Answers

Short answers

1 Oesophageal pH monitoring, which is used widely as an index of oesophageal acid exposure—it measures the frequency and duration of episodes of acid reflux.^{1 2}

2 Multiple episodes of gastro-oesophageal reflux—113 reflux episodes in 20 hours and 52 minutes (5.3 per hour) (table). Some of the reflux episodes were prolonged, and the longest reflux event lasted for 31 minutes. Overall, pH was <4 for 9.7% of the study, which is indicative of severe gastro-oesophageal reflux.

3 The limitations of the pH study are that it does not detect non-acidic reflux episodes, it cannot diagnose pulmonary aspiration, it gives no indication of the volume of refluxate, the location of the probe must be confirmed radiographically, it cannot detect anatomical abnormalities (such as hiatus hernia or stricture), and it does not provide an objective measure of inflammation.

4 Medical treatment should be the first option. Infants respond favourably to changes in positioning, and some small infants respond well to thickening of feeds.³ Gastric acidity can be reduced by a histamine (H₂) antagonist (such as ranitidine) or a proton pump inhibitor (such as omeprazole or lansoprazole).³ A prokinetic agent, such as domperidone or low dose erythromycin, can be used to accelerate emptying of the stomach.³ Surgical treatment is only indicated when adequate medical treatment fails.

Long answers
1 The investigation
Oesophageal pH monitoring is a valid and reliable measure of acid reflux,^{1 2} and it is used to establish the presence of abnormal acid reflux, to determine a temporal association between acid reflux and symptoms, and to assess the adequacy of treatment in patients who do not respond to medical treatment.²

Intraoesophageal pH is recorded by a microelectrode that is placed into the lower oesophagus via the nasal passage.² An episode of acid reflux is usually defined as oesophageal pH <4 for a specified minimum duration, usually 15-30 seconds.⁴ The recording device, diet, position, and activity during the study affect the measurement of oesophageal pH. Sequential 24 hour pH monitoring studies show technical and biological variability, but this variability seems to affect the interpretation of results in a small number of patients only.⁵

Data from pH studies may be expressed as the number and duration of reflux episodes each day and the reflux index (percentage of time that oesophagus pH is <4). The most sensitive marker of acid reflux on pH study is the reflux index, which has a reported sensitivity and specificity of greater than 94%.⁶ The gastroesophageal reflux guidelines committee of the North American Society for Pediatric Gastroenterology and Nutrition (NASPGN) performed an evidence based review and defined the upper limit of normal for the reflux index as 12% in the first year of life and up to 6% thereafter.⁷

Patients need to stop antireflux drugs before the study. Gaviscon should be stopped 24 hours before the study, proton pump inhibitors 72 hours before, and H₂ receptor antagonist 72 hours before.⁶

The presence of endoscopic and histopathological oesophagitis is strongly associated with abnormal oesophageal pH monitoring. Around 95% of paediatric patients with endoscopic oesophagitis (ulcerations or erosions) or biopsy confirmed oesophagitis will have an abnormal reflux index.^{8 9} However, not all patients with gastro-oesophageal reflux have oesophagitis.

2 The abnormality
Gastro-oesophageal reflux is defined as the effortless regurgitation of gastric contents into the oesophagus. Gastro-oesophageal reflux disease occurs when gastric contents reflux into the oesophagus or oropharynx and produce symptoms. Little is known about the prevalence or natural history of the disease in children and adolescents.⁷ The pathogenesis of the disease is multifactorial and complex, and it depends on the frequency of reflux, gastric acidity, gastric emptying, oesophageal clearing mechanisms, the oesophageal mucosal barrier, visceral hypersensitivity, and airway responsiveness.

The presenting gastrointestinal symptoms are often subtle. Even when patients are old enough to help provide a history, they may not be able to localise the symptoms in the gastrointestinal tract. The common respiratory symptoms of reflux are wheeze, nocturnal cough, recurrent chest infections, recurrent otitis media, upper airway obstruction, stridor, tooth decay, and rarely apnoea. Wheezing and nocturnal cough are common and often unresponsive to treatment with bronchodilators. Non-respiratory symptoms of gastro-oesophageal reflux disease in children are vomiting, poor weight gain, dysphagia, abdominal or substernal pain, and oesophagitis. In infants, the disease may present as an acute life threatening event, also known as near miss sudden infant death syndrome.¹⁰

In preterm infants, apnoea secondary to reflux is more likely within one to two hours of feeding, and it may present with obstruction (persisting respiratory symptoms) rather than central apnoea (absent respiratory effort), which may reflect apnoea of prematurity.¹¹

One study of 23 children with recurrent chest infections (3-25 months old), found that 21 children had an abnormal pH study (14 had a reflux index of >10%).¹² The NASPGHAN consensus statement recommends a 24 hour oesophageal pH study in cases of recurrent pneumonia where gastro-oesophageal reflux disease is suspected.⁷

