Cough Frequency and Type-2 Inflammation Biomarkers in Severe Asthma

Patients with severe asthma and low biomarkers of Type-2 (T2) inflammation do not have elevated cough frequency, suggesting that cough in asthma is caused by T2 eosinophilic inflammation. This further suggests that suppressing T2 inflammation may be effective in treating cough in asthma. These were among study findings published recently in the European Respiratory Journal.

Although previous studies link troublesome cough with poor asthma control, cough is not considered in the Asthma Control Questionnaire. There is also a lack of understanding of how objective measurements of cough relate to T2 biomarkers of airway inflammation. Investigators sought to examine relationships between asthma control, objective cough frequency, cough quality-of-life, and T2 asthma inflammation biomarkers.

Investigators in the United Kingdom conducted a single-center, prospective observational study between October 2017 and September 2019 of 42 patients with currently stable severe asthma, recruited from a Specialist Severe Asthma Service in Belfast City Hospital, Ireland, and a comparison cohort of 19 patients with mild/moderate asthma, currently stable, recruited from local health care providers. All 61 patients underwent ambulatory cough monitoring, and measurement of fractional exhaled nitric oxide (FeNO) and peripheral blood eosinophil count (PBE) and subsequently classified by T2-low (FeNO <20ppb and PBE <150 cells/µl), T2- intermediate (FeNO ≥20ppb or PBE ≥150 cells/µl) or T2-high (FeNO ≥20ppb and PBE ≥150 cells/µl).

The cohort with severe asthma presented higher cough rates than the comparison cohort (total 24-hour cough count geometric mean 170.3±2.7 vs 60.8±4.1; P =.002; cough frequency geometric mean 7.1±2.7coughs/hour vs 2.5±4.1c/h; P =.002). Patients with severe asthma stratified as T2-low (n=6) presented significantly lower 24-hour cough frequency (64.0±1.6) compared with patients stratified as T2-intermediate (n=14; 305.6±2.2) and T2-high (n=22; 157.4±2.6).

Study limitations included the underpowered sample, the assessment of all patients at a single point in time, and the disparate proportion of females in severe (69%) vs moderate (42%) asthma cohorts.

The researchers concluded that “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.”

Reference

Holmes J, McGarvey LP, Birring SS, Fletcher H, Heaney LG. An observational study to determine the relationship between cough frequency and markers of inflammation in severe asthma. Eur Respir J. Published online July 1, 2022. doi:10.1183/13993003.03205-2021