Intragastric Acid Control and Healing Status in Erosive Esophagitis
Intragastric Acid Control and Healing Status in Erosive Esophagitis
Aim: To assess the relationship between the percentage of time intragastric pH >4.0 and healing of erosive oesophagitis.
Methods: In this proof-of-concept study, adults with endoscopically verified Los Angeles grade C or grade D erosive oesophagitis were randomly assigned to oral esomeprazole 10 or 40 mg once daily for 4 weeks. On day 5, patients underwent 24-h pH monitoring. At 4 weeks, erosive oesophagitis healing status was endoscopically assessed. Investigators scored gastro-oesophageal reflux disease symptoms on a 4-point scale [none to severe (0-3)] before and 4 weeks after treatment. The percentage of time intragastric pH was >4.0 and healing status were correlated and tested for significance using a Spearman rank correlation (r).
Results: 103 patients had evaluable data (mean age, 48.7 years; 65% men). Mean percentages of time with intragastric pH >4.0 on day 5 in patients with healed and unhealed erosive oesophagitis were 61% and 42%, respectively (P = 0.0002), indicating that erosive oesophagitis healing rates were positively related to the percentage of time intragastric pH was >4.0. Greater intragastric acid control correlated with lower final daytime and night-time heartburn and acid regurgitation symptom scores (r = −0.029, −0.029 and −0.021; P = 0.003, 0.003 and 0.032, respectively).
Conclusion: A positive relationship between intragastric acid control and erosive oesophagitis healing was demonstrated.
Gastro-oesophageal reflux disease (GERD) is common and affects an estimated 19 million people in the United States. During oesophagogastroduodenoscopic evaluation of patients with GERD, approximately one in three are found to have erosive oesophagitis (EE). The lesions characteristic of EE occur when the oesophageal mucosa is exposed to gastric refluxate, which can cause a decrease in mucosal resistance. Severity of EE is related to the duration of time that the oesophageal mucosa is exposed to gastric acid and the pH of the refluxate. A pH level <4.0 has been identified as the threshold at which aggressive refluxate and non-aggressive refluxate differentiate in part because of the relationship between injury and the activation of pepsin at this pH. Therefore, pathological reflux is determined by the percentage of time with oesophageal pH <4.0, or, conversely, acid control can be defined by the time during which the pH level remains >4.0.
Although the relationship between mucosal injury and pH is accepted, a direct correlation between acid control and healing has not been established. Indirect evidence suggests that greater intragastric acid control relates to improved healing of EE. At present, the most effective pharmacological agents for acid suppression are proton pump inhibitors (PPIs), and results of clinical studies have shown that PPIs are more effective than other acid-suppressive agents for the treatment of EE. However, the primary end points of these studies were healing of EE, and the degree of acid control was not assessed. The correlation between intragastric acid control and healing of EE was assessed in a meta-analysis by Bell et al. using data from treatment trials that assessed healing of reflux oesophagitis. To obtain corresponding 24-h acid-suppression data for each drug and dose used in the EE studies, Bell et al. used acid-suppression data from a previous meta-analysis of trials in patients with duodenal ulcers and showed a relationship between the EE healing rates of the various drug regimens from the reflux oesophagitis studies and the mean intragastric acid control values for those regimens in patients with duodenal ulcers. These data provide the best available evidence to date for the relationship between intragastric acid control and healing of EE. However, the limitations of this meta-analysis are that it was a retrospective analysis that included several small studies with potentially confounding effects, examined 19 different drug treatments (each of which had different pharmacokinetic and pharmacological properties) and measured several endoscopic end points. Most importantly, the acid suppression and healing data were not obtained from the same patients.
Despite the issues with study design, the findings of the meta-analysis by Bell et al. showed that there likely is a relationship between healing and pH control. However, a prospective study that directly compares EE healing with 24-h intragastric pH data would be required to expand on this concept. The primary objective of the current study was to evaluate the relationship between intragastric pH control and healing of moderate to severe EE [Los Angeles ( LA) grades C and D]. Secondary objectives included assessing the relationship between intragastric pH control and symptom resolution, intragastric pH control and symptom severity and EE healing status and rescue medication use. Intragastric pH control was studied because intragastric acid suppression is the most direct result of PPI pharmacodynamics. This is the first prospective study to report direct observations about the effects of acid control on healing of EE in the same patients.
