Characteristics of high-resolution esophageal manometry in children without dysphagia

Abstract

Background:

The absence of high-resolution esophageal manometry (HREM) norms in pediatrics limits the assessment of children with dysphagia. This study aimed to describe HREM parameters in a cohort of children without dysphagia.

Methods:

Children ages 9–16 years with a negative Mayo Dysphagia Questionnaire screen and normal histologic findings underwent HREM after completion of esophagogastroduodenoscopy. Ten swallows of 5 ml 0.45% saline boluses per subject were captured in supine position. Analyzed data included resting and integrated relaxation pressures (IRP) of lower (LES) and upper (UES) esophageal sphincters, peristaltic contractile integrals, transition zone (TZ) breaks, velocities, and lengths associated with proximal and distal esophagus.

Key Results:

33 subjects (15 female) with mean (range) age 12.9 (9–16) years completed the study. Two of 330 analyzed swallows failed. The UES mean resting pressure, and its 0.2 s and 0.8 s IRPs were 48.3 (95% CI 12.9) mmHg, 2.9 (95% CI 1.9) mmHg, and 12.1 (95% CI 2.5) mmHg, respectively. The LES mean resting pressure and its 4 s IRP were 29.0 (95% CI 4.0) mmHg and 9.2 (95% CI 1.3) mmHg. The mean proximal (PCI) and distal (DCI) esophageal contractile integrals were 231 (95% CI 54.8) mmHg-s-cm and 1789.3 (95% CI 323.5) mmHg-s-cm, with mean TZ break 0.5 (95% CI 0.3) cm.

Conclusions & Inferences:

This is the first study to describe HREM parameters in children without dysphagia. Most of the reported measurements were significantly different and less variable from reported adult norms. This emphasizes the need for child-specific catheters, norms, and protocols to define pediatric esophageal motility disorders.

1 ∣. INTRODUCTION

Children suffering from symptoms such as dysphagia, non-cardiac chest pain, and regurgitation generally trigger a battery of tests including but not limited to upper endoscopy, videofluoroscopic swallow study, and esophagogram. If symptoms persist after exclusion of mucosal and anatomic abnormalities are excluded, esophageal motility testing is indicated to further assess esophageal function.

Over the past two decades, the development of solid-state high-resolution manometry (HRM) catheters has advanced our understanding and management of esophageal motility disorders. The acquired data describing normal and abnormal esophageal motility were captured and summarized in the Chicago Classification,^1-4 with the intent to develop diagnostic features of abnormal esophageal motility. Both normative and diagnostic data used to develop these criteria were acquired in adults using a solid-state HRM assembly with a 4.2-mm outer diameter and 36 circumferential pressure sensors spaced 1-cm apart. Due to ethical issues concerning pediatric research and the invasive nature of such studies, there is complete lack of pediatric normative data. Application of Chicago Classification in the clinical setting has shown to be adequate in assessment of children with achalasia; however, evaluation of hypotensive or hypertensive disorders of the esophagus has been challenging. A small number of studies have attempted to describe the differentiating features of pediatric manometry profiles with use of mathematical modeling, application of adult normative data, and using pediatric data from symptomatic children.^5-8 These studies are unfortunately inadequate for development of specific pediatric norms. Another valid concern that has not been addressed relates to the specific manometric assembly used to acquire the data. The aforementioned 4.2-mm catheter with circumferential pressure sensors used to acquire adult data is often found uncomfortable and poorly tolerated in the pediatric population given its size and rigidity. Pediatric studies are usually captured with smaller (2.7-mm diameter), more pliable, catheter with unidirectional pressure sensors. Multiple studies have shown that the size of the catheter and directionality of the pressure sensors (unidirectional vs circumferential) have to be considered in data interpretation as these affect esophageal sphincter pressure and relaxation measurements as well as derivation of esophageal contractile integral.^9-11 These factors thus raise significant concern relating to the extrapolation of adult derived data to pediatric populations.

We hypothesized that appropriate pediatric norms could be acquired by capturing manometry data in children undergoing endoscopy for other symptoms than dysphagia and with the use of a more child-friendly catheter. The aim of our study was to analyze manometric features of both upper and lower esophageal sphincter as well as peristalsis pattern in children without dysphagia.

