**2. How many people are affected by GERD? we do not know**

There has never been a unifying definition for GERD; consequently, GERD diagnosis has never had a gold standard. Mostly, it is made based on questionnaires in combination with a few additional examinations and tests, including responsiveness to acid-suppressive drugs, esophagogastroduodenoscopy (EGD), and ambulatory reflux monitoring. Weekly heartburn or acid regurgitation is the first indicator of GERD. Heartburn refers to a retrosternal burning sensation that typically occurs after a meal or when in a reclined position, and regurgitation is the backflow of stomach contents into the mouth or throat. However, some GERD patients are asymptomatic. As reported in Europe, 44–46% of the patients with Barrett's Esophagus never showed any sign of heartburn or acid regurgitation [3]. Among those presenting these symptoms, on the other hand, a significant proportion is caused by other pathological conditions rather than GERD. As evidenced in the United Kingdom, only 66% of the patients with heartburn or regurgitation were confirmed to be GERD by endoscopic examination and 24-hr pH monitoring [4]. Likewise, among the real GERD patients, only 49% ever experienced heartburn or

acid regurgitation. Therefore, having GERD symptoms does not necessarily mean having GERD.

In addition to heartburn and acid regurgitation, other less common discomforts can also be connected to GERD, including burping, hiccups, water brash, dysphagia, odynophagia, chronic cough, chronic laryngitis, asthma, nausea, and vomiting. However, these symptoms are often seen in other disorders as well, such as eosinophilic esophagitis [5], functional dyspepsia [6], gastroparesis [7], and coronary artery disease [8].

Nowadays, many acid-suppressive drugs are accessible without prescription. Taking these medications, especially Proton Pump Inhibitors (PPI), can conceal GERD-induced esophageal abnormalities. In such cases, even EGD cannot always identify GERD, but ambulatory esophageal pH monitoring can help to correlate the symptoms with pathological acid exposure. Barium radiographs can also be helpful in the detection of esophagitis, esophageal strictures, hiatal hernia, and esophageal tumors.

All of these factors often make GERD diagnosis difficult. As a result, the exact number of people affected by GERD remains to be a mystery. We can only guess how many GERD people are out there, based on the published data. A recent metaanalysis using the data from January 1, 1947, to June 30, 2018, might be able to give us a general idea. According to this study, the global GERD population is likely to be around 1.03 billion (920,661,200–1,148,796,172), representing 13.98% of the current human population on this planet. To make matters worse, the number is still growing year after year.
