Pathophysiology and clinical presentations of cough,☆☆,

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Abstract

The human cough reflex is still poorly understood, although it is known to occur independently of bronchoconstriction. Sensitization of the cough reflex is a unifying hypothesis for chronic dry cough in several conditions, including gastroesophageal acid reflux, angiotensin-converting enzyme inhibitor cough, and cough-variant asthma. The most common cause of chronic dry cough is a group of related conditions of chronic rhinitis, sinusitis, and postnasal drip. In these cases the cough reflex may be sensitized through an action of inflammatory mediators from the nasal mucosa on the airways or a reflex sensitization of airway sensory nerves. The association of cough with gastroesophageal reflux may occur through a local esophageal–tracheobronchial reflex. Angiotensin-converting enzyme inhibitor cough is a side effect of treatment in about 10% of patients; it probably results from inhibition of the degradation of kinins, particularly bradykinin, in the airway. Why some patients with asthma have cough as the principal feature of their disease is unclear. Tachykinins are probably involved in the mechanism of sensitization of the cough reflex, and the development of neuropeptide antagonists may open new research opportunities. A study that used ambulatory recording of cough in a group of subjects with asthma confirmed the presence of significant cough, the frequency of which did not correlate with lung function or diurnal variation in peak flow. This finding highlights the problem of cough in patients with asthma, a problem that probably has been underestimated in the past. (J ALLERGY CLIN IMMUNOL 1996;98:S91-7.)

Section snippets

CLINICAL PRESENTATIONS OF CHRONIC DRY COUGH

The cough reflex can be initiated at numerous anatomic sites, and it is therefore not surprising that chronic cough may have a variety of causes. Irrespective of the site of the pathologic disorder, patients with a chronic dry cough invariably have a persistent tickle or irritation in the throat, a condition described as sensory hyperalgesia, which is akin to sensory hyperalgesia of the skin.16 Two and sometimes three conditions may occur together in the same patient, thus complicating the

GER

GER has been found to be a common cause of chronic dry cough in published case series. Routine investigations for chronic cough are incomplete without a search for GER when other causes have been excluded.8 Until recently, it was uncertain whether the association of cough with GER is coincidental or pathologically related. Although cough resulting from GER may present with typical symptoms of dyspepsia, it is occult in the majority of patients.43 Although some patients may have reflux up to the

CONCLUSIONS

Chronic dry cough is an important clinical problem. Sensitization of the cough reflex is a common feature in these patients irrespective of the underlying cause. The pathogenetic mechanism of sensitization is unclear. A better understanding of the cough reflex is necessary to help answer this question and to devise appropriate antitussive agents. The synthesis of neuropeptide antagonists that can be used safely in human beings may open new research opportunities in the investigation of the

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    From the Department of Thoracic Medicine, National Heart and Lung Institute.

    ☆☆

    Reprint requests: K. Fan Chung, MD, FRCP, Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse St., London SW3 6LY, United Kingdom.

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