|Journal of Pediatric Gastroenterology and Nutrition Volume 21, 253-262. (c)1995, Lippincott-Raven Publishers.
Used with Permission.
INDICATIONS FOR PEDIATRIC ESOPHAGEAL pH MONITORING: A Medical Position Statement of the North American Society for Pediatric Gastroenterology and Nutrition
Richard B. Colletti, MD, Department of Pediatrics, University of Vermont College of Medicine
Dennis L. Christie, MD, Department of Pediatrics, University of Washington School of Medicine
Susan R. Orenstein, MD, Department of Pediatrics, University of Pittsburgh School of Medicine
[This Medical Position Statement was published in the Journal of Pediatric Gastroenterology, October 1995, and is edited for electronic communication by R. Colletti.]
Gastroesophageal reflux (GER), defined as the regurgitation of gastric contents into the esophagus, is a common physiologic self-limited condition in infants.1 Half of two-month old infants regurgitate twice a day or more, but only 1% of twelve- month old infants do so.2 Regurgitation by an infant, even when frequent, generally is not a concern if the infant is otherwise healthy, because the natural history is usually spontaneous resolution.2 However, a small percentage of infants will develop pathogenic gastroesophageal reflux, termed GER disease (GERD), with esophagitis, stricture, Barrett's esophagus, respiratory disease, apnea or failure to thrive. GERD is often a diagnosis of exclusion. Numerous disorders can present with chronic regurgitation that mimics GERD; these disorders include hydronephrosis, brain tumor or other causes of increased intracranial pressure, intestinal obstruction and metabolic disorders, such as uremia.1,3
While older children, like adults, with GERD often have heartburn, regurgitation with reswallowing, and a chronically acid taste, it may be difficult to establish the presence of GERD in pre-verbal infants or young children on the basis of symptoms and signs. Children, particularly infants, are different from adults in the manifestations of reflux disease, in the safety and ease of alternative diagnostic techniques, in the documented safety of therapies and in the potential lifetime duration of disease or therapy.
Since its introduction in 1974, esophageal pH monitoring (EpHM), the continuous measurement and recording of intra- esophageal pH, has become a test administered commonly to children with suspected or manifest GERD.1-12 It is based on the detection within the esophageal lumen of acidic gastric fluid, and the measurement of the frequency and duration of episodes of acid reflux. It is the most reliable test for the detection of occult GER episodes, and, in certain circumstances, for establishing a temporal relationship between GER episodes and symptoms.13-16
The test is performed by the transnasal placement of a standardized microelectrode into the lower esophagus, in the hospitalized or ambulatory patient, for continuous measurement and recording of intra-esophageal pH by either a strip chart or computerized device.17-19 The frequency and duration of episodes of reflux are measured manually or by computer, with computation of the number of episodes longer than five minutes, the longest episode, the percentage of time pH is less than 4, and the relationship of reflux to eating, position, sleeping, activity and symptoms.
Although a large number of normal asymptomatic controls have not been studied to establish clearly normative data for all ages, numerous studies have demonstrated that measurement of the percentage of time pH is less than 4, called the Reflux Index, is a reliable, clinically useful measure when obtained under standardized conditions.20-27 When compared to a global clinical diagnosis, the Reflux Index has been reported to have a sensitivity and specificity of 94% or better.9,28,29 In children with endoscopically or histopathologically documented reflux esophagitis, EpHM has been reported to have a sensitivity of 93- 96%.21,30-32
Correct performance of the test requires a properly trained technician, suitable and well-maintained recording equipment and probes, and a physician trained in the technique and interpretation of EpHM as well as in the clinical disorders under consideration.19,33,34 Even with standardized technique, variability has been reported with sequential testing or with simultaneous recording with two pH probes.35,36
Compared to other tests for GER, EpHM cannot determine the presence of a hiatal hernia, stricture or other anatomic abnormality, aspiration or the presence of esophagitis. It cannot detect reflux when the gastric contents are not acid, as may occur immediately after a meal of non-acidic food, such as infant formula, or in the presence of achlorhydria or duodenogastric reflux.37,38 Nor can EpHM measure the quantity of acid refluxate.1,39
No single test, such as EpHM, by itself should dictate a diagnosis or treatment of a patient. EpHM should be only one facet of a thoughtful and informed medical evaluation by a physician who is familiar with the patient and knowledgeable about the strengths and weaknesses of the test. The decision to perform EpHM is also influenced by the availability of the test and necessary expertise, as well as its cost. Additional research that investigates cost, risk and benefit in comparison to other diagnostic and treatment options is needed to determine the optimal usage of EpHM in numerous clinical situations.
CLINICAL SITUATIONS WHERE EpHM IS GENERALLY USEFUL
Like all tests, EpHM should not be performed unless it will lead to a clinically important alteration in diagnosis, treatment or prognosis. It is not necessary to perform EpHM when the diagnosis of GERD is already established by symptoms and signs or other tests. If reflux esophagitis has been diagnosed by endoscopy or biopsy, then EpHM is not necessary to document the presence of GERD. However, EpHM can be a very useful clinical tool to detect occult GER or to demonstrate a temporal relationship between a symptom and GER episodes.
Certain non-gastrointestinal symptoms caused by GER, such as stridor, can present without other clinical manifestations of GERD. If such symptoms occur frequently, then EpHM can be performed to determine if symptoms occurring during the course of the test occurred at the same time as episodes of reflux. The Symptom Index (S.I. = number of occurrences of a symptom with pH 40-42 Patients with symptoms of chest pain, abdominal pain or infantile irritability that persist despite anti-reflux therapy can be similarly studied.
Other disorders, such as recurrent pneumonia and failure to thrive, may be manifestations of occult GER. Because these disorders are continuous rather than intermittent during a 24- hour study, the Symptom Index is not applicable. However, EpHM may be useful to detect occult GER that presents without other evidence of GER by demonstrating the presence of clinically significant, quantifiably excessive GER.
