MRI ventilation phenotypes of severe asthma

Introduction The clinical relevance of ventilation patterns identified by MRI in severe asthma and the degree to which they differ between patients is unclear. Therefore, this study aimed to identify MRI-defined ventilation phenotypes of severe asthma and to examine their associated demographic, clinical, physiological and inflammatory characteristics. Methods This was a retrospective analysis of adults with severe asthma who underwent 129Xe ventilation MRI (n=75). Nineteen quantitative ventilation MRI variables were extracted for principal component analysis and unsupervised K-means clustering. Results were externally validated (n=55). Results Three distinct ventilation phenotypes were identified. They were significantly different with respect to demographic, lung function, inflammatory biomarkers and imaging measurements (p<0.05), but not asthma control or medication requirements. There was a stepwise increase observed from phenotype 1 to phenotype 3 in airway disease severity. Phenotype 1 (10, 13%; mean±SD age, 42±11 years; 80% female) reflected normal ventilation characterised by a high prevalence of obesity and asthma masqueraders with low total lung volume. Phenotype 2 (41, 55%; 52±15 years; 56% female) reflected markedly abnormal ventilation with a high prevalence of obesity and history of cardiovascular disease. Phenotype 3 (24, 32%; 54±14 years; 46% female) reflected severely abnormal ventilation with a high prevalence of inflammation (87% abnormal sputum cell counts) and mucus plugs (91%, ≥4 plugs). The validation cohort showed similar findings. Discussion There are three unique MRI ventilation phenotypes of severe asthma. The discordance in ventilation between phenotypes, and their characteristics, suggests different mechanisms may be related to symptom burden.