T. V. K. Herregods

Pathophysiology of gastroesophageal reflux disease: new understanding in a new era

The prevalence of gastroesophageal reflux disease (GERD) has increased in the last decades and it is now one of the most common chronic diseases. Throughout time our insight in the pathophysiology of GERD has been characterized by remarkable back and forth swings, often prompted by new investigational techniques. Even today, the pathophysiology of GERD is not fully understood but it is now recognized to be a multifactorial disease. Among the factors that have been shown to be involved in the provocation or increase of reflux, are sliding hiatus hernia, low lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, the acid pocket, obesity, increased distensibility of the esophagogastric junction, prolonged esophageal clearance, and delayed gastric emptying. Moreover, multiple mechanisms influence the perception of GERD symptoms, such as the acidity of the refluxate, its proximal extent, the presence of gas in the refluxate, duodenogastroesophageal reflux, longitudinal muscle contraction, mucosal integrity, and peripheral and central sensitization. Understanding the pathophysiology of GERD is important for future targets for therapy as proton pump inhibitor‐refractory GERD symptoms remain a common problem.

Normative values in esophageal high-resolution manometry.

Esophageal high‐resolution manometry (HRM) has rapidly gained much popularity worldwide. The Chicago Classification for esophageal motility disorders is based on a set of normative values for key metrics that was obtained using one of the commercially available HRM systems. Thus, it is of great importance to evaluate whether these normative values can be used for other HRM systems as well.

Patients with refractory reflux symptoms often do not have GERD.

In patients with typical reflux symptoms that persist despite proton pump inhibitors (PPIs) it is sometimes overlooked that treatment fails due to the presence of other disorders than gastroesophageal reflux disease (GERD). The aim of this study was to determine the underlying cause of reflux symptoms not responding to PPI therapy in tertiary referral patients.

Diagnostic yield of 24-hour esophageal manometry in non-cardiac chest pain

In the past, ambulatory 24‐h manometry has been shown useful for the evaluation of patients with non‐cardiac chest pain (NCCP). With the diagnostic improvements brought by pH‐impedance monitoring and high‐resolution manometry (HRM), the contribution of ambulatory 24‐h manometry to the diagnosis of esophageal hypertensive disorders has become uncertain. Our aim was to assess the additional diagnostic yield of ambulatory manometry to HRM and ambulatory pH‐impedance monitoring in this patient population.

Determinants of reflux-induced chronic cough

Objective Gastro-oesophageal reflux is considered to be an important contributing factor in chronic unexplained cough. It remains unclear why some reflux episodes in the same patient causes cough while others do not. To understand more about the mechanism by which reflux induces cough, we aimed to identify factors which are important in triggering cough. Design In this multicentre study, 49 patients with reflux-associated chronic cough were analysed using 24-hour pH-impedance-pressure monitoring. The characteristics of reflux episodes that were followed by cough were compared with reflux episodes not associated with cough. Results The majority (72.4%) of the reflux episodes were acidic (pH<4). Compared with reflux episodes that were not followed by cough, reflux episodes that were followed by a cough burst were associated with a higher proximal extent (p=0.0001), a higher volume clearance time (p=0.002) and a higher acid burden in the preceding 15 min window (p=0.019) and higher reflux burden in the preceding 30 min window (p=0.044). No significant difference was found between the two groups when looking at the nadir pH, the pH drop, the acid clearance time or the percentage of reflux episodes which were acidic. Conclusions The presence of a larger volume of refluxate and oesophageal exposure to reflux for a longer period of time seems to play an important role in inducing cough, while the acidity of the refluxate seems to be less relevant. This helps explain the observation that most patients with chronic cough tend not to benefit from acid inhibitory treatment.

