Inhaled ethanol potentiates the cough response to capsaicin in patients with airway sensory hyperreactivity

Abstract

A suggested explanation for airway symptoms induced by chemicals and scents is sensory hyperreactivity (SHR) of airway mucosal nerves. Patients with SHR have increased cough sensitivity to inhaled capsaicin, mediated by transient receptor potential (TRP) ion channels.

In animal experiments, some TRP receptors are potentiated by ethanol, which is why in this study, the aim was to evaluate whether a pre-inhalation of ethanol could influence the capsaicin cough response in patients with SHR. Fifteen patients with SHR and 15 healthy controls were provoked on three occasions with two concentrations of inhaled capsaicin. Before each capsaicin provocation, a pre-inhalation of saline or one of two concentrations of ethanol was given in a double-blind, randomized fashion. The participants reacted in a dose-dependent way with cough on the capsaicin inhalations. Among the patients, but not in the control group, pre-inhalation of ethanol increased the cough response dose-dependently. The results suggest that the pathophysiology of SHR is related to airway mucosal TRP receptors in the sensory nerves. In scented products, the combination of ethanol as a solvent and perfume may augment an airway reaction in sensitive individuals.

Introduction

Upper and lower airway symptoms induced by chemicals and scents are a common problem in society, and sometimes the experienced symptoms are excessive, leading individuals to seek health care [1], [2]. A suggested explanation for this condition is a hyperreactivity of the sensory nerves of the entire airways. The condition is therefore called “sensory hyperreactivity (SHR)”, and it affects more than 6% of the adult population in Sweden [3]. Common symptoms are nasal blockage, rhinorrhea, eye irritation, heavy breathing, cough, hoarseness, and phlegm, as well as general symptoms, such as headache and nausea [4], [5]. After capsaicin inhalation, changed levels of nerve growth factor in nasal secretions have been detected, indicating a neurochemical imbalance in the airways, which is related to SHR [6]. Cough sensitivity to capsaicin is a measure of airway sensory reactivity [7], [8]. Patients with SHR react more strongly than healthy individuals to provocation with inhaled capsaicin, and the cutoff values for a positive reaction have been determined [4]. The capsaicin inhalation test in the diagnosis of SHR has good short-term and long-term reproducibility [5], [9].

Capsaicin, the main, pungent ingredient in chili, stimulates the unmyelinated C-fibers of the sensory nervous system, giving a burning sensation by activating the ion channel of transient receptor potential vanilloid subunit 1 (TRPV1) [10]. This receptor is also activated by other stimuli, including noxious heat, lipids, and protons [11], [12]. An increased expression of TRPV1 is found in several conditions characterized by general hypersensitivity, such as thermal hyperagesia, vulvodynia, rectal hypersensitivity, esophagitis, and chronic cough [13], [14], [15], [16], [17], [18]. Recently, it has been found that ethanol potentiates the response of TRPV1 to capsaicin in different organs in rats and guinea pigs [19], [20], [21], [22]. If a corresponding effect could be achieved in humans, this would strongly indicate the role of the transient receptor potential (TRP) ion channels in the pathogenesis of SHR. In the future, the TRP ion channels may be an important key to understand airway symptoms induced by chemicals and scents, our knowledge of which is so far limited. The aim of this study was therefore to evaluate whether pre-inhalation of ethanol could influence the capsaicin response in patients with SHR.