July 1978 The Journal o f P E D I A T R I C S 2 3

Incompetent lower esophageal sphincter and gastroesophageal reflux in recurrent acute pulmonary disease of infancy and childhood

Fiftee n patients with recurrent acute respirator)' symptoms were evaluated for gastroesophageal reflux.

All 15 had barium esophagrams. Ten o f 15 had acid reflttx tests performed and lower esophageal

sphhwter pressures measured. Tire data were compared to those in 23 patients with no acid reflux and

23 patients with positive acid re.flux but no respirator)' symptoms. Ten of ten patients with respirator)"

s)'tnptoms who were evaluated by the acid reflux test had positive results. The retnahring five

demonstrated GER by barium esophagram. LES pressure tneasurements in the ten patients were

1~.3 • 1.5 mm llg, which was significantly lower than the pressures hr the acid reflax-negative group

(20.3 • 1.3 tnm tlg, P < 0.001) but trot different than in the patients with GER but no respiratory

s)'tnptoms (13.9 • 1.5 mm 11g, P > 0.05). GER secotidary to an incompetent lower esophageal sphincter

tn[ty be one cause o f recttrrent acute respirator)' disease in infants and children.

Dennis L. Christie, M.D. ,* Lilla R. O 'Grady , M.D. , and Donald V. Mack ,

Seatt le , Wash .

PULMONARY DISEASE secondary to aspiration of gastric contents from gastroesophageal reflux remains a controversial entity. In adult patients, investigators have attributed recurrent bronchitis, interstitial fibrosis, and pneumonia to gastroesophageal reflux with aspiration. I" However, the demonstration of gastric acid in the lungs of these patients has not been accomplished, and some believe that mainly debilitated or comatose patients are at risk for significant aspiration? Aspiration from GER may not be appreciated in pediatric patients; two recently published textbooks have not included GER in the differential diagnosis of recurrent respiratory disease. ~=

The present investigation was designed to answer two questions: (I) Is there a relationship between recurrent pulmonary disease in pediatric patients and incompetence

From the Department o f Medicine, Section o f Pediatric Gastroenterolog), The Mason Clinic, and the Children's Orthopedic llospital and Medical Center.

Supported b)' a National March o f Dhnes Medical Service Grant (No. C-112).

*Reprint address: Department of Medicine. Section of Pediatric Gastroenterolog); The Mason Clinic, 1100 Ninth Are., Seattle, WA 98101.

of the lower esophageal sphincter? (2) Are there charac- teristics in children found to have RPD and GER that would enable a physician to recognize these patients clinically?

I Abbreviations used GER: gastroesophageal reflux LES: lower esophageal sphincter

�9 R P D : recurrent pulmonary disease

M A T E R I A L S A N D M E T H O D S

Fifteen pediatric patients with recurrent acute respira- tory symptoms were referred for evaluation between July, 1976, and July, 1977. The children studied had symptoms of acute cough, tachypnea, dyspnea, or wheezing occur- ring intermittently for longer than two months, with asymptomatic periods between episodes of illness. All had abnormalities by physical examination of the chest and by chest radiographs during the time of illness. The majority had been referred because of respiratory symptoms. Eight of the 15 were under 2 years of age, with an average age of 3.1 years and a range of 4 months to 16 years. The data obtained on these 15 patients were compared to those in a group of 46 infants and children evaluated during the

0022-3476/78/0193-0023500.50/0 ~ 1978 The C. V. Mosby Co. VoL 93, No. 1, pp. 23-27

2 4 Christie, O'Grady, and Mack The Journal of Pediatrics July 1978

Table I. Clinical characteristics of patients with recurrent acute pulmonary disease

Symptom [ Total No. 15

Nonseasonal occurrence of symptoms 14 Recurrent acute cough 10 Wheezing 9 Chronic regurgitation 7 Fever during acute illness 7 Tachypnea 6 (Miscellaneous) Failure to thrive, anemia, hematemesis 6 Chest radiographs

Interstitial infiltrate 7 Consolidation

Diffuse 3 Focal 2

Atelectasis 2 ttyperinflation 1

Age of onset less than one year 10

same time period because of recurrent vomiting, regurgitation, dysphagia, heartburn, or abdominal pain. The average age of this second group was 6.3 years with an age range of one month to 17 years.

