Cough

Abstract

Cough is the most common reason why patients seek medical attention. Acute cough due to viral upper respiratory tract infection is usually self-limiting and seldom requires investigation. In contrast, chronic cough is challenging to manage since it often remains unexplained despite thorough investigation. Cough reflex hypersensitivity is a key abnormality in patients with cough and the term ‘cough hypersensitivity syndrome’ (CHS) has recently been proposed to emphasise this. The evaluation of patients with CHS includes identifying reversible cough hypersensitivity, minimizing aggravating factors of cough and non-specific antitussive therapy.

Introduction

Cough is a defence mechanism that protects the airways from aspiration and clears secretions. It is often described as an inspiration followed by a forced expiratory effort against a transiently closed glottis, which results in a rapid expulsion of air.¹ An impaired cough reflex is seen in patients with neuromuscular disease and following stroke and can lead to an increased risk of aspiration and pulmonary infection.² In contrast, a heightened cough reflex is a typical finding in patients with chronic cough. Cough is the most common reason for patients to seek a medical consultation.³ The prevalence of cough in the community is estimated at 9–33% and the economic cost to society related to cough is substantial; more than £100 million pounds is spent on antitussive drugs every year in the UK.3, 4 Although most of this relates to acute cough due to viral upper respiratory tract infection, chronic cough (defined as cough lasting >8 weeks) is also common, accounting for 10% of respiratory out-patient clinic referrals.⁵ It is associated with significant physical and psychological morbidity; syncope, urinary incontinence, chest pain, sleep disturbance, relationship difficulties, social embarrassment and depression are just some of the adverse consequences.6, 7, 8 Chronic cough is challenging to manage since many cases remain unexplained after detailed investigation. This has led to proposals for a greater focus on the key underlying mechanism – heightened cough reflex sensitivity – and a new name, ‘cough hypersensitivity syndrome’ (CHS) for this condition.9, 10, 11 This review will focus on the evaluation and assessment of patients with cough, with particular emphasis on chronic cough.

Viral upper respiratory tract infection is by far the most common cause of acute cough (duration <2 weeks). Acute cough is associated with transient heightened cough reflex sensitivity and in most cases does not require assessment or therapy. There is little evidence that antitussive drugs are efficacious.¹² The best evidence for antitussive therapy supports the use of honey and vapour rubs containing camphorated oils for children, and the opioid-like, N-methyl-D-aspartate receptor antagonist, dextromethorphan for adults.13, 14, 15 In some patients, the cough persists and is often referred to as post-infectious, post-viral or sub-acute cough. The prevalence of post-infectious cough and its pathophysiology are unclear but it is common and challenging to treat in primary care. Most patients with post-infectious cough do not require investigation. The most important differential diagnosis for subacute cough is asthma. Anti-tussive drugs, bronchodilators and inhaled corticosteroids are often prescribed to treat sub-acute cough. There is limited evidence for their efficacy; the most encouraging data available are for inhaled corticosteroids.¹⁶

Cough receptors, found throughout the airways and lung parenchyma, are activated by a wide range of triggers (Figure 1). Many patients report laryngeal paraesthesia, suggesting afferent nerve hypersensitization.¹⁷ The brainstem coordinates inputs from peripheral afferent nerves and from central regulatory cortical fibres and then activates the motor pathway of the cough reflex. Cough reflex hypersensitivity is assessed with cough challenge tests, using tussive agents such as capsaicin, but these do not discriminate subjects with cough from healthy subjects reliably and are of limited clinical value.¹⁸ Cough reflex hypersensitivity is transient or reversible when associated with infection, eosinophilic airway inflammation and angiotensin-converting enzyme (ACE) inhibitor drug therapy, but in most patients with unexplained chronic cough it is persistent.⁹ The mechanism of sensitization of the cough reflex is poorly understood and deserves further study. There is a clinical need to develop pharmacological therapy that can down-regulate cough reflex sensitivity to physiological levels.