Neuromodulatory therapies and speech pathology–based cough suppression are suggested treatment options for unexplained chronic cough in new guidelines from the CHEST Expert Cough Panel.
The panel noted, however, that evidence supporting the diagnosis and management of unexplained chronic cough is limited. As part of the guideline development, they considered approaches for improving related research.
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“Persistent cough of unexplained origin is a significant health issue that occurs in up to 5% to 10% of patients seeking medical assistance for a chronic cough and from 0% to 46% of patients referred to specialty cough clinics. Patients with unexplained chronic cough experience significant impairments in quality of life ... there is a need to identify effective treatment approaches,” Dr. Peter Gibson of Hunter Medical Research Institute, New South Wales, Australia, and his colleagues reported on behalf of the panel (Chest. 2016;149[1]:27-44).
The panel defined unexplained chronic cough as a cough that persists longer than 8 weeks, and that remains unexplained after evaluations and supervised therapeutic trials are conducted according to guidelines.
The panel also suggested the following therapeutic approaches:
• That adult patients have objective testing for bronchial hyperresponsiveness and eosinophilic bronchitis, or be offered a trial of corticosteroid therapy.
• That adult patients have a trial of multi-modality speech pathology therapy.
• That inhaled corticosteroids not be prescribed in adult patients who test negative for bronchial hyperresponsiveness and eosinophilia.
• That a therapeutic trial of gabapentin be offered as long as the risk-benefit profile is discussed with the patient, and as long as reassessment of the risk-benefit profile be conducted at 6 months – before continuing the drug. The recommended starting dose is 300 mg daily in those without contraindications, with dose escalation daily as tolerated up to a maximum tolerable dose of 1,800 mg daily in two divided doses.
• That adult patients with a negative workup for acid gastroesophageal reflux disease not be prescribed a proton pump inhibitor.
The panel’s suggestions are the result of a systematic review of 11 randomized controlled trials and 5 systematic reviews to discern whether treatment is more efficacious than usual care with respect to cough severity, cough frequency, and cough-related quality of life.
Studies reviewed included data on 570 subjects over age 12 years with chronic cough who received a variety of interventions. Positive effects on cough-related quality of life were noted for both gabapentin and morphine, but the panel determined that only gabapentin was supported as a treatment recommendation.
After controlling for intervention fidelity bias, inhaled corticosteroids were not found to be effective for unexplained chronic cough, and esomeprazole was not effective in patients without features of gastroesophageal acid reflux.
Most of the recommendations are based on consensus opinion and limited data. As a result, the panel examined clinical trial design, chronic cough registries, and potential research questions in an effort to identify ways to improve research. Among other conclusions, the panel said future trials should include comparison groups as a significant placebo effect can occur in cough trials. Also, quality of life should be used as the primary study outcome.
“Registries for unexplained chronic cough could be used to document patient characteristics and outcomes, as well as clinical trials in progress. They could also serve as a source of research participants for trials and may allow for phenotyping according to age, sex, cough duration, cough severity, cough reflex sensitivity, and other biomarkers. Registries can be used for genetic studies in chronic cough.”
“Unexplained chronic cough requires further study to determine consistent terminology and the optimal methods of investigation using established criteria for intervention fidelity,” the panel concluded.
Dr. Gibson reported having no disclosures. One other author, Dr. Lorcan McGarvey, reported serving on advisory boards for Novartis and GlaxoSmithKline in relation to novel compounds with a potential role in treatment of cough, and serving as chairman for the Mortality Adjudication Committee for UPLIFT and TIOSPIR – two phase IV chronic obstructive pulmonary disease clinical trials for Boehringer Ingelheim.