New concepts in the management of chronic cough
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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