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A new paradigm for adult cough

Professor Alyn Morice describes how patients with chronic cough may actually have a reflux problem

Chronic cough is arbitrarily defined as cough lasting greater than eight weeks, as post-infectious cough has usually abated by that time.

It is an extremely common problem and one primary care survey found 12% of the population complained of a chronic cough on a daily or weekly basis and 7% said that it interfered with their activities of daily living.1

Fainting while coughing – cough syncope – is thought by the DVLA to be responsible for a number of road fatalities per year.

Cough hypersensitivity – a different way to look at chronic cough

Three underlying pathologies have been suggested to underlie chronic cough in those presenting with dry non-productive cough:

• asthma

• postnasal drip or rhinitis

• reflux disease.

The patients who did not fit into this triad acquired the label idiopathic cough.2

But the traditional division of chronic cough into the three aetiological factors outlined above does not bear close examination.

The asthma is almost invariably of late onset – a typical patient will be a middle-aged woman and bronchoconstriction may be absent. This form of asthmatic cough shares very few characteristics with classic childhood asthma other than a response to steroids.

The symptoms of postnasal drip appear to bear no relation to coughing and the diagnosis relies on response to first-generation antihistamines.

Finally, the classic symptom of GORD or heartburn is only present in about half of patients presenting with a chronic cough.

Patients with chronic cough of whatever aetiology describe a similar set of trigger factors – a change in atmosphere, such as going from a warm to a cold room, will trigger paroxysms as will exposure to minute quantities of environmental stimulants.

This has led to the concept that the patient with a chronic cough is expressing a hypersensitivity of the sensory nerves. This hypersensitivity is not the same as the hyperresponsiveness of asthma, which leads to bronchoconstriction.

It can be objectively demonstrated in the lab by the inhalation of protussive agents, such as pepper extract or acid aerosols.

Thus, the modern paradigm of chronic cough is that almost all patients exhibit a profound hypersensitivity of the airway sensory nerves. In fact, patients with chronic cough have a very characteristic constellation of trigger factors, which point to the aetiology being due to reflux – but this is not the same sort of reflux that causes heartburn and is caused by a gaseous mist that may be non-acidic.

The irritation and inflammation it causes lead to upregulation of the irritant receptors, giving rise to the hypersensitivity component of chronic cough.

While there are many possible causes for chronic cough, the overwhelming majority of patients who present with a history of non- or minimally productive chronic cough with a normal chest X-ray will have some form of airway reflux.

How this reflux manifests itself in terms of symptom profile depends on the constitution of the patient. Cough hypersensitivity syndrome is an overarching diagnosis analogous to COPD.

It is obvious that COPD consists of a number of different syndromes, such as emphysema and chronic bronchitis, yet it is only useful to differentiate this ‘disease’ when it is therapeutically important.

Investigating chronic cough

• Chest X-ray: mandatory as cough may be the sole presenting feature of a serious pathology.

• Spirometry: may be useful in identifying COPD.

• If available, exhaled nitric oxide: a measure of eosinophilic inflammation in the airways and may guide more aggressive steroid treatment of asthmatic cough.3

• The Hull Airways Reflux Questionnaire (HARQ): developed to identify reflux-related triggers and can be downloaded from the column to the right. Normal people score an average of 4 out of 70 and the upper limit of normal is 13.

In the overwhelming majority of patients, there will be a normal chest X-ray and normal investigations, but a high score on the airways reflux questionnaire.


Proton-pump inhibitors (PPI) are not a treatment for reflux. They block acid secretion, but reflux events are virtually unaffected – so in airway reflux, PPIs tend not to be useful unless the patient suffers from significant heartburn. In those patients, twice-daily dosing with food significantly enhances full acid suppression.

Pro-motility agents are a far better option. It is impossible to tell which agent will successfully manage a particular patient so therapeutic trials should last a month.

In our clinic we use:

• metoclopramide 10mg/tds followed by

• domperidone 10mg/tds, followed by

• azithromycin 250mg/od (an agonist of the hormone motilin as well as an antibiotic) and finally:

• baclofen 5mg/tds, which inhibits opening of the lower oesophageal sphincter.

If these therapeutic trials are unsuccessful, then cough suppression is tried. Low-dose morphine – not its prodrug codeine – helps one-third of intractable cases of cough. At 5mg slow release bd, it has no propensity for addiction but may lead to constipation.

Still coughing despite the therapeutic trials?

Two strategies are available. Firstly, the use of speech therapy has been well described as providing strategies for patients to cope with their coughing. Unfortunately, the local therapist needs to be aware of the technique.

Secondly, Nissan fundoplication has been successfully used by a number of groups to treat chronic cough.

Our own experience in over 60 patients reveals an approximately two-thirds success rate. Obviously, operative treatment needs to be carefully considered and full oesophageal studies, particularly oesophageal manometry, is required.

Fundoplication is not without its complications, including excessive flatulence and weight loss, so carefully informed consent is required.

Cough sensitivity syndrome in other respiratory diseases

Even though a patient with late-onset asthma responds to inhaled steroids, it may be a response to cough hypersensitivity syndrome. Associated features should be present on the questionnaire.

Similarly, with ‘frequent flyer’ COPD patients, another aetiology may be responsible for their exacerbations. If using

HARQ reveals a startlingly high score, that indicates that the actual cause of the exacerbation is micro aspiration following reflux.

Patients with cystic fibrosis and bronchiectasis frequently have exacerbations that are characteristic of reflux and aspiration episodes. Even pulmonary fibrosis in some patients is clearly caused by airways reflux.

If in doubt, in any patient with atypical or treatment-resistant pulmonary disease, the HARQ may point to reflux as the cause of previously occult aetiology.

Professor Alyn H Morice is professor of respiratory medicine at the University of Hull, Hull York Medical School

Chronic cough may be a hypersensitive reaction to gas released from the lower oesophageal sphincter Chronic cough Mandatory investigations in a patient with chronic cough

• Chest X-ray
• Spirometry
• Hull Airways Reflux Questionnaire
• Exhaled nitric oxide3 (if available)

The Hull Airways Reflux Questionnaire