Alimentary Pharmacology & Therapeutics Symposium Series最新文献

The special needs of the elderly must be considered in the treatment of acid-related disorders in older patients. Workshop participants discussed the Genval workshop report algorithm as a step toward building a consensus on the management of elderly patients in Asia.

The consensus reached is summarized as follows:

(i) old age alone is an indication for endoscopic investigation of reflux symptoms;

(ii) elderly patients should undergo endoscopy when they present with acid reflux symptoms;

(iii) a biopsy-based test for Helicobacter pylori should be performed if endoscopy is done, and eradication of H. pylori is warranted as it will reduce the risk of peptic ulcers and may retard the progression of early precancerous gastric lesions;

(iv) it is not recommended to routinely take additional biopsies for histology in patients with H. pylori infection in the absence of any macroscopic suspicious lesions;

(v) patients with reflux disease LA grade B or below should be started on a standard-dose proton pump inhibitor for 4–8 weeks, and then followed by step-down to on-demand therapy;

(vi) patients with LA grade C or above reflux oesophagitis should be initially given standard-dose proton pump inhibitor therapy for at least 8 weeks and then continue with maintenance proton pump inhibitor therapy.

Major points of controversy identified by the workshop included:

(i) symptom assessment of acid-related disorders in children, where vomiting was identified as a potential confounding feature, abdominal pain as a common feature of paediatric gastro-oesophageal reflux disease;

(ii) extra-oesophageal manifestations of paediatric gastro-oesophageal reflux disease;

(iii) abdominal pain perceived as a common feature of Helicobacter pylori-related disorders;

(iv) role of testing for H. pylori in children;

(v) test-and-treat strategies for H. pylori infection in children before long-term proton pump inhibitor therapy;

(vi) an underutilization of triple therapy and proton pump inhibitors in children in areas with a high prevalence of H. pylori infection;

(vii) the role of empiric proton pump inhibitor therapy in children.

It is critical for the clinician who cares for children to distinguish between normal physiological gastro-oesophageal reflux (GER), and signs and symptoms that occur due to the persistent reflux, defined as gastro-oesophageal reflux disease (GERD).

The underlying natural history of physiological GER in the paediatric population up to about 12 years of age, is quite distinct from normal reflux in adults. Conversely, the underlying pathophysiology of GERD in both age groups is for the most part similar.

Regurgitation symptoms, which peak by 4-6 months of age, appear to resolve commonly by 12-18 months of life. However, there is a growing body of evidence that demonstrates that GERD may not be outgrown in a subset of children. In practice, many clinicians include an empiric therapeutic trial of an H₂ receptor antagonist (H₂RA) or proton pump inhibitor accompanied by symptom resolution for the diagnosis of GERD. GERD-associated symptoms in the paediatric population range from regurgitation, often accompanied by arching and irritability, to feeding refusal, and/or poor growth to respiratory symptoms such as nocturnal and/or chronic cough. Upper endoscopy with biopsy may be useful in documenting the presence and severity of macroscopic and microscopic mucosal abnormalities, as well as excluding other disorders such as eosinophilic oesophagitis.

Conservative management, particularly useful in mild GERD, consists of positioning during and after feeds, a 2- to 4-week trial of hydrolysate formula, addition of cereal to formula, and smaller, more frequent feeds. Among the current pharmacotherapeutic options available in the United States (US), the prokinetic agent metaclopramide and the acid-inhibitory agents (H₂RAs, proton pump inhibitors) are the most widely prescribed. Numerous clinical investigations in both adults and children demonstrated that the proton pump inhibitors are more effective than the H₂RAs in the relief of GERD symptoms and healing of erosive oesophagitis. The safety profile of the proton pump inhibitors in children is excellent with no significant adverse events observed either in the short- or long-term (>5.5 years continuous use). Finally, surgical procedures for GERD may also be indicated in certain circumstances.

Specific patient groups consisting of those with nasogastric or gastrostom feeding tubes such as those with stroke neurological impairment or other etiologies, patients with difficulty swallowing (i.e. oral pharyngeal dysfunction), unconscious patients and children who dislike or refuse taking or cannot swallow tablets require special attention with regard to the pharmacological treatment of acid-related disorders.

In particular, these groups of patients require special formulations in order to achieve optimal compliance with acid suppression therapy. Formulations such as the syrup histamine (H₂)-receptor antagonist in a syrup formulation, or for proton pump inhibitors, either the multiple unit pellet capsules, fast dissolving tablets or intravenous formulations, can be used to overcome swallowing problems or bitter taste.

