New concepts in the management of chronic cough

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Abstract

There has been significant progress in the field of cough in the past 10 years. Obstructive sleep apnoea, tonsillar enlargement and environmental fungi have recently been described as causes of chronic cough. The advances in the assessment of gastro-oesophageal reflux (GOR) have led to a greater understanding of the relationship between cough and GOR and are likely to change the approach to managing patients with GOR-cough. The investigation of the phenotype of patients with idiopathic chronic cough has provided novel insights. Patients with an idiopathic chronic are predominantly female, have an onset of cough around the menopause and have a high prevalence of organ specific autoimmune disease, particularly hypothyroidism. The presence of bronchoalveolar lymphocytosis suggests there is homing of inflammatory cells from primary sites of autoimmune inflammation to the lungs. A heightened cough reflex is a key feature of most patients with chronic cough and has led some investigators to suggest that chronic cough be recognised as a unique entity called Cough Hypersensitivity Syndrome (CHS). A number of subjective and objective tools have been developed recently to assess cough severity. Antitussive drug development is an emerging and exciting area of cough research.

Introduction

The management of patients with chronic cough is challenging on many fronts. The evaluation of patients involves numerous investigations and treatment trials. The optimal approach is not known, for example, the evidence for the role of proton pump inhibitor therapy for gastro-oesophageal reflux associated chronic cough is conflicting [1]. A significant number of patients with chronic cough remain unexplained. The reasons for this are unclear and there are few effective treatment options. Cough reflex hypersensitivity is a key feature of chronic cough but the mechanism of sensitisation is not known and it currently has little role in the management of patients. Few randomised controlled trials have been performed in chronic cough to guide clinical practice. The evaluation of antitussive drugs until recently had been hampered by a lack of validated and objective tools to assess cough severity and the difficulty in interpreting data in a clinically meaningful way. This review will discuss some of the recent advances in the field of cough that begin to address some of the key challenges.

Section snippets

New chronic cough conditions

The recent identification of a number of conditions associated with unexplained chronic cough may lead to new therapeutic options for appropriately selected patients (Table 1).

Advances in gastro-oesophageal reflux-cough

GOR-cough is one of the most commonly reported causes of chronic cough. The cornerstone of therapy for GOR-cough is proton pump inhibitors (PPI). A recent Cochrane meta-analysis review has highlighted that whilst observational studies report a reduction in cough severity with PPIs, a number of randomised controlled trials have not confirmed this [1]. A limitation of the studies included in the Cochrane meta-analysis was that they contained small numbers of patients. Fathi and colleagues have

Clinical characteristics

Up to 42% of patients with chronic cough remain unexplained in specialist clinics and they represent a significant challenge [13]. The striking phenotype of patients with idiopathic chronic cough (ICC) suggests a unique underlying disorder. The defining features of ICC are patients with chronic cough duration greater than 8 weeks and negative investigations and therapeutic trials for asthma, GOR and rhinitis. Clinical examination, chest radiograph and spirometry by definition are normal.

Cough hypersensitivity syndrome (CHS): the new paradigm for chronic cough

Cough reflex hypersensitivity is a key feature in most patients with chronic cough [23]. It can be assessed by a variety of tussive agents used in cough challenge tests agents such as capsaicin, citric acid, tartaric acid and fog. A wide range of environmental stimuli can trigger cough by activating cough receptors that sense heat, acid, stretch and noxious stimuli. There is evidence of increased cough receptor expression in the airways of patients with cough. Transient receptor potential

Advances in cough outcome measures

The assessment of cough has seen the most rapid and exciting developments in the last 5 years. The assessment of cough severity with validated tools is essential to the development of new therapies. Well established tools such as cough diary scores and visual analogues scales can now be complemented with health related quality of life (QOL) measures and objective cough monitoring. Although cough reflex testing has been used to determine the efficacy of drugs in the past due to the lack of

Antitussive therapy

A number of randomised controlled trials have recently been performed in patients with chronic cough; they represent a new era of cough research. The advances in the development of cough outcome measures have facilitated these studies. Morphine, codeine, erythromycin, esomeprazole, itraconazole, zafirlukast and nociceptin opioid like receptor agonists (NOP1) are amongst some of the drugs that have been evaluated in patients with chronic cough [8], [9], [35], [42], [43], [44]. Many lessons have

Conclusions

We now have the tools to do high quality research studies and clinical trials to address areas of uncertainty in cough. Clinicians and researchers have an exciting opportunity to explore new approaches to cough and develop much needed antitussive drug therapy. This will require raising the profile of cough amongst research funders, the pharmaceutical industry and the public.

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