Chronic cough – 2019 ERS update

The European Respiratory Society (ERS) has published new guidelines on the assessment of chronic cough. The purpose of the guidelines is to improve diagnostic accuracy and promote evidence-based therapy for both adult and paediatric populations

Most recent guidelines define the duration of chronic cough to be eight weeks in adults and four in children, however, this is relatively arbitrary. Some patients may cough on a daily basis over many years, others may have symptoms that relapse and remit making a definition, based purely on a period of time, difficult.

Cough is a common medical problem and a mainstay of the GP surgery. Meta-analysis suggests a global prevalence of about 10 per cent, with a higher prevalence in Europe, America and Oceania than in Africa or Asia. Its socioeconomic burden is high, however, there is no precise data on its burden due to the fact that cough has usually been perceived to be a consequence of another respiratory condition.

It appears to predominantly affect women with the most common age of presentation being in the 50s and 60s. A recent study of 10,032 patients attending specialist cough clinics showed two-thirds of patients being female. 

Approximately 35 per cent of preschool children will report a cough at any given time in a month.

Aetiology

Cough is a vital reflex preventing aspiration into the lung. Poor cough reflex can result in recurrent aspirations frequently misdiagnosed as chest infections.

It is evoked by stimulation of afferents carried by the 10th cranial nerve – important due to receptive fields not only in the larynx and conducting airways, but also in the alveolar septa and lung parenchyma, pharynx, oesophagus, and even the ear. This may result in stimulation due to multiple different conditions such as pulmonary embolism, heart failure or altitude sickness.

Phenotypes

Asthmatic cough

Asthma is a clinical diagnosis, with no singular agreed diagnostic test.

Three subgroups of asthmatic cough exist:

Classic asthma – airflow variability and bronchial hyperresponsiveness. Spirometry is an accepted investigation.

Cough variant asthma – Patients with asthma and cough as their sole symptom, where  bronchodilators improve coughing.

Eosinophilic bronchitis, without bronchoconstriction or hyperresponsiveness.

Reflux cough

The role of reflux is controversial, as is oesophageal dysmotility in chronic cough. A systemic review showed no significant benefit over proton-pump inhibitors (PPI) vs placebo in patients without acid reflux and only modest benefits in patients with acid reflux. It has been suggested that non-acid reflux – liquid or gaseous may be a factor. However, as no reliable technology exists, validated questionnaires such as the Hull Airway Reflux Questionnaire or Reflux Symptom Index together with clinical history are required. Patients with chronic cough have a high prevalence of oesophageal dysmotility and as a result oesophageal-pharyngeal reflux may be the issue rather than GORD.

Post-nasal drip syndrome/Upper airways cough syndrome

The 2006 American College of Chest Physicians cough management guidelines used the umbrella term ‘upper airways cough syndrome (UACS)’ to cover the range of symptoms more commonly referred to as post-nasal drip syndrome, rhinitis, and rhinosinusitis. Meanwhile, there continues to be controversy as to the existence of this condition and its specific mechanism. However, the ERS suggests that UACS could be accepted as a cause of chronic cough, triggering cough hypersensitivity despite its mechanism remaining unclear.

Traditionally a first-generation antihistamine and decongestant were recommended as treatment despite any appropriate randomised control trial evidence. First-generation antihistamines are believed to be anti-tussive as they act on centrally penetrant anticholinergics.

The lack of evidence for treatment may suggest that UACS may simply be the result of generalised airway inflammation as a result of asthma or airway reflux.

Iatrogenic cough

Chronic cough has a prevalence of approximately 15 per cent of all patients taking angiotensin converting enzyme inhibitors (ACEI). ACEI increases the cough reflex sensitivity in most subjects, as a result it is likely that other factors are required to have a clinical impact.

The ERS recommends that no patient with a cough or who subsequently develops one should be given an ACEI. Angiotensin II antagonists do not affect the cough reflex.

Bisphosphonates and calcium channel antagonists may worsen reflux disease resulting in increased coughing.

Prostanoid eyedrops (latanoprost) once applied may irritate the pharynx when they descend the lacrimal duct.

Chronic cough in children

There are several differences in chronic cough presentations between children and adults. Chronic cough in a paediatric populations is defined as a cough which lasts more than four weeks as opposed to eight weeks traditionally with adults. As a result, child-specific protocols should be considered.

During childhood, as several anatomical structures and physiological processes related to the nervous and respiratory systems mature, the cough reflex can be affected. Infection and congenital abnormalities remain the main causes of cough in children.

Tracheomalacia, protracted bacterial bronchitis (PBB), bronchiectasis, asthma and post-infectious cough can all cause chronic cough.

ERS guidelines suggest the presence of PBB in the presence of all three of the following:

Continuous chronic wet/productive cough (>four weeks).

Absence of any other causes of cough.

Cough resolved following antibiotic course of two-to-four weeks.

