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

David G. Mummy, Katherine J. Carey, Michael D. Evans, Loren C. Denlinger, Mark L. Schiebler, Ronald L. Sorkness, Nizar N. Jarjour, Sean B. Fain

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29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)831-839.e6
JournalJournal of Allergy and Clinical Immunology
Issue number4
StatePublished - Oct 2020

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2020 American Academy of Allergy, Asthma & Immunology


  • Asthma
  • airway obstruction
  • functional
  • magnetic resonance imaging
  • patient outcomes assessment


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