In a small, first-in-kind study, functional heartburn or reflux hypersensitivity affected fully 75% of patients whose gastroesophageal reflux disease symptoms had not improved with once-daily proton pump inhibitor therapy.
At the same time, proton pump inhibitor (PPI) responders and nonresponders had similar impedance and pH parameters, reported Jason Abdallah, MD, of Case Western Reserve University, Cleveland, and his associates. The findings show “the important role of esophageal hypersensitivity in this patient population.” For these patients, the investigators suggested adding a neuromodulator and possibly psychotherapy, such as cognitive-behavioral therapy, hypnotherapy, relaxation techniques, mindfulness, and biofeedback.
Symptoms in up to 45% of patients with gastroesophageal reflux disease (GERD) persist despite once-daily PPI therapy, Dr. Abdallah and his associates wrote in Clinical Gastroenterology and Hepatology. For the study, they compared reflux characteristics and patterns between 13 patients whose GERD symptoms had fully resolved on standard once-daily PPIs and 16 patients who reported at least twice-weekly heartburn, regurgitation, or both for at least 3 months, despite treatment. Patients in both groups continued PPIs and underwent upper endoscopy and combined esophageal impedance–pH monitoring.
The average age of patients in this study was 54.5 years, with a standard deviation of 14.5 years. Demographic and clinical characteristics were similar between groups, and patients in both groups were receiving omeprazole, esomeprazole, or pantoprazole. Four (31%) PPI responders had abnormal pH test results, as did four (25%) nonresponders. Responders and nonresponders had similar numbers of reflux events; proportions of events that were acidic, weakly acidic, or alkaline; and mean total time with pH less than 4.0.
Additionally, most patients in both groups had normal endoscopic findings. One PPI responder had Los Angeles grade A erosive esophagitis, and two PPI responders had short-segment Barrett’s esophagus. Three PPI responders and two PPI nonresponders had nonobstructive Schatzki rings, and one PPI nonresponder had an esophageal stricture. Finally, five PPI responders (38%) and three nonresponders (19%) had hiatal hernias (P = .41).
In patients with GERD, “PPI failure” does not reflect a unique pattern of reflux events, acid exposure, or nonacidic reflux parameters, Dr. Abdallah and his associates concluded. The fact that most PPI nonresponders had a concurrent functional esophageal disorder – either reflux hypersensitivity or functional heartburn – “support[s] the hypothesis that PPI failure is primarily driven by esophageal hypersensitivity.”
This was a small study – recruitment “was hampered by the invasive nature of some of the procedures,” they wrote. “In addition, it is our experience that many patients who have responded to PPI [therapy] are reluctant to undergo invasive testing as part of a study protocol. Therefore, we believe that these types of prospective, invasive studies are rather difficult to perform but, at the same time, provide essential insight into the understanding of refractory GERD.”
No external funding sources were acknowledged. The senior author reported ties to Ironwood Pharmaceuticals, Mederi Therapeutics, Ethicon, AstraZeneca, and Takeda. The other researchers reported no conflicts of interest.
SOURCE: Abdallah J et al. Clin Gastroenterol Hepatol. 2018 Jun 15. doi: 10.1016/j.cgh.2018.09.006.