Phenotyping Asthma and/or COPD Using 129Xe MRI and Comprehensive Physiologic Testing

Rationale: Asthma and chronic obstructive pulmonary disease (COPD) significantly overlap by conventional diagnostic criteria, yet important treatment differences remain, and people with both asthma and COPD ('asthma+COPD') have worse clinical outcomes than people with a single diagnosis. Hyperpolarized xenon-129 magnetic resonance imaging (129Xe MRI) and pulmonary function tests (PFTs) are sensitive to lung function and structure. Objective: To determine whether 129Xe MRI alongside PFTs can aid phenotyping of real-world patients with asthma and/or COPD. Methods: Patients ≥16 years with physician-assigned asthma and/or COPD were recruited from primary care. 129Xe and proton MRI, multiple-breath nitrogen washout, airwave oscillometry, transfer factor of the lung for carbon monoxide (TLco), body plethysmography, and spirometry were assessed post-bronchodilator. Differences between diagnostic groups were assessed. Results: The study assessed 165 patients. 129Xe MRI and PFT metrics differed significantly between diagnostic groups. On 129Xe MRI, patients with COPD had significantly reduced and more heterogeneous ventilation, greater acinar dimensions and lower gas transfer, in addition to lower spirometry, greater airways resistance and reactance, and more air trapping than patients with asthma. Similarly, 129Xe MRI metrics demonstrated greater abnormalities in COPD than asthma when comparing only those with normal forced expiratory volume in 1 second or TLco. Lung function and structure were worse in asthma+COPD than asthma and better than COPD. Conclusions: 129Xe MRI alongside PFTs provide phenotypically distinct airway disease signatures to aid diagnosis of asthma and/or COPD. 129Xe MRI is highly sensitive to minimal lung disease and identifies functional/structural phenotypes that may help to guide treatment decisions.