Characterization of acinar airspace involvement in asthmatic patients by using inert gas washout and hyperpolarized 3helium magnetic resonance

Background The multiple breath washout (MBW) parameter Sacin is thought to be a marker of acinar airway involvement, but has not been validated using quantitative imaging techniques in asthma. Objective We aimed to utilise 3He diffusion magnetic resonance ( 3 He-MR) at multiple diffusion timescales and quantitative computed tomography (CT) densitometry to determine the nature of acinar airway involvement in asthma. Methods Thirty-seven patients with asthma and seventeen age-matched healthy controls underwent spirometry, body plethysmography, MBW (using the tracer gas sulphur hexafluoride) and He-MR. A subset of patients with asthma (n = 27) underwent quantitative CT densitometry. Results Ninety-four percent (16/17) of patients with an elevated Sacin had GINA treatment steps 4/5 asthma and 13/17 had refractory disease. The apparent diffusion coefficient (ADC) of 3 He at 1s was significantly higher in patients with Sacin-high asthma compared to healthy controls (0.024 vs 0.017, p < 0.05). Sacin correlated strongly with ADC at 1s (R = 0.65, p < 0.001), but weakly with ADC at 13ms (R = 0.38, p < 0.05). ADC at both 13ms and 1s correlated strongly with the mean lung density expiratory / inspiratory ratio, a CT marker of expiratory air trapping (R = 0.77, p < 0.0001 for ADC at 13ms; R = 0.72, p < 0.001 for ADC at 1s). Conclusion Sacin is associated with alterations in long-range diffusion within the acinar airways and gas trapping. The precise anatomical nature and mechanistic role in severe asthma requires further evaluation