The relation between poorly controlled asthma and acid reflux is complicated. Up to 60% of children with asthma had abnormal oesophageal pH monitoring studies.^{13 14 15} A Cochrane review evaluated 12 studies, four of which looked at the role of acid reflux in children with asthma.¹⁶ These studies identified some children in whom reflux was temporally associated with asthma,¹⁷ but anti-reflux drugs had no consistent effect of on asthma outcomes in these studies. Two studies showed a significant improvement in reported symptoms of wheeze. A Cochrane review found no overall improvement in asthma control after treatment for reflux in patients with asthma and gastro-oesophageal reflux. Subgroups of patients may gain benefit, but it is difficult to predict who will respond.¹⁶

Another study that looked at 222 children with a double probe (simultaneous oesophageal and pharyngeal pH monitoring) over 24 hours found that 168 (76%) had abnormal findings in either one or both of the probes.¹⁸ Of those, 46% (78/168) had evidence of increased pharyngeal acid reflux with normal oesophageal acid exposure times. Patients with laryngeal or pulmonary manifestations had significantly more pharyngeal acid reflux (P<0.001) than those with non-respiratory symptoms.

Cough and gastro-oesophageal reflux often coexist. A Cochrane review assessed three paediatric studies but none was suitable for analysis.¹⁹ A validated clinical algorithm can identify adults whose cough is caused by reflux. A 24 hour oesophageal pH study is one investigation included,¹⁹ but the algorithm has not been validated in children.

More work is also needed to assess whether 24 hour oesophageal pH studies can help to differentiate children with coexistent reflux and wheeze or cough from those children with wheeze or cough caused by reflux.⁶ The relation between reflux and respiratory disease is complex, and further research is needed.

3 Limitations of the test
Oesophageal pH studies detect acid reflux only. Oesophageal pH studies in children being given milk containing feeds may miss reflux episodes. To increase the sensitivity of the test, the milk can be acidified or additional feeds with acidic liquids, such as apple juice, may be given.²⁰ In infants, a dual probe (that measures oesophageal pH and gastric pH) permits a more accurate evaluation of the low acid and non-acid components of gastro-oesophageal reflux disease.²¹

In some patients, oesophageal pH monitoring may be within the normal range, but brief episodes of gastro-oesophageal reflux may cause complications such as acute life threatening event, cough, or aspiration pneumonia.^{9 20}

It is crucial that the operator is trained and the equipment is well maintained. The test could be misleading if, for example, medications have inadvertently been continued, equipment is not calibrated before each test, or the probe tip is misplaced or displaced.²²

Newer techniques like pH monitoring combined with multichannel impedance measurements are more sensitive in detecting non-acid reflux and can even measure the level of reflux. Intraluminal impedance measures reflux from retrograde flow of a liquid bolus as it passes from the stomach through the oesophagus toward the oropharynx,^{23 24 25} and it is independent of pH. Intraluminal impedance is increasingly being used in conjunction with pH studies.

The presence of gastro-oesophageal reflux disease should be actively sought in children who present with lung disease of unknown cause. However, clinical decision making is complicated because lung disease may cause gastro-oesophageal reflux, probably because of changes in intrathoracic pressure caused by a less compliant lung or increased airway resistance. Gastro-oesophageal reflux is common in asymptomatic children but it may not be harmful, and we still lack a test to identify clinically important reflux. Reflux may cause respiratory disease or it may be the other way round, and pH studies will not delineate which association is stronger.

We have no gold standard test for gastro-oesophageal reflux, but pH studies have a sensitivity of 93-96% in identifying acid reflux in patients diagnosed with oesophagitis on endoscopy (by both macroscopic and histological appearances).⁷ The test will be more useful if a clear diagnostic question is defined. So for a child with possible apnoea secondary to gastro-oesophageal reflux disease, it is essential to include accurate documentation of the chronology of symptoms during the pH study.⁶

4 Treatment
To date, no medical treatment targets the primary mechanism of gastro-oesophageal reflux, which is a transient relaxation of the lower oesophageal sphincter. The primary goals of treatment are to relieve the patient’s symptoms, promote normal weight gain and growth, heal inflammation caused by refluxed gastric contents (oesophagitis), and prevent respiratory and other complications associated with chronic reflux of gastric contents.

Medical treatment is the first treatment of choice:

• Infants often respond favourably to a change of position (raising the head end of the crib).
  
• Thickened feeds may be useful in small infants³
  
• A reduction of gastric acidity with a histamine (H₂) antagonist (such as ranitidine) or a proton pump inhibitor (such as omeprazole) may help.³ Omeprazole and lansoprazole are more potent and produce more sustained inhibition of acid secretions than ranitidine. Omeprazole seems to be better than ranitidine in patients with a worse reflux index⁶
  
• A prokinetic agent can be used to accelerate emptying of the stomach, improve sphincter tone, and increase oesophageal emptying. Commonly used prokinetic agents are low dose domperidone (10-20 mg/kg three to four times a day) and erythromycin.³
  

Surgical treatment is only indicated when adequate medical treatment has not led to an improvement in the gastrointestinal and respiratory symptoms. Nissen’s fundoplication is the most commonly used procedure.³ This may be performed as a laparoscopic or endoscopic procedure.

Outcome
Our patient responded very well to the medical treatment. Both frequency and severity of respiratory exacerbations were dramatically reduced.

Cite this as: BMJ 2009;338:b1255