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The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study

https://doi.org/10.1016/S2213-2600(13)70006-7Get rights and content

Summary

Background

Emphysema is a key contributor to airflow limitation in chronic obstructive pulmonary disease (COPD) and can be quantified using CT scanning. We investigated the change in CT lung density in a longitudinal, international cohort of patients with COPD. We also explored the potential relation between emphysema and patient characteristics, and investigated if certain circulating biomarkers were associated with decline in CT lung density.

Methods

We used a random coefficient model to assess predictors of both CT lung density and its longitudinal change over 3 years in 1928 patients with COPD enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Lung density was measured for every voxel in the CT scan and after correcting for lung volume was expressed as the density at lowest 15th percentile point of the distribution. This study is registered with ClinicalTrials.gov, number NCT00292552.

Findings

Lung density at baseline was influenced by age, sex, body-mass index, current smoking status and smoking history, and severity of airflow limitation. The observed decline in lung density was variable (mean decline −1·13 g/L [SE 0·06] per year). The annual decline in lung density was more rapid in women (additional −0·41 [SE 0·14] g/L per year, p=0·003) than men and in current smokers (additional −0·29 [SE 0·14] g/L per year, p=0·047) than in former smokers. Circulating levels of the biomarkers surfactant protein D (SP-D) and soluble receptor for advanced glycation endproduct (sRAGE) were significantly associated with both baseline lung density and its decline over time.

Interpretation

This study shows that decline in lung density in COPD can be measured, that it is variable, and related to smoking and gender. We identified potential biochemical predictors of the presence and progression of emphysema.

Funding

GlaxoSmithKline.

Introduction

Chronic obstructive pulmonary disease (COPD) is characterised by poorly reversible airflow limitation that usually worsens with time1 and is thought to be related to an enhanced inflammatory response to inhaled particles and gases.2 Quantitative pathological studies of the lung have shown that airflow limitation can be caused by a loss of lung elastic recoil due to emphysematous destruction of the lung parenchyma,3 by destruction or remodelling of the small airways,4, 5 or by some combination of these processes.

Emphysema can be quantified by CT scanning,6, 7 since low density areas in the lungs have been shown to correlate with the degree of lung function impairment8, 9, 10 and can be used to predict an accelerated decline in forced expiratory volume in 1 s (FEV1).1, 10, 11 Thus, serial CT scanning has been proposed as a potential method to monitor the progression of emphysema.12 In fact, trials of α1-antitrypsin augmentation therapy have used change in CT lung density as an outcome measure.13, 14 However, in COPD, the prevalence of emphysema and its relation to FEV1 varies substantially between patients.15, 16 There are currently little data about the change in CT lung density and the role of potential biomarkers in predicting emphysema progression in COPD.10

We used data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study,17 a large observational 3-year study with detailed assessment of patients with COPD, to: examine the variability of CT lung density at baseline and over the time course of this study; explore the potential relation between emphysema and patient characteristics; and investigate if certain circulating biomarkers are associated with decline in CT lung density.

Section snippets

Study design and patients

Our analysis used data collected in the ECLIPSE study, as described elsewhere.8, 15, 17 In brief, patients between 40 and 75 years of age with COPD were included if they had a history of 10 or more pack-years of smoking, an FEV1 of less than 80% of predicted value, and a ratio of FEV1 to forced vital capacity of 0·7 or less; both were measured after bronchodilator use.

The ECLIPSE study included 2161 patients with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages II–IV COPD,

Results

The baseline characteristics of the 1928 patients are shown in table 1. Mean age was 63·4 (SD 7·1) years, 1229 (64%) were men, 695 (36%) were current smokers, and the mean post-bronchodilator FEV1 was 1·35 (SD 0·52) L (48·5% [SD 15·7] of predicted). Overall 1199 (67%) patients had evidence of emphysema on CT (defined as an attenuation area >10%), 625 (32%) reported symptoms of chronic bronchitis, and 395 (22%) had both emphysema and chronic bronchitis at baseline (table 1). Patients with less

Discussion

This study confirms that the presence and severity of emphysema varies greatly in patients with COPD and identifies several clinical (older age, male gender, low BMI, former smoking, severity of airflow limitation, and previous exacerbations) and biochemical (SP-D and sRAGE) factors associated with emphysema. It also shows that the progression of emphysema over time (annual PD15 change) can be measured and varies substantially between patients (depending on sex, BMI, and smoking status), and

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    Members of the ECLIPSE steering and scientific committees and the study investigators are listed in the appendix

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