Summary and Introduction
Summary
Aim: To assess the relationship between the percentage of time intragastric pH >4.0 and healing of erosive oesophagitis.
Methods: In this proof-of-concept study, adults with endoscopically verified Los Angeles grade C or grade D erosive oesophagitis were randomly assigned to oral esomeprazole 10 or 40 mg once daily for 4 weeks. On day 5, patients underwent 24-h pH monitoring. At 4 weeks, erosive oesophagitis healing status was endoscopically assessed. Investigators scored gastro-oesophageal reflux disease symptoms on a 4-point scale [none to severe (0-3)] before and 4 weeks after treatment. The percentage of time intragastric pH was >4.0 and healing status were correlated and tested for significance using a Spearman rank correlation (r).
Results: 103 patients had evaluable data (mean age, 48.7 years; 65% men). Mean percentages of time with intragastric pH >4.0 on day 5 in patients with healed and unhealed erosive oesophagitis were 61% and 42%, respectively (P = 0.0002), indicating that erosive oesophagitis healing rates were positively related to the percentage of time intragastric pH was >4.0. Greater intragastric acid control correlated with lower final daytime and night-time heartburn and acid regurgitation symptom scores (r = −0.029, −0.029 and −0.021; P = 0.003, 0.003 and 0.032, respectively).
Conclusion: A positive relationship between intragastric acid control and erosive oesophagitis healing was demonstrated.
Introduction
Gastro-oesophageal reflux disease (GERD) is common and affects an estimated 19 million people in the United States. During oesophagogastroduodenoscopic evaluation of patients with GERD, approximately one in three are found to have erosive oesophagitis (EE). The lesions characteristic of EE occur when the oesophageal mucosa is exposed to gastric refluxate, which can cause a decrease in mucosal resistance. Severity of EE is related to the duration of time that the oesophageal mucosa is exposed to gastric acid and the pH of the refluxate. A pH level <4.0 has been identified as the threshold at which aggressive refluxate and non-aggressive refluxate differentiate in part because of the relationship between injury and the activation of pepsin at this pH. Therefore, pathological reflux is determined by the percentage of time with oesophageal pH <4.0, or, conversely, acid control can be defined by the time during which the pH level remains >4.0.
Although the relationship between mucosal injury and pH is accepted, a direct correlation between acid control and healing has not been established. Indirect evidence suggests that greater intragastric acid control relates to improved healing of EE. At present, the most effective pharmacological agents for acid suppression are proton pump inhibitors (PPIs), and results of clinical studies have shown that PPIs are more effective than other acid-suppressive agents for the treatment of EE. However, the primary end points of these studies were healing of EE, and the degree of acid control was not assessed. The correlation between intragastric acid control and healing of EE was assessed in a meta-analysis by Bell et al. using data from treatment trials that assessed healing of reflux oesophagitis. To obtain corresponding 24-h acid-suppression data for each drug and dose used in the EE studies, Bell et al. used acid-suppression data from a previous meta-analysis of trials in patients with duodenal ulcers and showed a relationship between the EE healing rates of the various drug regimens from the reflux oesophagitis studies and the mean intragastric acid control values for those regimens in patients with duodenal ulcers. These data provide the best available evidence to date for the relationship between intragastric acid control and healing of EE. However, the limitations of this meta-analysis are that it was a retrospective analysis that included several small studies with potentially confounding effects, examined 19 different drug treatments (each of which had different pharmacokinetic and pharmacological properties) and measured several endoscopic end points. Most importantly, the acid suppression and healing data were not obtained from the same patients.
Despite the issues with study design, the findings of the meta-analysis by Bell et al. showed that there likely is a relationship between healing and pH control. However, a prospective study that directly compares EE healing with 24-h intragastric pH data would be required to expand on this concept. The primary objective of the current study was to evaluate the relationship between intragastric pH control and healing of moderate to severe EE [Los Angeles ( LA) grades C and D]. Secondary objectives included assessing the relationship between intragastric pH control and symptom resolution, intragastric pH control and symptom severity and EE healing status and rescue medication use. Intragastric pH control was studied because intragastric acid suppression is the most direct result of PPI pharmacodynamics. This is the first prospective study to report direct observations about the effects of acid control on healing of EE in the same patients.
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