CT densitometry in emphysema: a systematic review of its clinical utility

Abstract

Background: The aim of the study was to assess the relationship between computed tomography (CT) densitometry and routine clinical markers in patients with chronic obstructive pulmonary disease (COPD) and alpha-1 anti-trypsin deficiency (AATD).

Methods: Multiple databases were searched using a combination of pertinent terms and those articles relating quantitatively measured CT densitometry to clinical outcomes. Studies that used visual scoring only were excluded, as were those measured in expiration only. A thorough review of abstracts and full manuscripts was conducted by 2 reviewers; data extraction and assessment of bias was conducted by 1 reviewer and the 4 reviewers independently assessed for quality. Pooled correlation coefficients were calculated, and heterogeneity was explored.

Results: A total of 112 studies were identified, 82 being suitable for meta-analysis. The most commonly used density threshold was -950 HU, and a significant association between CT density and all included clinical parameters was demonstrated. There was marked heterogeneity between studies secondary to large variety of disease severity within commonly included cohorts and differences in CT acquisition parameters.

Conclusion: CT density shows a good relationship to clinically relevant parameters; however, study heterogeneity and lack of longitudinal data mean that it is difficult to compare studies or derive a minimal clinically important difference. We recommend that international consensus is reached to standardize CT conduct and analysis in future COPD and AATD studies.

Keywords: CT; alpha-1 anti-trypsin deficiency; chronic obstructive pulmonary disease; computed tomography; densitometry; emphysema.

Figure 1

PRISMA flow diagram. Abbreviations: CENTRAL, Cochrane Central Register of Controlled Trials; CT, computed tomography; COPD, chronic obstructive pulmonary disease; AATD, alpha-1 anti-trypsin deficiency.

Figure 2

Forest plot of all studies included in the meta-analysis that correlated FEV₁ percent predicted with −950 HU. Notes: The ranges of correlation coefficients are from −0.09 to −0.67. Pooled correlation coefficient =−0.54 (p<0.0001), χ² test for heterogeneity =591 and I² score for inconsistency =97.2%. Abbreviation: FEV₁, forced expiratory volume in 1 second.

Figure 3

The effect of CT algorithm on heterogeneity of results with respect to −950 HU and FEV₁ percent predicted. Notes: (A) Forest plot demonstrating individual Pearson’s correlation coefficients and pooled result for those studies comparing −950 HU and FEV₁ percent predicted. SH weighted mean correlation coefficient =−0.54, I²=99.3%, χ²=587.85. (B) Forest plot demonstrating the effect on heterogeneity once the same reconstruction algorithm, slice thickness and software program were used. SH weighted mean correlation coefficient =−0.66, I²=91.8%, χ²=33.59. Abbreviations: CT, computed tomography; FEV₁, forced expiratory volume in 1 second; SH, Schmidt-Hunter.

Figure 4

The effect of CT algorithm on heterogeneity of results with respect to PD15 and FEV₁/FVC. Notes: (A) Forest plot of all studies comparing FEV₁/FVC with PD15. SH weighted mean correlation coefficient =−0.26, I²=94.9%, χ²=81.78. (B) Forest plot of all studies comparing FEV/FVC with PD15 using the same CT parameters. SH weighted mean correlation coefficient =−0.47, I²=4.1%, χ²=3.23. Abbreviations: CT, computed tomography; PD15, 15th percentile point; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; SH, Schmidt-Hunter.

Figure 5

The effect of CT algorithm on heterogeneity of results with respect to PD15 and DLCO percent predicted. Notes: (A) Forest plot demonstrating correlation coefficient confidence intervals and pooled correlation coefficient for those studies comparing DLCO percent predicted with PD15. SH weighted mean correlation coefficient =0.3, I²=91.5%, χ²=40.98. (B) Forest plot of those studies comparing PD15 and DLCO percent predicted once all studies using the same CT variables have been re-analyzed. SH weighted mean correlation coefficient =0.69, I²=0%, χ²=2.72. Abbreviations: CT, computed tomography; PD15, 15th percentile point; DLCO, diffusing capacity of the lungs for carbon monoxide; SH, Schmidt-Hunter.

Figure 6

(A) Bar chart to demonstrate variety of software programs used in all studies. (B) Bar chart to demonstrate the variety of reconstruction algorithms reported. (C) Bar chart to demonstrate variety of slice thicknesses reported in all studies.

Figure 6

(A) Bar chart to demonstrate variety of software programs used in all studies. (B) Bar chart to demonstrate the variety of reconstruction algorithms reported. (C) Bar chart to demonstrate variety of slice thicknesses reported in all studies.

Figure 7

(A) Funnel plot for studies correlating −950 HU with FEV₁ percent predicted. (B) Funnel plot for studies correlating −950 HU with DLCO percent predicted. Abbreviations: FEV₁, forced expiratory volume in 1 second; DLCO, diffusing capacity of the lungs for carbon monoxide.