By altering the biomechanical environment of adjacent healthy tissue, 3-dimensional (3D) “super clusters” in patients with chronic obstructive pulmonary disease (COPD) could play a key role in the progression of COPD to emphysema, according to the results of a study conducted at Kyoto University Hospital in Japan and published in CHEST.

Emerging 3D super clusters have been observed during follow-up computed tomography (CT) scans in patients with COPD, with these large defects appearing to drive structural deterioration of nearby lung regions and leading to an overall decline in pulmonary function.

Investigators sought to examine distributions of 3D low-attenuation volumes in patients with COPD, which they theorized would follow a power law distribution and offer a more complete assessment of the mechanisms underlying disease progression among these individuals. They obtained CT scans and pulmonary function tests from an observational database of 12 patients with COPD and 12 control patients. Baseline and 2 annual follow-up evaluations were included in the data set. 3D representations of the lungs were reconstructed from 22D axial CT slices, with low-attenuation volumes being identified as contiguous voxels <−960 Hounsfield units.


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With the exception of large, individual outliers, which were termed super clusters and deviated from the expected distribution, low-attenuation sizes generally followed a power law distribution. Super cluster volume was linked to disease severity (% total low-attenuation, ρ, 0.950) and clinical measures of lung function, which included forced expiratory volume in 1 second (ρ, −0.849) and diffusing capacity of the lung for carbon monoxide (ρ, −0.874).

To interpret their findings, the researchers developed a personalized computational model of supercluster emergence. On the basis of their simulations, disease progression was more likely to be observed near existing emphysematous regions, thus activating a biomechanical, force-induced mechanism of super cluster growth.

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The investigators concluded that low-attenuating super clusters are quantitative, defining features of parenchymal destruction that dominate disease progression in patients with COPD, particularly those with advanced disease. Morphologic progression of these 3D super clusters was observed during follow-up CT scans.

Reference

Mondoñedo JR, Sato S, Oguma T, et al. CT-based low-attenuation super clusters in 3D and the progression of emphysema [published online October 4, 2018]. CHEST. doi:10.1016/j.chest.2018.09.014