Acidification of the oesophagus acutely increases the cough sensitivity in patients with gastro‐oesophageal reflux and chronic cough

Abstract

Gastro-oesophageal reflux disease (GORD) is one of the most common causes of chronic cough; however, the mechanisms by which GOR initiates coughing are incompletely understood. We address the hypothesis that acidification of oesophagus acutely increases the cough reflex sensitivity in patients with GORD and chronic cough. Nine patients with GORD with chronic cough and 16 patients with GORD without cough were recruited. In a randomized double blind study, saline and acid (HCl, 0.1 mol L(-1)) were separately infused into oesophagus via naso-oesophageal catheter. Cough reflex sensitivity to inhaled capsaicin was determined immediately after completion of each infusion. Infusion of acid into oesophagus increased capsaicin cough reflex sensitivity in patients with GORD and chronic cough. In contrast, acid had no effect on the cough sensitivity in patients with GORD without cough. In a separate study, acid infusion into oesophagus did not affect the cough sensitivity in 18 healthy subjects. We conclude that acid in the oesophagus acutely increases the cough reflex sensitivity to capsaicin in patients with GORD and chronic cough. This phenomenon may contribute to the pathogenesis of cough due to GORD.

Response of Chronic Cough to Acid-Suppressive Therapy in Patients With Gastroesophageal Reflux Disease

“…Furthermore, it was shown that many patients had cough associated with both acid and weakly acidic refl ux. Finally, building upon earlier experimental observations of increased sensitivity of the cough refl ex with esophagitis 42 and an acute lowering of the tussigenic threshold to inhaled capsaicin by esophageal acid perfusion in patients with GERD irrespective of whether they had chronic cough, 5 Smith and colleagues observed increased sensitivity to a tussigenic challenge in the subset of patients with cough preceded by refl ux. Together, these observations strongly implicate increased cough sensitivity as an important operant mechanism in patients with refl ux cough.…”

“…First, in patients with chronic cough, acid infusion into the distal esophagus increases the frequency of coughing 4 and cough refl ex sensitivity. 5 Second, approximately one-half of unselected patients with chronic cough show a positive symptom association between cough and refl ux during refl ux monitoring. 6 However, unlike heartburn, which is usually caused by acid refl ux, 7 chronic cough has a diverse range of potential causes.…”

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine

“…The concept of the ''oesophago-bronchial reflex'' has been supported by studies that have infused acid into the distal oesophagus to cause increased cough frequency [61] and cough reflex sensitivity [62] in patients with chronic cough and associated gastro-oesophageal reflux disease. Oesophageal acid infusion does not change cough reflex sensitivity in healthy volunteers [62]. This oesophago-bronchial reflex seems to be unique to those patients with chronic cough and associated gastro-oesophageal reflux disease.…”

The Role of Microaspiration in the Pathogenesis of Gastroesophageal Reflux-related Chronic Cough

“…19 Additionally, refluxrelated cough was suppressed with esophageal lidocaine instillation or tracheal ipratropium inhalation. 11 Javorkova et al 20 showed that the acidification of the distal esophagus increased cough sensitivity in patients with GERD and chronic cough in comparison to healthy volunteers and patients with GERD only. This effect was also observed in asthma patients without cough or GERD.…”