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Ventilation defects on hyperpolarized helium-3 MRI in asthma are predictive of 2-year exacerbation frequency - 05/10/20

Doi : 10.1016/j.jaci.2020.02.029 
David G. Mummy, PhD a, b, Katherine J. Carey, MS c, d, Michael D. Evans, MS e, Loren C. Denlinger, MD, PhD f, Mark L. Schiebler, MD d, Ronald L. Sorkness, PhD g, Nizar N. Jarjour, MD f, Sean B. Fain, PhD c, d, h,
a Department of Radiology, Duke University, Durham, NC 
b Center for In Vivo Microscopy, Duke University, Durham, NC 
c Department of Medical Physics, University of Wisconsin-Madison, Madison, Wis 
d Department of Radiology, University of Wisconsin-Madison, Madison, Wis 
e Clinical and Translational Science Institute, University of Minnesota-Twin Cities, Minneapolis, Minn 
f Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin-Madison, Madison, Wis 
g School of Pharmacy, University of Wisconsin-Madison, Madison, Wis 
h Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis 

Corresponding author: Sean B. Fain, PhD, Wisconsin Institutes for Medical Research, Department of Medical Physics, Rm 2488, 1111 Highland Ave., Madison WI 53705.Wisconsin Institutes for Medical ResearchDepartment of Medical PhysicsRm 24881111 Highland Ave.MadisonWI53705

Abstract

Background

There is an unmet need for an objective biomarker to predict asthma exacerbations.

Objective

Our aim was to assess the ventilation defect percent (VDP) on hyperpolarized helium-3 magnetic resonance imaging as a predictor of exacerbation frequency following imaging.

Methods

Subjects underwent hyperpolarized helium-3 and conventional clinical measurements, including pulmonary function tests, during a period of disease stability, and exacerbations were recorded prospectively over the following 2 years. We used a Poisson regression tree model to estimate an optimal VDP threshold for classifying subjects into high- versus low-exacerbation groups and then used statistical regression to compare this VDP threshold against conventional clinical measures as predictors of exacerbations.

Results

A total of 67 individuals with asthma (27 males and 40 females, 28 with mild-to-moderate asthma and 39 with severe asthma) had a median VDP of 3.75% (1.2% [first quartile]-7.9% [third quartile]). An optimal VDP threshold of 4.28% was selected on the basis of the maximum likelihood estimation of the regression tree model. Subjects with a VDP greater than 4.28% (n = 32) had a median of 1.5 exacerbations versus 0.0 for subjects with a VDP less than 4.28% (n = 35). In a stepwise multivariate regression model, a VDP greater than 4.28% was associated with an exacerbation incidence rate ratio of 2.5 (95% CI = 1.3-4.7) versus a VDP less than or equal to 4.28%. However, once individual medical history was included in the model, VDP was no longer significant. Nonetheless, VDP may provide an objective and complementary quantitative marker of individual exacerbation risk that is useful for monitoring individual change in disease status, selecting patients for therapy, and assessing treatment response.

Conclusion

VDP measured with magnetic resonance imaging shows promise as a biomarker of prospective asthma exacerbations.

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Graphical abstract




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Key words : Asthma, magnetic resonance imaging, functional, airway obstruction, patient outcomes assessment

Abbreviations used : ACQ, ACT, BMI, CT, ED, Feno, FVC, GERD, 3He MRI, ICS, IRR, MRI, OCS, Q1, Q3, SARP III, UW-Madison, VDP


Plan


 Funding for this study was provided by National Institutes of Health/National Heart, Lung, and Blood Institute grant U10 HL109168, National Institutes of Health Clinical Translation and Science Award grant UL/TR000427, National Institutes of Health/National Center for Advancing Translational Sciences S10 OD016394, and a Wisconsin Alumni Research Foundation technology transfer training grant. The funding sources had no involvement in study design; the collection, analysis, or interpretation of data; the writing of this report; or the decision to submit this article for publication.
 Disclosure of potential conflict of interest: D. G. Mummy has consulted with Polarean plc on topics unrelated to this article. L. C. Denlinger has had grant support from the National Heart, Lung and Blood Institute (including grant R01HL115118 relating to asthma exacerbation mechanisms) and has consulted with AstraZeneca and Sanofi-Regeneron on topics unrelated to this article. M. L. Schiebler is a shareholder of Healthmyne, Inc, Stemina Biomarker, Inc, and X-vax, Inc, none of which are germane to this article. N. N. Jarjour has received honoraria for consultation from Boehringer Ingelheim and AstraZeneca on topics unrelated to this article. S. B. Fain receives grant support from GE Healthcare, serves on the scientific advisory board of Xemed LLC, and is a consultant for the COPD Gene Project. The rest of the authors declare that they have no relevant conflicts of interest.


© 2020  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 146 - N° 4

P. 831 - octobre 2020 Retour au numéro
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