Patients with severe, refractory asthma constitute approximately 5% of all asthma patients but are responsible for over 50% of all asthma-related healthcare costs. Biologic treatments for asthma, drugs which target specific etiological pathways in particular asthma cases, have begun to emerge in the market as the first individualized treatments for severe asthma. Cost of these biologics currently ranges from $10-$40k per year and does not always improve asthma symptoms in some patients. The clinical decision to keep a patient on a particular biologic is based on exacerbation count and asthma questionnaire responses at 12 weeks following treatment initiation, by which time the patient has had 3 doses (at 0 weeks, 4 weeks, and 8 weeks). Exacerbation count and patient responses to questionnaires were the primary endpoints of the clinical trials which resulted in approval and are the primary biomarkers used in clinical evaluation of response, but patient- specific biomarkers of lung function would be most beneficial for evaluation of response to these patient- specific drugs. The lack of biomarkers which can predict response to biologic treatment is an unmet clinical need. This study will address this unmet need by evaluating the potential of hyperpolarized 129Xe MRI (HPG) to detect and predict biologic response in individual patients. Hyperpolarization is the process by which the nuclear magnetism of 129Xe is greatly enhanced allowing it to be directly imaged by MRI. Subjects inhale the xenon gas, and MRI are collected yielding high-resolution maps of regional lung ventilation. The overarching hypothesis is that HPG MR can be performed in a routine clinical setting and will predict which patients respond to treatment with mepolizumab, an anti-IL-5 biologic, 8 to 12 weeks sooner than standard clinical assessment. HPG MRI will be performed in asthma patients slated to receive treatment by mepolizumab at baseline, 4-week, and 12-week time points in order to assess its potential to assess, detect, and predict patient response to mepolizumab. This may dramatically reduce costs and improve outcomes for these patients.

Public Health Relevance

Biologic treatments of asthma are revolutionary, albeit expensive, new methods of severe asthma management; however, the current standard of care assesses individual patient response to treatment at 12 weeks following treatment initiation based on exacerbation count and patient responses to asthma questionnaires. Only an estimated 60-80% of patients treated with biologics demonstrate response. Patient- specific biomarkers of lung function which may predict response are an unmet clinical need in this patient cohort, and early detection of response to treatment could improve patient outcomes and reduce costs. In this proposal we will employ one of the most sensitive methods of assessing lung function ? hyperpolarized 129Xe MRI (HPG) ? to address our hypothesis that early responders to biologic treatment of severe asthma (mepolizumab in particular) can be detected by HPG.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Clinical Translational Imaging Science Study Section (CTIS)
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Noel, Patricia
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University of Missouri-Columbia
Schools of Medicine
United States
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