Most children with recurrent respiratory symptoms had a medical evaluation which included serum lgE, quantita - tive immunoglobulins, sweat tests by pilocarpine ionto- phoresis, alpha1 antitrypsin by immunodiffusion, arterial blood gases while in room air during acute illness, and chest radiographs. Chest radiographs were reviewed and classified into the following categories: interstitial infil- trate, consolidation (diffuse or focal), atelectasis, or hyper- inflation.

Esophageal motility was performed using a 3-lumen catheter assembly fused to a Cecar microcombination pH electrode. Side holes, 0.5 mm in diameter, were cut in two polyvinyl catheters, each with an internal diameter of 0.8 mm. These side holes were located 3 and 5 cm, respec- tively, from the tip of the electrode. A third catheter with an internal diameter of 1.1 mm was fused to the electrode for instillation of HC 1. Total outside diameter of the fused tubes and electrode was 4.8 mm. The distal occlusion of each perfused catheter caused pressure rises of greater than 800 mm Hg per second. The catheters were infused with Water by a high-fidelity h~'draulic capillary infusion system at a rate of 0.6 cc per minute, s Intraluminal pressures were transmitted to external transducers (Sta- tham P 23 De) and output from these transducers was recorded on a multichannel Grass 7 P polygraph recorder. The catheter a ssemblywas slowly pulled through the lower esophageal sphincter three consecutive times. The

peak sphincter pressure was measured in midrespiration with gastric pressure as zero reference. The amplitudes of the recorded sphincter pressures were then averaged to obtain a value for LES pressure. Lower esophageal sphincter length was measured in centimeters as the

distance between the first rise above zero gastric pressure and negative esophageal pressure when the manometric catheters were withdrawn through the gastroesophageal junction. All patients aged 5 years or less were sedated with intramuscular meperidine (2 mg/kg), chlorproma- zine (1 mg/kg), and promethazine (i mg/kg) one hour prior to the procedure.

After determination of LES pressure, the acid reflux test was performed. The electrode was positioned in the stomach and 0. IN hydrochloric acid was introduced. The volume infused was calculated on a basis of 300 cc per i.73 m'-'. The electrode was then withdrawn from the stomach and was positioned first at 2 and then 5 cm above the previously determined lower esophageal.sphincter.

If the pH did not rise to at least 6 after the electrode was withdrawn across the gastroesophageal junction, distilled water was infused to raise the starting, the test. Sponta- neous reflux was defined as a drop in pH to less than 4 on two occasions while the patient was in the supine or in the right or left lateral positions. If spontaneous reflux had ' not occurred in 10 minutes, the unsedated patients carried out Valsalva and leg-raising maneuvers or the examiner compressed the child's abdomen by hand. The sedated patients had similar pressure applied to the abdomen. A drop in p i t to less than 4 on two occasions was taken as evidence of induced reflux.

Barium esophagrams were performed, and each patient was evaluated for spontaneous reflux and for induced reflux after abdominal pressure. Esophageal motility and deglutition were observed under fluoroscopy at the time of the barium esophagram.

T R E A T M E N T

Each patient found to have gastroesophageal reflux by either spontaneous or induced acid reflux testing was placed on a medical regimen which included the follow- ing: (1) 10 to 30 ml of a magnesium hydroxide antacid one and three hours after meals and at bedtime, (2) elev/~tion of the head of the bed by 15 cm or positioning in an infant seat while asleep, and (3) formula feedings thickened with cereal for infants. Medical treatment was used for a six- week period before being considered a medical failure. Medical failure was defined as a recurrence of respiratory symptoms during treatment or failure of symptoms to improve. Patients with esophageal strictures had surgery and esophageal dilation performed.

