Low morphometric complexity of emphysematous lesions predicts survival in chronic obstructive pulmonary disease patients

Abstract

Objectives

To investigate whether morphometric complexity in the lung can predict survival and act as a new prognostic marker in patients with chronic obstructive pulmonary disease (COPD).

Methods

COPD (n = 302) patients were retrospectively reviewed. All patients underwent volumetric computed tomography and pulmonary function tests at enrollment (2005–2015). For complexity analysis, we applied power law exponent of the emphysema size distribution (Dsize) as well as box-counting fractal dimension (Dbox3D) analysis. Patients’ survival at February 2017 was ascertained. Univariate and multivariate Cox proportional hazards analyses were performed, and prediction performances of various combinatorial models were compared.

Results

Patients were 66 ± 6 years old, had 41 ± 28 pack-years’ smoking history and variable GOLD stages (n = 20, 153, 108 and 21 in stages I−IV). The median follow-up time was 6.1 years (range: 0.2−11.6 years). Sixty-three patients (20.9%) died, of whom 35 died of lung-related causes. In univariate Cox analysis, lower Dsize and Dbox3D were significantly associated with both all-cause and lung-related mortality (both p < 0.001). In multivariate analysis, the backward elimination method demonstrated that Dbox3D, along with age and the BODE index, was an independent predictor of survival (p = 0.014; HR, 2.08; 95% CI, 1.16–3.71). The contributions of Dsize and Dbox3D to the combinatorial survival model were comparable with those of the emphysema index and lung-diffusing capacity.

Conclusions

Low morphometric complexity in the lung is a predictor of survival in patients with COPD.

Key Points

A newly suggested method for quantifying lung morphometric complexity is feasible.

Morphometric complexity measured on chest CT images predicts COPD patients’ survival.

Complexity, diffusing capacity and emphysema index contribute similarly to the survival model.

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Abbreviations

BODE:

Integrated COPD prognostic index of four factors: the body mass index (B), the degree of airflow obstruction (O) and dyspnoea (D) and exercise capacity (E), measured by the 6-min walk test

cDLCO%:

Percentage of diffusing capacity of the lung for carbon monoxide corrected by haemoglobin to the expected value

CI:

Confidence interval

C-index:

Concordance index

Dbox3D :

Box-counting fractal dimension of the lung parenchyma in full-3D

Dsize :

Power law exponent of the size distribution of emphysema clusters

EI%:

Percentage of the lung volume occupied by emphysema

HR:

Hazard ratio

KOLD:

Korean obstructive lung disease

LAA:

Low attenuation area

PLE:

Power law exponent

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Acknowledgements

Dain Eun designed the schematic representations in Fig. 1.

Funding

This study has received funding by the Basic Science Research Program through the National Research Foundation of Korea (NRF-2016R1D1A1A02937317).

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Authors

Corresponding authors

Correspondence to Sang Min Lee or Namkug Kim.

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Guarantor

The scientific guarantor of this publication is Namkug Kim.

Conflict of interest

The authors of this article declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

Nayoung Kim kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

The study subjects are from Korean Obstructive Lung Disease (KOLD) cohort. There are 54 articles by KOLD study group, and more than 100 articles stating the exact phrase “Korean Obstructive Lung Disease”. We suppose that many of those would have a substantial extent of subject overlaps with our current study. However, the key point of our current study was to suggest new imaging biomarkers, and those biomarkers, Dbox and Dsize, have never been measured for any of the subjects before, making our current finding novel.

Methodology

• retrospective

• diagnostic or prognostic study

• multicentre study

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Hwang, J., Oh, Y., Lee, M. et al. Low morphometric complexity of emphysematous lesions predicts survival in chronic obstructive pulmonary disease patients. Eur Radiol 29, 176–185 (2019). https://doi.org/10.1007/s00330-018-5551-7

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Keywords

  • COPD
  • Emphysema
  • Fractals
  • Lung
  • Survival