I Left My Heart(burn) in San Francisco

Although many people suffer from acid reflux and are treated successfully for it with proton pump inhibitors (PPIs) and other medications, there is a smaller cohort of sufferers whose reflux is not acidic. It is therefore more difficult to both diagnose and treat.

EndoNurse spoke to several manufacturers to find out what tools and technologies are now available to differentiate non-acid reflux from the more familiar acid reflux. Read on to discover more about this uncommon malady.

Causes

"Non-acid reflux can occur in adults who have an incompetent lower esophageal sphincter (LES) and are on acid-suppressive medication, to counteract the damaging effects of acid on the esophagus," says Stans Slaats, global product manager of gastroenterology for Alpine Biomed. "The medication changes the pH of the refluxate, but patients continue to reflux, since the underlying problem (an incompetent LES) still exists. Refluxate can contain pepsin, bile and other potentially damaging substances."

The problem is not limited to adults, she adds. "Non-acid reflux also occurs in infants and children."

"The mechanism of non-acid reflux is no different than that of non-acid reflux," explains Jerry E. Mabary, vice president of Sandhill Scientific, Inc. "Known primary causes of all reflux event types are transient esophageal sphincter relaxations (TLESR) and LES incompetence. In the simplest of terms, all episode types are the result of some mechanism of antireflux barrier incompetence."

Essentially, Mabary adds, the only difference between acid reflux episodes and non-acid reflux episodes is the pH of the refluxate. "In both cases, gastric contents move proximally into the esophagus," he continues.

Non-acid reflux commonly happens in two primary scenarios, he adds. "No. 1, the gastric content is neutralized by the contents of a recently ingested meal. We know that approximately 50 percent of reflux episodes that occur in the first hour of the postprandial time period are non-acid due to meal buffering. No. 2, the gastric content is rendered neutral by an antireflux medication. In a patient with 100 percent acid control during PPI treatment, we would expect all reflux episodes to be non-acid. Please bear in mind that anti-acid medications such as PPI treatments do not stop reflux; they merely block gastric acid production."

Symptoms

Regardless of the acidity, reflux can cause pain, discomfort, and other symptoms.

"The ACG practice guidelines define acid reflux and non-acid reflux as follows:

Acid Reflux = reflux that reduces esophageal pH to below 4 or reflux that occurs when esophageal pH is already below 4

Non-Acid Reflux = esophageal reflux where the pH remains > 7 or increases to > 7

"To define how pH is measured during an ambulatory reflux study, use a pH sensor that measures pH on a scale of 1-8 pH," says Jeff Sawyer, director of marketing and product development for Sierra Scientific Instruments, Inc.

"Symptoms can be similar to acid reflux," Slaats says. "Non-acid reflux can also cause atypical (respiratory) reflux symptoms, such as asthma, chronic cough, or laryngitis. In children and infants, non-acid reflux is associated with breathing and other respiratory problems as well, such as asthma and apnea."

In fact, many children who suffer from asthma often have reflux as an underlying problem, but the reflux is never diagnosed—the child is simply treated for asthma. In an article from the December 2006 Pediatric News, author Damian McNamara writes, "Reflux prompted coughing for more than a third of pediatric patients with asthma in a study, suggesting both acid and non-acid reflux can be important triggers for some patients.¹

"Multiple studies suggest an association between often-undetected gastroesophageal reflux and asthma symptoms in adults; data in children are fewer. However, treatment of reflux with a proton pump inhibitor (PPI) did not improve asthma symptoms in two large adult studies or one prospective pediatric study," he continues.

"While some symptoms, such as heartburn, tend to more frequently be associated with acid reflux, the literature has clearly established that all symptoms traditionally known to be temporally associated with acid reflux can also be temporally associated with non-acid reflux," Mabary explains. "Some symptoms, such as regurgitation and cough, have been shown to be as likely to be associated with non-acid reflux as acid reflux. This suggests that any mechanism of symptom triggering may be multifactorial and is not merely associated with a chemically based response."

According to a study of both acid and non-acid reflux in a cohort of 168 patients, "Empiric proton pump inhibitor (PPI) trials have become increasingly popular, leading to gastroenterologists’ frequently evaluating gastroesophageal reflux disease (GERD) patients only after they have ‘failed’ PPI therapy. Combined multichannel intraluminal impedance and pH (MII-pH) monitoring has the ability to detect gastroesophageal reflux (GER) episodes independent of their pH and evaluate the relationship between symptoms and all types of GER."²

The authors, Mainie et all, used this technique to identify the frequency of both types of reflux and their relationship to typical and atypical GER symptoms in patients on PPI therapy. They found that 69 (48 percent) symptomatic patients had a positive SI for at least one symptom—16 (11 percent) with acid reflux and 53 (37 percent) with non-acid reflux (NAR).

