Further study is needed before link between gastroesophageal reflux disorder and otitis media can be firmly established

Does gastroesophageal reflux disorder (GERD) lead to middle ear infections in young children? Otitis media (OM) or ear infection, has the highest incidence, 62.9 percent, among all medical conditions in children younger than age five. Recent studies have suggested that GERD may cause OM.

Previous research into GERD revealed that regurgitation of breast-milk or formula was reported in half of 0- to 3-month-olds, peaked at 67 percent at four months of age, and decreased dramatically to five percent at 10 to 12 months of age. An analysis of children who had undergone a myringotomy found that the fluid in the middle ear (effusion) of four of five cases of ear infection in children aged two to eight years tested positive for pepsin or pepsinogen, a digestive enzyme, in concentrations that were roughly 1000 times higher than those found in serum (a fluid in the blood). In addition, they found no evidence of pepsin production in three middle ear specimens, leading to a conclusion that pepsin found in middle ear effusions was probably due to the reflux of gastric contents rather than material in plasma (a fluid in the blood).

Other studies have confirmed an association between gastric contents and middle ear effusion. However, association does not equal causation, especially in OM where the cause of the infection is usually multifactorial.

A new study has been completed that set out to investigate the causal relationship of GERD and OM by 1) confirming the finding of pepsin/pepsinogen in the middle ear fluid of children undergoing myringotomy and tube placement for chronic or recurrent OM; and 2) querying parents about symptoms that suggest the presence of GERD in these children. The authors of “Association of Reflux with Otitis Media in Children” are Judith E. C. Lieu MD, P. Ganesh Muthappen, and Ravindra Uppaluri MD, PhD, all from the Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO. Their findings are being presented on September 21, 2004, at the American Academy of Otolaryngology-Head and Neck Surgery Foundation Annual Meeting & OTO EXPO, being held September 19-22, 2004, at the Jacob Javits Convention Center, New York City, NY.

Methodology:

The prospective observational study included 34 children, aged seven months to seven years, recruited from the clinical practice of the Division of Pediatric Otolaryngology at St. Louis Children’s Hospital. Middle ear fluid samples were collected from 22 children; a total of 36 samples were tested. Researchers were usually able to collect at least 100 microliters of middle ear fluid per ear.

The subjects were required to have a history of recurrent otitis media (ROM) or chronic otitis media with effusion (OME) and meet the criteria for placement of tympanostomy tubes. OME was defined as the presence of middle ear fluid for at least 3 months documented by physical examination or Type B tympanogram in at least one ear. Those excluded from the study ROM had a medical history of disorders known to be associated with an increased prevalence of ROM, OME, or gastroesophageal reflux disease (GERD).

Outcomes of the research included measurement of Pepsin/pepsinogen in middle ear fluid: Middle ear fluid samples were examined for the presence of pepsin using a proteolytic enzyme assay and ELISA specific for pepsinogen I.

Parents of the children were asked about current symptoms that may be suggestive of gastroesophageal reflux, using validated questionnaires. These questionnaires included the Infant Gastroesophageal Reflux Questionnaire (I-GERQ) for children two years old and younger, and the GER3-9P for children age three to seven years.

Results:

Out of the 36 samples, 67 percent were positive for pepsin of pepsinogen I using the proteolytic assay, and 69 percent were positive using ELISA. For the proteolytic assay, pepsin/pepsinogen was present in positive samples in the range of 1.33 micrograms (mcg)/mL to 275 mcg/mL. For the ELISA, pepsin/pepsinogen was present in positive samples in the range of 2.68 mcg /mL to 196 mcg /mL. Agreement between assays was fair, with a kappa of 0.33. Each type of fluid tested positive in each type of assay, but not all of the effusions (which had to be one of the four types) were positive for pepsinogen.

Symptoms of reflux in our group of children were not more prevalent than in previously published studies of normal children with no pathologic reflux. Of children two years old or younger, only 1/22 (4.5 percent) had an IGERQ score >7, indicating symptomatic GERD. Of 9 children aged 3-7 years with symptom data, one complained of nausea during the past week, and 3 complained of stomachache. No one had heartburn, epigastric pain, sour taste in the mouth, or pain while swallowing.

Conclusions:

The findings revealed pepsin or pepsinogen in middle ear fluid specimens from children with OME and is consistent with previous research. The likely mechanisms for finding pepsin or pepsinogen in middle ear fluid include 1) pepsinogen produced within the middle ear, 2) gastroesophageal or esophagonasopharyngeal reflux, or 3) fluid passed through a membrane obtained from serum. However, concentrations of pepsin/pepsinogen are approximately 10-1000 times the concentration in serum, making transudation an unlikely mechanism.

The lack of symptoms associated with reflux disease among the children in this study does not support reflux as the mechanism for pepsin or pepsinogen to be found in the middle ear. However, others have documented that supra esophageal reflux is often asymptomatic. In addition, the questionnaires ask about current or recent symptoms, and may not reflect symptoms these children had at the onset of their recurrent or chronic OM.

This pilot study replicates the finding of pepsin/pepsinogen in the middle ear fluid of many children with chronic or recurrent OM, although an increased incidence in symptoms associated with GERD in children was not found. The researchers suggest additional study is needed before a causative link between GERD and OM can be firmly established.