Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage

Abstract

Background-Gastro-oesophageal reflux is often associated with cough. Patients with reflux show an enhanced tussive response to bronchial irritants, even in the absence of respiratory symptoms. Aim-To investigate the eVect of mucosal damage (either oesophageal or laryngeal) and of oesophageal acid flooding on cough threshold in reflux patients. Patients-We studied 21 patients with reflux oesophagitis and digestive symptoms. Respiratory diseases, smoking, and use of drugs influencing cough were considered exclusion criteria. Methods-Patients underwent pH monitoring, manometry, digestive endoscopy, laryngoscopy, and methacholine challenge. We evaluated the cough response to inhaled capsaicin (expressed as PD5, the dose producing five coughs) before therapy, after five days of omeprazole therapy, and when oesophageal and laryngeal damage had healed. Results-In all patients spirometry and methacholine challenge were normal. Thirteen patients had posterior laryngitis and eight complained of coughing. Twenty patients showed an enhanced cough response (basal PD5 0.92 (0.47) nM; mean (SEM)) which improved after five and 60 days (2.87 (0.82) and 5.88 (0.85) nM; p<0.0001). The severity of oesophagitis did not influence PD5 variation. On the contrary, the response to treatment was significantly diVerent in patients with and without laryngitis (p=0.038). In patients with no laryngitis, the cough threshold improved after five days with no further change thereafter. In patients with laryngitis, the cough threshold improved after five days and improved further after 60 days. Proximal and distal oesophageal acid exposure did not influence PD5. Heartburn disappeared during the first five days but the decrease in cough and throat clearing were slower. Conclusions-Patientswith reflux oesophagitis have a decreased cough threshold. This is related to both laryngeal inflammation and acid flooding of the oesophagus but not to the severity of oesophagitis. Omeprazole improves not only respiratory and gastro-oesophageal symptoms but also the cough threshold. (Gut 2000;46:762-767)

Antitussive Drugs—Past, Present, and Future

“…As discussed above, the results of studies evaluating the antitussive effects of PPIs have been disappointing (Chang et al, , 2011Faruqi et al, 2011;Shaheen et al, 2011). There have, however, also been several remarkable results with PPIs in patients with cough (Benini et al, 2000;Oribe et al, 2005;Ebihara et al, 2007). Thus, it is noteworthy that PPIs are pro-drugs that require acid activation for inhibition of not only proton pumps but also sodium pumps.…”

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.…”

The diagnosis and management of chronic cough

“…Association of conservative and lifestyle measures with H 2 -antagonists and/ or prokinetic agents for a period ofy3 months resolves GORinduced cough in 70-100% of patients [46]. Proton pump inhibitors9 administration for 8 weeks produces a significant, long-lasting reduction in GOR-induced cough [71], and increases the cough threshold in patients with reflux oesophagitis [72]. Failure of proton pump inhibitors must be considered only after adequate dosage (40 mg b.i.d.)…”