2 ∣. MATERIALS & METHODS

This prospective study was approved by Children's Wisconsin Hospital Institutional Review Board (#12018807). An informed consent/assent approved by this IRB was reviewed and signed by all children and two legal guardians prior to participation.

2.1 ∣. Subjects

Subjects ages 9–16 were recruited for this study from the outpatient Pediatric Gastroenterology Clinic at Children's Wisconsin. All subjects underwent HREM for research purposes only after the completion of upper endoscopy with or without colonoscopy. The indication for endoscopy was clinical evaluation of symptoms other than dysphagia, heart burn, chest pain, or esophageal pathology. Patients with chest pain, difficulty swallowing, or those who had significant esophageal mucosal macroscopic or histologic abnormalities were excluded from the data analysis. All subjects were prescreened for a history of surgical intervention involving the foregut anatomy or any esophageal pathology. Prior to the esophageal manometry, all participants completed the adult dysphagia screen with the assistance of their parents (Mayo Dysphagia Questionnaire).

2.2 ∣. High-Resolution Manometry (HRM)

All studies were performed with 2.7-mm-diameter solid-state catheter incorporating 36 1-cm-spaced unidirectional pressure sensors and 12 2-cm-long impedance segments (Unisensor USA Inc, Portsmouth, NH). Measurements were captured and analyzed by commercially available Medical Measurement System database software (MMS, Dover, NH, USA). The data-acquisition frequency was 50 Hz for each sensor.

2.3 ∣. Study protocol

All upper endoscopies were performed under general anesthesia, and routine proximal and distal esophageal biopsies were obtained per standard of care. Upon completion of endoscopy, the esophageal manometry catheter was placed under endoscopic supervision and secured with tape. Shortly after the procedure, subjects were escorted to the Post-Anesthesia Care Unit for recovery. Once subjects were fully awake, the esophageal manometry protocol was initiated. Subjects were placed in supine position with head resting at no more than 30 degrees pending adequate level of comfort. Subjects were subsequently coached to take ten 5 ml swallows of 0.45% NaCl with sufficient break between the swallows. All studies were performed by the same pediatric gastroenterologist.

2.4 ∣. Statistical analysis

Means, 95% confidence intervals, medians, and interquartile ranges were calculated for all the metrics developed and are summarized in the ensuing figures and tables. In addition, Student's t test was used to assess whether acquired metrics were gender dependent. Regression analysis was used to describe the relationship between height and esophageal length.

3 ∣. RESULTS

3.1 ∣. Demographics

A total of 38 subjects were enrolled and attempted to participate. Five subjects were excluded from the data analysis because of histologic findings of significant esophageal mucosal inflammation or participant's request to terminate the research study participation. Mean (range) age was 12.9 (9–16) years, and 15 (45%) were female. Mean height and weight among all subjects were 157.5 (95% CI 4.5) cm and 52.6 (95% CI 5.7) kg, respectively. Table 1 shows demographics, anthropometrics, indications for endoscopy, the final diagnostic yield of endoscopy, co-morbidities, and medications taken at the time of endoscopy.

TABLE 1.

