Increased Sensitivity of Cough Reflex is Not the Mechanism of Cough Attributed to Laryngopharyngeal Reflux

Abstract

Objectives: In laryngopharyngeal reflux (LPR) patients acid reaches laryngopharyngeal area and stimulates/sensitizes respiratory nerve terminals mediating cough. We addressed several hypothesis: if stimulation of respiratory nerves is responsible for coughing then acidic LPR should correlate with coughing and proton pump inhibitor (PPI) treatment should reduce both LPR and coughing. If sensitization of respiratory nerves is responsible for coughing then cough sensitivity should correlate with coughing and PPI should reduce both coughing and cough sensitivity.

Study design/methods: In this prospective single center study, patients with positive reflux symptom index (RSI > 13) and/or reflux finding score (RFS > 7) and ≥1 LPR episode/24 hours were enrolled. We evaluated LPR by dual channel 24-hour pH/impedance. We determined number of LPR events with pH drop at levels 6.0, 5.5, 5.0, 4.5, and 4.0. Cough reflex sensitivity was determined as lowest capsaicin concentration causing at least 2/5 coughs (C2/C5) by single breath capsaicin inhalation challenge. For statistical analysis C2/C5 values were -log transformed. Troublesome coughing was evaluated on the scale 0-5.

Results: We enrolled 27 LPR patients. The number of LPR events with pH 6.0, 5.5, 5.0, 4.5, and 4.0 was 14[8-23],4[2-6],1[1-3],1[0-2] and 0[0-1], respectively. There was no correlation between number of LPR episodes at any pH level and coughing (Pearson range -0.34 to 0.21, P = NS). There was no correlation between cough reflex sensitivity C2/C5 and coughing (R = -0.29 to 0.34, P = NS). Of patients that completed PPI treatment, 11 had RSI normalized (18.36 ± 2.75 vs. 7 ± 1.35, P < 0.01). There was no change in cough reflex sensitivity in PPI-responders. C2 threshold was 1.41 ± 0.19 vs. 1.2 ± 0.19 (P = 0.11) before and after PPI.

Conclusions: No correlation between cough sensitivity and coughing and no change in cough sensitivity despite improvement of coughing by PPI argue that an increased cough reflex sensitivity is not mechanism of cough in LPR. We identified no simple relationship between LPR and coughing suggesting that this relationship is more complex.

Keywords: Acid; Cough; Cough reflex sensitivity; Gastroesophageal reflux; Laryngopharyngeal reflux.