Perifissural nodule count as a biomarker for COPD GOLD stages and emphysema measurements?

Purpose/Objectives: One of the main pathophysiological mechanisms of chronic obstructive pulmonary disease (COPD) is inflammation mediated by the immune system. Intrapulmonary lymph nodes have a distinctive computed tomography (CT) morphology as perifissural nodules (PFN). The purpose of this study was to evaluate the relation between the number of PFNs and emphysema scores. Methods and Materials: CT scans, lung function performances, and clinical data were obtained from the COPDGene study. Forty participants were randomly selected per GOLD stages groups 0 through 4, (n=200). The baseline scans were screened for nodules by a trained medical researcher with support from computer-aided detection (CAD) software. Nodules which were considered solid, had sharp borders, lacked spiculation, and were not completely calcified were assessed independently by two experienced radiologists. The number of these nodules classified as PFNs was counted per scan and averaged per GOLD stage group, and normalized emphysema score (NormES-950)- and 10mm airway lumen perimeter (Pi10)-based groups divided by quartiles. Statistical analyses was done using descriptive statistics, one-way ANOVA, and Cohen's kappa. Results: Three of 200 (1.5%) scans could not be processed by the CAD. Out of 175 scans, 584 CAD annotations were accepted and an additional 172 nodules were identified. 174 calcified, 20 ground glass, 8 subsolid, and 136 spiculated, unsharp, or irregularly shaped solid nodules were excluded by the trained medical researcher. The median diameter and volume of the remaining 418 nodules were 3.9mm (25th percentile (P25)=2.6mm, 75thpercentile (P75)=5.6mm) and 18.4mm3 (P25=8.1mm3, P75=40.4mm3), respectively. Readers A and B independently classified 198/418 (47.4%) and 311/418 (74.4%) of the remaining nodules as PFNs, respectively. The interrater agreement was 0.34 (Cohen's kappa). The average number of PFNs found in GOLD groups 0 to 4 were, respectively, 0.90, 1.00, 0.98, 1.15, and 1.00 for Reader A (p=0.97), and 1.44, 1.55, 1.38, 1.70, and 1.83 for Reader B (p=0.84). The medians of the NormES and Pi10 were 7.24HU (P25=2.45HU, P75=19.17HU) and 2.35mm (P25=1.95mm, P75=2.80mm), respectively. ANOVA of the average number of PFNs between the NormES and Pi10 quartiles respectively resulted in p-values of <0.001 and 0.499 for Reader A, and 0.001 and 0.585 for Reader B. Conclusion: Despite fair interreader agreement, higher NormES is associated with greater average numbers of PFNs. There are no statistically significant differences across GOLD stages and Pi10 quartiles. In practice, a scan may only contain whole numbers of PFNs; additionally, due to high variation, PFN count is not recommended for differentiating stages of COPD.