Subject characteristics and final diagnostic yield of endoscopy

	Female	Male	Total
Number of Subjects	15	18	33
Average Age (range)	13.4 (9–15)	12.4 (9–16)	12.9 (9–16)
Height (95% CI) cm	157.3 (4.8)	157.7 (7.2)	157.5 (4.5)
Weight (95% CI) kg	56.4 (7.4)	49.4 (8.4)	52.6 (5.7)
BMI (95% CI) kg/m2	22.4 (2.1)	19.3 (2.0)	20.7 (1.5)
Upper Endoscopy (%)	12 (80)	3 (17)	15 (45)
Upper and Lower Endoscopy (%)	3 (20)	15 (83)	18 (55)
Indications for Endoscopy
Abdominal pain (%)	8 (53)	10 (56)	18 (55)
Diarrhea (%)	2 (13)	8 (44)	10 (30)
Hematochezia (%)	1 (7)	3 (17)	4 (12)
Weight Loss (%)	1 (7)	4 (22)	5 (15)
Nausea (%)	6 (40)	1 (6)	7 (21)
Fatigue (%)	1 (7)	2 (11)	3 (9)
Positive Inflammatory Markers	1 (7)	8 (44)	9 (27)
Positive Celiac Screen	2 (13)	1 (6)	3 (9)
Emesis	2 (13)	2 (11)	4 (12)
Other	0 (0)	3 (17)	3 (9)
No Symptoms (%)	1 (7)	2 (11)	3 (9)
Endoscopic Findings
Inflammatory Bowel Disease (%)	1 (7)	8 (44)	9 (27)
Celiac Disease (%)	3 (20)	1 (6)	4 (12)
Familial Adenomatous Polyposis (%)	0 (0)	2 (11)	2 (6)
Low Disaccharidases (%)	2 (13)	2 (11)	4 (12)
H. Pylori (%)	1 (7)	0 (0)	1 (3)
Normal (%)	8 (53)	5 (28)	13 (39)
Comorbidities
Atopy (Asthma, Allergy) (%)	5 (33)	2 (11)	7 (21)
Mood Disorder (%)	0 (0)	2 (11)	2 (6)
Type 1 Diabetes (%)	0 (0)	1 (6)	1 (3)
Hypothyroidism (%)	1 (7)	0 (0)	1 (3)
Urinary Incontinence (%)	1 (7)	0 (0)	1 (3)
Tethered Spinal Cord (%)	1 (7)	0 (0)	1 (3)
ADHD	0 (0)	1 (6)	1 (3)
No Comorbidities (%)	8 (53)	13 (72)	21 (64)
Medications
Cetirizine (%)	1 (7)	3 (17)	4 (12)
Cyproheptadine (%)	1 (7)	2 (11)	3 (9)
Fluticasone (%)	2 (13)	1 (6)	3 (9)
Clonidine (%)	1 (7)	0 (0)	1 (3)
Lisdexamfetamine (%)	1 (7)	0 (0)	1 (3)
Adderall (%)	1 (7)	0 (0)	1 (3)
Insulin (%)	1 (7)	0 (0)	1 (3)
Fluticasone propionate / Salmeterol (%)	1 (7)	0 (0)	1 (3)
Loratadine (%)	1 (7)	0 (0)	1 (3)
Proton Pump Inhibitors (%)	3 (20)	1 (6)	4 (12)
Oxybutinin (%)	1 (7)	0 (0)	1 (3)
Remicade (%)	1 (7)	0 (0)	1 (3)
Trileptal (%)	0 (0)	1 (6)	1 (3)
Citalopram (%)	0 (0)	1 (6)	1 (3)

3.2 ∣. Mayo dysphagia questionnaire (MDQ), upper endoscopy, and mucosal biopsies

Per the MDQ instrument, all 33 subjects included in the final analyses reported no symptoms with swallowing. Per endoscopic evaluation of the esophagus, all included subjects had a normal appearing mucosa. Four subjects were found to have signs of minimal microscopic inflammation, which was deemed clinically insignificant and left untreated.

3.3 ∣. High-resolution manometry results

All 33 studied subjects were carefully coached to allow accurate recording of upper esophageal sphincter (UES) relaxation, peristaltic pressures of the whole esophagus, and lower esophageal sphincter (LES) relaxation (Figure 1). Once subjects mastered the skill needed to perform measurable individual swallows, we captured manometric data of ten swallows. In total, 330 swallows were measured and analyzed for esophageal length, sphincter relaxation pressures, distal latency, peristaltic vigor, and velocity. After careful review of all acquired swallows, there were only two failed swallows with lack of complete bolus clearance, as measured by the impedance properties of the catheter and lack of smooth muscle peristalsis.

FIGURE 1.

20 mmHg isocontour of a sample swallow and acquired measurements. UES - Upper Esophageal Sphincter; LES - Lower Esophageal Sphincter; IRP - Integrated Relaxation Pressure; PCI - Proximal Contractile Integral; TZ - Transition Zone; DCI - Distal Contractile Integral; DL - Distal Latency; CDP - Contractile Deceleration Point.

