ERS guidelines on the diagnosis and treatment of chronic cough in adults and children

In chronic cough patients with normal chest radiographs and physical examination, rates of any positive findings on chest CT scan varied widely in the literature. However, the task force members found that these abnormalities were unlikely to explain cough and may not influence management of the patients.

For those patients without a clear diagnosis or a chronic cough that is refractory to treatment of associated conditions, a high-resolution CT scan of the chest may identify subtle interstitial lung disease not visible on chest radiographs, e.g. pulmonary fibrosis, hypersensitivity pneumonitis and bronchiectasis, or areas of mucus plugging, which may prompt the need for bronchoscopy for clearance, lavage and culture. However, whether these subtle changes are the cause of the cough or a consequence of an underlying condition, such as recurrent aspiration, is unknown.

There is a concern about potential cancer risk from CT radiation exposure [89]. According to an estimation study [88], a projected number of future cancers that could be related to chest CT scans performed in the US was 4100 (95% uncertainty limits 1900–8100) cases from 7 100 000 scans, and the estimated rates were higher in children and females.

• There is a need for convenient, safe, and practical tests for detecting and predicting anti-inflammatory treatment responses in chronic cough. In randomised controlled trials of patients with different respiratory conditions, F_eNO or blood eosinophil levels were positively associated with anti-inflammatory treatment responses [133–135]. However, there is no high-quality evidence to guide the use of F_eNO or blood eosinophil counts as treatment response predictors in patients with chronic cough. In addition, there are still no optimal cut-off levels determined for the use in chronic cough populations.

Asthmatic cough (CVA and eosinophilic bronchitis) is a frequent phenotype of chronic cough. Evidence for ongoing airway eosinophilic inflammation can be collected by performing differential cell counts on samples from sputum induction or bronchoalveolar lavage; however, these tests are not available at most clinics. Moreover, there is no high-quality evidence for the routine use of F_eNO or blood eosinophil counts in patients with chronic cough (as recommendation 2). Therefore, empirical therapy for asthmatic cough may be considered.

In the literature, there is a heterogeneity in the efficacy of ICS in adult patients with chronic cough. The variability in the treatment response is probably primarily related to patient characteristics, particularly eosinophilic inflammation.

Available evidence suggests that a high dose of ICS might be more effective than a low-to-moderate dose regimen, as an empirical trial.

A treatment response is usually seen within 2–4 weeks. Thus, the empirical trial should be stopped if there is no response within 2–4 weeks.

The task force members were concerned about long-term overuse of ICS in the absence of evidence or treatment response. In addition, they were concerned about pneumonia in relation to fluticasone use in patients comorbid with COPD.

Overall remarks are the same as those in adults.

The empirical trial should be stopped if there is no response within 2–4 weeks.

Overall remarks are similar to those for ICS.

Currently, clinical evidence is only available in specific subgroups of patients, such as CVA or atopic cough. Overall efficacy of leukotriene receptor antagonist in nonspecific chronic cough patients is uncertain.

The empirical trial should be stopped if there is no response within 2–4 weeks.

There is a concern about pneumonia in relation to fluticasone use in patients comorbid with COPD. The empirical trial should be stopped if there is no response within 2–4 weeks.

Anti-acid drugs are unlikely to be useful in improving cough outcomes, unless patients have peptic symptoms or evidence of acid reflux.

Clinical benefits from PPI over placebo on cough outcomes are not significant in patients without acid reflux and only modest in those with acid reflux. These agents effectively block gastric acid production and relieve acid-related symptoms, but have little effect on the number and volume of reflux events. Gastric acid does not appear to play a major role in the aetiology of chronic cough.

PPIs are mostly considered to be well tolerated. However, there is a potential concern about increased risks of complications, such as pneumonia, iron deficiency, vitamin B₂ deficiency, small intestinal bacterial overgrowth, Clostridium difficile-associated diarrhoea or bone fracture [118].

Current evidence only supports the use of azithromycin in patients with chronic bronchitis phenotype. However, mechanisms of azithromycin in improving cough outcomes are suggested to include prokinetic effects [136].

Since oesophageal dysmotility is a frequent finding in chronic cough patients, promotility agents such as metoclopramide, domperidone and azithromycin might be considered, although the clinical trial evidence in cough is sparse.

Agents acting directly on cough hypersensitivity rather than the treatable traits causing hypersensitivity is a promising strategy for future developments. Current agents have been shown to be effective, but the side-effect profile is significant and may be mitigated by the use of lower doses than that used to treat pain. Clinical experience suggests that only a proportion of patients (approximately half) respond to opiates. In responders, treatment response is very rapid and clear (usually seen in a week). Thus, discontinuation is recommended if there is no response in 1 or 2 weeks.

Codeine is generally not recommended (except where it is the only available opiate) due to interindividual genetic variability in drug metabolism (CYP2D6) and consequent less predictable treatment response and side-effect profile, particularly in children.

• Clinical experience suggests the response rates of gabapentin and pregabalin are lower than that of opiates, and adverse events are more common. Common adverse effects are blurred vision, disorientation, dizziness, dry mouth, fatigue and nausea.

• Multi-component physiotherapy/speech and language therapy interventions may be considered for short-term improvement of health-related quality of life and cough frequency in patients with refractory chronic cough or who wish an alternative to drug treatment. However, this is a complex intervention that requires further study to determine which components are of value. Thus, experienced practitioners should undertake cough-directed physiotherapy and speech and language therapy intervention. The pool of individuals qualified for cough control therapy is currently lacking in many countries and should be increased.

Protracted bacterial bronchitis is a common treatable trait in children. Preferred antibacterial, dose and duration of therapy is unknown.

Signs and symptoms suggestive of specific disease should always be investigated.