Severe Asthma Risk May Be Linked to Capsaicin Cough Reflex Sensitivity

woman coughing hand over mouth
woman coughing
Capsaicin cough reflex sensitivity may be associated with an increased risk of severe asthma.

Capsaicin cough reflex sensitivity (C-CS) may be associated with an increased risk of severe asthma, a study in the American Journal of Respiratory and Critical Care Medicine suggests.

Researchers from Japan prospectively enrolled a total of 157 patients with asthma, including 122 patients with severe step 4/5 asthma as dictated by the 2015 Global Initiative for Asthma (GINA) guideline. Patients received blood tests, completed the Asthma Control Test (ACT), had fractional exhaled nitric oxide measured, underwent spirometry, and underwent the capsaicin cough challenge test.

An index of C-CS was defined by the concentration required to induce ≥5 coughs by capsaicin (C5). The researchers assessed associations between biomarkers and 4 clinical features of severe asthma defined by the European Respiratory Society/American Thoracic Society guidelines (poor control; ACT <20, n=58), frequent exacerbations (≥2 /y; n=28), admissions (≥1 /y; n=17), and airflow limitation (forced expiratory volume in 1 second percent predicted [FEV1%) <80; n=30).

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In a univariate analysis, factors associated with C-CS included poor asthma control (P <.0001), frequent exacerbations (P =.01), and admissions (P =.009). In the multivariate regression analysis, the researchers found heightened C-CS, or C5 ≤2.44 μM, was a significant risk factor of frequent exacerbations (odds ratio [OR], 2.83; 95% CI, 1.04-7.71; P =.04) and poor asthma control (OR, 4.83; 95% CI, 1.97-10.4; P =.0004).

Airflow limitation (FEV1% <80%) was also associated with frequent exacerbations (OR, 5.42; 95% CI, 1.77-16.6; P =.003) and poor asthma control (OR, 2.99; 95% CI, 1.13-7.94; P =.03). Having a history of smoking affected the risk of admissions (OR, 6.52; 95% CI, 1.89-22.4; P =.003), whereas the risk of airflow limitation included the presence of diabetes (OR, 7.17; 95% CI, 2.25-22.8; P =.0009) and chronic rhinosinusitis (OR, 2.78; 95% CI, 1.04-7.43; P =.04).

Study limitations included the lack of a safety analysis for the capsaicin cough challenge test, as well as the lack of evaluation of sputum eosinophils and neutrophils.

The researchers suggested the knowledge about “airway neuronal dysfunction in severe non-type 2 asthma would be profoundly important to establish a new therapeutic target for severe asthma refractory to existing therapies.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Kanemitsu Y, Fukumitsu K, Kurokawa R, et al. Increased capsaicin sensitivity in severe asthmatics associated with worse clinical outcome [published online January 28, 2020]. Am J Respir Crit Care Med. doi:10.1164/rccm.201911-2263OC