3.3.1 ∣. Upper esophageal sphincter

Measured properties of the UES include average resting pressure and 0.2 s and 0.8 s integrated relaxation pressures (IRP) of UES (0.2sIRP and 0.8sIRP). For the measurement of mean UES resting pressure, we used the MMS software during a period of minimum 10 s at a time when subjects were holding their swallow and were comfortable in a supine neutral position. The mean UES resting pressure was 48.3 (95% CI 12.9) mmHg. Similarly, the mean UES 0.2sIRP and 0.8sIRP among all 330 swallows were 2.9 (95% CI 1.9) mmHg and 12.1 (95% CI 2.5) mmHg, respectively (Table 2). There was no statistical difference between genders (p>0.3 for all three parameters).

TABLE 2.

Summary of manometricparameters describing features of upper esophageal sphincter, esophagealperistalsis and lower esophageal sphincter

	Female		Male		Total
Metrics	Mean	95% CI	Mean	95% CI	Mean	95% CI	Median	IQR
UES Mean Resting Pressure (mmHg)	41.9	[33.8 – 50.0]	53.7	[31.0 – 76.3]	48.3	[35.4 – 61.2]	41.0	[31.0 – 54.0]
UES 0.2sIRP (mmHg)	3.1	[0.0 – 6.2]	2.8	[0.5 – 5.2]	2.9	[1.1 – 4.8]	3.3	[−0.4 – 6.6]
UES 0.8sIRP (mmHg)	13.1	[9.3 – 16.8]	11.4	[8.1 – 14.6]	12.1	[9.7 – 14.6]	10.5	[7.5 – 16.4]
PCI (mmHg-s-cm)	238.8	[156.6 – 321.0]	224.5	[148.9 – 300.0]	231.0	[176.1 – 285.8]	203.5	[102.6 – 318.4]
DCI (mmHg-s-cm)	1583.9	[1196.7 – 1971.1]	1960.6	[1466.9 – 2454.2]	1789.3	[1465.8 – 2112.8]	1426.7	[1040.1 – 2411.6]
ErL (cm)	19.4	[18.3 – 20.4]	19.5	[18.2 – 20.7]	19.4	[18.6 – 20.2]	19.5	[17.6 – 20.6]
EcL (cm)	18.9	[18.2 – 19.6]	18.7	[17.5 – 19.9]	18.8	[18.1 – 19.5]	18.6	[17.0 – 20.0]
Length of Proximal Contractile Esophagus (cm)	4.9	[4.2 – 5.6]	4.8	[4.2 – 5.4]	4.8	[4.4 – 5.3]	4.7	[4.3 – 5.5]
TZ break (cm)	0.6	[0.2 – 1.1]	0.4	[0.1 – 0.7]	0.5	[0.2 – 0.8]	0.1	[0.0 – 0.5]
Length of Distal Contractile Esophagus (cm)	13.4	[12.8 – 14.0]	13.6	[12.5 – 14.6]	13.5	[12.8 – 14.1]	13.8	[12.2 – 15.0]
MELH ratio	0.120	[0.117 – 0.124]	0.118	[0.115 – 0.122]	0.119	[0.117 – 0.122]	0.121	[0.116 – 0.124]
PEcV (cm/s)	1.76	[1.52 – 2.00]	1.64	[1.40 – 1.87]	1.70	[1.53 – 1.86]	1.53	[1.35 – 2.04]
DEcV (cm/s)	1.96	[1.72 – 2.20]	1.78	[1.57 – 1.99]	1.86	[1.70 – 2.02]	1.87	[1.49 – 2.11]
EcV (cm/s)	2.09	[1.88 – 2.31]	1.89	[1.72 – 2.06]	1.99	[1.85 – 2.12]	1.98	[1.70 – 2.27]
DL (s)	6.4	[6.0 – 6.9]	6.6	[6.3 – 7.0]	6.5	[6.3 – 6.8]	6.6	[6.2 – 6.9]
LES Mean Resting Pressure (mmHg)	28.3	[21.7 – 34.8]	29.7	[24.7 – 34.6]	29.0	[25.1 – 33.0]	27.0	[21.0 – 37.0]
LES 4sIRP (mmHg)	9.3	[7.1 – 11.4]	9.2	[7.6 – 10.8]	9.2	[7.9 – 10.5]	9.1	[7.2 – 10.7]

3.3.2 ∣. Peristalsis

To assess contractile vigor, contractile velocity, contractile length, and transition zone length of striated (proximal) and smooth (distal) muscle esophagus, we defined three manometric determinants. These included 1) the end of UES relaxation at the distal end of UES 20 mmHg isocontour; 2) the transition zone (TZ) determinant (point or break); and 3) the point where 20 mmHg isocontour of the end of esophageal peristalsis and LES meet.