In adults EpHM is generally indicated for patients with atypical symptoms of reflux, patients with reflux symptoms who are not responsive to standard medical therapy, and in the follow-up of patients who have been treated medically or surgically.43 These three broad criteria also apply to the pediatric patient. EpHM may be useful in the pediatric patient to diagnose gastroesophageal reflux that is manifest as hoarseness, stridor, chest pain, recurrent pneumonia, and in the evaluation of therapy of reflux.
Laryngeal symptoms. Proximal rather than distal esophageal acid exposure is more likely to lead to laryngeal symptoms and laryngoscopic findings of posterior laryngitis.44- 46 In a study of 40 adult patients with gastroesophageal reflux, 25 had persistent laryngeal symptoms including cough, sore throat, and hoarseness.47 Ambulatory dual-electrode EpHM with the proximal electrode placed just distal to the upper esophageal sphincter demonstrated significant proximal esophageal acid exposure in those patients with laryngeal symptoms. Nocturnal proximal esophageal acidification occurred in over 50% of these patients but in none of the 15 adults who served as controls. The authors concluded that increased proximal esophageal acid exposure can occur in a subgroup of adults with gastroesophageal reflux who experience laryngeal symptomatology. These adults are much more likely to exhibit laryngoscopic abnormalities consistent with acid laryngitis than patients with gastroesophageal reflux without laryngeal symptoms. When dual-electrode EpHM was performed on 182 adults with otolaryngologic disorders who were suspected of having gastroesophageal reflux, 55 (30%) had gastroesophageal reflux into the pharynx.48
In a pediatric study, 8 children (2 months to 7.5 years old) who had recurrent laryngotracheitis including episodes of croup had dual-electrode EpHM with the upper probe placed in the pharynx.49 The symptoms in these children included nocturnal stridor, chest retraction, and barking cough. Six control children (1 month to 13 years old) were also evaluated. There was significantly greater total reflux time in the lower esophagus and a greater number of reflux episodes in the pharynx in the children with laryngeal symptoms than in the control group. In a study of laryngoscopically-demonstrated laryngitis, 3 of 5 children 50 These studies provide evidence to support the concept that proximal acid reflux can induce recurrent laryngeal symptoms in the pediatric as well as the adult patient.
Chest pain. Of 16 children with chest pain and asthma, 11 had endoscopic and histologic evidence of esophagitis, 4 had a positive Bernstein test, 7 had significant GER on EpHM, and 9 (56%) responded to medical therapy with cessation of chest pain.51 EpHM can be performed to detect significant reflux but, since chest pain may not occur in all patients during the study, the Bernstein test can be performed to determine if the chest pain is related to esophageal acidification.
Recurrent pneumonia. Establishing a definite relationship between gastroesophageal reflux and recurrent pneumonia is problematic.1,52-55 When microaspiration is suspected, radiographic evaluation of the oropharynx and esophageal body is usually the first screening test indicated. It is difficult to know precisely the importance of microaspiration or the role of esophageal-respiratory reflexes as a cause of recurrent respiratory disease.56 Patients with aspiration tend to reflux more to the proximal esophagus.57 Nocturnal reflux is statistically correlated with chronic aspiration. Delayed clearance of refluxed material and clustering of reflux events may precipitate respiratory symptoms in pediatric patients. 58,59
Physicians have long recognized the relationship between recurrent pneumonia and reactive airway disease and their association with gastroesophageal reflux.60 Recently, of 23 patients (3 to 25 months old) with recurrent bronchopulmonary infections,61 21 had abnormal EpHM, and 14 of the 21 had a Reflux Index greater than 10%. The study concluded that EpHM was the best single test for diagnosing gastroesophageal reflux and its association with recurrent bronchopulmonary disease. There was no control population.
In a retrospective study, 93% of 128 children with reflux- related respiratory symptoms had a prolonged mean duration of reflux episodes during sleep, compared to none of 131 children with respiratory symptoms due to other causes.62 The authors concluded that the measurement of the mean duration of reflux during sleep was the best single method to identify correctly the presence or absence of respiratory symptoms associated with gastroesophageal reflux. Other investigators, who examined the effectiveness of Nissen fundoplication in children with bronchopulmonary dysplasia, also concluded that EpHM was the definitive test to predict which patient would have an improvement in respiratory symptoms after surgery.63 These investigators found that the mean duration of nocturnal episodes of reflux was longer in patients responding favorably to surgery for gastroesophageal reflux than in those who did not improve. A study of 11 adults with recurrent pneumonia, chronic cough and morning hoarseness, who had respiratory symptoms within 3 minutes after a reflux episode, demonstrated that they also had a reflux index greater than 11.4%.64
Because it is difficult to establish a causal relationship between gastroesophageal reflux and recurrent respiratory disease, it is important to consider other diagnostic modalities.65 Endoscopy and esophageal biopsy can document evidence of chronic esophagitis.10 Bronchoscopy can document the lack of a tracheo-esophageal communication, identify laryngeal or tracheal abnormalities, exclude the presence of a foreign body and obtain tracheal aspirates for lipid laden macrophages.18 A modified Bernstein test can demonstrate whether cough, bronchospasm or stridor occur during the infusion of acid. Newer methods to look at oropharyngeal aspiration such as the radionuclide salivagram may help further identify these patients.66
Evaluation of the treatment of gastroesophageal reflux. EpHM can be performed to verify the success of a particular drug or surgical therapy in improving or ameliorating gastroesophageal reflux. It has been shown in adults and children with Barrett's esophagus that EpHM performed at intervals following treatment with fundoplication or omeprazole is valuable in assessing success of therapy.67-70 Of 24 children with severe gastroesophageal reflux and respiratory symptoms who were treated with cisapride, GER was controlled in 22, as indicated by an improvement in their EpHM and clinical course, and 18 patients showed a definite improvement in their pulmonary disease.71
