Rationale and Objectives
The effect of smoking cessation on centrilobular emphysema (CLE) and centrilobular nodularity (CN), two manifestations of smoking-related lung injury on computed tomography (CT) images, has not been clarified. The objective of this study is to leverage texture analysis to investigate differences in extent of CLE and CN between current and former smokers.
Materials and Methods
Chest CT scans from 350 current smokers, 401 former smokers, and 25 control subjects were obtained from the multicenter COPDGene Study, a Health Insurance Portability and Accountability Act–compliant study approved by the institutional review board of each participating clinical study center. Additionally, for 215 of these subjects, a follow-up CT scan was obtained approximately 5 years later. For each CT scan, 5000 circular regions of interest (ROIs) of 35-pixel diameter were randomly selected throughout the lungs. The patterns present in each ROI were summarized by 50 computer-extracted texture features. A logistic regression classifier was leveraged to classify each ROI as normal lung, CLE, or CN, and differences in the percentages of normal lung, CLE, and CN by study group were assessed.
Results
Former smokers had significantly more CLE ( P < 0.01) but less CN ( P < 0.001) than did current smokers, even after adjustment for important covariates such as patient age, GOLD stage, smoking history, forced expiratory volume in 1 second, gas trapping, and scanner model. Among patients with longitudinal CT scans, continued smoking led to a slight increase in CLE ( P = 0.13), whereas sustained abstinence from smoking led to further reduction in CN ( P < 0.05).
Conclusions
The proposed texture-based approach quantifies the extent of CN and CLE with high precision. Differences in smoking-related lung disease between longitudinal scans of current smokers and longitudinal scans of former smokers suggest that CN may be reversible on smoking cessation.
Introduction
Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality in the United States and is projected to be the fourth leading cause of mortality worldwide by 2030 . COPD, which is strongly associated with smoking, is characterized by persistent airflow obstruction and a reduced ratio of forced expiratory volume in 1 second (FEV 1 ) to forced vital capacity. Currently, the most effective treatment for COPD is smoking cessation, which slows down the progressive decline in lung function and leads to a transient improvement in FEV 1 .
Smoking-related lung injury manifests on computed tomography (CT) images as centrilobular nodularity (CN) and centrilobular emphysema (CLE). CN, or micronodules centered in the pulmonary lobule , is generally thought to represent smoking-related respiratory bronchiolitis and is the earliest and most common manifestation of smoking-related lung inflammation , which may subsequently lead to emphysema. CLE is associated with low attenuation values similar to the density of air because of the destruction of alveolar walls in lung tissue. The severity and extent of CLE and CN in patients with COPD is commonly assessed by radiologists reading CT images. Nevertheless, qualitative assessment of CT images for extent of CLE and, more notably, CN is associated with high interobserver variability . For example, when 9–11 pulmonologists and radiologistsreviewed each of 395 CT scans at the COPDGene Study CT Imaging Workshop in 2010, average κ values for quantifying CLE and CN were 0.33 and 0.12, respectively .
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Materials and Methods
Subjects
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Table 1
Description of Subjects From the COPDGene Study Cohort Used in this Study
Variable Nonsmokers Former Smokers Current Smokers Training Application Training Application Training Application ( n = 19) ( n = 25) ( n = 18) ( n = 401) ( n = 22) ( n = 350) Subject data Men/women 8/11 12/13 9/9 203/198 11/11 173/177 Age at enrollment (y) 63.1 ± 8.0 65.0 ± 9.2 62.1 ± 8.0 65.3 ± 8.0 56.9 ± 7.3 58.0 ± 8.3 Smoking history Cigarettes/day NA NA 34.3 ± 14.0 27.4 ± 12.1 17.2 ± 10.1 18.9 ± 10.6 Smoking duration (y) NA NA 34.1 ± 13.0 34.5 ± 11.4 41.1 ± 8.2 41.2 ± 8.7 Time since smoking cessation (y) NA NA 11.6 ± 10.6 13.4 ± 10.9 NA NA GOLD stage Unclassified \* NA NA — 64 — 64 0 NA NA 7 91 4 76 1 NA NA 2 96 8 90 2 NA NA 1 92 7 84 3 NA NA 4 29 3 17 4 NA NA 4 29 — 19 Scanner Siemens Definition 14 11 13 81 11 85 Siemens Definition AS+ 1 3 2 27 1 40 Siemens Definition Flash 3 11 1 38 — 28 Siemens Sensation 64 1 — 2 104 10 97 Measurements FEV 1 3.0 ± 0.7 2.9 ± 0.8 2.0 ± 1.1 2.3 ± 0.7 2.3 ± 0.8 2.2 ± 0.8 FEV 1 % predicted 106.2 ± 11.7 98.9 ± 13.4 66.0 ± 34.1 74.1 ± 23.8 76.9 ± 20.3 76.4 ± 21.7 FEV 1 /FVC 0.80 ± 0.05 0.79 ± 0.05 0.55 ± 0.21 0.63 ± 0.15 0.66 ± 0.07 0.66 ± 0.14 % Emphysema † 1.3 ± 0.9 1.7 ± 1.8 14.6 ± 14.8 9.7 ± 10.7 2.4 ± 2.8 5.0 ± 7.7 % Gas trapping ‡ 6.6 ± 4.3 7.0 ± 6.0 35.8 ± 24.9 26.2 ± 19.0 16.9 ± 12.7 18.2 ± 17.5
Data are expressed as mean ± standard deviation or as numbers.
