Parametric Response Mapping as an Imaging Biomarker in Lung Transplant Recipients

• Published in: American journal of respiratory and critical care medicine Vol. 195; no. 7; pp. 942 - 952
• Main Authors: Belloli, Elizabeth A., Degtiar, Irina, Wang, Xin, Yanik, Gregory A., Stuckey, Linda J., Verleden, Stijn E., Kazerooni, Ella A., Ross, Brian D., Murray, Susan, Galbán, Craig J., Lama, Vibha N.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.04.2017
• Subjects: Adult; Airway Obstruction - diagnostic imaging; Airway Obstruction - physiopathology; Biomarkers; Cohort Studies; Female; Forced Expiratory Volume; Graft Rejection - diagnostic imaging; Graft Rejection - physiopathology; Humans; Image Processing, Computer-Assisted - methods; Lung - diagnostic imaging; Lung - physiopathology; Lung Transplantation; Male; Middle Aged; Original; Reproducibility of Results; Tomography, X-Ray Computed - methods; Transplant Recipients; chronic lung allograft dysfunction; bronchiolitis obliterans syndrome; computed tomography of the chest; prognosis; parametric response mapping
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201604-0732OC

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. 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. PRM-based computed tomography metrics quantifying functional small airways disease (PRM ) and parenchymal disease (PRM ) were compared between bilateral lung transplant recipients with irreversible spirometric decline and control subjects matched by time post-transplant (n = 22). PRM at spirometric decline was evaluated as a prognostic marker for mortality in a cohort study via multivariable restricted mean models (n = 52). Patients presenting with an isolated decline in FEV (FEV First) had significantly higher PRM than control subjects (28% vs. 15%; P = 0.005), whereas patients with concurrent decline in FEV and FVC had significantly higher PRM than control subjects (39% vs. 20%; P = 0.02). Over 8.3 years of follow-up, FEV First patients with PRM greater than or equal to 30% at spirometric decline lived on average 2.6 years less than those with PRM less than 30% (P = 0.004). In this group, PRM greater than or equal to 30% was the strongest predictor of survival in a multivariable model including bronchiolitis obliterans syndrome grade and baseline FEV predicted (P = 0.04). PRM is a novel imaging tool for lung transplant recipients presenting with spirometric decline. Quantifying underlying small airway obstruction via PRM helps further stratify the risk of death in patients with diverse spirometric decline patterns.