Parametric Response Mapping as an Imaging Biomarker in Lung Transplant Recipients

Abstract

Rationale: The predominant cause of chronic lung allograft failure is small airway obstruction arising from bronchiolitis obliterans. However, clinical methodologies for evaluating presence and degree of small airway disease are lacking.

Objectives: To determine if parametric response mapping (PRM), a novel computed tomography voxel-wise methodology, can offer insight into chronic allograft failure phenotypes and provide prognostic information following spirometric decline.

Methods: PRM-based computed tomography metrics quantifying functional small airways disease (PRM^fSAD) and parenchymal disease (PRM^PD) were compared between bilateral lung transplant recipients with irreversible spirometric decline and control subjects matched by time post-transplant (n = 22). PRM^fSAD at spirometric decline was evaluated as a prognostic marker for mortality in a cohort study via multivariable restricted mean models (n = 52).

Measurements and main results: Patients presenting with an isolated decline in FEV₁ (FEV₁ First) had significantly higher PRM^fSAD than control subjects (28% vs. 15%; P = 0.005), whereas patients with concurrent decline in FEV₁ and FVC had significantly higher PRM^PD than control subjects (39% vs. 20%; P = 0.02). Over 8.3 years of follow-up, FEV₁ First patients with PRM^fSAD greater than or equal to 30% at spirometric decline lived on average 2.6 years less than those with PRM^fSAD less than 30% (P = 0.004). In this group, PRM^fSAD greater than or equal to 30% was the strongest predictor of survival in a multivariable model including bronchiolitis obliterans syndrome grade and baseline FEV_1% predicted (P = 0.04).

Conclusions: PRM is a novel imaging tool for lung transplant recipients presenting with spirometric decline. Quantifying underlying small airway obstruction via PRM^fSAD helps further stratify the risk of death in patients with diverse spirometric decline patterns.

Keywords: bronchiolitis obliterans syndrome; chronic lung allograft dysfunction; computed tomography of the chest; parametric response mapping; prognosis.