Parametric Response Mapping at the Time of Potential CLAD Predicts CLAD Onset and Survival

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There is a need for better non-invasive lung allograft monitoring to facilitate an early diagnosis of chronic lung allograft dysfunction (CLAD). Parametric response mapping (PRM) is a novel imaging technique applicable to high resolution CT images allowing quantitative measurement of small airway and parenchymal disease. We aimed to evaluate the distribution of PRM measurements and PRM's predictive capabilities at the time of potential CLAD in our lung transplant population at Michigan Medicine. 5-year CLAD-free survival time was compared between PRM groups using unadjusted Cox model (Kaplan-Meier plot in Figure 1). The log rank test was used to compare the difference between all three groups and pair-wisely. Fisher's exact test was used to compare the frequency of clinical parameters between groups. 61 patients with an HRCT near the time of potential CLAD were identified. Twenty-five patients (41%) had elevated parenchymal disease (PD) defined as >30% of lung volume. Seven patients (11%) had elevated functional small airways disease (fSAD) similarly defined as > 30% of lung volume. The remainder had predominantly normal lung parenchyma. Patients with high PD or fSAD were more likely to develop CLAD or death compared to patients with mostly normal lung as measured by PRM (Log rank p=0.005). At 1 year, 57% of the high fSAD group and 68% of the high PD group had developed CLAD or death compared to only 31% of the group with more normal parenchyma (p= 0.005). All patients in the high fSAD group developed CLAD or death by 2.15 years. At the time of potential CLAD, there was no difference in frequency of clinical infection between groups (p=0.18). In summary, we demonstrate that quantitative evaluation of parenchymal disease and functional small airways disease by this digital imaging modality at the time of early lung function decline provides prognostic information regarding risk of CLAD development and survival. This is the first investigation of PRM at the time of potential CLAD.