COUGH SENSITIVITY IN LOCALIZED SCLERODERMIA WITH NO CLINICAL SYMPTOMS FROM LOWER AIRWAYS

R. Pecova1, Z. Frlickova2, J. Pec2, M. Tatar1



1Department of Pathophysiology and 2Department of Dermatology, Jessenius Medical School, Comenius University, Martin, Slovak Republic


  Cough sensitivity is increased in patients with atopic dermatitis, although they have no clinical symptoms from the lower airways. In the present study we examined the cough sensitivity to capsaicin in patients, who had no clinical respiratory symptoms, with sclerodermia localized to the skin. Cough sensitivity was defined as the lowest capsaicin concentration, which evokes 2 or more coughs. Twelve patients and 12 healthy matched volunteers, as a comparison group, inhaled deep breaths (2 L) of a capsaicin aerosol in doubled concentrations (from 0.02 to 200 µmol/L). Cough sensitivity, expressed as a geometric mean (95% CI) of capsaicin concentration, was 0.15 µmol/L (0.04 to 0.56) in the patients with localized sclerodermia and 4.96 µmol/L (2.50 to 9.85) in controls, which made a significant difference towards higher cough sensitivity in sclerodemia, respiratory symptom-free patients. Thus, disease processes localized outside the respiratory tract may have surreptitious pulmonary manifestation that is brought to light by the capsaicin cough test.

Key words: capsaicin, cough sensitivity, sclerodermia, skin, respiratory symptoms



INTRODUCTION

Capsaicin (trans-8-methyl-N-vanillyl-6-noneamide) is the pungent extract of red pepper which, when inhaled, induces cough in a reproducible manner without tachyphylaxis (1). Inhalation of increasing doses of capsaicin is a sensitive way of assessing the cough reflex in a variety of disease states (2). There are clinical experiences that cough can be elicited, especially in pathological conditions, from many other sites (pharynx, nose and paranasal sinuses, pericardium, and gastrointestinal tract) (3). However, there is no conclusive evidence that afferent nerve endings localized in these sites of the upper respiratory tract can directly mediate the cough reflex (4). Cough sensitivity is increased in patients with atopic dermatitis, who have not been complaining of cough and other respiratory symptoms but in those suffering from psoriasis vulgaris no significant changes were noted in comparison with healthy subjects (5). The cough reflex, as tested with capsaicin, is markedly increased in patients with cryptogenic fibrosing alveolitis, which is a disabling form of interstitial pulmonary fibrosis (6). It also is an increased in patients with interstitial lung disease, which may represent sensitization of airway sensory nerves (7, 8).

The aim of this study was to investigate the cough sensitivity to capsaicin in patients with sclerodermia localized to the skin only, as opposed to the organ involvement in progressive systemic sclerosis. These patients had no respiratory symptoms (cough, dyspnoea, etc.), which may be present in other forms of the disease due to alterations and fibrosis of connective tissue in internal organs including the lung (9).


MATERIAL AND METHODS

Subjects

The study population consisted of 12 patients (F/M; 7/5, mean age 55 years) with localized sclerodermia currently attending the Department of Dermatology, Jessenius Medical School at Martin with no clinical respiratory symptoms, normal spirometry and transfer factor (CO single breath test), and no history of acute respiratory infection (last 6 weeks) who were recruited consecutively. Twelve 12 non-allergic healthy subjects (F/M; 7/5, mean age 37 years) with normal pulmonary function constituted a control group. Based on a structured, interviewer-led questionnaire, each subject was asked about respiratory symptoms and a past and family history of bronchial asthma, allergic rhinitis, gastroesophageal reflux, cardiovascular diseases, metabolic diseases, ACE inhibitor treatment. All patients were examined at the same time of day. They attended the laboratory to undergo a cough reflex sensitivity test, spirometry and transfer factor (CO single breath test). The study was approved by the Ethics Committee of Jessenius Medical School and informed consent was obtained from all subjects after the purpose of the test had been explained.

Assessment of localized sclerodermia

Skin examination, specific and non-specific immunity were determined and skin biopsy was performed. Patients with localized sclerodermia were treated for their disease only topically with Excipial ointments/w/o, cremes, solutions or Balmandol bath (Spirig, Switzerland) - all not containing corticosteroids.

Assessment of cough sensitivity

Measurements of the cough threshold were carried out by progressively increasing concentrations of inhaled capsaicin, which was preceded by physiologic saline inhalation, according to the method reported by Fujimura et al. (10). Each subject inhaled an aerosol of capsaicin solution (0.024, 0.049, 0.098, 0.195, 0.39, 0.781, 1.562, 3.125, 6.25, 12.5, 25, 50, 100, 200 µmol/L). Two litres of aerosol were inhaled every 60 seconds by deep mouth breaths, with a nose clip in place, from a Pari Provokationstest I (Pari Werck, Germany). Increasing concentrations were inhaled until two or more coughs were elicited. Mass median diameter of the particle was 1.2 µm. Two medical technicians counted the number of capsaicin-induced coughs. Capsaicin cough threshold, the lowest concentration of capsaicin eliciting 2 or more coughs, was taken as an index of airway cough sensitivity.

Data analysis

The capsaicin cough threshold was expressed as a geometric mean value with 95% confidence intervals (CI) of the capsaicin concentration causing two or more coughs and was calculated for each group. Data were analysed by a non-parametric Mann-Whitney-Wilcoxon test and a value of P<0.05 was considered to be significant.


RESULTS AND DISCUSSION

Cough sensitivity was 0.15 µmol/L (0.04 to 0.56 µmol/L) in 12 patients with localized sclerodermia and 4.96 µmol/L (2.50 - 9.85 µmol/L) in 12 healthy volunteers (P<0.002), which was a significant increase in the patients (Fig. 1).

Fig. 1. Cough sensitivity expressed as geometric mean and 95 % CI of capsaicin concentration inducing 2 or more coughs in patients with localized sclerodermia and healthy controls (*P<0.002 - compared with controls).

The aim of this study was to evaluate the sensitivity of airway nerve-endings mediating cough in patients with localized sclerodermia (pathological process of the skin) without respiratory symptoms (cough, dyspnea, etc.). We found that cough sensitivity was significantly increased in the patients. Localized sclerodermia was used as a model of a pathological autoimmune process clinically manifested in the skin. But the spectrum of disease is wide, with localized and systemic forms. The process could be generalized with organ involvement and influence respiratory system function. Pulmonary interstitial fibrosis is involved in progressive systemic sclerosis (9). Cough sensitivity is increased in some respiratory diseases (2, 3, 6, 7). We can choose a model of a disease that is morphologically and clinically localized outside the respiratory tract, but it is known that it can be manifested in pulmonary parenchyma (9).

Our data suggest that a capsaicin cough test can show a functional change of airway afferent nerve-endings mediating cough during a sclerodermic process localized to the skin. Although very little is known about the sclerodermic process "spreading" to the airways and its detection by the capsaicin cough test, this observation is of interest and merits further investigation.

Acknowledgments: This work was supported by National Research Grant VEGA 1/9322/02.


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