The TZ point is defined as the minimal peak pressure within continuous 20 mmHg isocontour and signifies the division between esophageal smooth and striated muscle. Once minimal peak pressure is identified, a horizontal tangent is extended to the beginning and the end of 20 mmHg isocontour at that level (Figure 1).

Proximal contractile integral (PCI) is derived by drawing a contractile integral box between the first determinant (end of UES relaxation) and the point where the horizontal tangent extended from the TZ point intersects the end of 20 mmHg isocontour. Similarly, distal contractile integral (DCI) is derived by drawing a contractile integral box between the point located at the beginning of the 20 mmHg isocontour at the level of the TZ point and the third determinant (the point where 20 mmHg isocontour of end of esophageal peristalsis and LES meet). If individual swallows were found to have a TZ break, then the distal vertex of the PCI box is determined at the point of convergence between the horizontal tangent of the most distal point and the vertical tangent of the last point on the time scale of the proximal esophageal 20 mmHg isocontour. Similarly, if a TZ break is present, the most proximal vertex of the DCI box is determined at the point of convergence between the horizontal tangent of the most proximal point and the vertical tangent of the first point on the time scale of the distal esophageal 20 mmHg isocontour (Figure 2A).

FIGURE 2.

(A) Sample measurement of PCI and DCI with TZ break. (B) Contractile velocity is derived by division of the length (cm) of a particular contractile segment by its duration (s).

The mean PCI and DCI were found to be 231.0 (95% CI 54.8) mmHg-s-cm and 1789.3 (95% CI 323.5) mmHg-s-cm, respectively (Table 2). There was no statistically significant difference between genders in mean PCI (p = 0.8) or DCI (p = 0.25) values.

By defining PCI and DCI for 20 mmHg isocontour, we were able to measure average TZ break on the same isocontour. We found that 24 out of 33 subjects (73%) had a mean TZ break less than 0.5 cm. The mean TZ break was 0.5 (95% CI 0.3) cm (Table 2). TZ break was not significantly different between genders (p = 0.34).

To derive the esophageal contractile velocity (EcV), the proximal esophageal contractile velocity (PEcV), and the distal esophageal contractile velocity (DEcV), we used the same three determinants used for measuring PCI and DCI. PEcV and DEcV were derived from the drawn boxes used to measure respective contractile integrals at 20 mmHg isocontour. EcV was derived similarly except that we used only the first and third determinants as described above (Figure 2B). Average EcV, PEcV, and DEcV were found to be 1.99 (95% CI 0.13) cm/s, 1.7 (95% CI 0.16) cm/s, and 1.86 (95% CI 0.16) cm/s, respectively. There was no statistically significant difference between genders in any of the three measurements, p = 0.16, p = 0.47, and p = 0.28, respectively (Table 2).

We defined the average esophageal contractile length (EcL) as an average distance between lower border of UES immediately before the onset of esophageal peristalsis and upper border of LES at the end of esophageal peristalsis as determined by 20 mmHg isocontour. Within the same isocontour, we also measured the distance from the lower margin of UES to the upper margin of LES during the resting period to determine the esophageal resting length (ErL). The average EcL and ErL were found to be 18.8 (95% CI 0.71) cm and 19.4 (95% CI 0.81) cm, respectively (Table 2). Both EcL and ErL were found to have high linear correlation with measured height (r = 0.83 and r =0.77, respectively). Mean manometric esophageal length to height (MELH) ratio was 0.119 (95% CI 0.003). The average TZ break, and contractile segment of striated and smooth muscle esophagus were 2.5% (95% CI 1.4%), 25.9% (95% CI 2.3%), and 71.7% (95% CI 1.8%), respectively, when measured in 20 mmHg isocontour. Length of esophagus or its muscle segments were not found to be significantly different between the genders (p > 0.7).

