A pilot trial on the treatment of gastroesophageal reflux-related cough in infants

Abstract

Background: Diagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheeze. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents.

Objectives: The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms.

Methods: Infants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB.

Results: Nineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported.

Conclusions: In infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option.

Keywords: Cough; esophagus; gastroesophageal reflux; pediatric asthma.

Figure 1

Test process.

Figure 2

Infants had pH probes done before and after study medications. Compared to pre-study pH probe data, the PP group (white bars, n=4) did not show any improvement in measures of percent time with pH<4 (RI%) (A), the number of episodes with pH<4 (B), or a combined score (C). In contrast, the OB group (n=6) showed a decrease in RI% (p=0.028), a decrease in episodes (P=0.028), and a decrease in score (P=0.07). The OP (n=3) and BP (n=3) groups also showed a decrease in RI%, episodes, and score, but with the smaller number of patients these improvements did not reach statistical significance.

Figure 3

Each infant was assessed for the number of GER events/day (visible emesis and/or rumination). After one-month post-study medication, use of PP did not decrease the amount of GER episodes compared to their pre-study value. Treatment with either OB or OP decreased the number of GER episodes per day compared to their study entry, though this was statistically significant only for the OB group (P=0.028). After an open label period of bethanacol and omeprazole, the PP group demonstrated a decrease in GER episodes similar to OB though it did not reach statistical significance (P=0.06) (B).

Figure 4

Each infant was assessed for coughing spells/day. Post-therapy, PP (n=4) did not decrease the amount of coughing compared to the group’s pre-study value (A). In contrast, the three treatments of OB (n=6), OP (n=4), and BP (n=5) did decrease the number of coughing episodes per day, but these data only reached statistical significance for the OB group (P=0.028). After open label therapy of bethanacol and omeprazole, the PP group demonstrated a decrease in cough that was similar in magnitude to the OB study period though it did not reach statistical significance (P=0.06, Figure 3B).

Figure 5

Treatment of GER improved respiratory scores (RS). At study entry, all infants had evidence of abnormal respiratory scores, which were similar among the groups (A). After the study period, PP did not improve the RS (n=4). The three treatments of OB (n=6), OP (n=4), and BP (n=5) did decrease the RS, but these data only reached statistical significance for the OB group (P=0.04). After being on open label double therapy, PP also showed an improved RS though it did not reach statistical significance (P=0.10) (B).