Pathology of Idiopathic Pulmonary Fibrosis Assessed by a Combination of Microcomputed Tomography, Histology, and Immunohistochemistry

Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease showing the histology of usual interstitial pneumonia (UIP). While the pathologist's visual inspection is central in histological assessments, three-dimensional microCT assessment may complement pathologist's scoring. This study examined associations between the histopathological features of UIP/IPF in explanted lungs and quantitative microCT measurements including alveolar surface density, total lung volume taken up by tissue (tissue%), and terminal bronchiolar number. Sixty frozen samples from 10 air-inflated explanted lungs with severe IPF and 36 samples from 6 donor control lungs were scanned with microCT and processed for histology. An experienced pathologist scored 3 major UIP criteria (patchy fibrosis, honeycomb, and fibroblastic foci), 5 additional pathological changes such as emphysema, and immunohistochemical staining for CD68, CD4, CD8, and CD79a positive cells, graded on a 0-3+ scale. The alveolar surface density and terminal bronchiolar number decreased and the tissue% increased in IPF compared to controls. In lungs with IPF, lower alveolar surface density and higher tissue% were correlated with greater scores of patchy fibrosis, fibroblastic foci, honeycomb, CD79a-positive cells, and lymphoid follicles. A decreased number of terminal bronchioles was correlated with honeycomb score, but not with the other scores. The three-dimensional microCT measurements reflect the pathological UIP/IPF criteria and further suggest that the reduction in the terminal bronchioles may be associated with honeycomb cyst formation

Morphometric differences between central vs. surface acini in A/J mice using high-resolution micro-computed tomography.

Through interior tomography, high-resolution microcomputed tomography (μCT) systems provide the ability to nondestructively assess the pulmonary acinus at micron and submicron resolutions. With the application of systematic uniform random sampling (SURS) principles applied to in situ fixed, intact, ex vivo lungs, we have sought to characterize morphometric differences in central vs. surface acini to better understand how well surface acini reflect global acinar geometry. Lungs from six mice (A/J strain, 15-20 wk of age) were perfusion fixed in situ and imaged using a multiresolution μCT system (Micro XCT 400, Zeiss). With the use of lower-resolution whole lung images, SURS methods were used for identification of central and surface foci for high-resolution imaging. Acinar morphometric metrics included diameters, lengths, and branching angles for each alveolar duct and total path lengths from entrance of the acinus to the terminal alveolar sacs. In addition, acinar volume, alveolar surface area, and surface area/volume ratios were assessed. A generation-based analysis demonstrated that central acini have significantly smaller branch diameters at each generation with no significant increase in branch lengths. In addition to larger-diameter alveolar ducts, surface acini had significantly increased numbers of branches and terminal alveolar sacs. The total path lengths from the acinar entrance to the terminal nodes were found to be higher in the case of surface acini. Volumes and surface areas of surface acini are greater than central acini, but there were no differences in surface/volume ratios. In conclusion, there are significant structural differences between surface and central acini in the A/J mouse

Central Airway Tree Dysanapsis Extends to the Peripheral Airways.

status: Published onlin

Pectoralis muscle area and its association with indices of disease severity in interstitial lung disease.

RATIONALE The pathophysiology of interstitial lung disease (ILD) impacts body composition, whereby ILD severity is linked to lower lean mass. OBJECTIVES To determine i) if pectoralis muscle area (PMA) is a surrogate for whole-body lean mass in ILD, ii) whether PMA is associated with ILD severity, and iii) if the longitudinal change in PMA is associated with pulmonary function and mortality in ILD. METHODS Patients with ILD (n = 164) were analyzed retrospectively. PMA was quantified from a chest computed tomography scan. Peripheral oxygen saturation (SpO2), 6-min walk distance (6MWD), and pulmonary function were obtained as part of routine clinical care. Dyspnea and quality of life were assessed using the UCSD Shortness of Breath Questionnaire and European Quality of Life 5 Dimensions questionnaire, respectively. RESULTS PMA was associated with whole-body lean mass (p  0.05). The annual negative PMA slope was associated with annual negative slopes in FVC, FEV1, and DLCO (all p < 0.05), but not FEV1/FVC (p = 0.46). Annual slope in PMA was associated with all-cause mortality (hazard ratio = -0.80, 95% CI:0.889-0.959; p < 0.001). CONCLUSION In patients with ILD, PMA is a suitable surrogate for whole-body lean mass. A lower PMA is associated with indices of ILD severity, which supports the notion that ILD progression may involve sarcopenia