CT, computed tomography; FEV 1 , forced expiratory volume in 1 second; FVC forced vital capacity; NA, not applicable.
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Image Acquisition
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Radiologist Assessment
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Classifier Training
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Classifier Precision Analysis
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Texture-based CT Analysis
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Statistical Analysis
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Results
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Table 2
Texture-based %CLE and %CN Are Shown for Nonsmokers, Former Smokers, and Current Smokers as Mean ± Standard Deviation
Nonsmokers Former Smokers Current Smokers_P_ (NS vs. FS)P (NS vs. CS)P (FS vs. CS) % Normal ROIs 96.6 ± 2.7 78.6 ± 23.4 80.6 ± 19.5P < 10 −4 P < 10 −5 P < 0.21 \* % CLE ROIs 1.1 ± 1.2 16.9 ± 23.5 9.6 ± 17.0P < 10 −4 P = 0.01P < 10 −6 % CN ROIs 2.3 ± 2.9 4.5 ± 8.4 9.8 ± 13.7P < 0.18 \* P < 0.01P < 10 −10
CLE, centrilobular emphysema; CN, centrilobular nodularity; CS, current smokers; FS, former smokers; NS, nonsmokers; ROIs, regions of interest.
Two-sample t tests were used to evaluate the statistical significance of differences between groups.
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Table 3
Correlations Between %CLE and %CN and Pertinent Variables in 401 Former Smokers and 350 Current Smokers
Correlation With Variable %CLE %CN Mean of two radiologists ( n = 250) CLE extent 0.84( P < 0.01) NA CN extent NA 0.31( P < 0.01) Densitometry( n = 776) % Emphysema 0.75( P < 0.01) −0.29( P < 0.01) % Gas trapping 0.58( P < 0.01) −0.34( P < 0.01) Clinical variables( n = 776) GOLD stage 0.44( P < 0.01) −0.30( P < 0.01) FEV 1 −0.32( P < 0.01) 0.01( P = 0.73) Time since smoking cessation −0.16( P < 0.01) 0.07( P = 0.16) Smoking pack-years 0.26( P < 0.01) −0.10( P = 0.12)
CLE, centrilobular emphysema; CN, centrilobular nodularity; FEV 1 , forced expiratory volume in 1 second; NA, not applicable.
Correlation coefficients and P values were computed using Pearson correlation.
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Table 4
For 215 Subjects With CT Scans From Both Phases 1 and 2, %CLE and %CN Are Listed as Mean ± Standard Deviation
Phase 1 Phase 2P Value Former smokers in P1 and P2 ( n = 134) % Normal ROIs 79.5 ± 22.8 76.1 ± 27.5 0.27 % CLE ROIs 15.7 ± 22.8 20.9 ± 28.3 0.10 % CN ROIs 4.9 ± 8.5 3.1 ± 5.6 0.04 Current smokers in P1 and P2 ( n = 52) % Normal ROIs 81.5 ± 18.7 77.9 ± 23.3 0.39 % CLE ROIs 8.9 ± 15.9 14.7 ± 22.5 0.13 % CN ROIs 9.7 ± 10.5 7.4 ± 11.5 0.30 Former smokers in P1, current smokers in P2 ( n = 5) % Normal ROIs 78.5 ± 22.4 59.0 ± 42.4 0.39 % CLE ROIs 10.6 ± 16.4 23.0 ± 36.5 0.51 % CN ROIs 10.9 ± 22.1 18.0 ± 37.7 0.72 Current smokers in P1, former smokers in P2 ( n = 24) % Normal ROIs 71.9 ± 25.6 62.5 ± 32.5 0.27 % CLE ROIs 19.4 ± 26.0 29.5 ± 34.4 0.26 % CN ROIs 8.7 ± 16.3 8.0 ± 18.3 0.90
CLE, centrilobular emphysema; CN, centrilobular nodularity; CT, computed tomography; P1, phase 1; P2, phase 2; ROIs, regions of interest.
Two-sample t tests were used to evaluate the statistical significance of differences between phase 1 and phase 2 measurements.
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Discussion
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Appendix
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Appendix
Supplementary Data
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Figure S1
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Table S1
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