The overproduction of acid and the associated illnesses linked to hypersecretion have a lifetime prevalence of 25-35% in the United States [1]. Probably, these figures are not very accurate, because (1) in the modern literature there is no unambiguous definition of hydrochloric acid hypersecretion, (2) there is no clear unanimous list of diseases that can be considered acid-dependent diseases, (3) and there is not a guess why almost half of the population of the United States has acid-dependent diseases of the digestive tract and another does not.

In the historical aspect, ideas about the hypersecretion of hydrochloric acid can be divided into two periods. Prior to the introduction of pH monitoring of the esophagus, i.e., almost until the end of the 20th century, all studies argued that gastritis and gastric ulcers, as well as duodenal ulcers, occur mainly because of gastric hypersecretion [2,3,4]. For example, Christie and Ament concluded "that, on the average, hypersecretion of gastric acid does occur in children with duodenal ulcer disease [3]. Uspenski? showed, that an increase in the number of main cells, and parietal cells of the stomach, that are observed in duodenal ulcer and pre-ulcer condition, "they are observed in normal subjects with constitutional hypersecretion of hydrochloric acid and pepsin" [4]. Collen et al concluded "that a subgroup of patients with long-standing symptomatic gastroesophageal reflux disease who do not respond to standard ulcer-healing doses of histamine2-receptor antagonists are hyper secretors of basal gastric acid" [5].

Numerous studies have confirmed the validity of this hypothesis, which stated that acid-dependent diseases occur in individuals with hypersecretion of hydrochloric acid. This hypothesis has become a generally accepted theory, since up to the present day not a single study has been published that contradicts it. It served as the basis for the development and successful use of acid-suppressing drugs. Studies have shown that all people are divided into normally acid-secreting, gastric hyper secretors and hypo secretors [6]. Since the reason for this difference was unknown, it was presented as a constitutional origin [6]. The experiment proved that the damaging power of gastric juice depended not only on the amount of hydrochloric acid, but also on the presence of endogenous pepsin. For example, the intragastric infusion of hydrochloric acid alone and hog purified pepsin failed to produce duodenal ulcers in rats although gastric lesions in the body of the stomach were produced.  However, pooled secretagogue-stimulated gastric juice (with endogenous rat pepsin), infused intragastrical, produced duodenal ulcers in 11 of 12 rats" [7].

During this period, it was believed that healthy people could not have a reflex. Therefore, the very fact of reflux testified to the failure of the antireflux function of the esophageal-gastric junction (EGJ). The detection of reflux in physiological studies, which is an X-ray examination, was considered evidence of a disease that was called gastroesophageal reflux (GER) [8,]. Inflammatory and ulcerative processes in the esophagus, as well as the so-called hiatal hernias (HH), revealed during endoscopic examination, did not raise doubts about the presence of GER [9,10].

The first studies of esophageal pH found that "reflux into the oesophagus of gastric contents of low pH occurs almost as commonly in people without symptoms as in those with symptoms." [11]. Next, you see how practical doctors draw conclusions that contradict the fundamental laws of physiology and common sense. Since it was not possible to differentiate normal from abnormal based on pH monitoring, Patrick concluded that "The oesophageal measurements of pH have a limited use as a diagnostic measure". At the same time, he stated, «Normal people without symptoms of reflux do in fact reflux small quantities of acid into the oesophagus and This 'physiological' incompetence in the upright position is not of great importance" [11]".  On what basis did he declare investigated without reflux symptoms healthy, despite the presence of acid in the esophagus? Why does he not offer other explanations, but categorically states that "physiological" reflux is possible? Perhaps these subjects were healthy, and their reflux appeared due to irritation of the esophagus with a pH probe, which violated the physiology of the EGJ? There is a high probability that they had GERD, since it is known that more than 30% of patients with GERD do not complain of gastrointestinal problems, which will be discussed below. This is even more likely because "an approximate prevalence of GERD of 10%–20% in Europe and the USA" [12]. An analysis of this work indicates that the author had no scientific basis to declare the possibility of physiological reflux, without excluding other options explaining the results of the study.

By the end of the 20th century, revolutionary changes took place in gastroenterology. 1) Thanks to the introduction of acid-suppressing drugs, the number of gastric and duodenal ulcers has sharply decreased. 2) This was facilitated by the introduction of Helicobacter pylori eradication. 3) As well as the widespread introduction of esophagogastroduodenoscopy. It turned out that in most gastroenterological patients, endoscopic studies ? already did not reveal changes in the stomach and duodenum. Therefore, the main attention of gastroenterologists switched to the study of gastroesophageal reflux. Since then, began to study the pH in the esophagus [11,13,14]. 

A new (second) stage in the development of gastroenterology began with the articles by DeMeester et al [15,16].  In 1974 they published an article proposing a normal range for esophageal pH monitoring. It was defined as pH < 4 for 4% of the 24 hours of monitoring 5 cm proximal to the LES. To do this, the authors examined 15 individuals who believed that they had no problems with the digestive system. Since then, this boundary has been called the "DeMeester score", and the proposed method of pH monitoring has long been considered the gold standard for diagnosing gastroesophageal reflux disease.

Any science begins with a precise definition of the boundary of the norm.  However, there is a methodology for scientific research. First, a rigorous selection of healthy individuals based on objective criteria is necessary. Secondly, the study must be standardized and not change the physiology of the organs. Thirdly, it must be planned in accordance with the physiology of the body. Fourth, the reliability of the results obtained should be comparable to the results of the previous gold standard.

