honeycomb changes, and normal lung tissue, is characteristic. Fibrosis consists of eosinophilic collagen, which thickens alveolar septa and forms patchy ridges. Honeycomb changes are

Preclinical evidence

Preclinical evidence of acid aspiration–induced lung injury dates back several decades. In 1952, investigators reported that the degree of lung tissue response (pneumonia, inflammation, fibrosis) in rabbits increased with increasing volume of instilled acid and as pH decreased from 2.5 to 1.5.4 Shortly thereafter, data were reported from a dog model displaying a chemical pneumonitis related to acid damage.5 Gastric juice was found to have rapid distribution in the lung, moving to the periphery

Clinical evidence

A Veterans Administration case-control study (N = 101,366) was conducted from 1981 to 1994, in which subjects with sinus, pharyngeal, laryngeal, and pulmonary diseases were compared with controls without esophagitis or esophageal stricture. Multivariate logistic regression analysis demonstrated that erosive esophagitis was associated with a number of respiratory diseases, including chronic bronchitis, asthma, pneumonia, and, notably, an odds ratio (OR) for pulmonary fibrosis of 1.36 (95%

Gastroesophageal reflux in patients with idiopathic pulmonary fibrosis

To investigate prospectively the possible association of GER and idiopathic pulmonary fibrosis, Tobin et al.17 studied 17 consecutive subjects with biopsy-proven idiopathic pulmonary fibrosis. Along with 8 controls with interstitial lung disease, these study subjects underwent dual-channel, ambulatory esophageal pH monitoring. Sixteen of the 17 subjects had abnormal distal and/or proximal esophageal acid exposure, compared with 4 of 8 controls (P = 0.02). Additionally, for study subjects, the

Conclusion

Evidence concerning the pulmonary implications of GER appears to be mounting. Compelling data indicate that a high percentage of patients with idiopathic pulmonary fibrosis also experience abnormal esophageal acid exposure. Additional outcomes-based studies and therapeutic trials are needed to clarify the association between, and the mechanisms of, GER and lung disease. Considering the high mortality rates associated with idiopathic pulmonary fibrosis, evolving clinical knowledge concerning

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