The researchers concluded, "The results of this multicenter study indicate that 37 percent of patients on at least twice-daily PPIs with study day symptoms had a positive SI (symptom index) for NAR. These patients would have been interpreted as negative if they were studied using conventional pH only. We also found that symptoms after acid reflux on at least twice-daily PPI occurred in a minority of patients (11 percent) and 52 percent of patients on at least twice daily PPI with study day symptoms had a negative SI during the 24 hour MII-pH study. This finding is important in the overall management of these patients, as an alternative diagnosis rather than GERD can be sought."

Tools for Diagnosis

"Ambulatory reflux monitoring has benefits and limitations based upon the clinician or specialty group you are speaking with," says Sawyer.

But new products are continually being developed to improve upon previous market offerings. "We are currently launching an ambulatory reflux diagnostic system to detect both acid and non-acid episodes," he says. "Our AccuTrac pH-z system offers many new innovations. These include mainly our software display of data including ‘impedance contour plotting’ and ‘anatomically correct display’ as well as our graphical tools."

Many physicians tend to wait to use these diagnostic tools until after the patient has first tried pharmaceutical intervention. However, that is not the case across the board. "There are several different views as to when these tools should be used," Sawyer says.

"The only current diagnostic tool to detect both acid and non-acid reflux episodes and determine any symptom associations is impedance-pH reflux monitoring," Mabary observes. "This technology has the unique ability to detect all reflux episodes and categorize the acidity of the refluxate. Impedance is used to detect the reflux episodes, and pH is used to categorize acidity; the key is the novel combination of the abilities of impedance and pH sensors into a single monitoring system."

"Impedance detects the movement of refluxate (liquid and gas) into the esophagus and measures how high up into the esophagus the refluxate reaches," Slaats explains. "Bilitec detects the presence of bile in the refluxate (regardless of the pH). Bile has been shown to be a particularly noxious agent that can damage the esophagus through a different mechanism than acid alone. Gastroesophageal scintigraphy can be done, but is expensive and exposes the patient to radiation."

Treatments

Fundoplication surgery can increase the competence of the sphincter, thereby decreasing reflux, Slaats observes. "A number of newer GERD therapies also increase the competence of the sphincter. Oral baclofen has been shown to increase the competence of the sphincter by decreasing transient lower esophageal sphincter relaxations, which means there are fewer unnecessary openings of the sphincter," she says.

Patients who have symptoms only of acid reflux typically achieve symptom relief when they receive properly administered anti-acid based medical treatment, Mabary says. However, he adds, "Patients with ongoing symptoms that are temporally associated with non-acid reflux in an environment of effective acid control require an anti-reflux treatment. The treatment options are fundoplication or an endoscopic antireflux procedure. Early publications demonstrate positive symptom relief outcomes in properly qualified fundoplication patients," he points out.

Costs of Delayed Treatment

The ramifications of delaying diagnosis and treatment are arguable. No one is quite sure exactly how extensive damage might be from non-acid reflux; it’s still a new malady that requires additional research. "[The cost of delayed treatment] is difficult to say, as we are just beginning to understand the consequences of this type of reflux. Some studies even show a possible relationship to SIDS, so detecting this type of reflux is very important. Consequences can be quite serious," Slaats says.

However, Mabary posits, unlike acid reflux, non-acid reflux is not known to be associated with esophageal damage. "The impact of non-acid reflux is therefore specifically related to the significant quality-of-life compromises seen in patients with ongoing symptoms despite effective medical acid control treatment. It is commonly believed that approximately 30 percent of patients taking PPI medications are not happy with their level of symptom relief. When these patients are tested on medication with impedance-pH monitoring, 48 percent are found to have a positive symptom index to non-acid reflux; these are the patients who are candidates for antireflux treatment," he concludes.

Works Cited

1. www.accessmylibrary.com/coms2/summary_0286-29087505_ITM
2. Acid and Non-acid Reflux in Patients with Persistent Symptoms Despite Acid Suppressive Therapy. A Multicentre Study Using Combined Ambulatory Impedance-pH Monitoring; Maine et al; Gut 2006; 55:1398.