An observational study to determine the relationship between cough frequency and markers of inflammation in severe asthma

The relationship between objectively measured cough and type-2 biomarkers and other measures of asthma control and severity is poorly understood. The objective of this study was to assess the relationship between objective and subjective cough measurement tools and clinical biomarkers of asthma.Patients with severe asthma and mild/moderate asthma completed validated asthma and cough-related measurement tools (including ambulatory cough monitoring) and measurement of spirometry and T2-biomarkers (fractional exhaled nitric oxide measurement (FeNO) and peripheral blood eosinophil count (PBE)). Patients were classified according to T2-status based on T2-low (FeNO<20ppb AND PBE<150 cells·µl-1), T2-intermediate (FeNO≥20ppb OR PBE≥150 cells·µl-1) or T2-high (FeNO≥20ppb AND PBE≥150 cells·µl-1).In total, 61 patients completed the study measurements (42 severe asthma, 19 mild/moderate asthma). Patients with severe asthma had higher rates of cough than those with mild/moderate asthma in terms of total 24-hour cough counts (geometric mean 170·3 (sd 2·7) versus 60·8 (sd 4·1), p=0·002) and cough frequency (geometric mean, 7·1 c·h-1 (sd 2·7) versus 2·5 c·h-1 (sd 4·1), p=0·002). T2-low patients with severe asthma had significantly lower 24-hour cough frequency compared to T2-intermediate and T2-high patients.In patients with low biomarkers of T2 inflammation, cough frequency measurements were not elevated, suggesting that the mechanism for cough in asthma is underlying T2-eosinophilic inflammation and the logical first step for treating cough in asthma may be to achieve adequate suppression of T2 inflammation with currently available therapies.