We also measured the distal latency (DL) for all 330 swallows. It is defined as a time interval from UES relaxation to the inflection point (CDP) in the wavefront velocity proximal to the esophagogastric junction. The average DL was found to be 6.5 s (95% CI 0.3 s). There was no statistically significant difference between the genders (p = 0.54).

3.3.3 ∣. Lower esophageal sphincter

Measured properties of LES include average resting pressure and 4 s integrated relaxation pressures of LES (4sIRP). We measured average LES resting pressure with the help of MMS software across a minimum period of 10 s at the time when subjects were holding their swallow and were comfortable in a supine neutral position. The average resting LES pressure was found to be 29.0 (95% CI 4.0) mmHg. Similarly, the average 4sIRP among all 330 swallows was 9.2 (95% CI 1.3) mmHg (Table 2). Both measures were not statistically different between genders (p > 0.7).

4 ∣. DISCUSSION

This is the first pediatric prospective study of its kind that describes detailed esophageal manometry metrics in children without dysphagia. We describe and report multiple parameters applied in adults, such as integrated relaxation and average pressures of UES and LES, distal latency, and contractile integrals of esophageal peristalsis. This study also reports specific metrics that describe the length of the esophagus and its contractile segments. In addition, this is the first study to introduce several novel metrics that describe the velocity of the entire esophageal peristalsis and its segments.

The measured UES parameters including UES resting pressure, 0.2sIRP and 0.8sIRP, were found to be different than previously reported in a pediatric retrospective study of a large cohort of patients with variety of disorders.⁸ The mean and median values were variably different with much smaller 95% confidence interval and interquartile range. Similarly, our results are also different than reported norms in both preterm infants and adults.^9,12 These reported differences between studies are not surprising given that UES pressures and relaxation are significantly affected by numerous factors. These include subject position and comfort level, composition of the bolus, presence of esophageal pathology, size of the catheter, and the position of the catheter (particularly if the catheter has unidirectional pressure sensors).

The findings pertaining to esophageal peristalsis emphasize several features that are important to consider when assessing a child with dysphagia. Our study showed that failed swallows are extremely rare in children. However, per adult criteria outlined in the Chicago Classification,⁴ less than 50% of failed or ineffective swallows can be seen in a normal adult study. Similarly, the vast majority of our subjects did not have any TZ break, while several adult studies have shown normal TZ break >5 cm.¹⁰ Consequently, the current adult criteria define a pathologic TZ break as >5 cm in length.⁴ This differs markedly from our findings of a mean TZ break of 0.5 cm. The reported average TZ break and average values for PCI and DCI are essential to understand and define hypo- and hyper-contractile disorders in pediatrics. Similarly, the metrics defining the contractile velocity of esophagus and its segments have the potential to further delineate specific features of esophageal peristalsis in children. We also demonstrate that BMI and PCI or DCI have poor linear correlation (Figure 3A). At this time, given the unpredictability and subjectivity of electing CDP, the mean distal latency value is incompletely defined in pediatric esophageal manometry and should be used with caution. We found poor correlation between DL and esophageal length or height (Figure 3B).

FIGURE 3.

A) Correlation of BMI and contractile integrals. B) Correlation of esophageal contractile length(EcL) and distal latency (DL), and height and DL. C) Correlation of height and EcL

This study also delineates the contractile length of the esophagus (EcL) and the distribution of its contractile segments in children without dysphagia. We showed that there is a high linear correlation between EcL and height (Figure 3C). This lead us to derive esophageal length to height (MELH) ratio.¹³ This ratio helps us understand the expected growth and development of esophagus and its pressure areas in a rapidly developing pediatric population. These values can ultimately help diagnose abnormalities and determine future management in children with congenital (ie, tracheoesophageal fistula) or post-surgical (ie, fundoplication) anatomic abnormalities.

