ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Response to Benralizumab in Severe Asthma: Oscillometry and MRI Ventilation Defect Improvements in Participants with Abnormal FeNO
Session Title
C4 - C004 BEST OF IMAGING 2021: FROM PHENOTYPING TO TREATMENT
Abstract
A1111 - Response to Benralizumab in Severe Asthma: Oscillometry and MRI Ventilation Defect Improvements in Participants with Abnormal FeNO
Author Block: M. Mcintosh1, H. K. Kooner1, R. L. Eddy2, C. Licskai3, C. Yamashita4, A. Gendron5; 1Department of Medical Biophysics, Robarts Research Institute, London, ON, Canada, 2UBC Centre for Heart Lung Innovation, Vancouver, BC, Canada, 3Division of Respirology, Department of Medicine, Western University, London, ON, Canada, 4Lawson Health Research Institute, London, ON, Canada, 5Medical, AstraZeneca, Mississauga, ON, Canada.
RATIONALE: In severe eosinophilic asthma, benralizumab (anti-IL5-Rα) has been shown to reduce exacerbations and steroid use while also improving quality-of-life1; the mechanism of action of this anti-eosinophilic therapeutic approach on airway inflammation and function however, is not well understood. The fraction of exhaled nitric oxide (FeNO) as implemented in clinical studies has been used as an indirect measure of eosinophilic airway inflammation.2 FeNO measurements significantly improved in response to Dupilumab3 but not Benralizumab.4,5 Other measurements of airway function include airway oscillometry which quantifies respiratory resistance and reactance, both of which may be related to airway luminal narrowing.6 Hyperpolarized 129Xe magnetic resonance imaging (MRI) also provides a direct measurement of airway function via the ventilation defect percent (VDP). We evaluated 27 participants with eosinophilic asthma before and after treatment with benralizumab and hypothesized that those with baseline FeNO>50ppb would report significant oscillometry and VDP responses, and this would not be observed in participants with normal baseline FeNO.
METHODS: Twenty-seven participants with severe eosinophilic asthma provided written informed consent to undergoing FeNO, 129Xe MRI and oscillometry on the day of first injection and 28-days post-benralizumab injection (30 mg). Participants were stratified based on baseline FeNO (low [<25 ppb] n=8, intermediate [25-50 ppb] n=9, high [>50 ppb] n=10).7 Potential differences in baseline demographics and improvements after 28 days of treatment were evaluated using ANOVA.
RESULTS: At baseline, there was no significant difference between the 3 subgroups except for FeNO (p<0.001). ANOVA revealed that the oscillometry measurements of elastance at 5 Hz (X5) (p=0.001) and reactance area (AX) (p=0.009) were significantly different post-benralizumab across subgroups. In addition, both X5 and AX were significantly different after 28-days of benralizumab in the FeNO high subgroup (p=0.002, p=0.007 respectively). Clinically relevant VDP improvements8 were also observed in the FeNO intermediate (∆=-5%) and FeNO high (∆=-6%) subgroups only.
CONCLUSIONS: The level of baseline FeNO predicted significant oscillometry and MRI VDP responses to benralizumab, 28-days post-therapy. These findings suggest that abnormally augmented FeNO values may be used to identify severe asthma patients with a greater potential small airways response to benralizumab and they also provide clues about the mechanism of action of benralizumab on airway inflammation and function.
REFERENCES:1Skolnik, N.S. CurrMedResOpin (2019). 2Alving, K. ERJ (1993). 3Wenzel, S. Lancet (2016). 4Bleecker, E.R. Lancet (2016). 5FitzGerald, J.M. Lancet (2016). 6Karayama, M. ClinExpAllergy (2018). 7Dweik, R.A. AJRCCM (2011). 8Eddy, R.L. ERJ (2018).
Author Block: M. Mcintosh1, H. K. Kooner1, R. L. Eddy2, C. Licskai3, C. Yamashita4, A. Gendron5; 1Department of Medical Biophysics, Robarts Research Institute, London, ON, Canada, 2UBC Centre for Heart Lung Innovation, Vancouver, BC, Canada, 3Division of Respirology, Department of Medicine, Western University, London, ON, Canada, 4Lawson Health Research Institute, London, ON, Canada, 5Medical, AstraZeneca, Mississauga, ON, Canada.
RATIONALE: In severe eosinophilic asthma, benralizumab (anti-IL5-Rα) has been shown to reduce exacerbations and steroid use while also improving quality-of-life1; the mechanism of action of this anti-eosinophilic therapeutic approach on airway inflammation and function however, is not well understood. The fraction of exhaled nitric oxide (FeNO) as implemented in clinical studies has been used as an indirect measure of eosinophilic airway inflammation.2 FeNO measurements significantly improved in response to Dupilumab3 but not Benralizumab.4,5 Other measurements of airway function include airway oscillometry which quantifies respiratory resistance and reactance, both of which may be related to airway luminal narrowing.6 Hyperpolarized 129Xe magnetic resonance imaging (MRI) also provides a direct measurement of airway function via the ventilation defect percent (VDP). We evaluated 27 participants with eosinophilic asthma before and after treatment with benralizumab and hypothesized that those with baseline FeNO>50ppb would report significant oscillometry and VDP responses, and this would not be observed in participants with normal baseline FeNO.
METHODS: Twenty-seven participants with severe eosinophilic asthma provided written informed consent to undergoing FeNO, 129Xe MRI and oscillometry on the day of first injection and 28-days post-benralizumab injection (30 mg). Participants were stratified based on baseline FeNO (low [<25 ppb] n=8, intermediate [25-50 ppb] n=9, high [>50 ppb] n=10).7 Potential differences in baseline demographics and improvements after 28 days of treatment were evaluated using ANOVA.
RESULTS: At baseline, there was no significant difference between the 3 subgroups except for FeNO (p<0.001). ANOVA revealed that the oscillometry measurements of elastance at 5 Hz (X5) (p=0.001) and reactance area (AX) (p=0.009) were significantly different post-benralizumab across subgroups. In addition, both X5 and AX were significantly different after 28-days of benralizumab in the FeNO high subgroup (p=0.002, p=0.007 respectively). Clinically relevant VDP improvements8 were also observed in the FeNO intermediate (∆=-5%) and FeNO high (∆=-6%) subgroups only.
CONCLUSIONS: The level of baseline FeNO predicted significant oscillometry and MRI VDP responses to benralizumab, 28-days post-therapy. These findings suggest that abnormally augmented FeNO values may be used to identify severe asthma patients with a greater potential small airways response to benralizumab and they also provide clues about the mechanism of action of benralizumab on airway inflammation and function.
REFERENCES:1Skolnik, N.S. CurrMedResOpin (2019). 2Alving, K. ERJ (1993). 3Wenzel, S. Lancet (2016). 4Bleecker, E.R. Lancet (2016). 5FitzGerald, J.M. Lancet (2016). 6Karayama, M. ClinExpAllergy (2018). 7Dweik, R.A. AJRCCM (2011). 8Eddy, R.L. ERJ (2018).
