Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations

Overview

Asthma is a chronic inflammatory disorder of the airways characterized by lower respiratory tract (LRT) symptoms such as wheeze, cough and airway obstruction. Patients with asthma frequently suffer from exacerbations, which can be triggered by allergens and, in particular, viral respiratory infections. It has recently been shown that mepolizumab, a humanized monoclonal antibody that neutralizes interleukin(IL)-5, markedly reduces the exacerbation rate in asthma patients with eosinophilic airway inflammation. Previous studies have indicated that in a mixed population (eosinophilic and non eosinophilic) of mild asthma patients, mepolizumab did not have an impact on lung function and asthma symptom scores upon allergen provocation, although it did on markers such as sputum and blood eosinophils. Together, these observations led to the hypothesis that mepolizumab treatment reduces the exacerbation rate by limiting virus-induced asthma exacerbations. The investigators hypothesize that neutralization of IL-5 during virus infection in patients with allergic asthma: 1. Reduces virus-induced bronchial inflammation 2. Attenuates virus-induced asthma symptoms, airflow limitation and bronchial hyperresponsiveness. 3. Enhances cellular immune responses to the virus. The aims of this study are to: 1. To investigate whether IL-5 neutralization reduces the inflammatory response to viral airway infections in allergic asthma patients 2. To investigate whether IL-5 neutralization prevents or reduces asthma symptoms during virus-induced asthma exacerbations 3. To investigate whether IL-5 neutralization affects the cellular immune response to viral airway infections in allergic asthma patients

Mild allergic asthma subjects receive three times an infusion containing 750 mg of mepolizumab. Two weeks after the third infusion, subjects will be experimentally infected with RV16. One day before and six days after infection a bronchoscopy will be performed to collect bronchoalveolar lavage fluid and bronchial brushes. Blood will be collected at each infusion and each bronchoscopy and at least 6 weeks after infection. Lung function will be evaluated throughout the study.