The European Association of Endoscopic Surgery (EAES) states that the two main GORD diagnostic tools are upper endoscopy and long-term impedance esophageal pH monitoring. Indeed, the combined information obtained from clinical symptoms, endoscopy and pH testing is usually considered to be sufficient and specific for the diagnosis of GORD. The EAES also highlight that “…further diagnostic investigations may be needed to verify functional abnormalities and establish the indication for surgery or other invasive therapies.”2 These additional diagnostic tools include high-resolution manometry (HRM), video-radiography and scintigraphy. For patients who have more severe symptoms, such as dysphagia and odynophagia, those who do not respond to acid suppression, or those in whom Barrett oesophagus is suspected, such additional diagnostic tools should be employed.3 Unfortunately, this comes at a sizeable financial cost.
In Germany, the incidence of GORD is high and the associated healthcare costs have been estimated at €4.8 billion.4 In the United States, GORD represents the most common GI-related diagnosis; annually, GORD accounts for 8.9 million patient visits to the clinic and endoscopy exams cost $32.4 billion.5 These budgets emphasize the need for alternative, cheaper diagnostic methods for GORD and, ideally, noninvasive ones. Encouragingly, we might be on the right track with two recently published studies on novel GORD diagnostic tools, namely pepsin detection in saliva and minimally invasive oesophageal mucosal impedance testing.
Several pathological settings may lead to pepsin being found in the laryngeal and paranasal sinus mucosa, saliva, middle ear effusion, tracheal secretions and bronchoalveolar lavage fluid. In their study, Hayat and co-workers sought to determine the value of salivary pepsin for discriminating patients with reflux-related symptoms from those with functional heartburn (FH).6 Pepsin was more likely to be detected in the saliva of patients with GORD and hypersensitive oesophagus (HO) and at higher concentrations than in the saliva of controls or FH patients. As such, the authors propose that salivary pepsin testing may complement GORD diagnosis.6 The fact that salivary pepsin can distinguish between GORD/HO and FH is extremely relevant, as most GORD patients benefit from pharmacological or surgical anti-reflux therapy, whereas FH patients do not. Interestingly, the detection of pepsin in saliva may also help in the diagnosis of laryngopharyngeal reflux (LPR).7 Despite the belief that LPR symptoms primarily result from GORD-related alterations of the laryngeal mucosa by gastric fluids, LPR differs from GORD in symptomatology and treatment modalities. A higher concentration of pepsin and bile acids has also been found in the saliva of patients with early laryngeal cancer than in the saliva of healthy volunteers, suggesting that LPR plays a role in the development of laryngeal carcinoma and might have utility as a disease biomarker.8
The question of how specific pepsin is for the diagnosis of GORD then arises. Indeed, is salivary pepsin diagnosing GORD, LPR or laryngeal carcinoma in development? As it currently stands, the measurement of salivary pepsin seems to represent a quick, cost-effective, noninvasive and simple 'office-based' method for GORD diagnosis, which I believe should be followed or paralleled with other disease-specific methods. Nonetheless, it holds a great value on its own in pinpointing the next step; for instance, the absence of pepsin could be taken as a sign of null or low frequency reflux events.
Ates and co-workers have developed a minimally invasive device to assess oesophageal mucosal impedance as a marker of chronic reflux in GORD, where impedance is measured close to the squamocolumnar junction.9 They found that the impedance values were significantly lower in patients with GORD, with mucosal impedance patterns being identified in patients with oesophagitis at higher levels of specificity and positive predictive values than wireless pH monitoring.9
Despite being a simple method that’s easy to use and provides immediate results, it is unlikely that mucosal impedance will fully replace current GORD diagnosis tools, as it is unable to distinguish between different GORD symptoms or even GORD-related disorders, which require different therapeutic approaches. Still, it represents an excellent strategy to differentiate between GORD and FH, much like salivary pepsin. Though measurement of mucosal impedance is still invasive, the procedure is quick, which makes it attractive for patients who cannot (or will not) tolerate a transnasal probe that must be in place for 24 hours.
Salivary pepsin levels and oesophageal mucosal impedance stand as two recent major breakthroughs in GORD diagnosis, but more are needed. I hope to see a lot of new and exciting discoveries on GORD diagnosis and management this October at UEG Week 2015. In the meantime, please feel free to browse the UEG Education Library for more resources.
- Subramanian CR and Triadafilopoulos G. Refractory gastroesophageal reflux disease. Gastroenterol Rep (Oxf) 2015; 3: 41–53.
- Fuchs KH, Babic B, Breithaupt W, et al. EAES recommendations for the management of gastroesophageal reflux disease. Surg Endosc 2014; 28: 1753–1773.
- Badillo R and Francis D. Diagnosis and treatment of gastroesophageal reflux disease. World J Gastrointest Pharmacol Ther2014; 5: 105–112.
- UEG White Book Brochure [https://ueg.eu/epaper/WhiteBook.Brochure/index.html].
- Medical Economics. Treatment of GERD evolving [May 2013, accessed April 14, 2015].
- Hayat JO, Gabieta-Somnez S, Yazaki E, et al. Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease. Gut 2015; 64: 373–380.
- Ocak E, Kubat G and Yorulmaz I. Immunoserologic pepsin detection in the saliva as a non-invasive rapid diagnostic test for laryngopharyngeal reflux. Balkan Med J 2015; 32: 46–50.
- Sereg-Bahar M, Jerin A and Hocevar-Boltezar I. Higher levels of total pepsin and bile acids in the saliva as a possible risk factor for early laryngeal cancer. Radiol Oncol 2015; 49: 59–64.
- Ates F, Yuksel ES, Higginbotham T, et al. Mucosal impedance discriminates GERD from non-GERD conditions. Gastroenterology2015; 148: 334–343.