In a double-blind controlled study, the efficacy of sodium alginate to reduce gastroesophageal reflux in infants was assessed by EpHM, which demonstrated improvement in all variables including the percent of total reflux time and the mean duration of reflux during sleep.72 In addition, in a double-blind placebo-controlled trial, the efficacy of domperidone in 17 children (5-11 years old) was assessed by EpHM, which demonstrated a reduction in the total number of reflux episodes in the 2-hour postprandial period.73
CLINICAL SITUATIONS WHERE EpHM IS GENERALLY NOT USEFUL
Regurgitation in infants. Regurgitation is a manifestation of GER in infancy, although it does not necessarily represent reflux disease. If simple regurgitation is the sole manifestation of reflux, diagnostic or therapeutic measures are generally unnecessary. If regurgitation is associated with failure to thrive or other symptoms, diagnostic evaluation and therapy are usually indicated, but EpHM often does not contribute to the diagnostic evaluation.74
Reflux esophagitis. Having diagnosed reflux disease by demonstrating esophagitis (endoscopic erosions or histologic esophagitis),75-77 it is unnecessary to quantify acid reflux except possibly to evaluate inadequate response to therapy.30,32,78-82
Untreated common symptoms of reflux: chest or epigastric pain. Older children who describe typical heartburn and pyrosis are often treated, as adults are, with an 8-week course of pharmacologic therapy with an H2-receptor antagonist and/or cisapride, despite the lack of FDA approval.83 Intractability or recurrence of these symptoms is generally evaluated initially by endoscopy rather than by EpHM. Although the pros and cons of empiric therapy for adults have been identified,84 empiric therapy in children, comparing costs, risks and benefits, has not been evaluated. Chronic therapy without any diagnostic evaluation is generally not recommended.
Dysphagia. Esophageal dysphagia in pediatric patients is more likely to be secondary to neuromuscular disorders, or intrinsic and/or extrinsic mechanical lesions. Occasionally dysphagia may be secondary to GER.85-87 A barium esophagram, esophageal motility and endoscopy are generally considered the preferred diagnostic tests in most children with dysphagia.
CLINICAL SITUATIONS WHERE EpHM IS GENERALLY CONDITIONAL
Infantile apnea. Reflux may be the underlying cause in up to 20% of cases of infantile apnea.88 EpHM has been used in infants with apnea to quantify reflux, to identify possibly hazardous reflux patterns, and to document a temporal association between reflux episodes and apneic episodes. Such studies have been particularly difficult because of the lack of clear criteria for diagnosing reflux-associated apnea. The resultant subjectivity of the studies makes their evaluation particularly difficult.
Since quantitatively greater-than-normal reflux and apnea can coexist without being causally related,89,90 simply quantifying reflux is of limited value in these patients. Reflux during sleep, particularly prolonged episodes of reflux, have been found to occur more frequently in infants with apnea believed due to reflux.91,92 However, there have been no studies evaluating the efficacy of pharmacologic treatment of GER to prevent apnea in infants with abnormal EpHM.
Apnea related to reflux usually occurs when the infant is awake, within 1-2 hours following a meal, in the supine or seated position, and appears to be obstructive (with persistence of respiratory effort) rather than central (absence of respiratory effort), and it may occur in infants with no history of regurgitation.92-96 Documentation of a temporal association between reflux and apnea requires concurrent pneumocardiography, with simultaneous multichannel recording of heart rate, oxygen saturation, chest wall movement and ventilation as recorded by nasal thermister or end-tidal CO2,94 as well as esophageal pH. This technique can quantify GER and identify GER patterns, temporal associations between reflux and apnea, types of apnea (central, obstructive, or mixed), and the occurrence of hypoxemia or bradycardia. The usefulness of this test is limited if apnea does not occur during the monitoring. Detection of postprandial reflux by EpHM also requires that acid meals (e.g. apple juice) be fed.37,38 Although a multichannel test has a somewhat greater cost than simple EpHM, it may be offset by the much greater amount of information obtained. In infants monitored for cardiorespiratory events at home, unexplained hypoxia has been a frequent and sometimes lethal event;97,98 some of these episodes are likely to have been obstructive apnea with reflux as the underlying cause.
EpHM generally will not be useful when apnea is clearly central or when, although obstructive, it occurs in conjunction with an upper respiratory illness; such apnea is unlikely to be caused by GER. Nor will EpHM be useful when there has been a single episode of apnea, which is unlikely to recur during monitoring. Nor is EpHM generally indicated when apnea is clearly related to reflux, e.g., the postprandial infant placed supine for a diaper change who has formula appear at the mouth or nose during an episode of apnea.
Infantile irritability, intractable crying, and refusal to eat. These symptoms may be infantile correlates of adult complaints of pyrosis, heartburn, and dysphagia, but the non-verbal nature of infants makes these symptoms far less easily characterized as having reflux as their cause.99- 101 Feeding difficulties or excessive irritability ("atypical colic") can be due to GER and may be unresponsive to anti-reflux therapy.1,80,102 Of infants presenting to an emergency room with acute, unexplained crying, 2% were diagnosed with reflux as the cause;100 the prevalence of reflux as a cause of more prolonged symptoms and with other indications of GERD is much higher.99 In another study, only 15 per cent of crying episodes during EpHM occurred at the time of an episode of reflux.80While esophageal suction biopsy is a more efficient means of identifying the infant with esophagitis,103 in some cases EpHM may be necessary to establish a causal relationship between episodic crying and GER. The validity of such an approach to this problem, and the value of empiric therapy of such cases, has not been studied.
