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Review Asthma Asthma and Gastroesophageal Reflux Disease in Children – Completing the Puzzle Fernando Maria de Benedictis, 1 Anna Maria Tocco 2 and Giuliano Lombardi 2 1. Salesi Children Hospital Foundation, Ancona, Italy; 2. Division of Pediatrics, Ospedale Santo Spirito, Pescara, Italy M any findings support a possible association between gastroesophageal reflux disease (GERD) and asthma in children, but there is not enough evidence to support the causality of this association. Longitudinal studies with long-term follow-up are urgently required to cover the many gaps that persist in this area. Treatment of GERD with proton pump inhibitors (PPIs) in children with uncontrolled asthma does not substantively improve asthma outcomes but large, controlled trials in children symptomatic of both asthma and GERD are lacking. Since there are significant safety concerns for long-term PPIs use in children, physicians should carefully balance their therapeutic decisions in individual cases. Keywords Asthma, gastroesophageal reflux, comorbidity, microaspiration, pH measurement, proton pump inhibitors Disclosure: Fernando Maria de Benedictis, Anna Maria Tocco and Giuliano Lombardi have no conflicts of interest to declare in relation to this article. No funding was received for the publication of this article. Gastroesophageal reflux (GER), the intermittent ascent of acid contents into the oesophagus, is a normal physiological process. In contrast, gastroesophageal reflux disease (GERD) is present when the reflux of acid contents causes troublesome symptoms and/or complications. 1 Asthma and symptomatic GER are both common disorders in childhood and symptoms of GER are frequently reported among children with asthma. 2,3 Historically, respiratory manifestations have been recognized as a potential consequence of GERD, and the relationship between asthma and GERD has been largely debated in the literature. Compliance with Ethics: This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. The aim of this article is to critically review the nature and the clinical aspects of this association in childhood and shed light on one of the most controversial fields of respiratory medicine. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Exploring the association between asthma and gastroesophageal reflux disease Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 17 October 2016 Accepted: 25 January 2017 Citation: European Respiratory & Pulmonary Diseases, 2017;3(1):29–31 Corresponding Author: Fernando Maria de Benedictis, Salesi Children’s Hospital Foundation, 11, via Corridoni, I-60123 Ancona, Italy. E: pediatria@fmdebenedictis.it Over the last 30 years, several studies have evaluated the prevalence of GERD in children with asthma. Data are controversial, the differences in the reported prevalence being determined mainly by the criteria used for definition of GERD (that is, symptoms versus laboratory investigation), the asthmatic population included (mild versus severe asthma), the design of the study (interventional, cross-over, retrospective) and the presence of a control group. It is, therefore, not surprising that the mean prevalence of GERD in children with asthma varied from 19.6% to 62.9% when GERD was identified by gastrointestinal symptoms or oesophageal pH monitoring, respectively. 4 Few studies included a control group, and the prevalence of GERD was 4.8% in healthy children. The pooled odds ratio for the association between GERD and asthma was 5.6 in controlled studies. 4 Exploring the relationship between asthma and GERD in children is hampered by many shortcomings. A global, evidence-based consensus on the definition of GERD in the paediatric population suggests that GERD be defined by using a “patient-centred symptom-based” method. 5 However, symptom-based criteria for GERD have significant limitations in children, because reporting of symptoms may be unreliable until the age of eight years. 5 Furthermore, asthma and GERD may have similar symptoms in childhood, such as nocturnal cough, chest tightness and exercise-induced discomfort, thus making difficult to determine which children actually have GERD. 6 Children and adolescents with GERD more commonly manifest cough and other respiratory symptoms than the typical oesophageal complaint of heartburn in adults. 7,8 Indeed, in a recent study in children with poorly controlled asthma, no gastrointestinal symptom differentiated those with and without GER identified by oesophageal pH monitoring. 9 Taken together, these findings emphasise that the prevalence of GERD in asthmatic children identified in studies that used symptom scores as inclusion criteria and/or endpoints is likely biased by the inability to differentiate symptoms of asthma from those of GER. 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