Most Symptoms in PPI Non-Responders Unrelated to Reflux

Up to 60% of patients with gastroesophageal reflux disease (GERD) continue to have symptoms despite proton-pump inhibitor (PPI) therapy.

In these PPI non-responders, GERD symptoms might be driven by non-reflux mechanisms such as visceral hypersensitivity and hypervigilance, a study published in Neurogastroenterology and Motility indicates.

To make this conclusion, the study authors looked at 2 types of belching: gastric belching of swallowed air mixed with stomach contents, which should elicit symptoms, and supragastric belching (aerophagia), a common problem in patients who have GERD and swallow excess air.

They enrolled 78 patients who had persistent GERD symptoms despite PPI therapy, excluding those with previous a history of scleroderma, esophagogastric surgery, or Barrett’s esophagus.

Patients had 3 forms of GERD symptoms: persistent acid reflux (n=7), reflux-sensitive esophagus (n=28), and functional symptoms (n=43).

The researchers looked at acid exposure events that could be expected to trigger reflux, and they found that fewer than 10% of patients experienced symptoms. Risk was only weakly associated with reflux content characteristics; in other words, most symptoms had nothing to do with acid reflux.

More than 85% of patients experienced gastric belches, reflux starting with a gastric belch, and proximal reflux events. Symptomatic supragastric belching with proximal liquid reflux and swallow-induced proximal reflux caused symptoms more often than other forms of reflux.

Both reflux types are voluntary efforts to reduce discomfort. Reflux characteristics were independent of PPI dosing frequency.

Across PPI non-responders, the causes of therapeutic resistance varied. The authors believe medications that reduce reflux events are unlikely to succeed in clinical practice because few reflux events are symptomatic.

For those with supragastric reflux, the authors recommend focusing on reducing hypersensitivity and providing speech therapy to teach patients not to swallow air.