Software for symptom association analysis in pediatric gastroesophageal reflux disease

Abstract

Gastroesophageal reflux (GER) disease is a serious complication of the upper gastrointestinal tract. Cardiorespiratory symptoms such as apnea, oxygen desaturation and bradycardia may be related to GER. Thus, the recommended diagnostic methodology in pediatric patients requires 24-h synchronized esophageal and cardiorespiratory monitoring. However, there is no computer tool available for this purpose and therefore, researchers and physicians are forced to seek for customized solutions. This paper presents an open source computer program for the analysis of symptom association. It allows a convenient visualization of the biological signals and implements the three main metrics for symptom association, that is, the symptom index, the symptom sensitivity index and the symptom association probability. This software represents a flexible solution and will facilitate caregivers an easy assessment of the existence of temporal association between GER and cardiorespiratory episodes. This would ideally reduce inappropriate medical and surgical treatments and would provide an early diagnosis of the medical condition.

Introduction

Physicians have agreed to define gastroesophageal reflux (GER) as ‘the passage of gastric contents into the esophagus with or without regurgitation and vomiting’ [1]. It is a physiological condition that occurs in healthy adults and children [1], [2]. However, if it is associated with symptoms and complications then it turns into a pathology known as GER disease (GERD). According to Tsoukali and Sifrim [3], GERD is the most expensive gastrointestinal disease. It affects approximately 20% of the western population and there are 5 in 1000 new cases every year [4]. In pediatric patients it seems to be a growing problem [2] and in some occasions, it may be behind infant sudden death [5]: the gastric content may block the upper airways or trigger central apneas via vagal reflex mechanisms [1], [6], [7].

Silny et al. [8] proposed the intraluminal impedance method to monitor the esophageal motility. It is, along with pH monitoring, the gold standard for the diagnosis of GERD. Combined multiple intraluminal impedance and pH (MII-pH) allows detecting acid and non acid GER episodes and is recommended for the evaluation of symptom association in pediatric patients with cardiorespiratory (CR) symptoms [1]. In particular, the North American Society for Pediatric Gastroenterology, Hepathology and Nutrition and the European Society for Pediatric Gastroenterology, Hepathology and Nutrition suggest performing synchronized 24-h CR and MII-pH monitoring in children with apnea or apparent life-threatening events. This methodology allows identifying accurately all GER and CR events. Once identified the onset of GER and acute extra-digestive symptoms, there are three different estimators to evaluate a possible temporal relationship: the symptom index (SI) [9], the symptom sensitivity index (SSI) [10] and the symptom association probability (SAP) [11]. Note there is no agreement between these indices [12], [13] and generally, caregivers prefer to contrast the results of at least two of them before making decisions. Symptoms are considered to be related if they occur within a given time interval around the onset of a reflux episode. This is known as the window of association. As there is currently no consensus about the optimal width of the window of association, several studies have considered different window lengths, in particular comprised between 15 and 600 s [14], [15], [16], [17].

Physicians are demanding software applications able to show a synchronized representation of esophageal and CR monitoring. Commercial applications do not provide a solution for this problem so that clinicians end of calculating complex parameters by hand or following inappropriate definitions [17]. This paper presents a description of a computer program for the evaluation of symptom association in newborn patients with CR symptoms. It is a complete and flexible tool that considers the three main symptom association estimators. It allows varying the window of association and analyzing the existence of a temporal relationship between different events: acid, non-acid and/or pH-only reflux episodes on the one hand, and bradycardia, oxygen desaturation and/or apnea on the other.