First: This study had no theoretical basis. It contradicted both the physiology of the digestive system and the existing ideas in the scientific world, which had not been refuted by any previous research.

• The esophageal-gastric junction (EGJ), like all sphincter zones of the body, is designed to promote a bolus in the cranio-caudal direction and prevent back reflux.
• This axiom was the result of numerous studies, based on which the disease was called "gastroesophageal reflux" (GER) and it was diagnosed in the presence of an episode of reflux during physiological (radiological) examination.
• The authors started a study that a priori suggested that reflux could be physiological, but they had no reason to.

Based on histological studies of Chandrasoma it has been shown that reflux begins in the penetration of hydrochloric acid into the abdominal part of the lower esophageal sphincter (LES), which weakens and opens because of damage. At this moment, acid has not yet entered the esophagus. Acid enters the esophagus in a later period, when the squamo-oxyntic gap increases to more than 25 mm [17, 18]. It follows that reflux as a normal phenomenon, i.e., physiological reflux, can't be. Surprisingly, that Demeester is the co-author of two contradictory views.

Second: Demeester et al defined the "normal" limit based on a survey of 15 controls who denied typical symptoms of reflux disease.

• However, it is known that “Ambulatory 24-hour esophageal pH measurement is the standard for detecting abnormal esophageal acid exposure (AEAE), but it has a false negative rate of 15% to 30%” [19]. So Lemire showed that reflux occurs in more than 25% of asymptomatic patients on x-ray [20]. The overall prevalence of esophageal disorders among health individuals by GI endoscopy was 17.3% [21]. Stel et al stated that "Symptom evaluation is not sufficient to exclude significant gastroesophageal reflux in healthy volunteers" [22].  There was not a single study that was considered the gold standard. Moreover, none of the scientists relied on clinical symptoms in diagnosis. Before 1974, X-ray, manometric, endoscopic and histological examination was used to diagnose reflux disease. Shortly after the introduction of pH monitoring into practice, it became clear that: " the 24-hour intraesophageally pH monitoring may present false negative results that limit overall sensitivity of the test" [23]. 
• Initially GERD is defined in the presence of complaints of heartburn and regurgitation. It is now recognized that a range of extraesophageal symptom may be its sole or accompanying manifestation. For example, voice hoarseness [24], chronic cough, asthma, posterior laryngitis, dental erosion [25,26], and adenoid hypertrophy [27]. Importantly, "Upper gastrointestinal endoscopy and pH monitoring are poorly sensitive for diagnosing reflux in this group of patients' [25].

In a recent review, many years of pH monitoring advocates showed "that DMS (DeMeester score) has some limitations and strengths. Although there is not a single instrument to precisely diagnose GERD in all of its variances, pH monitoring analyzed at the light of DMS is still a reliable method for scientific purposes ..." [28]. This is not a conclusion of supporters, but propagandists of pH monitoring, because if this study is not a reliable diagnostic method, then it cannot be used for scientific research.

Thirdly: Any study must be standardized. It is known that the volume and quality of food affects the volume and quality of gastric juice. Therefore, when examining gastric juice, the patient received a standard breakfast. With 24-hour pH monitoring, the patient is not limited in eating, which affects the results of the study and is a violation of the methodology of science.

Fourth: The study is not physiological, as the presence of a probe in the esophagus affects the physiology of the esophagus and LES.

An analysis of the literature shows that pH monitoring is not a scientifically based method according to any of the main definitions of scientific methodology. It diagnoses only severe forms of GERD, that is, in almost 30% of patients with GERD, pH meter does not detect reflux, and these patients do not receive pathogenetic treatment until they develop a severe form that is difficult to treat.

The misconceptions that have spread and become generally accepted through pH monitoring are hard to list. Here are some of them:

• It is claimed that reflux can be physiological, in connection with which the name of the disease was changed from GER to GERD. There was an idea of transient LES relaxation, which supposedly can be normal.
• The presence of heartburn, as a typical symptom of GERD, with a DeMeester score within the normal range, began to be explained by hypersensitivity of the esophagus. This change is contrary to common sense since the norm for monitoring pH was determined based on typical reflux symptoms.
• Hiatal hernia (HH), which was previously considered evidence of severe GER, is considered predisposing factor for the development of GERD, as GERD in HH is not always confirmed during pH monitoring.
• Due to the low sensitivity of pH monitoring, it is not used to rule out GERD when selecting controls for high-resolution manometry. As a result, those patients who were previously diagnosed with GERD, became known as "esophageal achalasia", "jackhammer esophagus", etc. In these patients with the already weakened LES, the sphincter is crossed with part of the esophagus.
• The idea of hypersecretion of hydrochloric acid has shifted towards specific diseases and syndromes [29] (Figure 1). GERD is not study as one of the acid-dependent diseases, the cause of which is still not understood.

This table does not include the most common acid-dependent diseases (gastritis, duodenitis, esophagitis and ulcers), which implies that these diseases supposedly do not depend on hypersecretion of gastric juice, which contradicts the above scientific data.

Figure 1: Table of etiological classification of gastric acid hypersecretory states (from Osefo et al [24]).

A significant part of the population has hypersecretion of gastric juice, which can cause the so-called acid-dependent diseases of the digestive tract. Timely diagnosis of this condition can prevent the development of the disease or lead to a quick recovery. pH monitoring of the esophagus is designed with multiple methodological flaws. The diagnostic value of this method is very low, and the ideas about the esophageal physiology and the pathophysiology of GERD on its basis, does not correspond to reality. This method and the pathophysiology of GERD need to be re-evaluated.

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