Functional Lung MRI for Early Treatment Response Assessment for Patients With Eosinophilic Asthma

Description

Asthma is a chronic disease and affects approximately 300 million people worldwide. Of these patients 3-10% have severe asthma which is defined as asthma remaining uncontrolled despite treatment with high-dose inhaled glucocorticoids combined with other controllers (long-acting 2-agonist, long-acting antimuscarinic agent, leukotriene receptor antagonist or theophylline) and/or treatment with systemic glucocorticoids for at least 6 months. Severe asthma causes a high amount of medical expenses in asthma. For patients suffering from severe uncontrolled asthma, an IL-5 antibody (mepolizumab) has been approved for therapy when a type 2 inflammation was present. Treatment is well tolerated and a significant reduction of exacerbations, oral glucocorticoid use was reported. Another IL-5 antibody (reslizumab) and an IL-5 receptor antibody (benralizumab) are available now.

Patients with severe eosinophilic asthma will be placed on biologics if they continue to be uncontrolled under maximal therapy or if they are only controlled under oral corticosteroids. Among biologics, 80% of patients improve, 20% are non-responders, but there is no way to identify them early. Among the responders, about 30% respond very well (so-called super responders), the rest shows moderate improvements. The main problems at the moment are that lung function improvements are only delayed, the response (or non-response) can only be reliably estimated after 4 to 12 months. This leads on the one hand to prolonged use of medication in non-responders (overtreatment), on the other hand to unjustified and premature termination of therapy (undertreatment) (GINA report 2019).

Study Rationale Functional lung MRI has the potential to show early changes in lung microstructure, regional ventilation and perfusion and thus has the potential for early detection of therapy response. Very promising results of dynamic regional ventilation and perfusion mapping using phase resolved functional lung (PREFUL) MRI have been shown recently. This technique holds the promise to mature into a patient friendly sensitive MRI spirometry test, with novel clinically relevant information to guide clinical decision making and improve patient monitoring. PREFUL MRI typically uses standard 1.5T or 3T MRI equipment and is based on a routine gradient echo fast low angle shot (FLASH) sequence. PREFUL is well suited also for children, because it is a free breathing exam without the need for i.v. contrast and has a relatively short examination time. The ventilation, perfusion and dynamic flow-volume loop maps are reconstructed entirely after the image acquisition using complex registration and post processing algorithms developed and validated at Hannover Medical School. Preliminary unpublished data show that PREFUL MRI may detect changes in regional ventilation 3 months after anti IL 5 antibody therapy treatment.

However, if functional lung MRI can reliably detect changes at 3 months of Mepolizumab treatment and can predict long term patient outcome is still unknown, which is of high clinical relevance for future clinical decision making.

The aim of this study is to examine if early treatment changes of Mepolizumab treatment can be detected at 3 months measured by functional lung MRI and predict clinical outcome at 12 months of treatment.

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