A workshop on acid-related disorders in paediatric and elderly populations was held in Asia in 2006 to raise awareness that: (i) these particular age groups require special consideration in their disease management; (ii) to clarify what issues need to be addressed in these populations and (iii) to reach a consensus on recommendations for the management of gastro-oesophageal reflux disease and other acid-related disorders in children and the elderly.

Of note, acid-related disorders, particularly gastro-oesophageal reflux disease in these populations are less well recognized and studied than those in the adult population between the ages of 20 and 60 years.

A distinguished faculty of practicing gastroenterologists and key opinion leaders from several Asian countries and the United States were thus enlisted to address these issues in the workshop.

The population of Japan is rapidly ageing and this, along with the Westernization of the diet, is expected to increase the prevalence of gastro-oesophageal reflux disease.

Issues that call for attention by Asian gastroenterologists in the management of gastro-oesophageal reflux disease in the geriatric population include functional changes associated with ageing, such as a lower sensitivity to acid stimulation or pain leading to more atypical presenting symptoms vs. greater severity of disease, common swallowing problems, polypharmacy, and the slower metabolism of the drugs by the kidney.

The optimal management of acid-related disorders in the elderly will need to adequately address all these issues.

The workshops developed eight concensus statements for the diagnosis and management of paediatric acid-related disorders or GERD, and five statements for geriatric acid-related disorders or GERD, suitable for clinical use in Asia.

Gastro-oesophageal reflux disease can manifest typically with heartburn and regurgitation and atypically with extra-oesophageal symptoms, such as chest pain, worsening asthma, chronic cough or laryngitis.

Although acid-suppressive therapy can help identify individuals in whom gastro-oesophageal reflux disease is the cause of their symptoms, diagnostic testing is often needed to evaluate those with persistent symptoms.

Recent advances in oesophageal diagnostic testing include the advent of a wireless pH-monitoring device that eliminates the need for a transnasal catheter as well as an ambulatory impedance monitoring device that allows measurement of weakly acidic or non-acidic refluxate.

The advantages and disadvantages as well as clinical utility of these new, as well as traditional, oesophageal-measuring devices are discussed in this review.

Once daily, or even twice daily, dosing with proton-pump inhibitors does not reliably achieve optimal control of nocturnal intragastric acidity. The phenomenon of nocturnal acid breakthrough, defined as intragastric pH < 4 for more than 1 h in the overnight period, was initially described during twice daily dosing with proton-pump inhibitors and found to affect around 70% of individuals.

Given recent renewed interest in the potential consequences of nocturnal oesophageal acid exposure, it is appropriate to consider alternative pharmacological approaches to optimizing the control of nocturnal intragastric acidity.

Nocturnal acid control is considered to be the maintenance of intragastric pH > 4 for the duration of the night-time period. At pH > 4, gastric refluxate entering the oesophagus is non-caustic because pepsin is biologically inactive in this pH range.

Although conventional delayed-release proton-pump inhibitors effectively control daytime, food-stimulated gastric acid secretion, they allow recovery of acid secretion during the night. Bedtime administration of immediate-release omeprazole with sodium bicarbonate (Zegerid, Santarus, Inc., San Diego, CA, USA) has been shown to be highly effective in maintaining overnight intragastric pH above 4 for prolonged periods.

Pharmacodynamic studies in patients with gastro-oesophageal reflux disease have compared the effects of bedtime administration of immediate-release omeprazole, to either predinner or bedtime administration of three different delayed-release proton-pump inhibitors. Bedtime administration of immediate-release omeprazole was more effective at controlling overnight intragastric acidity than predinner administration of pantoprazole or bedtime administration of lansoprazole.

Gastro-oesophageal reflux disease is very common and presents with a spectrum of symptoms with or without oesophageal damage. Gastro-oesophageal reflux disease has an adverse impact on quality of life, especially in those with nocturnal symptoms.

Prolonged exposure of the oesophageal mucosa to acidic gastric contents with pepsin and bile increases the risk of oesophageal mucosal injury. The frequency and severity of symptoms and oesophagitis correlate with the frequency, severity and duration of acid exposure, particularly at night-time.

This study reviews the mechanisms and evidence for acid-induced symptoms and oesophageal injury, from superficial mucosal injury to Barrett's oesophagus and the long-term risk of oesophageal adenocarcinoma.

Optimizing the choice and dose regimen of proton-pump inhibitor is essential for treating gastro-oesophageal reflux disease, and nocturnal acid control is important in preventing complicated gastro-oesophageal reflux disease.