Reactive airways disease. Patients with asthma are probably a heterogeneous group.104,105 Bronchospasm may have identifiable precipitants which differ among patient groups; some may wheeze in response to inhalant allergens, some to ingested allergens, some during viral infections, and some to reflux. It has been suggested that patients with reflux-induced bronchospasm have not only reactive airways but also esophagitis, and that having either one alone is not sufficient for reflux-induced bronchospasm.104-106As many as half of asthmatic children have esophagitis,31,107 and an even higher proportion of those with predominantly nocturnal wheezing have abnormal EpHM.108 However, the proportion of asthmatics in whom reflux is a cause, rather than a result, of the airway obstruction is unclear. Reported responses to anti-reflux therapy depend on the patients selected and the efficacy of therapy, and vary widely.59,109-111
Diagnostic approaches to identify reflux as an etiology for otherwise intractable asthma include: (1) modified Bernstein test (with pulmonary function testing after saline and after acid infusions),59,104,105,109,112-114 (2) endoscopy and/or esophageal histology,104,105,109,110,113 (3) EpHM with documentation of temporal relationship to wheezing episodes,59,108,114 (4) EpHM to quantify reflux (either in terms of total reflux time or sleep reflux time),31,58,59,108,110,113,114 or (5) trial of empiric therapy for reflux.
The modified Bernstein test linked with pulmonary function testing is an efficient method to document the association between reflux and bronchospasm, although it has not been thoroughly evaluated.104,105,115 Endoscopy and esophageal histology showing esophagitis,32 document both the presence of reflux disease requiring therapy and the presence of the esophageal inflammation which may be necessary for reflux-associated bronchospasm. EpHM may be used with pulmonary function testing or with close observation for wheezing episodes if those episodes are intermittent,116 or simply to document abnormal quantity of reflux,117 or abnormal quantity of sleep reflux,58,62,118 to justify chronic therapy. A two-month course of empiric treatment with acid suppression could also be considered.113 Because of the ambiguity of the relationships between asthma, asthma medications, and reflux,52 the optimal approach to diagnostic evaluation has not yet been established and varies from case to case dependent on clinical judgement.
Prior to fundoplication. Intractable reflux disease in children as in adults may require surgery.119,120 Some surgeons have reported that prolonged reflux during sleep (mean duration of nocturnal reflux episodes >4.5 minutes) predicts a favorable response to fundoplication in up to 95% of children operated,63,121 but normal pH probe studies have also been found in children who nonetheless had esophagitis and seemed to respond to surgery.122 In each of these situations, EpHM was not the only criterion used in selection for surgery. Prior to medical therapy EpHM should not be the sole indicator for this major and irreversible therapy, since it does not reliably predict medical intractability, at least in adults.123-126 However, following medical therapy, it is one of several ways to document intractability of reflux to medical therapy; symptoms alone are inadequate for this purpose. Thus, candidates for surgery, whose symptoms have been intractable to therapy, and in whom there is doubt about the presence or etiologic role of GER, may certainly benefit from EpHM. In this group, EpHM may identify patients whose reflux is indeed controlled by medical therapy, and whose persistent symptoms have a cause other than reflux; these patients would be saved an unnecessary surgery. EpHM is also useful in the unfortunate postoperative patient with persistent or recurrent symptoms to determine whether re-operation is necessary.
SUMMARY RECOMMENDATIONS FOR ESOPHAGEAL pH MONITORING IN INFANTS AND CHILDREN
The North American Society for Pediatric Gastroenterology and Nutrition (NASPGN) recognizes the need to develop a medical position statement on the indications for EpHM in infants and children, in order to promote optimal patient care, to foster learning and to guide practitioners, as well as to facilitate peer and other review of clinical practices. The following recommendations were prepared by the authors, with the critique and endorsement of the Subcommittee on Endoscopy and Procedures, the approval of the Patient Care Committee, and the authorization of the Executive Council of NASPGN. In addition, they have been endorsed by the American Gastroenterological Association Patient Care Committee and the American College of Gastroenterology Practice Parameters Committee. These recommendations are subject to change based on periodic review of subsequent research. Nonetheless, the authors provide the following recommendations, written in the context of the preceding literature review, as a tool for improving the outcomes of patient care and to advance our understanding of them.
- For infants with simple regurgitation it is generally not necessary to perform EpHM.
- If reflux esophagitis has been diagnosed by endoscopy or biopsy, then EpHM is not necessary to document the presence of GERD.
- EpHM is useful if it will lead to a clinically important alteration in diagnosis, treatment or prognosis.
- EpHM has little role in the evaluation of dysphagia. Similarly it is only occasionally useful in the management of chest or abdominal pain when features are typical of GERD.
- Certain non-gastrointestinal symptoms caused by GER, such as laryngeal symptoms or atypical chest pain, can present without other clinical manifestations of GERD. If such symptoms occur frequently, then EpHM can be useful to demonstrate a temporal relationship between symptoms and GER.
- In cases of unexplained recurrent pneumonia, it can be useful to perform EpHM to detect occult GER.
- EpHM may be indicated to determine whether the dosage of medication is optimal in Barrett's esophagus and in selected cases of severe intractable GERD. Similarly EpHM can be useful after fundoplication to evaluate the effectiveness of surgery when symptoms persist or recur.
- When a causal relationship between GER and apnea is suspected but not otherwise clinically evident, EpHM can be useful when it is part of a multichannel pneumocardiography test.
- The optimal approach to the diagnostic evaluation of intractable reactive airways disease has not yet been established; EpHM can be useful in some cases, dependent on clinical judgement.
- .Prior to fundoplication, candidates for surgery whose symptoms have been intractable to medical therapy, and in whom there is doubt about the presence or etiologic role of GER, can benefit from EpHM.
