In patients with established gastroesophageal reflux disease, TLESRs have a high prevalence and is two times more likely to be related to the reflux[26]

In patients with established gastroesophageal reflux disease, TLESRs have a high prevalence and is two times more likely to be related to the reflux[26]. suppression and add-on uses of baclofen or gabapentin. INTRODUCTION Gastroesophageal reflux-induced chronic cough (GERC) Edaravone (MCI-186) is a special form of gastroesophageal reflux disease with predominant cough symptom[1] and along with cough variant asthma, upper airway cough syndrome or eosinophilic bronchitis, is considered as a common cause of chronic cough[2,3]. Like gastroesophageal reflux disease, proton pump inhibitors (PPIs) alone or in combination with prokinetic brokers are a standard medical therapy for GERC and can resolve the cough in most patients[1]. However, a small percentage of patients with GERC are resistant to the standard anti-reflux treatment and this condition is also defined as refractory GERC[4]. This review summarizes our understanding about the definition, mechanism and management of refractory GERC. DEFINITION OF REFRACTORY GERC How to define refractory GERC remains to be controversial. There is no consensus around the refractory gastroesophageal reflux Edaravone (MCI-186) disease which Edaravone (MCI-186) GERC can refer to. The generally accepted definition of refractory gastroesophageal reflux disease is the prolonged classical reflux-related symptoms such as regurgitation and heartburn despite the treatment with PPIs twice daily for at least 4-8 wk[5]. Recently, Sifrim et al[6] proposed that refractory gastroesophageal reflux disease should be defined as the condition in which symptoms (heartburn and/or regurgitation) are not responsive to a stable double dose of PPIs during a treatment period of at least 12 wk and patients continue to statement bothersome symptoms while on PPIs at least thrice weekly for the last 3 mo[6]. As one of extraesophageal symptoms, cough can be caused Rabbit Polyclonal to Smad1 by many diseases other than GERC. A cause-effect association between reflux and cough is usually more difficult to establish than regurgitation and heartburn, and too long-lasting trial with PPIs may delay the diagnosis and treatment of the other etiologies of chronic cough. Therefore, we have defined refractory GERC as a condition of chronic cough with the objective evidence of abnormal reflux as demonstrated by multi-channel intraluminal impedance-pH monitoring (MII-pH), and resistant to a 8-wk standard medical anti-reflux treatment but responsive to the subsequent intensified anti-reflux therapy[4,7]. This definition is consistent with the principles recommended in several guidelines for the management of chronic cough[1,8] as well as the generally accepted definition of refractory gastroesophageal reflux disease[5]. The exact prevalence of refractory GERC is still unclear. It is estimated that 10%-40% patients with gastroesophageal reflux disease do not or only partially respond to the standard dose of PPIs[9]. Unlike erosive esophagitis, nonerosive reflux disease has basically normal esophageal mucosa under an endoscope and normal or slightly abnormal esophageal acid exposure as indicated by MII-pH, accounts for 70% of Edaravone (MCI-186) gastroesophageal reflux disease and is poorly responsive to PPIs treatment[10,11]. Therefore, nonerosive reflux disease is responsible for the majority of refractory gastroesophageal reflux disease. Our preliminary results have shown that refractory GERC accounts for about one third of GERC[12], and is comparable with the prevalence of refractory gastroesophageal reflux disease. MECHANISMS OF REFRACTORY GERC It is well known that GERC may be caused by microaspiration of the refluxate into the airways (reflux hypothesis) and esophageal-tracheobronchial reflexes mediated by the afferent nerves in the distal esophagus (reflex hypothesis)[1]. However, the mechanisms underlying the refractory GERC is poorly understood. It may be associated with the incomplete acid suppression, non-acid reflux, transient lower esophageal sphincter relaxations (TLESRs) and esophageal hypersensitivity. INCOMPLETE ACID SUPPRESSION Incomplete acid suppression has been documented in patients with persistent symptoms despite the therapy with PPIs at a standard dose. Several studies have shown 4%-17% patients presented Edaravone (MCI-186) with abnormal acid reflux[13,14] and 7%-11% patients had a positive symptom index[15,16] as revealed by 24-h esophageal pH monitoring when they were on PPIs. The residual acid reflux can continue to elicit cough through microaspiration or esophageal-tracheobronchial reflex[1]. In addition to poor compliance such as not taking PPIs in time or at the suitable time, ineffective acid.