Yoh,ne 93 Incompetent esophageal sphhwter 2 5 Number l

The Student t test was used for tests of significance between means and the data were expressed as mean ___

SEM.

C L I N I C A L C l l A R A C T E R I S T I C S

Table I demonstrates the clinical characteristics of the recurrent acute pulmonary disease group. Noteworthy is the nonseasonal occurrence of respiratory symptoms, the frequency of wheezing and of recurrent acute cough. The majority of patients had the onset of their disease by one year of age. Regurgitation in early infancy occurred in a significant percentage of patients but was not present after one year of age in the majority. Chest radiographs usually showed an interstitial infiltrate or consolidation.

Evaluation of other causes of recurrent pulmonary disease was within normal limits in the patients so studied (nine of nine normal sweat chloride, seven of seven normal immunoglobulin values, seven of seven normal serum IgE, I and six of six normal alpha, antitrypsin). Arterial blood gases were generally abnormal during the acute phase of the illness and demonstrated a decreased oxygen saturation but a normal carbon dioxide concentra- lion.

R E S U L T S

Acid reflux test. Ten of 15 children with recurrent pneumonia had the acid reflux test performed. Eight patients had spontaneous reflux. All ten had induced reflux when the electrode was positioned 2 or 5 cm above the manometrically determined lower esophageal sphinc- ter. Twenty-three patients in the comparison group had neither spontaneous nor induced reflux. The other 23 children had positive acid reflux tests, 13 having sponta- neous reflux and all 23 having induced acid reflux.

Barium esophagram. The five patients with recurrent acute pulmonary disease who did not have acid reflux testing performed had positive barium esophagrams demonstrating GER. Another three patients a l so had positive studies; thus, a total of 8 of 15 had reflux by barium esophagram. The 23 patients with negative acid reflux tests had normal barium esophagrams. Eleven of 23 children With positive reflux tests had barium esopha- grams that demonstrated reflux, with four also having esophageal strictures. No patient demonstrated asperation while swallowing the barium.

Lower esophageal sphincier pressures. The LES pres- sures of the 23 infants and children with negative acid reflux tests were 20.3 _ !.3 mm Hg. The LES pressure was 13.9 • 1.5 mm Hg in the 23 patients with positive reflux tests (P < 0.01). Ten of 15 patients with recurrent acute pulmonary disease had LES pressures measured;

4 0 . o

3 5

o = < 2 years

�9 = > 2 years

3 o

~" 2 5 -

20 �9

15 �9

~ ' 5 - .o o

A - - B - - C - -

lqg. I. LES pressure in acid reflux-negative patients (A) compared, to acid reflux-positive patients without (B) and with (C) respiratory symptoms. There was a statistically significant difference in LES pressure between Groups B and A (P ,--- 0.01) and Groups C and A (P *---0.001).

the mean pressure was 11.3--- 1.5 mm tlg, which is significantly lower than in the acid reflux-negative comparison group (P < 0.001) but not different than in the acid reflux-positive comparison patients (P > 0.05).

Lower esophageal sphincter length. The length of the lower esophageal sphincter was measured in all three groups, but no statistically significant difference was found. The recurrent acute respiratory disease group had a LES length of 1.3 --- 0.13 cm. This compared to a length of 1.6 -4- 0.12 cm for the acid reflux-negative group and 1.8 _ 0.13' cm for the acid reflux positive comparison group.

