Inhalation method determines outcome of capsaicin inhalation in patients with chronic cough due to sensory hyperreactivity

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Abstract

Background

For patients with idiopathic chronic cough, a subgroup is recognised with respiratory symptoms induced by scents and chemicals. The diagnosis of sensory hyperreactivity (SHR) has been suggested for this group of patients and can be made using a capsaicin inhalation test. The aim of the present study was to compare the results of inhaling capsaicin by tidal breathing with those obtained by the dosimeter method regarding repeatability, agreement, and ability to distinguish patients with SHR from healthy controls.

Methods

A total of 15 patients with chronic cough due to SHR and 15 healthy control subjects underwent a randomised cross-over protocol and were provoked in a double-blind, randomised fashion with vehicle and two concentrations of inhaled capsaicin, using either the tidal breathing or dosimeter method, in a total of four challenges opportunities, two with each method.

Results

Patients coughed more and showed more respiratory symptoms than healthy controls with each dose of capsaicin. Compared with tidal breathing, inhalation of capsaicin with the dosimeter method caused a significantly greater number of coughs and respiratory symptoms in both patients and controls. Among the patients, the mean number of coughs after inhalation of 1 mL of capsaicin 0.4 μmol/L from the first provocation with tidal breathing was 12 (95% CI: 7; 17) and after inhalation from the first provocation with the dosimeter method 32 (95% CI: 19; 46) (P<0.05). Both methods showed good repeatability and similar ability to distinguish patients with SHR from healthy control subjects.

Conclusions

For patients with SHR, capsaicin cough sensitivity is increased and repeatable. The dosimeter method caused more coughs and other respiratory symptoms than the tidal breathing method, indicating that the methods cannot be used interchangeably. Knowledge of the type of inhalation device used, the particle size, the airflow rate and the inspiratory flow rate are essential when comparing different studies of capsaicin-induced cough.

Introduction

Coughing is a common clinical problem and when it persists for more than 2 months is regarded as chronic [1], even if the definition of chronic cough varies in the literature. When pulmonary illnesses such as different infections, cancer, alveolitis, asthma and chronic obstructive pulmonary disease (COPD) are excluded, the reasons for a chronic cough may be gastro-oesophageal reflux, rhinitis or post-nasal drip [1] even if the existence of a post-nasal drip syndrome has been questioned [2]. However, differential diagnosis still leaves a group of patients with unexplained cough, also labelled as idiopathic cough, and in a specialist cough clinic as many as 40% of patients were diagnosed with idiopathic cough [3].

It has been suggested that patients with upper and lower airway symptoms induced by scents and chemicals, such as flower scents, perfume, cleaning agents, car exhaust fumes, and tobacco smoke, suffer from airway sensory hyperreactivity (SHR) [4]. Common symptoms are cough, hoarseness, heavy breathing, difficulty in getting air, phlegm, nasal blockage, rhinorroea, and eye irritation. These symptoms may be misinterpreted as asthma and/or allergy, except that the clinical set up shows no bronchial obstruction or IgE-mediated reactions. Such patients are often diagnosed as having idiopathic chronic cough, which only covers a limited part of the problem.

Stimulation of the unmyelinated C-fibres of the trigeminal and vagal nerves is likely involved in chemical-induced airway symptoms [5]. Supporting the hypothesis of SHR, these patients react with more coughing and other symptoms to inhaled capsaicin than healthy individuals and asthmatic patients, and the reactions can be blocked by preinhalation of a local anaesthetic [4], [6]. The suggested diagnosis of SHR can be tested using capsaicin inhalation to identify patients and to differentiate between patients with asthma and those with SHR [7], [8]. In this test, incremental concentrations of capsaicin are inhaled to induce coughing using a tidal breathing method. However, even though the capsaicin inhalation test has shown good reproducibility [4], [7], [8], the inhaler used in this method has been associated with difficulties in estimating the exact dose of nebulised capsaicin delivered. When introducing a cough testing device for use in various laboratories, the device needs to be compared to other inhalers, since technical factors may influence the results. We aimed to compare the tidal breathing and dosimeter methods in terms of agreement and repeatability of cough response to capsaicin inhalation in patients with SHR and in healthy controls. We also wanted to evaluate to what extent using capsaicin inhalation testing in conjunction with another method can distinguish patients from healthy control subjects.

Section snippets

Patient group

The study group included 15 patients, 12 women and 3 men, 21–70 years of age (mean 48 years). They were referred to an asthma and allergy outpatient clinic because of symptoms suggestive of asthma or allergy. The patients were screened using a questionnaire on airway symptoms and on symptoms in response to chemicals and scents. All had a history of at least 2 years of coughing and pronounced upper and lower airway symptoms induced by chemicals and scents. Data pertaining to reported symptoms

Results

Patients and controls coughed dose-dependently in terms of mean number of coughs for both methods in the provocation tests. The patients coughed significantly more than the healthy controls for each capsaicin dose (P<0.05) whether administered by the tidal breathing or dosimeter method (Fig. 1).

Discussion

In this study, we compared cough sensitivity to capsaicin exposure using the tidal breathing and dosimeter methods, in both patients with chronic cough defined as having SHR as an explanation for their symptoms and in healthy control subjects. We also compared the agreement between methods and the repeatability of each method. Two methods can be used interchangeably if they do not differ significantly or if the limits of agreement between the two methods are not clinically important [10]. We

Acknowledgements

We are thankful to Inger Winberg for performing the capsaicin inhalation tests, Marianne Wallgren for help with capsaicin preparations and to Anders Odén for statistical advice. This study was supported by grants from the Vårdal Foundation, the Regional Health Care Authority of West Sweden, the Local Research and Development Council for Gothenburgh and Southern Bohuslän, the Swedish Heart and Lung Foundation, the Sahlgrenska University Hospital Foundation, and the Konsul Th C Berghs Foundation.

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  • Cited by (38)

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