129Xe Gas Exchange MRI in Obesity-associated Asthma: Clinical Correlates and Regional Patterns

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Abstract Rationale. The complex interplay of factors contributing to the pathobiology of obesity-associated asthma is poorly understood. Advancing understanding of the unique disease mechanisms driving gas exchange abnormalities in asthma with comorbid obesity may improve patient management in this difficult to treat population. Hyperpolarized 129Xe MRI has revealed increased ventilation defect percent (VDP) in asthma, and, separately, increased membrane high percent (MHP) in obese healthy participants. However, XeMRI has not been studied specifically in obesity-associated asthma. Here, we characterized patterns of XeMRI gas exchange in obese asthma and assess correlations with clinical measures of lung function, including impulse oscillometry. Methods. N=23 asthma participants (18F, 47±9 years) and 7 healthy controls (5F, 46±12 years) underwent supine chest CT and XeMRI gas exchange imaging scans, spirometry, and impulse oscillometry. All subjects had BMI>30 kg/m2. Chest CT scans were analyzed with the VIDA software package to delineate segmental boundaries and registered to the XeMRI images, with bronchopulmonary segments broadly categorized as either “anterior” or “posterior”. Differences in VDP, MHP, and red blood cell defect percent (RDP) in asthma vs. controls were assessed using the Wilcoxon rank-sum test. Correlations between VDP and forced expiratory volume in 1 second (FEV1), resistance at 5Hz (R5), change in resistance (R5-20), and area of reactance (AX) on impulse oscillometry, and methacholine PC20 (MChPC20), were assessed using the Spearman correlation. Values of MHP in posterior vs. anterior segments was assessed using the Wilcoxon rank-sum test. Results. No significant differences were observed in VDP, MHP, or RDP in the asthma vs. control groups. Across all participants, VDP was correlated with AX (ρ=0.53, p<0.01) but not FEV1 (ρ=-0.31, p=0.11), and MHP was significantly higher in the posterior segments than the anterior segments (median [1Q-3Q] of 3.8% [0.9%-23.9%] vs. 0.6% [0%-7.6%] respectively, p<0.01). VDP was negatively correlated with MChPC20 (ρ=-0.56, p=0.03) in asthma participants. Conclusion. No significant differences were observed in XeMRI gas exchange function in obese asthma vs. obese control participants. VDP correlated with AX across all subjects, suggesting a link between peripheral airway compliance and VDP in obesity regardless of diagnosis. Further, the link between VDP and MChPC20 in subjects with obesity-associated asthma suggests airway hyperreactivity contributes to VDP, despite the lack of strong correlation with FEV1. Finally, increased MHP in posterior vs. anterior segments suggests gravitational dependence rather than regional inflammation or fibrosis. Ongoing work will assess regional gas exchange patterns pre- and post-bronchodilator in this complex population.

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