Screening for <b><i>Helicobacter pylori</i></b> in Idiopathic Pulmonary Fibrosis Lung Biopsies

Abstract

Background: Increasing evidence suggests a role of gastro-oesophageal reflux (GER) in idiopathic pulmonary fibrosis (IPF) pathogenesis. Recently, an association between serum Helicobacter pylori (HP) antibody positivity and more severe disease was described, but HP has not been directly analysed in lung tissue so far. Objective: To investigate the presence of HP in the lung tissue of IPF patients. Methods: Two tertiary interstitial lung disease care centre databases were screened for available lung biopsy material from IPF patients. Clinical and radiological data, including presence of GER and antiacid medication, were evaluated. HP-specific PCR was carried out on the IPF lung biopsy specimens. Results: A total of 39 IPF patients were included, of whom 85% were male. The patients' median age was 66 years, their vital capacity was 79% predicted, and their diffusing capacity for carbon monoxide was 53% predicted. In all, 82% of the lung biopsies were surgical and 18% transbronchial. Comorbidities were GER disease in 23% (n = 9), sleep apnoea in 13% (n = 5) and hiatal hernia in 38% of the cases (n = 15). Proton pump inhibitors were prescribed at the time of biopsy in 21% of the cases (n = 9). After a median follow-up of 25 months (range 6-69), there were 1 death, 1 lung transplantation and 8 acute exacerbations without relevant differences between the GER and non-GER subgroups. HP DNA was not detected in any of the lung tissue samples. Conclusion: The fact that no HP DNA was detected in the lung tissues calls into question the proposed relevance of HP to the direct pathogenesis of IPF.

Gastroesophageal Reflux Disease in Idiopathic Pulmonary Fibrosis: Uncertainties and Controversies

“…Abnormally prolonged TLESRs create an enlarged hypotensive area at the esophagogastric junction, which results in an increased reflux of gastric contents and gas. Patients with IPF have a hiatal hernia that may impair the structure and function of LES [10, 20, 21, 22, 27, 29, 35, 38], and are characterized with lower LES pressure and upper esophageal sphincter pressure, esophageal peristalsis, and more proximal and distal acid reflux, as compared with healthy controls [10, 30, 33, 34]. Other studies have shown that LES pressure and esophageal peristalsis are preserved in patients with IPF, indicating that TLESR, rather than defective LES, may mainly contribute to GER in IPF [28].…”

“…In vitro studies have revealed that bile acids, pepsin, and Hp VacA endotoxin may induce cytotoxic and inflammatory responses or epithelial-mesenchymal transition in lung epithelial cells or fibroproliferative responses in lung fibroblasts [48-50]. Controversially, however, Hp appears to be insignificantly present in the lungs of patients with IPF, as demonstrated by the analysis of DNA, histopathology of lung biopsies, and serological detection of Hp antibody [9, 38, 51]. The potential cellular and molecular mechanisms involving microaspiration in IPF are outlined in Figure 2.…”

Gastroesophageal Reflux in Idiopathic Pulmonary Fibrosis: More than a Gut Feeling?

“…While there are many potential explanations for the findings of Kreuter et al [10] that have little to do with the relationship of gastroesophageal reflux-induced microaspiration and IPF (e.g. perhaps there was no microaspiration occurring at the time of biopsy, or there was no H. pylori in the microaspirate at the time of biopsy), it is worth using this interesting study as a cautionary chapter in the ongoing story of gastroesophageal reflux and IPF.…”

“…In this issue of Respiration , Kreuter et al [10] apply an interesting approach in order to shed more light on the relationship between gastroesophageal reflux, in particular nonacid reflux, and IPF. Their approach was original; they investigated whether H. pylori -containing microaspiration could be involved in IPF pathogenesis by performing PCR screening for H. pylori DNA in lung biopsy specimens of IPF patients.…”

“…In the light of the recent ATS guidelines that suggest gastroesophageal reflux therapy be considered for use in IPF, this message needs to be heard loud and clear. Kreuter et al [10] should be commended for addressing this issue and for incorporating the nonacid component of reflux in their hypothesis. It is crucial that we prospectively study the impact of both acid and nonacid reflux in patients with IPF and test interventions such as proton pump inhibition (that treats primarily acid reflux) and gastric fundoplication (that treats both).…”