Effect of bronchodilators on the cough response to inhaled citric acid in normal and asthmatic subjects.

Abstract

Coughing was induced in seven normal and eight asthmatic subjects by giving successive inhalations of citric acid aerosols of progressively higher concentration (range 0.5-32%). A baseline cough response was obtained on each of four experimental days, and there was no significant difference between days in this respect. Then the subjects received by inhalation either a bronchodilator (salbutamol 5 mg or ipratropium 1 mg) or placebo, in a paired double blind crossover design. A second citric acid run followed and was used for paired drug-placebo comparisons. In the asthmatic subjects the cough response was diminished by both bronchodilators (p < 0.05), and the cough threshold was significantly higher after ipratropium but not salbutamol. In normal subjects no significant effects were found. Airways calibre was assessed, by an oscillatory technique that measures the resistance of the respiratory system (Siemens Siregnost FD 5), in four of the seven normal and all eight asthmatic subjects. The mean respiratory resistance was higher in asthmatic than in normal subjects, and fell significantly after both bronchodilators. In normal subjects smaller decreases in respiratory resistance occurred, significant only with salbutamol. The simplest hypothesis which explains the results relates change in cough response to altered neuroreceptor sensitivity associated with rapid changes in bronchial calibre.Cough is frequently the only presenting symptom in patients with bronchial asthma.' 2 The cough reflex arises from rapidly adapting receptors located in the larynx, trachea, and major bronchi.3'4 Impulses travel in afferent fibres in the vagus nerve to the cough centre in the brainstem. The tracheobronchial cough receptors are stimulated by touch and inhaled irritants5 and sensitised by bronchoconstriction, and this could explain why bronchoconstriction is associated with cough. Cough, in patients with uncomplicated bronchial asthma, is relieved by conventional aerosol bronchodilators.2 We have investigated cough induced by inhalation of citric acid in a group of normal and asthmatic subjects, and have assessed the effect of a f2 stimulant (salbutamol) and an anticholinergic (ipratropium) on the cough response. Methods SUBJECTSEight normal and eight asthmatic subjects were selected. All were non-smokers and had not had a

A noninvasive electromyographic study on threshold and intensity of cough in humans

“…Previous methods of quantifying cough responses based on cough frequency have been widely used and can provide valuable information [4,6,7,14]. However, they are limited, as they treat all coughs as equal and do not allow an evaluation of the strength of expiratory thrusts.…”

“…They include citric acid, capsaicin, histamine, bradykinin and prostaglandins [1][2][3][4][5], as well as ultrasonically nebulized distilled water (UNDW) and solutions low in permeant anion content [1,[6][7][8][9][10][11]. One of the most valuable indices of a subject's susceptibility to cough stimuli may be represented by the cough threshold [8][9][10], which has been employed in studies aimed at evaluating the separate role of osmolarity and ion content of inhaled water solutions both in normal subjects and asthmatic patients [8,9].…”

β2-Agonists block tussive responses in guinea pigsviaan atypical cAMP-dependent pathway

“…However, to date, clinical studies conducted to investigate the impact of b 2 -agonists on the tussive response have led to contradictory results [1][2][3][4][5][7][8][9], presumably due to the subjective nature of reporting in clinical trials prior to the advent of objective cough monitoring. Moreover, to our knowledge, the precise mechanism of action for this potential antitussive effect has not been studied.…”

“…This is important given that patients (especially those with idiopathic cough) find it very difficult to make an accurate assessment of their cough. Furthermore, it is commonly believed that, if b 2 -agonists do, indeed, suppress cough, bronchodilation is the likely mechanism of action [7,8]. Currently the dose regimen/protocol for b 2 -agonists in the clinic is routinely based around their relaxant properties and not geared to their antitussive activities (which may require higher doses), and we propose that this may be why a dominant antitussive property has hitherto not been discovered.…”

“…Clinical studies conducted to date have not managed to clearly establish whether or not b 2 -agonists attenuate cough. Indeed, although some clinical studies in normal volunteers [2] and in chronic cough associated with allergic [3] or obstructive conditions [4][5][6][7] have found a beneficial effect of b 2 -agonists, other trials have not found efficacy [8,9]. This confusion may exist, in part, due to the subjective nature of symptom scoring in comparison with objective cough monitoring, which has only recently become available, and the fact that few double-blind randomised placebo-controlled studies have been performed with cough as a primary end-point.…”