Lung Mass in Smokers

Rationale and Objective

Emphysema is characterized by airspace dilation, inflammation, and irregular deposition of elastin and collagen in the interstitium. Computed tomographic studies have reported that lung mass (LM) may be increased in smokers, a finding attributed to inflammatory and parenchymal remodeling processes observed on histopathology. We sought to examine the epidemiologic and clinical associations of LM in smokers.

Materials and Methods

Baseline epidemiologic, clinical, and computed tomography (CT) data (n = 8156) from smokers enrolled into the COPDGene Study were analyzed. LM was calculated from the CT scan. Changes in lung function at 5 years’ follow-up were available from 1623 subjects. Regression analysis was performed to assess for associations of LM with forced expiratory volume in 1 second (FEV 1 ) and FEV 1 decline.

Results

Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 chronic obstructive pulmonary disease had greater LM than either smokers with normal lung function or those with GOLD 2–4 chronic obstructive pulmonary disease ( P < 0.001 for both comparisons). LM was predictive of the rate of the decline in FEV 1 (decline per 100 g, −4.7 ± 1.7 mL/y, P = 0.006).

Conclusions

Our cross-sectional data suggest the presence of a biphasic radiological remodeling process in smokers: the presence of such nonlinearity must be accounted for in longitudinal computed tomographic studies. Baseline LM predicts the decline in lung function.

Introduction

Emphysema is defined as an abnormal, permanent dilation of the distal airspaces . The development and progression of this pathologic process are associated with a decline in lung function and progressive clinical impairment . Spirometric measures of lung function have been the benchmark for monitoring progression of disease and response to therapeutic intervention, but such investigations lack sensitivity and require large cohorts followed over relatively long periods of time . For these reasons, computed tomographic imaging of the chest is increasingly being leveraged as a source of intermediate study end points to objectively assess response to treatment .

Densitometric measures of the lung parenchyma to detect and quantify emphysema have been utilized in cross-sectional investigations for almost 30 years , including the percent low-attenuation area (%LAA—those regions of the lung less than a select attenuation value) and the percentage of lung volume less than the 10th or 15th percentile . Each of these measures may have relative advantages when considering disease severity and progression but are all focused on the low-attenuation values of the lung histogram, the tail that may be most sensitive for the detection of airspace dilation. This may limit the ability of such metrics to fully assess the remodeling process characteristic of chronic obstructive pulmonary disease (COPD).

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Materials and Methods

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Spirometric Measurements and COPD Definition

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Clinical Assessment

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CT Assessment

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Lung mass(g)=HU+10241024∗Voxel volume∗No of voxels Lung mass

(

)

1024

∗

Voxel volume

∗

No of voxels

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Statistical Analysis

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Results

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TABLE 1

Characteristics of the Subjects in the Baseline and of Those with a Second Visit

Characteristic Baseline ( N = 8156) Subjects with a Second Visit ( N = 1623) Age (y) 60 ± 9 61 ± 9 Male gender (%) 55 52 African-American race (%) 31 27 Height (cm) 170 ± 9 170 ± 9 Weight (kg) 82 ± 19 83 ± 18 Pack-years of smoking 44 ± 25 44 ± 24 Current smoking status (%) 51 43 FEV 1 (L) 2.3 ± 1.0 2.3 ± 0.9 FEV 1 change (mL/y) — −41 ± 52 FEV 1 (% predicted) 78 ± 27 80 ± 25 FVC (L) 3.4 ± 1.0 3.4 ± 1.0 FVC (% predicted) 89 ± 18 91 ± 17 FEV 1 /FVC ratio 0.65 ± 0.17 0.66 ± 0.16 %LAA-950 (%) 6.8 ± 10.0 7.1 ± 9.3 Lung mass (g) 902 ± 183 884 ± 174 Subjects with COPD (%) 50 50 One or more acute respiratory disease episodes in the prior year to enrollment (%) 21 18

COPD, chronic obstructive pulmonary disease; FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; %LAA, percent low-attenuation area.

Data are presented as mean ± standard deviation or proportion (%).

TABLE 2

Characteristics of the Subjects in the Baseline by GOLD Stage

Characteristic GOLD Stage 0 ( N = 4047) 1 ( N = 747) 2 ( N = 1786) 3 ( N = 1042) 4 ( N = 534) Age (y) 57 ± 8 62 ± 9 63 ± 9 64 ± 8 64 ± 8 Male gender (%) 53 58 54 58 59 African-American race (%) 41 22 24 20 18 Height (cm) 170 ± 9 170 ± 10 170 ± 9 170 ± 9 170 ± 9 Weight (kg) 84 ± 18 78 ± 16 83 ± 20 81 ± 20 73 ± 18 Pack-years of smoking 37 ± 20 45 ± 24 51 ± 27 55 ± 27 57 ± 29 Current smoking status (%) 59 55 49 36 23 FEV 1 (L) 2.9 ± 0.7 2.7 ± 0.7 1.9 ± 0.5 1.2 ± 0.3 0.7 ± 0.2 FEV 1 (% predicted) 98 ± 12 91 ± 9 65 ± 8 40 ± 6 23 ± 5 FVC (L) 3.7 ± 0.9 4.1 ± 1.0 3.2 ± 0.9 2.7 ± 0.8 2.1 ± 0.7 FVC (% predicted) 97 ± 12 108 ± 12 86 ± 13 71 ± 13 56 ± 14 FEV 1 /FVC ratio 0.79 ± 0.05 0.65 ± 0.04 0.58 ± 0.08 0.44 ± 0.09 0.32 ± 0.07 One or more acute respiratory disease episodes in the prior year to enrollment (%) 9 12 30 43 57

FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease.

Data are presented as mean ± standard deviation or proportion (%).

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TABLE 3

Effect of COPD Subjects’ Characteristics on FEV 1 at Baseline (mL) and on the Rate of Change in FEV 1 (mL/y) \*

Characteristic Baseline FEV 1 ( N = 4109) (mL) Rate of Change in FEV 1 ( N = 811) (mL/y) Estimate SE_P_ value Estimate † SE_P_ value Lung mass (per 100 g) 73.4 7.6 <0.0001 −4.7 1.7 0.006 Age (per 10 y) −142.3 11.9 <0.0001 2.7 2.6 0.30 Male gender 156.0 27.0 <0.0001 7.6 5.9 0.20 Height (per 5 cm) 115.2 7.6 <0.0001 3.2 1.6 0.051 Weight (per 5 kg) −22.0 2.9 <0.0001 −0.5 0.7 0.48 Current smoker −51.2 22.5 0.02 −12.5 4.8 0.009 Log %LAA-950 −272.1 10.7 <0.0001 −18.8 2.5 <0.0001 One or more acute respiratory disease episodes in the prior year to enrollment −310.5 19.5 <0.0001 −4.3 4.4 0.33 Baseline FEV 1 (mL) — — — −3.0 0.3 <0.0001

COPD, chronic obstructive pulmonary disease; FEV 1 , forced expiratory volume in 1 second; %LAA, percent low-attenuation area; SE, standard error

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Relationship Between LM and Change in FEV 1 in COPD Subjects

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Discussion

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Lung Mass in Smokers

Rationale and Objective

Materials and Methods

Results

Conclusions

Introduction

Materials and Methods

Spirometric Measurements and COPD Definition

Clinical Assessment

CT Assessment

Statistical Analysis

Results

Relationship Between LM and Change in FEV 1 in COPD Subjects

Discussion

References

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