Abstract Rationale Obesity increases the severity of asthma and modifies airway pathobiology, contributing to a lack of responsiveness to standard asthma therapies. The mechanisms driving altered lung function and airway remodeling in obese asthma are poorly understood. We hypothesized that in asthma with comorbid obesity, pulmonary ventilation defects identified using 129Xe magnetic resonance gas exchange imaging (129XeMRI) involve specific regional airway cellular changes that promote profibrotic signaling. Methods Asthma (n = 23) and non-asthma (n = 7) participants with obesity, defined as a body mass index (BMI) 30 kg/m2, underwent supine computed tomography (CT) and 129XeMRI, methacholine challenge, blood collection, spirometry, impulse oscillometry, and bronchoscopy. Spirometric indices included FEV1, FEV1/FVC, and FEF25-75. Chest CT scans were analyzed with the VIDA software package to delineate segmental boundaries and registered to the 129XeMRI images, with bronchopulmonary segments broadly delineated based on ventilation defects. Participants were then given a bronchodilator and both the 129XeMRI was repeated. Bronchoalveolar lavage (BAL), brushings, and endobronchial biopsies were performed at two identified segments in each participant: one with a bronchodilator-reversible ventilation defect and one with an irreversible defect. BAL fluid (BALF) was then analyzed for cell counts and differential, cytokines, and markers of oxidative stress. Results The average BMI in our cohort was 36.7 with a standard deviation of 4.7. In asthma participants, we observed no significant difference in the percentage of lung with a ventilation defect (VDP) when compared to control participants without asthma. However, among participants with asthma, we observed a decrease in VDP (improved ventilation) following a bronchodilator, which was not seen in the non-asthma population. Additionally, asthma participants, exhibited a negative association between the percentage of lung with a ventilation defect (VDP) and FEV1 (r= -0.41, p = 0.04), FEV1/FVC (p = -0.74, p 0.0001), and FEF25-75 (r = -0.64, p = 0.0006), indicating worse VDP is associated with worse spirometry (Fig 1. A). Such associations were not observed in the non-asthma control participants (Fig1. B). A positive correlation was observed between BALF nitrite, an end product of oxidative and nitrosative stress, and VDP (r = 0.42, p = 0.04) in participants with asthma but not in non-asthma controls (Fig1. C and D). Conclusions 129XeMRI identifies ventilation defects in people with both asthma and obesity that correlate with spirometric measures of lung function. These defects also correlate with measures of airway oxidant stress This abstract is funded by: NIH
Mccravy et al. (Fri,) studied this question.