A Causal Relationship Between Cough and Gastroesophageal Reflux Disease (GERD) has been Established: A Pro/Con Debate

Abstract

Along with upper airway cough syndrome (formerly, postnasal drip syndrome) and eosinophilic airway inflammation (asthma, non-asthmatic eosinophilic bronchitis), gastroesophageal reflux disease (GERD) is generally considered among the most common etiologies of chronic cough. Indeed, cough management guidelines published by numerous respiratory societies worldwide recommend evaluation and treatment of GERD as an integral component of the diagnostic/therapeutic algorithm for the management of chronic cough. However, a significant number of patients with chronic cough presumed due to GERD do not report improvement despite aggressive acid-suppressive therapy. Some of these refractory cases may be due to the recently appreciated entity of non-acid or weakly acidic reflux. Further contributing to the controversy are recent studies demonstrating that patients with chronic cough do not have excessive reflux events relative to healthy volunteers. Although a temporal relationship between cough and reflux events has been suggested by studies utilizing impedance-pH monitoring of reflux events and objective cough recording, consensus is lacking in terms of whether this temporal relationship proves a causal link between reflux and cough. The 4th American Cough Conference, held in New York in June, 2013, provided an ideal forum for the debate of this issue between two internationally recognized experts in the field of reflux and chronic cough.

Chronic cough: clinical characteristics and etiologies of 510 cases

“…The misdiagnosis of GER-related cough was also common in tertiary hospitals. Together with the UACS (formerly PNDS) and eosinophilic airway inflammation (asthma and nonasthmatic EB), GERD is generally considered among the most common etiologies of CC (21). Chinese experts have found that inflammation in nonasthmatic EB has some similarities with that in CVA, and recent evidence has also suggested a mechanistic link between airway neurogenic inflammation and GERC (22).…”

Regulation of cough by neuronal Na+–K+ ATPases

“…Although clinical results have been variable, multiple studies describe resolution of cough in patients receiving proton pump inhibitors [39][40][41][42][43][44][45]. This has typically been attributed to disease modification in patients suspected of or diagnosed with gastroesophageal reflux disease.…”

“…In a primary culture of hippocampal neurons (cells expressing both a 1 and a 3 subunits), which have high intrinsic firing rates at baseline, the administration of an a 3 -selective dose of ouabain produced an accumulation of sodium which depolarized these cells, halting their spontaneous activity [64]. By Table 1 Drugs that inhibit Na + -K + ATPase and prevent or reduce coughing Rat brain, kidney 6 mM Human, guinea pig [39][40][41][42][43][44][45][46][47][48] inducing an intracellular accumulation of Na + by transient superfusion with K + -free buffer, the authors were then able to demonstrate that inhibition of a 3 resulted in a markedly impaired ability of cells to extrude sodium. This suggests that a 3 subunits are essential for reestablishing ionic gradients under conditions of high intracellular sodium.…”

Toux traînantes chez l’enfant et l’adolescent

“…Des études chez l'adulte ont objectivé une relation temporelle entre des épisodes de RGO et le déclenchement de toux grâce à une pH-impédancemétrie couplée aux enregistrements objectifs de toux [11]. Cependant, un grand nombre de sujets chez lesquels le RGO a été identifié comme facteur causal ou aggravant d'une toux traînante (comme dans l'asthme), n'ont pas été améliorés sur le plan symptomatique après un traitement par inhibiteurs de la pompe à protons (IPP).…”