- Boyle JT. Gastroesophageal reflux in the pediatric patient. Gastroenterol Clin NA 1989;18:315-338
- Kibel MA, in Gellis SS (ed): Gastroesophageal Reflux, Report of the Seventy-Sixth Ross Conference on Pediatric Research. Columbus, Ohio, Ross Laboratories, 1979:39-42
- Herbst JJ. Gastroesophageal reflux. J Pediatr 1981;98:859-70
- Johnson LF, DeMeester TF. Twenty-four hour pH monitoring of the distal esophagus. A quantitative measure of gastroesophageal reflux. Am J Gastroenterol 1974;62:325-332
- Euler AR, Ament ME. Detection of gastroesophageal reflux in the pediatric-age patient by esophageal intraluminal pH probe measurement (Tuttle test). Pediatr 1977;60:65-68
- Jolley SG, Johnson DG, Herbst JJ, Pena A, Garnier R. An assessment of gastroesophageal reflux in children by extended pH monitoring of the distal esophagus. Surgery 1978;84:16-24
- Christie DL. The acid reflux test for gastroesophageal reflux. J Pediatr 1979;94:78-81
- Boix-Ochoa J, Lafuente JM, Gil-Vernet JM. Twenty-four hour esophageal pH monitoring in gastroesophageal reflux. J Pediatr Sur 1980;15:74-78
- Sondheimer JM. Continuous monitoring of distal esophageal pH: a diagnostic test for gastroesophageal reflux in infants. J Pediatr 1980;96:804-807
- Jolley SG, Herbst JJ, Johnson DG, Matlak ME, Book LS, Pena A. Postcibal gastroesophageal reflux in children. J Pediatr Surgery 1981;16:487-490
- .Jolley SG, Johnson DG, Herbst JJ, Matlak ME. The significance of gastroesophageal reflux patterns in children. J Pediatr Surg 1981;16:859-865
- Sondheimer JM. Gastroesophageal reflux: update on pathogenesis and diagnosis. Pediatr Clin NA 1988;35:103-116
- Arasu TS, Wyllie R, Fitzgerald JF, Franken EA, Siddiqui AR, Lehman GA, Eigen H, Grosfeld JL. Gastroesophageal reflux in infants and children--comparative accuracy of diagnostic methods. J Pediatr 1980;96:798-803
- Euler AR, Byrne WJ. Twenty-four hour esophageal intraluminal pH probe testing: a comparative analysis. Gastroenterol 1981;80:957-961
- Tappin DM, King C, Paton JY. Lower oesophageal pH monitoring- -a useful clinical tool. Arch Dis Child 1992;67:146-148
- Quigley EMM. 24-H pH monitoring for gastroesophageal reflux disease: already standard but not yet gold? Am J Gastroenterol 1992;87:1071-1075
- Newman LJ, Berezin S, SanFilippo JA, Halata M, Medow MS, Schwarz SM. A new ambulatory system for extended esophageal pH monitoring. J Pediatr Gastroenterol Nutr 1985;4:707-710
- Strobel CT, Byrne WJ, Ament ME, Euler AR. Correlation of esophageal lengths in children with height: application to the Tuttle test without prior esophageal manometry. J Pediatr 1979;94:81-83
- Working Group of the European Society of Pediatric Gastroenterology and Nutrition. A standardized protocol for the methodology of esophageal pH monitoring and interpretation of the data for the diagnosis of gastroesophageal reflux. J Pediatr Gastroenterol and Nutr 1992;14:467-471
- Vandenplas Y, Sacre-Smits L. Continuous 24-hour esophageal pH monitoring in 285 asymptomatic infants 0-15 months old. J Pediatr Gastroenterol Nutr 1987;6:220-224
- Vandenplas Y, Granckx-Goossens A, Pipeleers-Marichal M, Derde MP, Sacre-Smits L. Area under pH 4: advantages of a new parameter in the interpretation of esophageal pH monitoring data in infants. J Pediatr Gastroenterol Nutr 1989;9:34-39
- Vandenplas Y, Lepoudre R, Helven R. Dependability of esophageal pH-monitoring data in infants on cutoff limits: the Oscillatory Index. J Pediatr Gastroenterol Nutr 1990;11:304-309
- Cucchiara S, Staiano A, Casali LG, Boccieri A, Paone FM. Value of the 24 hour intraoesophageal pH monitoring in children. Gut 1990;31:129-133
- Vandenplas Y, Goyvaerts H, Helven R, Sacre L. Gastoesophageal reflux, as measured by 24-hour pH monitoring, in 509 healthy infants screened for risk of sudden infant death syndrome. Pediatr 1991;88:834-840
- Schindlbeck NE, Ippisch H, Klauser AG, Muller-Lissner SA. Which pH threshold is best in esophageal pH monitoring. Am J Gastoenterol 1991;86:1138-1141
- Grill B. Twenty-four hour esophageal pH monitoring: what's the score? J Pediatr Gastroenterol Nutr 1992;14:249-251
- Friesen CA, Hayes R, Hodge C, Roberts CC. Comparison of methods of assessing 24-hour intraesophageal pH recordings in children. J Pediatr gastroenterol Nutr 1992;14:252-255
- Dalt LD, Mazzoleni S, Montini G, Donzelli F, Zacchello F. Diagnostic accuracy of pH monitoring in gastro-esophageal reflux. Arch Dis Child 1989;64:1421-1426
- Jamieson JR, Stein HJ, DeMeester TR, Bonavina L, Schwizer W, Hinder RA, Albertucci M. Ambulatory 24-H esophageal pH monitoring: normal values, optimal thresholds, specificity, sensitivity, and reproducibility. Am J Gastroenterol 1992;87:1102-1111
- Winter HS, Madara JL, Stafford RJ, Grand RJ, Quinlan J, Goldman H. Intraepithelial eosinophils: a new diagnostic criterion for reflux esophagitis. Gastroenterol 1982;83:818-823
