pathophysiology of extraesophageal reflux disease

SGS is the most extensively studied laryngeal manifestation of GERD. There is popular agreement that PLPR is a causative factor in the development of SGS. However, the evidence linking these 2 pediatric conditions is weak and mainly based on either animal studies, or uncontrolled studies in humans. Trauma  and infection  are the 2 other etiological factors that have been implicated in the development of SGS.

 

extraesophageal symptoms of reflux eerd gerd
extraesophageal reflux

The damaging effects of gastric acid and pepsin on the subglottis have been demonstrated in animal models. Delahunty and Cherry , in their classic experimental study, demonstrated that the intermittent application of gastric acid to canine vocal cord produced granulomas, which was histologically similar to the early lesion of human SGS. In another canine model, application of gastric contents to subglottic mucosa once every alternate day for 3 to 4 weeks was sufficient to cause a 9-fold increase in SGS . (Squire R, et al ,2012)

Conversely, there was only a 1.5-fold increase in the control group. This study also showed a delay in reepithelization with exposure to acidic contents. Studies on the porcine subglottis showed that mucosa exposed to acid had reduced expression of messenger RNA (mRNA) for epidermal growth factor receptor (EGFR) . Downregulation of EGFR mRNA production was postulated to result in reduced mucosal turnover and impaired cellular repair. This resulted in basal cell hyperplasia and mucosal ulceration. In addition to disordered cellular repair, excessive deposition of connective tissue has also been associated with SGS. In vitro studies of human and rat tracheal tissue exposed to gastric juice displayed increased fibroblasts differentiation secondary to production of transforming growth factor beta 1 (TGF-h1) .( Jarmuz T, et al ,2004)

Presentation

There are no clinical presentations specific to PLPR. Patients often present with a wide range of atypical symptoms and signs. Parents generally do not perceive vomiting as a problem when it occurs no more than once daily, but are more likely to be concerned when vomiting is more frequent or when the volume of vomitus is large. Children may also present with excessive crying, irritability, failure to thrive, or feeding problems. Clinically, reflux symptoms are difficult to assess in infants and children. Although adults with esophagitis may complain of regurgitation, dysphagia, or heartburn, infants cannot describe their symptoms. Furthermore, the manifestations of PLPR often occur without the typical symptoms of reflux. Laryngeal symptoms that have been attributed to PLPR include hoarseness, a sensation of fullness at the back of the throat, postnasal drip with repetitive throat clearing, chronic cough, and laryngeal spasm. PLPR was found to be more prevalent in children with recurrent laryngotracheitis compared with a control cohort . An increased frequency of episodes of reflux in awake children with hoarseness has been previously reported .( Jamieson JR, et al , 2013)