Effect of Running on Gastroesophageal Reflux and Reflux Mechanisms

OBJECTIVES:Reflux symptoms are common among athletes and can have a negative impact on athletic performance. At present, the mechanisms underlying excess reflux during exercise are still poorly understood. The aim of this study was to investigate the effect of exercise on reflux severity and examine the underlying reflux mechanisms.METHODS:Healthy sporty volunteers were studied using both high-resolution manometry and pH-impedance monitoring. After a meal and a rest period, subjects ran on a treadmill for 30 min at 60% of maximum heart rate, followed by a short rest period and another 20-min period of running at 85% of maximum heart rate.RESULTS:Ten healthy volunteers were included. Exercise led to a significantly higher percentage of time with an esophageal pH<4 and a higher frequency and duration of reflux episodes. Moreover, exercise resulted in a decrease in contractility and duration of peristaltic contractions. The minimal lower esophageal sphincter resting pressure decreased during exercise, whereas the average and maximum abdominal pressure both increased. Importantly, the percentage of transient lower esophageal sphincter relaxations (TLESRs) that resulted in reflux significantly increased during exercise and all but one reflux episode occurred during TLESRs. In six subjects a hiatus hernia was detected during the exercise period but not during rest.CONCLUSIONS:Running induces gastroesophageal reflux almost exclusively through TLESRs. These are not more frequent during exercise but are more often associated with a reflux episode, possibly due to increased abdominal pressure, body movement, a change in esophagogastric junction morphology, and a decreased esophageal clearance during exercise.

Jackhammer esophagus: Observations on a European cohort

With the advent of high‐resolution manometry (HRM), a new diagnosis, jackhammer esophagus, was introduced. Little is known about this rare condition, and the relationship between symptoms and hypercontractility is not always straightforward. The aim of our study was to describe a large cohort of patients with jackhammer esophagus and to investigate whether manometric findings are associated with the presence of symptoms.

Determinants of the Association between Non-Cardiac Chest Pain and Reflux

Objectives:Gastroesophageal reflux is considered to be the most common gastrointestinal cause of non-cardiac chest pain (NCCP). It remains unclear why some reflux episodes in the same patient cause chest pain while others do not. To understand more about the mechanisms by which reflux elicits chest pain, we aimed to identify factors which are important in triggering chest pain.Methods:In this multicenter study, 120 patients with NCCP were analyzed using 24-h pH-impedance monitoring. In the patients with a positive association between reflux and chest pain, the characteristics of the reflux episodes which were followed by a chest pain episode were compared with chest pain-free reflux episodes.Results:Using 24-h pH-impedance monitoring, 40% of the NCCP patients were identified as having reflux as a possible cause of their chest pain. Reflux episodes that were associated with chest pain had a higher proximal extent (P=0.007), a higher volume clearance time (P=0.030), a higher 15-minute acid burden (P=0.041), were more often acidic (P=0.011), had a lower nadir pH (P=0.044), and had a longer acid duration time (P=0.027) than reflux episodes which were not followed by chest pain. Patients who experienced typical reflux symptoms were more likely to have reflux as the cause of their chest pain (52 vs. 31.4%, P=0.023).Conclusions:The presence of a larger volume of acid refluxate for a longer period of time appears to be an important determinant of perceiving a reflux episode as chest pain. 24-h pH-impedance monitoring is an important tool in identifying gastroesophageal reflux as a potential cause of symptoms in patients with NCCP.

Subtle lower esophageal sphincter relaxation abnormalities in patients with unexplained esophageal dysphagia

Esophageal dysphagia is a relatively common symptom. We aimed to evaluate whether subtle, presently not acknowledged forms of dysfunction of the lower esophageal sphincter (LES) could explain dysphagia in a subset of patients with normal findings at high‐resolution manometry (HRM) according to the Chicago classification v3.0.

Reflux-cough syndrome: Assessment of temporal association between reflux episodes and cough bursts

Gastro‐esophageal reflux can be the cause of chronic cough. In the assessment of the temporal association between reflux and cough, previous studies have used a two‐minute time window, based on studies in patients with heartburn. However, it remains unclear whether the optimal time window duration for the evaluation of reflux‐induced cough is two minutes as well. Therefore, we aimed to determine whether a two‐minute time window is optimal to diagnose reflux‐induced cough.