Prevalence of Gastroesophageal Reflux of Wheezers in Infancy and Early Childhood

In some severe recurrent wheezers who do not respond to asthma medication including inhaled corticosteroids, wheezing is caused by gastroesophageal reflux (GER) [1-2]. However, physiological GER is largely recognized in younger children [3] and gastroesophageal reflux disease (GERD) manifests various symptoms other than wheezing [4]. It remains unclear how GER is associated with wheezing. Additionally, it has not yet been determined whether recurrent wheezers in infancy later develop asthma. Therefore, we evaluated the prevalence of GER among infantile wheezers by 24-hour esophageal pH monitoring (EpHM).


Introduction
In some severe recurrent wheezers who do not respond to asthma medication including inhaled corticosteroids, wheezing is caused by gastroesophageal reflux (GER) [1][2]. However, physiological GER is largely recognized in younger children [3] and gastroesophageal reflux disease (GERD) manifests various symptoms other than wheezing [4]. It remains unclear how GER is associated with wheezing. Additionally, it has not yet been determined whether recurrent wheezers in infancy later develop asthma. Therefore, we evaluated the prevalence of GER among infantile wheezers by 24-hour esophageal pH monitoring (EpHM).

Object
This study investigated the prevalence of GERD among general wheezers in infancy and early childhood in Japan.

Subjects and Methods
The subjects were included in this study prospectively. 32 patients were admitted to Yokohama City Minato Red Cross Hospital because of wheezy exacerbation. The mean months of age in this patient group was 12.7±5.2 (range: 3 to 24). Past patient and family medical histories, laboratory data including serum IgE, peripheral eosinophils counts, specific-IgE (ImmunoCAP, Phadia AB, Sweden) including air-borne antigens: mites, house dust and Japanese cedar, and food-antigens: egg-white, cow's milk and wheat, and rapid Respiratory Syncytial virus antigen test of nasal swab were analyzed (Check RSV, SA Scientific Inc., USA). 11 of 32 patients (34.4%) were positive sensitization to aeroantigens and 17 patients (53.1%) ware positive sensitization to food antigens. 8 patients (25.0%) had treated as diagnosed asthma taking controller medication at admission, all had taken leukotriene receptor antagonist (4mg/day) and 3 patients had budesonide inhalation suspension (0.5mg/day) together.
All patients were treated with systemic administration of corticosteroids (soluble prednisolone 0.5mg/kg×4/day) and inhaled beta stimulant (salbutamol 0.1ml q 4-8hrs) for 4 or 5 days after admission. Twenty-four-hour esophageal pH monitoring (EpHM) was performed on the 6th or 7th hospitalized day after completion of acute treatment when the respiratory state had stabilized and wheeze, tachypnea and desaturation had disappeared (PH 101 ZS, Chemical Instruments CO., LTD., Japan). The ratio of the duration of pH less than 4.0 within the 24-hour monitoring period was expressed as the pH index. A positive pH index was defined as a ratio of 4% or higher [6]. In addition to pH index, we also calculated the numbers of reflux episodes while awake as defined by a number of episodes showing pH < 4.0, based on the previous report by Yoshida et al. [7].

Results
Among these 32 patients, 3 patients (9.4%) were found to have GER based on EpHM. The mean pH index based on the ratio of time under pH 4.0 was 1.36 (SD; 1.82) %. The mean numbers of reflux episodes while awake was 2.9 (SD; 3.4) /hr.

Discussion
Although it has been demonstrated that GER causes severe recurrent wheeze in infancy and early childhood, there are limited data on the prevalence of GER among wheezers in younger children, *Corresponding author: Atsushi Isozaki, Department of Pediatrics, Medical Center for Allergy and Immune Diseases, Yokohama City Minato Red Cross Hospital, 3-12-1 Shin-yamashita, naka-ku, Yokohama City, Japan, Tel. +81-45-6100; Fax. +81-45-6101; E-mail: isozaki.ped@yokohama.jrc.or.jp especially infants. Our data demonstrated that the prevalence of GER among wheezers in younger children was only 3 of 32 patients (9.4%).
In a study of 47 severe, recurrent wheezers ranging from 5 to 58 months old, Saglani and colleagues reported that GER was the predominant cause [2]. In that study, the frequency of GER was 23% among their subjects, that of asthma was 41% and 11 of 19 patients with definite asthma also had GER, as defined by abnormal pH. In a study limited to younger children, Gorenstein and colleagues reported that the prevalence of GERD was 41.8% among 153 asthmatic children aged 1.4 (SD; 2.8) years old [8]. Teixeira and colleagues indicated that the prevalence of GERD was 68.1% in 69 patients with a mean age of 2.6 years old [9].
There is a difference in the prevalence of GERD among asthmatic children between the present study and previous reports. Demographic differences may be reflected in the results of our study. Brand and colleagues proposed phenotypes of wheezing disorders in pre-school children as episodic wheeze and multiple-triggered wheeze based on temporal pattern [10]. Although the previous study included more severe multiple-triggered wheezers, our study included not only multiple-triggered wheezers but also episodic wheezers.
Although the prevalence of GERD among severe wheezers was higher in previous reports, our study concluded that the prevalence of GERD among general wheezers is lower in younger children. Data are expressed as number (ratio) or mean (SD).   This article was originally published in a special issue, Lung Disorders/ Injury handled by Editor(s). Dr. Yutong Zhao, University of Pittsburgh, USA