Reported measurements associated with esophagogastric junction such as LES resting pressure were found to be similar to adult studies despite the use of different catheters.¹⁰ Mean 4sIRP was found to be lower than reported in adults. Singedonk et al. ⁶ suggested based on mathematical modeling that 4sIRP is generally higher in pediatrics. However, it is important to emphasize that their analysis was based on symptomatic pediatric patients in the upright and semi upright position as well as adult asymptomatic subjects in the sitting position. 4sIRP is defined as an average of lowest maximal pressures during any non-contiguous 4 seconds in the designated 10 second window of LES relaxation. Given the method of its derivation, these values are affected by intrabolus pressure in the distal esophagus during LES relaxation and the simultaneously measured gastric pressure. Therefore, positioning of the patients and subjects will significantly affect the measurements.

Strengths of our study include the highly detailed analyses and novel metrics based of normal physiology in a high number of swallows. Further, in contrast to numerous studies of adult asymptomatic subjects, all subjects in the current study had esophageal biopsies to rule out significant esophageal inflammation that may affect esophageal motility. Based on several adult studies, 10–30% of patients with significant inflammatory changes in the esophagus are asymptomatic.^14-16 Other strengths of this study population include a similar gender representation, even age distribution ranging from 9 to 16 years and appropriate height and weight variability among both genders.

There are some limitations to our study. Since a validated pediatric dysphagia questionnaire is lacking, we decided to adopt a validated adult questionnaire (MDQ) with assistance of the subjects’ parents to help screen our subjects for dysphagia. This could possibly affect the classification of our study population. Similarly, in pediatric esophageal manometry, it is standard of care to place the catheter awake or under general anesthesia. There are no studies that address the effect of these very different approaches on esophageal motility. To help minimize subject discomfort and anxiety, the esophageal manometry catheters were placed under general anesthesia using the anesthetic agent sevoflurane and/or propofol in a few cases. Sevoflurane was administered to 22 out of 33 subjects during the procedure. There were no statistically significant differences between the subjects who received versus who did not receive sevoflurane in the measurements of PCI (p = 0.85), DCI (p = 0.75), 4sIRP (p = 0.18), or the average LES pressure (p = 0.68). Furthermore, there were no significant changes between the first and the last swallow in the protocol in regard to the measurements of PCI (p = 0.12), DCI (p = 0.78), or 4sIRP (p = 0.07). This suggests no further waning effects of anesthesia on the measurements during that time period. Similarly, the duration of time under anesthesia did not significantly affect the measurements when comparing subjects who underwent only upper endoscopy to those who underwent both upper and lower endoscopy: PCI (p = 0.27), DCI (p = 0.43), 4sIRP (p = 0.40), and average LES pressure (p = 0.49). All administered anesthetic agents have short elimination half-lives, and all subjects were given adequate time to fully awaken prior to the study. Still, some effects of general anesthesia on esophageal motility cannot be completely excluded. Another limitation is that subjects younger than nine years of age were not included in this study. This was due to challenges performing esophageal manometry in younger subjects given their limited ability to tolerate the nasal catheter and strict study protocol. Following experience we have gained in performing esophageal manometry studies in disease control subjects, we are planning to include children less than 9 years of age in a follow-up study.

The diagnostic algorithms and therapies for esophageal motility disorders in adults have significantly improved over the past two decades. This is mostly contributed to the invention of solid-state HRM catheters and applied research. Unfortunately, due to the lack of pediatric normative data, pediatric motility disorders are uniformly diagnosed according to established adult norms and using protocols and catheters designed for adults. This study highlights novel findings of significantly different pediatric esophageal measurements in children without dysphagia reinforces the importance of developing pediatric norms that can help address esophageal problems in children. Our study also emphasizes the importance of a very strict standardized esophageal manometry protocol that will help minimize external factors influencing esophageal manometry readings. This should include a universally accepted pediatric esophageal manometry catheter and a widely available bolus solution with acceptable taste and adequate impedance property (ie, 0.45%NaCl). Further research is needed to rigorously define pediatric normative data on esophageal motility pattern using both novel and previously defined metrics by means of age-appropriate protocols.

Key Points.

• Normative esophageal manometry parameters vary between children and adults.

• There is a need for standardized, pediatric esophageal manometry protocols.

• Several novel esophageal manometry metrics deserve consideration when assessing children with dysphagia.