Acid reflux and idiopathic pulmonary fibrosis: the search for definitive answers

It remains elusive whether interventions aimed at controlling acid reflux may influence the evolution of lung fibrosis. ‘Now, the time has come to search for evidence’, says Professor Wim Wuyts (University Hospital Leuven, Belgium) in an editorial of the European Respiratory Journal.

Does the treatment of acid reflux in patients with idiopathic pulmonary fibrosis (IPF) provide any benefit with respect to IPF? This question has occupied researchers for years. Fact is that there is ample epidemiological evidence for increased prevalence of acid reflux in IPF and other fibrotic disorders. Clinical and experimental data also suggest that chronic repeated acid exposure to the lower airways and alveoli may contribute to the fibrotic process in the lung. In addition, data suggest that occult aspiration may play a role in some cases of acute exacerbation of IPF. All these findings indeed support the hypothesis that treating acid reflux may influence IPF behaviour. So why not start treating acid reflux in patients with IPF immediately?

‘Evidence of efficacy of acid reflux treatment has yet to be made', explains Wuyts. 

Studies that evaluated the effect of antacid therapy demonstrate conflicting results. Antacids are substances that neutralize the acidity of the stomach. 'But these studies with antacids were retrospective', says Wuys, 'and not randomised for antacid therapy or stratified for imbalances in comorbidities. Only prospective randomised controlled studies will have the potential to answer definitively to the question of antacid therapy in IPF patients.’ Because treatment with antacids like proton pump inhibitors and H2 receptor antagonists does not suppress acid reflux, surgical correction of abnormal  acid reflux may be an appropriate treatment for patients with IPF to minimise further insults to the lung by acid reflux.

Interesting findings about this kind of treatment were reported in the same issue of the European Respiratory Journal. Researcher Rangu and colleagues report results from a study proving laparoscopic anti-reflux surgery (LARS) to be safe in a series of 27 IPF patients with worsening symptoms and pulmonary function, despite antacid therapy. Laparoscopic surgery is a modern surgical technique in which operations are performed through small incisions. There were no acute exacerbations of IPF in the post-operative period and no deaths in the 90-day period after LARS. In addition, the procedure effectively controlled GOR. A trend toward FVC stabilisation was observed, although the rate of FVC decline pre- and post-LARS was not statistically different.

This study seems to be promising, but Wuyts has more than one critical comment about it. Among other limitations, the study was uncontrolled and the patients were highly selected, as evidenced by young age and relatively preserved lung function. 'There is still an urgent need for adequately powered prospective and controlled trials to determine whether GOR-targeted therapy, either surgical or medical, is useful for IPF patients', concludes Wuyts. 

References:
Wuyts W and Crestani B. Gastro-oesophageal reflux and idiopathic pulmonary fibrosis: in search of evidence. Eur Respir J 2016; 48: 623–625
Raghu G, Morrow E, Collins BF, et al. Laparoscopic anti-reflux surgery for idiopathic pulmonary fibrosis at a single