Abstract
Background: Reflux aspiration secondary to gastroesophageal reflux disease (GERD) is one of the causes of chronic gastrointestinal and respiratory morbidity in children with esophageal atresia (EA). Currently there are no simple, validated non-invasive tests for the diagnosis of reflux aspiration in children.Objectives: The aim of this pilot study was to investigate pepsin detected in exhaled breath condensate (EBC) and saliva as a potential non-invasive marker of reflux aspiration in children with EA.Methods: EBC and saliva samples were prospectively collected from children with EA aged between 5 and 18 years attending a multidisciplinary EA Clinic. Pepsin in the samples was assayed by two methods, a commercial lateral flow device, the Peptest™ and an enzyme-linked immunosorbent assay (ELISA) and correlated with validated gastrointestinal and respiratory symptom questionnaires and objective measures of GERD and respiratory function.Results: EBC were collected from 18 children with EA, 15/18 also provided salivary samples. Pepsin was not detected in any of the EBC samples using the Peptest™ and only 1/14 (7.1%) samples by the ELISA. However, pepsin was detected in 33 and 83% of saliva samples when analyzed with Peptest™ and the ELISA respectively. Salivary pepsin levels were significantly higher in children with reflux symptoms or wheeze. Pepsin was detected by the Peptest™ in the saliva of 5/5 (100%) children with histological evidence of reflux esophagitis compared with 0/2 (0%) in children with normal histology (p = 0.048).Conclusions: Salivary pepsin was detected in a large proportion of children with EA and was significantly associated with GERD symptoms or wheeze. The role of salivary pepsin as a potential non-invasive marker of reflux aspiration in children with EA needs further validation in future studies with larger cohorts.
Highlights
Esophageal atresia associated with tracheo-esophageal fistula (EA), is commonly associated with long-term gastrointestinal and respiratory morbidity including gastroesophageal reflux disease (GERD), esophageal strictures, recurrent respiratory tract infections, chronic cough and asthma [1]
Salivary pepsin was detected in a large proportion of children with EA and was significantly associated with GERD symptoms or wheeze
Children with esophageal atresia associated with tracheaesophageal fistula have known gastrointestinal and respiratory complications, including gastro-esophageal reflux disease and reflux aspiration
Summary
Esophageal atresia associated with tracheo-esophageal fistula (EA), is commonly associated with long-term gastrointestinal and respiratory morbidity including gastroesophageal reflux disease (GERD), esophageal strictures, recurrent respiratory tract infections, chronic cough and asthma [1]. Detection and management of reflux aspiration is essential to prevent long-term respiratory morbidity in EA patients [2]. The diagnosis of micro-aspiration of gastric fluid remains challenging. Whilst invasive tests such as endoscopy, pH monitoring and multi-channel impedance are effective diagnostic tools for reflux, there is no currently available sensitive, specific, validated test for assessing reflux aspiration [4]. Reflux aspiration secondary to gastroesophageal reflux disease (GERD) is one of the causes of chronic gastrointestinal and respiratory morbidity in children with esophageal atresia (EA). There are no simple, validated non-invasive tests for the diagnosis of reflux aspiration in children
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