Recent pulmonary functional MRI findings of spatially and temporally persistent ventilation abnormalities in patients with asthma contrast with previous in silico modeling studies that suggest that in asthma, ventilation defects may be randomly distributed. In a case study that used pulmonary MRI, CT imaging, and pulmonary function tests, we prospectively evaluated over the course of 7 years, nonidentical female adult twins, each with a lifelong history of asthma. We evaluated pulmonary function and MRI ventilation heterogeneity at baseline and follow-up after 7 years. In both twins, there was a spatially identical MRI ventilation defect and an abnormal subsegmental left-sided upper lobe airway that persisted in the same spatial location after 7 years. If ventilation defects are randomly distributed, this bears a probability of approximately one per 130,000 people. Our MRI observations in related patients with asthma suggest that ventilation abnormalities may not be randomly distributed in patients with asthma and persist distal to airway abnormalities for long periods of time.