Study hypothesis We hypothesize that mepolizumab has a significant beneficial effect on small airways disease in severe asthmatics and that the evaluation of small airways before and during treatment may represent a distinctive marker of response and a novel target for a preferential use of this drug vs other biologics available for severe eosinophilic asthmatic patients.
Study objectives
* To evaluate a wide panel of validated small airways endpoints in eosinophilic severe asthmatics before mepolizumab treatment
* To evaluate longitudinal changes of these endpoints at different time points during mepolizumab treatment
* To relate small airways endpoints recorded at baseline and their changes over time to other functional, laboratory, clinical and patient reported outcomes
Study center The study will be conducted at the Asthma Center of the Fondazione Policlinico Universitario A. Gemelli, IRCCS, Respiratory, Allergy and ENT Physicians closely and sinergically collaborate in the framework of the Asthma Center with shared clinical and research activities aimed to an optimal management of asthma and its comorbidities, as well as with regular meetings for multidisciplinary clinical case discussion and collective decisions on treatment strategies. The Asthma Center is part of the Italian Severe Asthma Network (SANI) and will be soon one of the coordinating centers for the newborn Italian Mild-Moderate Asthma Network (MANI), therefore representing a center of excellence and reference at a national level, with easy and wide access to the study population.
Study design Asthmatic patients referred to the Asthma Center and eligible for starting Mepolizumab, after having optimized adherence, inhalation technique and comorbidity management following multidisciplinary assessment, will enter a single-site oservational prospective longitudinal cohort study. Subjects will be monitored for 12 months and SA endpoints will be recorded at the beginning of the biological therapy (T0) and after 3,6,12 months (T3, T6, T12). SA endpoints will be also related to other functional, clinical and patient reported outcomes.
Study population Male and female subjects addressed to the Asthma Center, aged ≥12 yrs with severe asthma as defined by ATS/ERS guidelines (≥12months high-dose ICS + additional controller treatments), ≥2 exacerbations (corticosteroid and/or ED visit and/or hospitalization in the previous 12 months), blood eosinophil ≥150 cells/µl at study entrance or ≥300cells/µl historically and a smoking history \<2 pack/year.
Study drug Mepolizumab 100mg via subcoutaneous administration
Study procedures
The following methodologies will be included in the study:
Clinical history, Demographics and questionnaires (i.e. ACT, ACQ, ACQLQ) Pulmonary function tests (i.e. spirometry, body plethysmography, single- and multi-breath nitrogen washout, impulse oscillometry) Airway inflammatory markers (i.e. fraction exhaled nitric oxide - FeNO) Allergy tests (i.e. skin-prick tests and immunoassays for total and specific serum IgE) Biological sampling (i.e. blood and sputum eosinophils)
Study endpoints The following endpoints relating to small airways involvement will be considered: R5, R20, X5, AX, RF, FEF25-75, TLC, RV, Raw, Gaw, DLCO, KCO, LCI
