Abstract Rationale Refractory chronic cough (RCC) is a disease identified in a subset of people who experience chronic cough for 8 weeks, despite adequate treatment for known cough-related etiologies; unexplained chronic cough (UCC) is diagnosed when an underlying condition is not determined despite adequate diagnostic testing. This systematic review summarizes literature on RCC/UCC patient characteristics, disease burden, and treatments, highlighting current evidence gaps. Methods A systematic literature review was conducted to identify and summarize existing RCC/UCC literature, per 2020 PRISMA guidelines. Searches of peer-reviewed literature were conducted using MEDLINE and Embase databases, with additional supplementary searches. Systematic reviews and observational studies with ≥50 participants published from 2015 onwards were included. Results Sixty-four RCC/UCC publications were identified. Demographic characteristics of patients with RCC/UCC across 12 countries (Australia, Austria, Belgium, Canada, China, Denmark, Israel, the Netherlands, South Korea, Spain, UK, US) were: female (40.0-95.5%), mean age 45.0-65.0 years, and White/Caucasian (58.8-87.0%). US patients were predominantly female (65.0-88.2%) and older (mean age 56.9-64.6 years). A total of 34 publications reported clinical characteristics: mean cough duration (2.0-9.6 years) and mean cough severity (Visual Analog Scale) score (29.7-65.2mm). In the US, paroxysmal coughing (56.0-73.3%) was the most common symptom. Studies capturing health-related quality of life reported a mean Leicester Cough Questionnaire score range between 9.9-15.4. Reported median data were consistent with these ranges. Common comorbidities in patients with RCC/UCC included obstructive sleep apnea (4.5-84.4%), gastroesophageal reflux disease (4.5-63.5%), obesity (10.8-39.9%), and hypertension (13.6-47.7%). Urinary incontinence (12.7-59.2%) was the most frequent complication reported. Anxiety/depression affected 1.6-53.6% of patients. Across 10 studies, imaging (CT scan/x-ray) as a diagnostic tool for RCC/UCC was employed in 4.8-100% of patients. Pharmacotherapies for RCC/UCC: neuromodulators (0.5-96.2%), gastrointestinal drugs (0-93.0%), opioid-derivate cough suppressants (0.2-79.5%), and respiratory drugs (1.2-87.8%). Non-pharmacotherapies: behavioral cough suppression therapy (5.4-91.9%), behavioral speech therapy (BST; 46.7%); BST and continuous positive airway pressure (46.7%). Conclusions For most (88%) studies in this review, patients with RCC/UCC were predominantly female, older, and White/Caucasian. Patients experience substantial morbidity and disease burden but remain without a disease-specific treatment. Reported estimates of all parameters varied considerably, likely due to differences in study populations, guideline recommendations for RCC/UCC management, and definitions of RCC/UCC. Further research and development of novel therapies is essential to reduce the burden faced by patients with RCC/UCC. This abstract is funded by: GSK study 222187
Rouette et al. (Fri,) studied this question.
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