- Baer M, Markku M, Nurminen J, Turjanmaa V, Pukander J, Vesikari T. Esophagitis and findings of long-term esophageal pH recording in children with repeated lower respiratory tract symptoms. J Pediatr Gastroenterol Nutr 1986;5:187-190
- Black DD, Haggitt RC, Orenstein SR, Whitington PF. Esophagitis in infants. Morphometric histological diagnosis and correlation with measures of gastroesophageal reflux. Gastroenterol 1990;98:1408-1414
- Klauser AG, Schindlbeck NE, Muller-Lissner SA. Esophageal 24- h pH monitoring: is prior manometry necessary for correct positioning of the electrode? Am J Gastroenterol 1990;85:1463- 1467
- Vandenplas Y, Goyvaerts H, Helven R. Do esophageal pH monitoring data depend on recording equipment and probes? J Pediatr Gastroenterol Nutr 1990;10:322-326
- Hampton FJ, MacFadyen UM, Mayberry JF. Variations in results of simultaneous ambulatory esophageal pH monitoring. Dig Dis Sci 1992;37:506-512
- Murphy DW, Yemin Y, Castell DO. Does the intraesophageal pH probe accurately detect acid reflux? Dig Dis Sci 1989;34:649-656
- Tolia V, Kauffman RE. Comparison of evaluation of gastroesophageal reflux in infants using different feedings during intraesophageal pH monitoring. J Pediatr Gastroenterol Nutr 1990;10:426-429
- Sutphen JL, Dillard VL. pH-adjusted formula and gastroesophageal reflux. J Pediatr Gastroenterol Nutr 1991;12:48-51
- Shay SS, Eggli D, Johnson LF. Simultaneous esophageal pH monitoring and scintigraphy during the postprandial period in patients with severe reflux esophagitis. Dig Dis Sci 1991;36:558-564
- Wiener GJ, Richter JE, Copper JB, et al. The symptom index: a clinically imprtant paramenter of ambulatory 24-h esophageal pH monitoring. Am J Gastroenterol 1988;83:358-361
- Breumelhof R, Smout AJPM. The symptom sensitivity index: a valuable additional parameter in 24-hour esophageal pH recording. Am J Gastroenterol 1991;86:160-164
- Johnston BT, McFarland RJ, Collins JSA, et al. Symptom index as a marker of gastro-oesophageal reflux disease. Br J Surg 1992;79:1054-1055
- Mattox HE, Richter JE. Prolonged ambulatory esophageal pH monitoring in the evaluation of gastroesophageal reflux disease. Am J Med 1990;89:345-356
- Orenstein SR, Orenstein DM, Whitington PF. Gastroesophageal reflux causing stridor. Chest 1983;84:301-302
- Wilson JA, White A, Von Haacke NP, Maran AGD, Heading RC, Pryde A, Piris J. Gastroesophageal reflux and posterior laryngitis. Ann Otol Rhinol Laryngol 1989;98:405-410
- Barish CF, Wu WC, Castell DO. Respiratory Complications of gastroesophageal reflux. Arch Intern Med 1985;145:1882-1888
- Jacob P, Kahrilas PJ, Herzon G. Proximal esophageal pH-metry in patients with 'reflux laryngitis'. Gastroenterology 1991;100:305-310
- Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 1991;101:1-78
- Contencin P, Narcy P. Gastropharyngeal reflux in infants and children. Arch Otolaryngol Head Neck Surg 1992;118:1028-1030
- Orenstein SR, Kocoshis SA, Orenstein DM, Proujansky R. Stridor and gastroesophageal reflux: Diagnostic use of intraluminal esophageal acid perfusion (Bernstein test). Pediatric Pulmonology 1987;3:420-424
- Berezin S, Medow MS, Glassman MS, Newman LJ. Esophageal chest pain in children with asthma. J Pediatr Gastroenterol Nutr 1991;12:52-55.
- Orenstein SR, Orenstein DM. Gastroesophageal reflux and respiratory disease in children. J Pediatr 1988;112:847-858
- Burton DM, Pransky SM, Katz RM, Kearns DB, Seid AB. Pediatric airway manifestations of gastroesophageal reflux. Ann Otol Rhinol Laryngol 1992;101:742-749
- Nelson HS. Gastroesophageal reflux and pulmonary disease. J Allergy Clin Immunol 1894;73:547-556
- Irwin RS, Zawacki JK, Curley FJ, French CL, Hoffman PJ. Chronic cough as the sole presenting manifestation of gastroesophageal reflux. Am Rev Respir Dis 1989;140:1294-1300
- Orenstein SR. Controversies in pediatric gastroesophageal reflux. J Pediatr Gastroenterol Nutr 1992;14:338-348
- Haase G, Ross M, Glance-Cleveland B, Kolack K. Extended four- channel esophageal pH monitoring: The importance of acid reflux patterns at the middle and proximal levels. J Pediatr Surg 1988; 23:32-37
- Jolley SG, Herbst JJ, Johnson DG, Matlak ME, Boos LS. Esophageal pH monitoring during sleep identifies children with respiratory symptoms from gastroesophageal reflux. Gastroenterology 1981;80:1501-1506
- Gustafsson PM, Kjeliman NIM, Tibbling L. Bronchial asthma and acid reflux into the distal and proximal oesophagus. Arch Dis Child 1990; 65: 1255-1258
- Danus O, Casar C, Larrain A, Pope CE. Esophageal reflux: an unrecognized cause of recurrent obstructive bronchitis in children. J Pediatr 1976;89:220-224
- Chen PH, Chang MH, Hsu SC. Gastroesophageal reflux in children with chronic recurrent bronchopulmonary infection. J Pediatr Gastroenterol Nutr 1991;13:16-22
- Halpern LM, Jolley SG, Tunnell WP, Johnson DG, Sterling CE. The mean duration of gastroesophageal reflux during sleep as an indicator of respiratory symptoms from gastroesophageal reflux in children. J Pediatr Surg 1991; 26(6):686-690.
