Mepolizumab and Physical Activity in Severe Asthma

Severe asthma is a debilitating condition associated with frequent symptoms, life-threatening exacerbations and corticosteroid side-effects. Exercise limitation due to exercise-induced bronchoconstriction, dynamic lung hyperinflation and comorbidity may be a strong determinant of the disease burden. Mepolizumab is a monoclonal anti-interleukin-5 (IL-5) antibody that reduces the rate of severe exacerbations, asthma symptoms and oral glucocorticoid requirement, and improves quality of life and work productivity in severe eosinophilic asthma. However, its impact on physical activity and exercise tolerance is unknown. We hypothesize that a 6-month treatment with mepolizumab is associated with an improvement in daily life physical activity and exercise tolerance in relation with enhanced ventilatory mechanics.

Inclusion Criteria: * Age between 18 and 75 years at the time of inclusion * Asthma diagnosed for at least one year including a history of 1. FEV1 and/or FVC reversibility of more than 12% and than 200 ml documented in the patient's record 2. OR FEV1 variability of more than 20% between two visits 3. OR positive methacholine test * Severe uncontrolled asthma monitored for at least six months in the investigation center with at least two assessments: 1. high-dose of inhaled corticosteroids (ICS \>1,000 μg/day of beclometasone equivalent) in combination with another controller at a stable dosage for at least three months 2. ACQ-5 score \>1.5 and/or more than two severe exacerbations (i.e exacerbation requiring ≥ 3 days of systemic corticosteroids, hospitalization or admission at the emergency department) in the past year 3. Blood eosinohils ≥300/mm3 within the 12 past months 4. Decision to introduce mepolizumab according to regulatory approval 5. Patient agreement to receive Mepolizumab * Body mass index (BMI) within the range \[18.5 - 35\] kg/m2. * Able to give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol Exclusion Criteria: * Body Mass Index \<18.5 or \>35 kg/m2 * Active smoker or active smoking during the last 6 months or cumulative \> 10 pack-years * All conditions responsible for physical disability (neurological, orthopedic, psychiatric, non-exhaustive list) or other condition limiting exercise in the investigator's opinion * Any chronic respiratory or cardiac pathology which may interfere with the assessment of asthma according to the investigator's opinion * Prior treatment with mepolizumab or benralizumab * Bronchial thermoplasty during the past 12 months * Contraindication to mepolizumab * Non-coverage by the social security insurance * Pregnant, breastfeeding, or lactating women * Patient unable to receive information * Refusal to sign the consent form * Unwillingness or inability to follow the study procedures, in the opinion of the investigator * Person deprived of the liberty Person benefiting from a system of legal protection (guardianship…)