R E S U L T S O F T R E A T M E N T

Five patients with recurrent acute respiratory symp- toms required surgery. Four patients had recurrent episodes of pneumonia; the fifth patient had continued attacks of wheezing, tachypnea, and dyspnea. Four had Nissen fundoplica!ions; one child with cerebral palsy had an esophageal diversion procedure. Three of the five patients requiring surgery had underlying disease, two with tracheoesophageal fistula which had already been repaired and one wi thcerebra l palsy. None of the five patients requiring surgery has had respiratory disease since surgery was performed. Follow-up has been one month to 12 months (mean 6.2 months). Five infants originally evaluated when less than one year of age have remained out of the hospital without recurrent acute respiratory symptoms since institution of medical ther-

2 6 Christie. O'Grad), and Mack The Journal of Pediatrics July 1978

apy; the follow-up period has been from three to six months. Three of the five remaining patients over the age of one )'ear have had no episodes of respiratory symptoms while on medical therapy and have been followed for longer than six months. Two others have only recently been started on medical therapy.

Eight of the 23 patients in the comparison group demonstrated to have GER by positive acid reflux tests required surgery, four because of stricture formation and four because of recurrent Vomiting and failure to thrive. The remaining 15 patients responded to initial medical treatment. Range of follow-up period is one month to 12 months (mean 7.3 months).

D I S C U S S I O N

The symptoms caused by GER in children include regurgitation, vomiting, failure to thrive, h ematemesis, chronic anemia, heartburn, or dysphagia. Danus et aP

I recently!described a group of infants with "recurrent obstructive bronchitis" who were thought to have GER as a contributing factor, they had recurrent episodes of wheezing, dysPnea, shortness of breath, fever, rales, and rhonchi over a per!od of several months. None of the patients, had characteristic chest roentgenographic changes; other tests for causes of recurrent pulmonary disease were not included. In Danus' study reflux was demonstrated in only 23 of the 43 infants by routine barium swallows, but all had abnormally low lower esophageal sphincter pressures as compared to those in a control population. A significant number improved with medical (ahlireflux) measures. In contrast, Herbst et al '~ have demonstrated no abnormality in LES pressure !n pediatric patients with recurrent pneumonia and GER. In fact, their patients with recurrent respiratory disease had higher pressures than did patients with GER but no respiratory symptoms.

Other physicians have previously associated GER with recurrent pulmonary disease in children,"- '~ but evalua- tion of LES pressure and the acid reflux test have not been used. The present investigation demonstrates that GER as diagnosed by the acid reflux test does occur in pediatric patients with recurrent acut e pulmonary disease. This test has been shown to be more sensitive than routine barium esophagram as a direct method to measure GER, both in adults and in pediatric patients.' ~. "

Although there is a correlation between decreased LES pressure and GER, a significant overlap of pressures does exist in symptomatic and asymptomalic adults. '~ There- fore, measurement of LES pressure by itself is not necessarily indicative of GER. Of interest, however, in the present stud), is the significantly decreased LES pressure in the recurrent acute Pulmonary disease group as

compared to the acid reflux-negative patients. The LES pressure in the recurrent pulmonary disease group was comparable to that in patients with GER but no respira- tory symptoms. This fact would suggest that some pediat- ric patients with recurrent acute pulmonary disease may aspirate gastric contents because of an incompetent lower esophageal sphincter.

Other factors in addition to LES pressure must be involved in determining sphincter competency. Total length of LES was no different in patients with and without reflux in our study, but we did not determine intra-abdominal length of the LES, which has been demonstrated to be shorter in patients with reflux. '~ '~

Whitington et al '~ have recently demonstrated recurrent pulmonary disease in patients with tracheoesophageal fistula because of an incompetent lower esophageal sphincter. O~ur data wou ld support their conclusion.

Studies are not available concerning the incidence of GER in infants and children with recurrent acute pulmo- nary disease. We conclude that GER may be an unrecog- nized provoking factor in recurrent acute (espiratory illness in infants and children; further studies are indi- cated to define the incidence and significance of GER in these patients.

Our data suggest that aspiration of gastric contents occurs secondary to an incompetent lower esophageal sphincter in pediatric patients and that aspiration may present as recurrent acute respiratory symptoms in early childhood. GER should be considered in the differential diagnosis of any pediatric patient with recurrent respira- tory disease.

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