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A6393 - Effect of Anti-Th2 Therapy on MRI Ventilation Heterogeneity in Prednisone-Dependent Asthma
Author Block: S. L. Svenningsen1, R. Eddy2, D. P. Capaldi2, M. Kjarsgaard3, K. Radford3, G. Parraga2, P. Nair1; 1Medicine, McMaster University, Hamilton, ON, Canada, 2Robarts Research Institute, Western University, London, ON, Canada, 3Firestone Institute for Respiratory Health, Hamilton, ON, Canada.
RATIONALE: Magnetic resonance imaging (MRI) regionally identifies the inflammatory and non-inflammatory components of airways disease in severe asthma.1 In asthmatics with sputum eosinophilia, MRI ventilation heterogeneity persists post-bronchodilator1 and this may be important for guiding anti-inflammatory treatment decisions (eg. anti-Th2 monoclonal antibodies). Therefore, our objective was to ascertain the effect of anti-Th2 therapy on MRI ventilation heterogeneity in asthmatics with sputum eosinophilia.
METHODS: Six prednisone-dependent asthmatics with sputum eosinophilia (≥3%) provided written-informed-consent to an ethics-board-approved protocol and underwent spirometry and hyperpolarized gas MRI pre- and post-bronchodilator (400µg salbutamol) and completed the Asthma Control Questionnaire (ACQ) during a single two-hour visit. All assessments were repeated following additional anti-Th2 directed therapy (increased daily prednisone or addition of an anti-Th2 monoclonal antibody). Ventilation heterogeneity was quantified using the MRI ventilation-defect-percent (VDP)2 and paired t-tests were performed to evaluate the effect of additional anti-Th2 therapy on ventilation heterogeneity, FEV1 and ACQ.
RESULTS: All six prednisone-dependent asthmatics (1 male/5 female; 45±12 years; prednisone dose: 7.5[2.5-30]mg/day; pre-bronchodilator FEV1: 57±17%pred; reversibility of FEV1: 23[0-70]%; ACQ: 2.2±0.8) had ongoing sputum eosinophilia (37.2[4.3-56.8]%) that was not controlled and MRI ventilation heterogeneity was abnormal pre- and post- bronchodilator (pre-bronchodilator VDP: 10±7%; post-bronchodilator VDP: 6±3%). Patients were re-evaluated 418[100-995] days after additional anti-Th2 therapy was initiated to control the ongoing sputum eosinophilia and MRI ventilation heterogeneity was significantly improved (∆ pre-bronchodilator VDP: -4±4%, p=0.04). As shown in Figure 1, focal ventilation defects that were non-responsive to bronchodilator therapy were responsive to anti-Th2 therapy. Mean FEV1 and ACQ score were also improved (∆ pre-bronchodilator FEV1: 7±5%pred, p=0.03; ∆ ACQ: -0.8±0.8, p=0.049). Importantly however, in all but two patients (Figure 1 Subject 1), residual ventilation abnormalities were qualitatively and quantitatively observed following anti-Th2 therapy (Figure 1 Subject 2) and this was concomitant with persistently abnormal mean ACQ score (1.4±0.8).
CONCLUSIONS: In prednisone-dependent asthmatics with sputum eosinophilia, MRI ventilation heterogeneity that persisted post-bronchodilator was improved following anti-Th2 therapy. This finding highlights the sensitivity of MRI to the inflammatory component of airways disease in severe asthma. In a subset of patients, focal ventilation abnormalities were non-responsive to therapy directed at both the inflammatory and non-inflammatory components of asthma. This suggests that additional therapy may be necessary to normalize ventilation heterogeneity and achieve asthma control.
1Svenningsen et al. Inflammatory and non-inflammatory contributions to ventilation heterogeneity in severe poorly-controlled asthmatics, AJRCCM 2017;195:A2665. 2Kirby et al. Hyperpolarized 3He magnetic resonance functional imaging semi-automated segmentation, Acad Radiol 2012;19(2):141-52.