Are there clinical features of a sensitized cough reflex?

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Abstract

Cough reflex hypersensitization is a key feature in patients with troublesome cough. The clinical consequence of this hypersensitive state is typified by bouts of coughing often triggered by low threshold stimuli encountered by the patient during normal daily activities including exposure to aerosols, scents and odours, a change in air temperature and when talking or laughing. These features are often perceived by cough patients to be the most disruptive aspect of their condition and undoubtedly contribute to impaired quality of life. Patients with troublesome cough may describe a range of additional symptoms and sensations including an ‘urge to cough’ or the feeling of an ‘itch’ at the back of the throat, or a choking sensation and occasionally chest pain or breathlessness. It is uncertain if these features arise due to the processes responsible for cough reflex sensitization or as a direct consequence of the underlying cough aetiology. In an attempt to understand the clinical features of a sensitized cough reflex, the spectrum of symptoms typically described by cough patients will be reviewed and possible underlying mechanisms considered. Since an intact cough reflex is crucial to airway protection, anti-tussive treatment that attenuates the hypersensitive cough state rather than abolishing the cough reflex completely would be preferable. Identifying such agents remains a clinical, scientific and pharmacological challenge.

Introduction

Coughing is an important and appropriate response to noxious stimuli. However, in many acute and chronic respiratory disease states, a cough may develop which is troublesome, seems purposeless and is refractory to medication. While most focus has correctly centred on the investigation and treatment of cough as a specific complaint [1], [2] there is increasing recognition that cough patients report a range of additional sensations including an ‘urge to cough’, the feeling of an ‘itch’ or ‘lump’ at the back of the throat, a choking feeling and occasionally chest discomfort and breathlessness. These patients also complain that bouts of coughing are triggered by relatively innocuous stimuli frequently encountered during normal daily routine such as exposure to aerosols, scents and odours, a change in air temperature or when talking or laughing. This airway sensory hyperreactivity (SHR) is often what disturb patients most about their condition and appears to be of sufficient importance to impact on health status [3]. In the development of the two most widely used cough quality of life questionnaires items most frequently perceived as important by cough patients included statements such as; ‘exposure to paint or fumes made me cough’ [4] and ‘I can no longer sing, for example, in church’ [5].

Very little is known regarding the pathophysiology of SHR but in this article we consider the evidence that it may arise as a direct consequence of the neuroinflammatory events considered mechanistically important in cough.

Section snippets

Clinical features of cough

The act of coughing may cause a variety of musculoskeletal (chest wall pain), cardiovascular (syncope) and neurological (headache) symptoms which arise as a consequence of the cough intensity or a direct and profound effect of vagal stimulation. Some of the reasons why patients seek medical attention for cough include insomnia, a feeling of exhaustion, concern of serious underlying illness and self-consciousness from repeated coughing in public [6], [7]. This information tells us more about the

How common is airway sensory hyperreactivity (SHR)?

Millqvist et al. first proposed the term airway sensory hyperreactivity (SHR) to define a syndrome of self-reported odour intolerance combined with heightened sensitivity to inhaled capsaicin [16]. An accurate estimate of the prevalence of SHR in the general population is difficult due to a lack of consistency in its definition. The range of terms commonly used and interchanged includes; airway symptoms from chemicals (ASC) [17], multiple chemical sensitivity (MCS) syndrome [18] and the

Prevalence of SHR in a specialist cough clinic

For the purpose of this brief overview, we have provided some preliminary information on the prevalence and characteristics of airway SHR in patients referred to a specialist cough clinic. As alluded to above we have considered chemical, thermal and mechanical stimuli as the important noxious stimuli that trigger bouts of coughing. We conducted a retrospective review of 135 consecutive patients referred to a specialist cough clinic. We defined airway sensory hyperreactivity (SHR) positive

The cough reflex

The protective (physiological) cough response to a noxious stimulus is likely to be elicited by direct activation of receptors on afferent sensory airway nerves with very little involvement from non-neuronal cells. The precise type of afferent sensory nerve responsible for cough in humans is unknown but there are a number of candidates; rapidly adapting receptors (RARs) located on Aδ-type nerves (chemo and mechanosensitive), small non-myelinated C-fibres (chemosensitive) and a specific sodium

Inflammation, cough reflex sensitization and airway sensory hyperreactivity

Cough reflex sensitization may occur peripherally and/or centrally [54], [55]. As the central processes involved are outside the scope of this review, our intention is to focus on the airway inflammatory events likely to be responsible for the sensitization of cough receptors. Acute and chronic cough are both associated with airway inflammation. Acute viral infection induces lower airway inflammation [56] which may persist long after the infection has resolved [57]. Inflammatory changes

Conclusions

There is an increased appreciation of the range of symptoms that disturb patients with acute and chronic cough. One of the most important, occurring in two-thirds of patients with chronic cough, is the bouts of coughing provoked by relatively innocuous airborne stimuli such as aerosols, scents and cold air. In the last few years, there have been significant advances in the understanding of mechanisms responsible for abnormal sensory responses such as chronic pain and itch. Much of this

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