PPI-Resistant Severe Reflux Esophagitis Reduces Saliva Secretion

CG image of highlighting the esophagus inside a man’s chest with stomach and small intestines. Other internal organs are faded on a black background.
Investigators examined saliva secretion and salivary epidermal growth factor in patients with proton pump inhibitor-resistant severe reflux esophagitis.

Patients with proton-pump inhibitor (PPI)-resistant severe reflux esophagitis had reduced saliva pH and secretion volumes. These case-control study findings from a single institution were published in Esophagus.

Investigators recruited patients with PPI-resistant (n=22) or PPI-responsive (n=22) severe reflux esophagitis from the Nippon Medical School Hospital in Japan between 2018 and 2020. They defined PPI-resistance as no response after 8 weeks of PPI intervention. All patients were in remission from PPI or vonoprazan therapies. Patients underwent a saliva secretion test, esophagogastroduodenoscopy, and high-resolution manometry.

Patients who were PPI-resistant and PPI-responsive were a median age of 76 and 66 years (P =.1242), 7 and 16 were men (P =.0148), median body mass index was 21.1 kg/m2 and 24.3 kg/m2 (P =.0128), and 7 and 1 had collagen disease (P =.0459), respectively.

Patients who were PPI-responsive secreted a median saliva volume of 4.9 (interquartile range [IQR], 4-7.8) mL, with a pH of 7.2 (IQR, 7.1-7.4) before and 6.4 (IQR, 6.1-6.5) after acid loading. The PPI-resistant cohort secreted a lower volume (median, 3.7 [IQR, 2.2-6.8] mL; P =.029), with a decreased pH before (median, 6.9 [IQR, 6.7-7.2]; P =.001) and after (median, 5.6 [IQR, 5.3-5.9]; P =.002) acid loading.

The majority of the responsive patients were categorized as having a high acid-buffering capacity (n=21) compared with half of the resistant group (n=11; P =.0032).

In the saliva samples with sufficient quantity, epidermal growth factor was significantly higher among the patients who were PPI-resistant (median, 3211.5 [IQR, 1865-4121.5] pg/mL) compared with those patients who were PPI-responsive (median, 1816 [IQR, 1123.5-2792.3] pg/mL; P =.041).

During esophagogastroduodenoscopy, no significant variations were observed nor were mucosal breaks identified.

These findings were limited by a study design that included only a single saliva secretion stimulation and decision not to assess each patient multiple times.

The study authors concluded that patients with PPI-resistant severe reflux esophagitis had decreased saliva secretion, which resulted in a reduction of swallowing frequency and acid-buffering capacity.

Disclosure: One author declared industry affiliations. Please refer to the original article for a full list of disclosures.


Tanabe T, Koeda M, Kitasako Y, et al. Stimulated saliva secretion is reduced in proton pump inhibitor-resistant severe reflux esophagitis patients. Esophagus. Published online February 15, 2021. doi:10.1007/s10388-021-00825-1