Impact of Emphysema Heterogeneity on Pulmonary Function

Ju, Jieyang; Li, Ruosha; Gu, Suicheng; Leader, Joseph K.; Wang, Xiaohua; Chen, Yahong; Wu, Shandong; Gur, David; Sciurba, Frank C.; Pu, Jiantao

doi:10.1371/journal.pone.0113320

Cited by 34 publications

(31 citation statements)

References 24 publications

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“…Ju et al showed that greater degree of lobar heterogeneity of emphysema on single-volume CT images was associated with less airflow obstruction. 31 We extend these findings by demonstrating that image-matching based measures of biomechanical heterogeneity (Jacobian and strain CVs) are predictive of lung function, and these biomechanical changes are provided on a lobar and sub-lobar basis. It is pertinent to note that the Jacobian CV and strain CV are more strongly associated with the prediction of the Cat CT category, one in which there is significant CT emphysema but the spirometric abnormality remains relatively masked.…”

Section: Discussionsupporting

confidence: 56%

CT-derived Biomechanical Metrics Improve Agreement Between Spirometry and Emphysema

et al. 2016

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Rationale and Objectives Many COPD patients have marked discordance between FEV1 and degree of emphysema on CT. Biomechanical differences between these patients have not been studied. We aimed to identify reasons for the discordance between CT and spirometry in some patients with COPD. Materials and Methods Subjects with GOLD stage I–IV from a large multicenter study (COPDGene) were arranged by percentiles of %predicted FEV1 and emphysema on CT. Three categories were created using differences in percentiles: Catspir with predominant airflow obstruction/minimal emphysema, CatCT with predominant emphysema/minimal airflow obstruction, and Catmatched with matched FEV1 and emphysema. Image registration was used to derive Jacobian determinants, a measure of lung elasticity, anisotropy and strain tensors, to assess biomechanical differences between groups. Regression models were created with the above categories as outcome variable, adjusting for demographics, scanner type, quantitative CT-derived emphysema, gas trapping, and airway thickness (Model 1), and after adding biomechanical CT metrics (Model 2). Results Jacobian determinants, anisotropy and strain tensors were strongly associated with FEV1. With Catmatched as control, Model 2 predicted Catspir and CatCT better than Model 1 (Akaike Information Criterion, AIC 255.8 vs. 320.8). In addition to demographics, the strongest independent predictors of FEV1 were Jacobian mean (β= 1.60,95%CI = 1.16 to 1.98; p<0.001), coefficient of variation (CV) of Jacobian (β= 1.45,95%CI = 0.86 to 2.03; p<0.001) and CV strain (β= 1.82,95%CI = 0.68 to 2.95; p = 0.001). CVs of Jacobian and strain are both potential markers of biomechanical lung heterogeneity. Conclusions CT-derived measures of lung mechanics improve the link between quantitative CT and spirometry, offering the potential for new insights into the linkage between regional parenchymal destruction and global decrement in lung function in COPD patients.

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Section: Discussionsupporting

confidence: 56%

CT-derived Biomechanical Metrics Improve Agreement Between Spirometry and Emphysema

et al. 2016

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“…38–40 The extent of emphysema was defined as the percentage of low attenuation areas (%LAA) relative to the total lung volume. To reduce overestimation of the percentage of emphysema possibly caused by image noise or artefact, small clusters of pixels below the −950 HU thresholds were removed.…”

Section: Methodsmentioning

confidence: 99%

Obesity and extent of emphysema depicted at CT

Li²,

Leader

et al. 2015

Clinical Radiology

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AIM To investigate the underlying relationship between obesity and the extent of emphysema depicted at CT. METHODS AND MATERIALS A dataset of 477 CT examinations was retrospectively collected from a study of chronic obstructive pulmonary disease (COPD). The low attenuation areas (LAAs; ≤950 HU) of the lungs were identified. The extent of emphysema (denoted as %LAA) was defined as the percentage of LAA divided by the lung volume. The association between log-transformed %LAA and body mass index (BMI) adjusted for age, sex, the forced expiratory volume in one second as percent predicted value (FEV1% predicted), and smoking history (pack years) was assessed using multiple linear regression analysis. RESULTS After adjusting for age, gender, smoking history, and FEV1% predicted, BMI was negatively associated with severe emphysema in patients with COPD. Specifically, one unit increase in BMI is associated with a 0.93-fold change (95% CI: 0.91–0.96, p < 0.001) in %LAA; the estimated %LAA for males was 1.75 (95% CI: 1.36–2.26, p < 0.001) times that of females; per 10% increase in FEV1% predicated is associated with a 0.72-fold change (95% CI: 0.69–0.76, p < 0.001) in %LAA. CONCLUSION Increasing obesity is negatively associated with severity of emphysema independent of gender, age, and smoking history.

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“…However, within an organ, diseases display a large degree of spatial heterogeneity , with the same organ containing both healthy and pathological regions [6–10]. Thus, some NCs may appear to efficiently target an organ, but it remains unknown if those NCs in fact target the pathological subregions rather than the nearby healthy regions.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions

Brenner

Bhamidipati

Glassman

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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Inflamed organs display marked spatial heterogeneity of inflammation, with patches of inflamed tissue adjacent to healthy tissue. To investigate how nanocarriers (NCs) distribute between such patches, we created a mouse model that recapitulates the spatial heterogeneity of the inflammatory lung disease ARDS. NCs targeting the epitope PECAM strongly accumulated in the lungs, but were shunted away from inflamed lung regions due to hypoxic vasoconstriction (HVC). In contrast, ICAM-targeted NCs, which had lower whole-lung uptake than PECAM/NCs in inflamed lungs, displayed markedly higher NC levels in inflamed regions than PECAM/NCs, due to increased regional ICAM. Regional HVC, epitope expression, and capillary leak were sufficient to predict intra-organ of distribution of NCs, antibodies, and drugs. Importantly, these effects were not observable with traditional spatially-uniform models of ARDS, nor when examining only whole-organ uptake. This study underscores how examining NCs’ intra-organ distribution in spatially heterogeneous animal models can guide rational NC design.

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Impact of Emphysema Heterogeneity on Pulmonary Function

Cited by 34 publications

References 24 publications

CT-derived Biomechanical Metrics Improve Agreement Between Spirometry and Emphysema

CT-derived Biomechanical Metrics Improve Agreement Between Spirometry and Emphysema

Obesity and extent of emphysema depicted at CT

Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions

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