Assessing regional pulmonary response to methacholine and mannitol challenge in asthma patients using hyperpolarized...

Ventilation heterogeneity is a feature of asthmatic bronchoconstriction and contributes to airway hyperresponsiveness and disease expression. This study characterized ventilation heterogeneity using hyperpolarized helium-3 magnetic resonance imaging (HP-MRI) in patients with mild asthma following methacholine and mannitol inhalational challenge and determined whether topographical differences exist in the response to these different stimuli.

Six patients with mild asthma were recruited (1 male, 5 females; age 35.3±11.4 years; BMI 22.8±3.0 kg/m²). Patients underwent HP-MRI and forced expiratory volume in 1 second (FEV1) at baseline and following crossover methacholine and mannitol challenge on separate days. Ventilation heterogeneity was assessed qualitatively and using ventilation defect percentage (VDP). Comparisons between the pre- and post-provocation scans, and the difference in regional changes induced by methacholine and mannitol were performed.

FEV1 was significantly reduced (p=0.0002) by methacholine (94.9±15.1 vs 70.2±9.7 %predicted) and mannitol (94.5±14.6 vs 73.8±18.1 %predicted). Accompanying this was a significant increase in VDP (p=0.02) from 8.5±4.5 to 19.8±6.9% after methacholine, and 8.4±3.4 to 17.8±6.3% after mannitol challenge. Regional differences were observed between the two provocation agents with methacholine having a larger impact on the peripheral airways (p=0.005) and mannitol on the central airways (p<0.05), despite comparable changes in FEV1 (p=0.62) and VDP (p=0.46).

Regional differences in ventilation heterogeneity exist when asthmatic airways are subjected to methacholine and mannitol challenge. These findings give new insights into the regional pathobiology of airflow obstruction in patients with asthma and highlight the role of HP-MRI as a valuable tool in understanding airway disease.