EXPERT ANALYSIS FROM CHEST 2016
LOS ANGELES – The optimal management of gastroesophageal reflux disease in patients with idiopathic pulmonary fibrosis has yet to be determined, according to Joyce S. Lee, MD.
“We need strong randomized clinical trial data to tell us whether or not medical or surgical treatment of GERD in IPF is indicated,” she said at the annual meeting of the American College of Chest Physicians.
Dr. Joyce Lee
Two proposed hypotheses explain the relationship between reflux and IPF. The first holds that reflux and microaspiration are involved in the pathogenesis of IPF. The second, favored by Dr. Lee, proposes that reflux and microaspiration impact the natural history, either through acute exacerbation, disease progression, or survival. Patients with IPF “have weakening of the lower esophageal sphincter, whether that’s due to the presence of a hiatal hernia, medications, or just aging of the tissue there,” she said. “We know how to diagnose reflux disease, but we don’t know how to diagnose microaspiration, which is defined as subclinical aspiration of small droplets of gastric contents. Reflux is a risk factor for the condition of microaspiration, but it is not a perfect surrogate. Not everybody with reflux will aspirate. There is a potential role for bronchoalveolar lavage pepsin and/or bile salt as a biomarker of microaspiration, but it is not validated or standardized in IPF yet.”
Reflux becomes pathologic when reflux of stomach contents causes troublesome symptoms and/or complications. “Troublesome” is defined as mild symptoms 2 or more days a week or moderate to severe symptoms more than 1 day a week. Dr. Lee said that chest physicians can diagnose GERD in their IPF patients the same way that gastroenterologists and primary care doctors do: with symptoms, barium swallow, 24-hour pH monitoring, impedance testing, and sometimes endoscopy. The 2015 IPF guidelines recommend that clinicians “use regular antacid treatment for patients with IPF (conditional recommendation, very low confidence in estimates of effect).” It does not extend to surgical treatment with fundoplication. (Am J Resp Crit Care Med. 2015 Jul 15;192[2]: e3-19).
In an effort to measure the relationship between antacid therapy and change in forced vital capacity, Dr. Lee and her associates evaluated IPF patients from placebo arms of the three Idiopathic Pulmonary Fibrosis Clinical Research Network randomized controlled trials. They found that, compared with patients who did not take antacid therapy at baseline, those who did experienced a slower decline in their forced vital capacity over time (Lancet Resp Med. 2013 Jul;1[5]:369-76). However, a more-recent analysis conducted by different investigators examined the placebo arms of three pirfenidone studies and found no significant effect of antacid therapy in IPF patients (Lancet Resp Med. 2016 May;4[5]:381-9). Dr. Lee said that both evaluations differed because they were secondary analyses of previously captured data. “There were also differences in the ways the trials obtained GERD history, medication indication, and dosing of the antacid therapy,” she said. “There were also differences in outcomes and different populations studied.”
Dr. Lee’s current approach to counseling IPF patients with GERD includes discussing lifestyle modifications and PPI therapy – either daily or twice a day dosing, depending on their symptoms. “Lifestyle modifications include weight loss, smoking cessation, raising the head of the bed 6-8 inches, and avoiding foods that cause acid reflux, including chocolate, alcohol, peppermint, and fatty or spicy foods, and avoiding large and late meals,” she said. “In terms of acid suppression therapy with H2 blockers and PPIs [proton pump inhibitors], symptom relief and healing of the esophagus occurs in 85%-90% of patients taking them correctly. This does not alter their risk of having microaspiration.” Laparoscopic antireflux therapy (fundoplication) is indicated only after the failure of medical therapy. “The goal is to correct any hernia and tighten the lower esophageal sphincter,” she said. “Efficacy and symptom relief is reported to be around 95%.”
An NIH-funded trial called Weighing Risks and Benefits of Laparoscopic Anti-Reflux Surgery in Patients with Idiopathic Fibrosis, is ongoing at six centers. Dr. Lee said that some results are expected within the next year. She reported having no financial disclosures.