- Eizaguirre I, Tovar JA. Predicting preoperatively the outcome of respiratory symptoms of gastroesophageal reflux. J Pediatr Surg 1992;27:848-851
- Patti MG, Debas HT, Pellegrini CA. Esophageal manometry and 24-hour pH monitoring in the diagnosis of pulmonary aspriation secondary to gastroesophageal reflux. Am J Surg 1992;163:401-406
- Hoyoux CI, Forget P, Lambrechts L, Geubelle F. Chronic bronchopulmonary disease and gastroesophageal reflux in children. Pediatr Pulmonol 1985;1:149-153
- Heyman S, Respondek M: Detection of pulmonary aspiration in children by radionuclide "salivagram." J Nucl Med 1989; 30:697- 699
- Hassall E, Weinstein WM. Partial regression of childhood Barrett's esophagus after fundoplication. Am J Gastroenterol 1992;87:1506-1512
- Williamson WA, Ellis FH, Gibb SP, et al. Effect of antireflux operation on Barrett's mucosa. Ann Thorac Surg 1990;49:537-542
- Skinner DB. Controversies about Barrett's esophagus. Ann Thorac Surg 1990;49:523-524
- Hassall E. Barrett's esophagus: new definitions and approaches in children. J Pediatr Gastroenterol Nutr 1993;16:345-364
- Malfroot A, Vandenplas Y, Verlinden M, Piepsz A, Dab I. Gastroesophageal reflux and unexplained chronic respiratory disease in infants and children. Pediatr Pulmonol 1987;3:208-213
- Buts JP, Barudi C, Otte JB. Double-blind controlled study on the efficacy of sodium alginate (Gaviscon) in reducing gastroesophageal reflux assessed by 24 hour continuous pH monitoring in infants and children. Eur J Pediatr 1987;146:156- 158
- Bines JE, Quinlan JE, Treves S, Kleinman RE, Winter HS. Efficacy of domperidone in infants and children with gastroesophageal reflux. J Pediatr Gastroenterol Nutr 1992;14:400-405
- Ferreira C, Lohoues MJ, Bensoussan A, Yazbeck S, Brochu P, Roy CC. Prolonged pH monitoring is of limited usefulness for gastroesophageal reflux. Amer J Dis Child 1993;147:662-664
- Biller JA, Winter HS, Grand RJ, et al. Are endoscopic changes predictive of histologic esophagitis in children? J Pediatr 1983;103:215-218
- Benjamin B, Pohl D, Bale PM. Endoscopy and biopsy in gastroesophageal reflux in infants and children. Ann Otol 1980;89:443-445
- Hoyoux C, Forget P, Garzaniti N, et al. Is the macroscopic aspect of the esophagus at endoscopy indicative of reflux esophagitis? Endoscopy 1986;18:4-6
- Dahms BB, Rothstein FC. Mucosal biopsy of the esophagus in children. Perspect Pediatr Pathol 1987;11:97-123
- Leape L, Bahn I, Ramenofsky M. Esophageal biopsy in the diagnosis of reflux esophagitis. J Pediatr Surg 1981;16:379-384
- Hyams JS, Ricci AJ, Leichtner AM. Clinical and laboratory correlates of esophagitis in young children. J Pediatr Gastroenterol Nutr 1988;7:52-56
- Shub MD, Ulshen MH, Hargrove CB, et al. Esophagitis: a frequent consequence of gastroesophageal reflux in infancy. J Pediatr 1985;107:881-884
- Groben PA, Siegal GP, Shub MD, et al. Gastroesophageal reflux and esophagitis in infants and children. Perspect Pediatr Pathol 1987;11:124-151
- Colletti RB, Christie DL, Orenstein SR. Endoscopy or pH probe? A survey of pediatric gastroenterologists on indications for esophageal pH monitoring. Gastrointest Endoscopy 1994;40:P50
- Johnson DA. Medical therapy for gastroesophageal reflux disease. Am J Med 1992;92(suppl 5A):88S-97S.
- Cucchara, et al. Esophageal motor abnormalities in children with gastroesophageal reflux and peptic esophagitis. J Pediatr 1986;108:907
- Gill, et al. Esophageal motor abnormalities in gastroesophageal reflux and the effects of fundoplication. Gastroenterol 1986;91:364
- Catto-Smith AG, Machida H, Butzner JD, Gall DG, Scott RB. The role of gastroestophageal reflux in pediatric dysphagia. J Pediatr Gastroenterol Nutr 1991;12:159-165
- Kahn A, Rebuffat E, Franco P, N'Duwimana M, Blum D. Apparent life-threatening events and apnea of infancy, in Beckerman R, Brouilette R, Hunt C (eds): Respiratory control disorders in infants and children. Baltimore, Williams & Wilkins, 1992:178- 189
- Walsh JK, Farrell MK, Keenan WJ, Lucas M, Kramer M. Gastroesophageal reflux in infants: relation to apnea. J Pediatr 1981;99(2):197-201.
- de Ajuriaguerra M, Radvanyl-Bouvet M, Huon C, Moriette G. Gastroesophageal reflux and apnea in prematurely born infants during wakefulness and sleep. Am J Dis Child 1991;145:1132-1136
- Jolley S, Halpern L, Tunnell W, Johnson D, Sterling C. The risk of sudden infant death from gastroesophageal reflux. J Pediatr Surg 1991; 26:691-696.
