Response to Benralizumab in Severe Asthma: <sup>129</sup>Xe MRI, Oscillometry and Clinical Measurements

McIntosh, Marrissa J; Eddy, Rachel L.; Knipping, Danielle; Barker, Andrea L.; Lindenmaier, Tamas J; Yamashita, Cory; Párraga, Grace

doi:10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a6244

Cited by 3 publications

(3 citation statements)

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“…Nevertheless, there are suggestions that treatment with benralizumab may lead to beneficial structural changes in the lungs. In a study of patients with severe eosinophilic asthma, ventilation heterogeneity, as measured by 129 Xe MRI and oscillometry, significantly improved 28 days after treatment with benralizumab [57]. A separate study of bronchial biopsies from patients with severe eosinophilic asthma showed a decrease in airway smooth muscle mass following treatment with benralizumab [58].…”

Section: Discussionmentioning

confidence: 99%

Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab

et al. 2022

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Introduction: Consensus definitions for clinical remission and super-response were recently established for severe asthma. Benralizumab is an interleukin-5 (IL-5) receptor a-directed monoclonal antibody for severe, uncontrolled asthma; efficacy and safety were demonstrated in previous pivotal phase 3 trials (SIROCCO, CALIMA, ZONDA). This analysis applied a composite remission definition to characterize individual responses to benralizumab after 6 and 12 months. Methods: In previous phase 3 studies, eligible patients were those with severe, uncontrolled asthma receiving medium-or high-dosage inhaled corticosteroids plus long-acting b 2 -agonists. This post hoc analysis included patients randomized to the approved benralizumab dose and not receiving oral corticosteroids (OCS) at baseline (SIROCCO/CALIMA) or OCS B 12.5 mg per day (ZONDA). Individual remission components were zero exacerbations; zero OCS use; Asthma Control Questionnaire-6

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Section: Discussionmentioning

confidence: 99%

Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab

et al. 2022

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“…The single snapshot is reproducible over short and long periods of time in patients, and is straightforward to acquire and quantify. Moreover, the static ventilation MRI provides a map of the time constants for lung filling which allows us to quantify and interpret studies of acute provocation 2,36,45,81,82 and treatment 5,6,12,49,82–85 …”

Section: Technological Challengesmentioning

confidence: 99%

“…In fact, following anti‐T2 therapy and subsequent reduction in airway eosinophilia, PfMRI VDP improved in asthma patients such that there was a greater improvement in those with worse baseline airway eosinophilia 49 . PfMRI can be used to detect response to biologic therapy in uncontrolled asthma, earlier than conventional pulmonary function tests, 84 where a significant treatment response, measured using PfMRI VDP, was observed in patients with a greater number of baseline mucus plugs 86 . As shown in Video 3, PfMRI ventilation improves following just a single dose of anti‐T2 therapy.…”

Section: Ongoing Clinical Studies and Opportunitiesmentioning

confidence: 99%

Pulmonary functional MRI: Detecting the structure–function pathologies that drive asthma symptoms and quality of life

et al. 2022

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Pulmonary functional MRI (PfMRI) using inhaled hyperpolarized, radiation‐free gases (such as 3He and 129Xe) provides a way to directly visualize inhaled gas distribution and ventilation defects (or ventilation heterogeneity) in real time with high spatial (~mm3) resolution. Both gases enable quantitative measurement of terminal airway morphology, while 129Xe uniquely enables imaging the transfer of inhaled gas across the alveolar–capillary tissue barrier to the red blood cells. In patients with asthma, PfMRI abnormalities have been shown to reflect airway smooth muscle dysfunction, airway inflammation and remodelling, luminal occlusions and airway pruning. The method is rapid (8–15 s), cost‐effective (~$300/scan) and very well tolerated in patients, even in those who are very young or very ill, because unlike computed tomography (CT), positron emission tomography and single‐photon emission CT, there is no ionizing radiation and the examination takes only a few seconds. However, PfMRI is not without limitations, which include the requirement of complex image analysis, specialized equipment and additional training and quality control. We provide an overview of the three main applications of hyperpolarized noble gas MRI in asthma research including: (1) inhaled gas distribution or ventilation imaging, (2) alveolar microstructure and finally (3) gas transfer into the alveolar–capillary tissue space and from the tissue barrier into red blood cells in the pulmonary microvasculature. We highlight the evidence that supports a deeper understanding of the mechanisms of asthma worsening over time and the pathologies responsible for symptoms and disease control. We conclude with a summary of approaches that have the potential for integration into clinical workflows and that may be used to guide personalized treatment planning.

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Clinical Applications of Hyperpolarised Xenon-129 MRI

Ng,

Grist,

Gleeson

et al. 2024

EMJ

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Conventional imaging modalities, the X-ray and CT, are essential diagnostic tools in respiratory medicine, providing qualitative information regarding the pattern and extent of pulmonary pathology. Neither provide information regarding the functional impact of pulmonary diseases and additional investigations are required to assess this. Hyperpolarised xenon-129 MRI (HPX-MRI) is a non-invasive, ionising-free imaging modality that can provide functional measurements of ventilation and diffusion within the lung. The MRI-based technique involves the subject breathing in an inert gas that has been hyperpolarised to make it visible using MR spectroscopy. The gas mirrors the flow of oxygen through the bronchial tree, across the alveolar membrane, and into the pulmonary capillaries, and thus disruptions in the passage of gas due to ventilation and diffusion abnormalities can be visualised and quantified. Functional measurements of ventilation and gas exchange within regional areas of the lung can be obtained. HPX-MRI has the potential to detect early lung disease not yet evident using standard investigations and has been shown to be a sensitive modality to assess treatment responses. The role of HPX-MRI in respiratory medicine has the potential to be wide-reaching, but to date it remains largely a research tool. This review article summarises the current and possible future clinical applications of HPX-MRI in the investigation and management of lung diseases, pitched at a level comprehensible and relevant to the respiratory-focused clinicians.

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Response to Benralizumab in Severe Asthma: ¹²⁹Xe MRI, Oscillometry and Clinical Measurements

Cited by 3 publications

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Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab

Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab

Pulmonary functional MRI: Detecting the structure–function pathologies that drive asthma symptoms and quality of life

Clinical Applications of Hyperpolarised Xenon-129 MRI

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Response to Benralizumab in Severe Asthma: 129Xe MRI, Oscillometry and Clinical Measurements

Cited by 3 publications

References 0 publications

Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab

Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab

Pulmonary functional MRI: Detecting the structure–function pathologies that drive asthma symptoms and quality of life

Clinical Applications of Hyperpolarised Xenon-129 MRI

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Product

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Response to Benralizumab in Severe Asthma: ¹²⁹Xe MRI, Oscillometry and Clinical Measurements