Initial assessment of children with chronic cough should include a detailed history and physical exam. Sudden onset of symptoms in an otherwise well preschool child may suggest foreign body aspiration and requires bronchoscopy. Chest x-ray and spirometry are recommended for assessment. Where chest x-ray and spirometry are normal and no specific cause identified another period of observation up to four weeks is recommended. Airborne irritants, allergen exposure, post-infectious cough may all be reasons for dry chronic cough. Where wet cough is present sputum cultures should be taken if possible. Habit cough is found particularly in children. Core clinical features include suppressibility, distractibility, suggestibility, variability.

Chronic refractory cough

This is cough that is refractory to conventional treatments. Trials of neuromodulatory drugs which have been successful, such as opioids, gabapentin, and P2X3 antagonists, suggest aberrant physiology is likely to underlie this condition.

Chronic cough in other diseases

Cough is associated with most chronic respiratory disease. This can be due to physical distortion like in lung cancer, cystic fibrosis or chronic bronchitis producing cough by mechanical effect. Cough hypersensitivity due to cell damage or inflammation is another cause in other conditions.

Chronic cough, tobacco, and nicotine

Smoking is the major remedial cause of chronic cough and is linked to COPD. Multiple studies show a suppressed cough reflex sensitivity in smokers to inhaled capsaicin. All patients should be encouraged to quit smoking and be counselled that there may be a transient increase in coughing.

Assessing cough

History, examination and investigations are vital to exclude treatable conditions.

The ERS guideline places a higher priority on managing ongoing pathology, such as reflux or airway eosinophilia before considering neuro-modulatory therapies.

History should be constructed to outrule malignancy, infection, foreign body inhalation or ACE use.

Impact may be assessed using a simple out of 10 score or a more detailed cough quality-of-life score or validated questionnaire such as HARQ.

Initial investigations should include spirometry and chest x-ray. Chest CT is not currently recommended as a routine investigation in patients with normal chest x-ray and spirometry.

Reflux

Abnormal oesophageal physiology is common in chronic cough, and may be detected by barium swallow, albeit with poor sensitivity. High resolution oesophageal manometry provides diagnostic and mechanism information in the majority of patients.

Upper airways

Routine laryngoscopy, rhinoscopy, or CT sinus are not routinely advised as nasal findings are not directly associated with cough.

Laryngoscopy may be of benefit to patients with upper airway symptoms, however it has shown poor sensitivity and specificity. It may, however, identify inducible laryngeal obstruction. Rhinoscopy may identify polyps.

Treatment

The ERS suggests trials of medications in turn and if no response is identified, that they be stopped. Length of trial is dependent of pharmacology. Treatment for several months may be required and subsequently withdrawn to assess remission.

Anti-asthmatic drugs

Short-term ICS trial (two-to-four weeks) in adult patients with chronic cough (conditional recommendation – low-quality evidence).

In children with chronic dry cough (two-to-four weeks) the ERS recommends a short trial of ICS (conditional recommendation – low-quality evidence).

Short-term trial anti-leukotriene trial (two-to-four weeks) in adult patients with chronic cough – in particular asthmatic cough.

Short-term trial (two-to-four weeks) of ICS and long-acting bronchodilator combination in adults with chronic cough and fixed airflow obstruction.

Antacids

PPIs and H2 antagonists should not be routinely prescribed in adult patients with chronic cough (conditional recommendation – low-quality evidence). They are unlikely to improve cough outcomes unless there is evidence of peptic symptoms or acid reflux. While PPIs are considered safe, studies report potential risks of iron and vitamin B12 deficiency, and osteoporosis-related bone fracture, among other issues.

Pro-motility drugs

The ERS suggests that there is insufficient evidence to recommend macrolide therapy in the management of chronic cough. A one-month trial of a macrolide may be considered in chronic bronchitis refractory to other therapy, dependent on local antibiotic guidelines.

Neuromodulators

Trial of low-dose slow release morphine (5-10mg bd) in adults with refractory chronic cough (strong recommendation).

Trials of gabapentin or pregabalin may also be considered in adults with refractory chronic cough – although there is lower-quality evidence to support this.

Non-pharmacological cough control therapy

Moderate support base to support physiotherapy/speech and language therapy.

Antibiotics for chronic wet cough in children

A trial of antibiotics is suggested in children presenting with chronic wet cough – with normal spirometry, normal chest x-rays and no warning signs. A single randomised controlled trial (RCT) investigated a two-week regimen of twice daily of oral amoxicillin and clavulanate, showing cough resolution rates >75 per cent.

Pertussis

Not mentioned in these current ERS guidelines, pertussis (whooping cough) can also cause chronic cough. Symptoms can appear seven-to-10 days post infection and often resemble a common cold with coryza symptoms. Within two weeks, cough may become more severe and may or may not present with the traditional whoop. Cough may initially occur at night increasing then with frequency during the day, and may persist for up to two months.

Antibiotic therapy is the treatment of choice, however, it should be commenced within two weeks of onset of symptoms.

Reference
Morice A, et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. European Respiratory Journal. 2019. https://erj.ersjournals.com/content/early/2019/09/02/13993003.01136-2019