- Newman LJ, Russe J, Glassman MS, Berezin S, Halata MS, Medow MS, Dozor AJ, Schwarz SM. Patterns of gastroesophageal reflux (GER) in patients with apparent life-threatening events. J Pediatr Gastroenterol Nutr 1989;8:157-60
- Spitzer AR, Boyle JT, Tuchman DN, Fox WW. Awake apnea associated with gastroesophageal reflux: a specific clinical syndrome. J Pediatr 1984; 104:200-5
- Herbst JJ, Minton SD, Book LS. Gastroesophageal reflux causing respiratory distress and apnea in newborn infants. J Pediatr 1979;95:763-768
- See CC, Newman LJ, Berezin S, Glassman MS, Medow MS, Dozor AJ, Schwarz SM. Gastroesophageal reflux-induced hypoxemia in infants with apparent life-threatening events. Am J Dis Child 1989; 143:951-4
- Menon AP, Schefft GL, Thach BT. Apnea associated with regurgitation in infants. J Pediatr 1985;106:625-9
- Poets C, Stebbens V, Samuels M, Southall D. The relationship between bradycardia, apnea and hypoxemia in preterm infants. Pediatr Res 1993;34:144-147
- Meny R, Carroll J, Carbone M, Kelly D. Cardiorespiratory recordings from infants dying suddenly and unexpectedly at home. Pediatr 1994;93:44-49
- Ryan P, Lander M, Ong TH, et al. When does reflux oesophagitis occur with gastro-oesophageal reflux in infants? A clinical and endoscopic study, and correlation with outcome. Aust Paediatr J 1983;19:90-93
- Poole S. The infant with acute, unexplained and excessive crying. Pediatrics 1991;88:450-455
- Dellert S, Hyams J, Geertsma, et al. Feeding resistance: An unappreciated complication of gastroesophageal reflux in infants. J Pediatr Gastroenterol Nutr 1993;17:66-71
- Ferry GD, Selby M, Pietro TJ. Clinical response to short- term nasogastric feeding in infants with gastroesophageal reflux and growth failure. J Pediatr Gastroenterol Nutr 1983;2:57-61
- Putnam PE, Orenstein SR. Blind esophageal suction biopsy in children less than 2 years of age. Gastroenterol 1992;102:A149
- Spaulding H, Mansfield L, Stein M, Sellner J, Gremillion D. Further investigation of the association between gastroesophageal reflux and bronchoconstriction. J Allergy Clin Immunol 1982;69(6):516-521
- Davis RS, Larsen GL, Grunstein MM. Respiratory response to intraesophageal acid infusion in asthmatic children during sleep. J Allergy Clin Immunol 1983;72:393-8
- Boyle JT, Tuchman DN, Altschuler SM, et al. Mechanisms for the association of gastroesophageal reflux and bronchospasm. Am Rev Respir Dis 1985;131
- cShapiro GG, Christie DL. Gastroesophageal reflux in steroid- dependent asthmatic youths. Pediatr 1979;63:207-212
- Martin ME, Grunstein MM, Larsen GL. The relationship of gastroesophageal reflux to nocturnal wheezing in children with asthma. Ann Allergy 1982;49:318-322
- Perrin-Fayolle M, Gormand F, Braillon G, et al. Long-term results of surgical treatment for gastroesophageal reflux in asthmatic patients. Chest 1989;96:40-45
- Hoyoux C, Forget P, Lambrechts L, et al. Chronic bronchopulmonary disease and gastroesophageal reflux in children. Pediatr Pulmonol 1985;1:149-153
- Tucci F, Resti M, Fontana R, Novembre E, Lami C, Vierrucci A. Gastroesophageal reflux and bronchial asthma: prevalence and effect of cisapride therapy. J Pediatr Gastroenterol Nutr 1993;17:265-270
- Kjellen G, Tibbling L, Wranne B. Bronchial obstruction after oesophageal acid perfusion in asthmatics. Clin Physiol 1981;1:285-292
- Harper PC, Bergner A, Kaye MD. Antireflux treatment for asthma. Arch Intern Med 1987;147:56-60
- Gustafsson PM, Kjellman NIM, Tibbling L. Oesophageal function and symptoms in moderate and severe asthma. Acta Paediatr Scand 1986;75:729-736
- Mansfield L, Stein M. Gastroesophageal reflux and asthma: a possible reflex mechanism. Ann Allergy 1978:41:224-226
- Johnson L. New concepts and methods in the study and treatment of gastroesophageal reflux disease. Med Clin North Am 1981;65(6):1195-1222
- Andze GO, Brandt ML, St. Vil D, Bensoussan AL, Blanchard H. Diagnosis and treatment of gastroesophageal reflux in 500 children with respiratory symptoms: The value of pH monitoring. J Pediatr Surg 1991;26(3):295-300
- Jolley SG, Halpern CT, Sterling CE, Feldman BH. The relationship of respiratory complications from gastroesophageal reflux to prematurity in infants. J Pediatr Surg 1990:25:755-757
- Leape LL, Ramenofsky ML. Surgical treatment of gastroesophageal reflux in children. Results of Nissen's fundoplication in 100 children. Am J Dis Child 1980;134:935-938
- Ashcraft KW, Holder TM, Amoury RA. Treatment of gastroesophageal reflux in children by Thal fundoplication. J Thorac Cardiovasc Surg 1981;82:706-712
- Johnson DG, Jolley SG, Herbst JJ, Cordell LJ. Surgical selection of infants with gastroesophageal relux. J Pediatr Surg 1981:16:587-594
- Tovar JA, Angulo JA, Gorostiaga L, Arana J. Surgery for gastroesophageal reflux in children with normal pH studies. J Pediatr Surg 1991:26:541-545
- Evans DF, Haynes J, Jones JA, et al. Ambulatory esophageal ph monitoring in children as an indicator for surgery. J Pediatr Surg 1986;21:221-223
- Ramenofsky ML, Powell RW, Curreri PW. Gastroesophageal reflux. pH probe-directed therapy. Ann Surg 1986;203:531-536
- Olden K, Triadafilopoulos G. Failure of initial 24-hour esophageal pH monitoring to predict refractoriness and intractability in reflux esophagitis. Am J Gastroenterol 1991;86:1142-1146
- Boesby S, Wallin L, Myrhoj T, et al. Twelve hour overnight oesophageal pH monitoring in patients with reflux symptoms. Gut 1991;32:10-11