CT strain metrics allow for earlier diagnosis of bronchiolitis obliterans syndrome after hematopoietic cell transplant

Abstract

Bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is associated with substantial morbidity and mortality. Quantitative computed tomography (qCT) can help diagnose advanced BOS meeting National Institutes of Health (NIH) criteria (NIH-BOS) but has not been used to diagnose early, often asymptomatic BOS (early BOS), limiting the potential for early intervention and improved outcomes. Using pulmonary function tests (PFTs) to define NIH-BOS, early BOS, and mixed BOS (NIH-BOS with restrictive lung disease) in patients from 2 large cancer centers, we applied qCT to identify early BOS and distinguish between types of BOS. Patients with transient impairment or healthy lungs were included for comparison. PFTs were done at month 0, 6, and 12. Analysis was performed with association statistics, principal component analysis, conditional inference trees (CITs), and machine learning (ML) classifier models. Our cohort included 84 allogeneic HCT recipients, 66 with BOS (NIH-defined, early, or mixed) and 18 without BOS. All qCT metrics had moderate correlation with forced expiratory volume in 1 second, and each qCT metric differentiated BOS from those without BOS (non-BOS; P < .0001). CITs distinguished 94% of participants with BOS vs non-BOS, 85% of early BOS vs non-BOS, 92% of early BOS vs NIH-BOS. ML models diagnosed BOS with area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.74-0.94) and early BOS with AUC of 0.84 (95% CI, 0.69-0.97). qCT metrics can identify individuals with early BOS, paving the way for closer monitoring and earlier treatment in this vulnerable population.

Graphical abstract

Figure 1.

Representative coronal cuts of CT chest scans with strain metrics of individuals with NIH-BOS, early BOS, mixed BOS, transient impairment, and nonpulmonary cGVHD with normal lungs (control). Jacobian mean of 1 indicates no lung expansion and >1 indicates increasing lung expansion. ADI mean of 0 indicates no directional asymmetry of strain and >0 indicates increasing directional asymmetry of strain. The corresponding color range is displayed for illustration.

Figure 2.

Individual strain metrics of initial CT chest distinguish early BOS from those who do not develop BOS and distinguish different types of BOS. Black dots represent mean, with black vertical lines being the SD of the mean. Red triangles represent median. The horizontal width of each violin plot represents the density of distribution.

Figure 3.

PCA of strain metrics from initial CT chest show early BOS has qCT values intermediate between NIH-BOS and controls or transient impairment. PC1 is the first principal component. PC2 is the second principal component. Each arrow represents a strain metric, with the arrow direction representing its contribution to a PC and the arrow length representing the magnitude of its contribution to the statistical variance of the data set. Each ellipse is the normal probability for the group. The units of each axis are a composite of linear combinations of the original strain metrics.

Figure 4.

Large volume expansion of the lungs with Jacobian of >1.98 distinguish controls or transient impairment from early BOS, and homogeneity of lung expansion with Jacobian_SD of ≤0.62 distinguish BOS from non-BOS. CIT in panel A partitions patients with their individual designations. The total number of individuals per node is displayed, and terminal nodes display the proportion of each disease state in that node (eg, patients with transient impairment [n = 8] are filtered from node 1 to node 5, and the 8 patients with transient impairment constitute 36% of 22 patients in node 5). CIT in panel B partitions a composite group of any form of BOS (NIH-BOS, early BOS, and mixed BOS) from a composite group of individuals with transient impairment and controls. B, NIH-BOS; EB, early BOS; MB, mixed BOS; T, transient impairment; C, control.