129Xe-MRI ventilation and acinar abnormalities highlight the significance of spirometric dysanapsis: findings from the NOVELTY ADPro UK substudy

Rationale Airways dysanapsis is defined by CT or spirometry as a mismatch between the size of the airways and lung volume and is associated with increased risk of developing chronic obstructive pulmonary disease (COPD). Lung disease in participants with dysanapsis and a label of asthma and/or COPD remains poorly understood. Methods In participants with asthma and/or COPD, we used 129 Xe-MRI to assess ventilation, acinar dimensions and gas exchange, and pulmonary function tests, and compared people with spirometric dysanapsis (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)<−1.64 z and FEV1>−1.64 z) to those with normal spirometry (FEV1, FVC and FEV1/FVC>−1.64 z). Results From 165 participants assessed in the NOVELTY (NOVEL observational longiTudinal studY) ADPro (advanced diagnostic profiling) study with a physician-assigned diagnosis of asthma and/or COPD, 43 had spirometric dysanapsis and were age-matched to 43 participants with normal spirometry. Participants with dysanapsis had significantly increased ventilation defects (median difference (md) (95% CI) = 4.0% (1.42% to 5.38%), p<0.001), ventilation heterogeneity (md (95% CI) = 2.56% (1.31% to 3.56%), p<0.001) and measures of acinar dimensions (md (95% CI) = 0.004 cm 2 .s −1 (0.0009 to 0.007), p=0.009) from 129 Xe-MRI, than those with normal spirometry. At the 1-year follow-up, only participants with dysanapsis had a significant increase in ventilation defects (md (95% CI)=0.45% (0.09% to 2.1%),p=0.016). Lower FEV1/FVC in the dysanapsis cohort was associated with increased ventilation defects (r=−0.64, R 2 =0.41, p<0.001) and increased acinar dimensions (r=−0.52, R 2 =0.38, p<0.001), with the highest values seen in those with an FVC above the upper limit of normal. Conclusions Participants with asthma and/or COPD, presenting to primary care with spirometric dysanapsis, exhibited increased lung abnormalities on 129 Xe-MRI, when compared with those with normal spirometry. Spirometric dysanapsis in asthma and/or COPD is therefore associated with significant lung disease, and the FEV1/FVC is related to the degree of airways abnormality on 129Xe-MRI.