Abstract
Rationale: Chronic lung allograft dysfunction (CLAD) results in significant morbidity after lung transplantation. Potential CLAD occurs when lung function declines to 80-90% of baseline. Better noninvasive tools to prognosticate at potential CLAD are needed. Objectives: To determine whether parametric response mapping (PRM), a computed tomography (CT) voxel-wise methodology applied to high-resolution CT scans, can identify patients at risk of progression to CLAD or death. Methods: Radiographic features and PRM-based CT metrics quantifying functional small airway disease (PRM(fSAD)) and parenchymal disease (PRM(PD)) were studied at potential CLAD (n = 61). High PRM(fSAD) and high PRM(PD) were defined as ⩾30%. Restricted mean modeling was performed to compare CLAD-free survival among groups. Measurements and Main Results: PRM metrics identified the following three unique signatures: high PRM(fSAD) (11.5%), high PRM(PD) (41%), and neither (PRM(Normal); 47.5%). Patients with high PRM(fSAD) or PRM(PD) had shorter CLAD-free median survival times (0.46 yr and 0.50 yr) compared with patients with predominantly PRM(Normal) (2.03 yr; P = 0.004 and P = 0.007 compared with PRM(fSAD) and PRM(PD) groups, respectively). In multivariate modeling adjusting for single- versus double-lung transplant, age at transplant, body mass index at potential CLAD, and time from transplant to CT scan, PRM(fSAD) ⩾30% or PRM(PD) ⩾30% continue to be statistically significant predictors of shorter CLAD-free survival. Air trapping by radiologist interpretation was common (66%), was similar across PRM groups, and was not predictive of CLAD-free survival. Ground-glass opacities by radiologist read occurred in 16% of cases and were associated with decreased CLAD-free survival (P < 0.001). Conclusions: PRM analysis offers valuable prognostic information at potential CLAD, identifying patients most at risk of developing CLAD or death.