Chronic obstructive pulmonary disease (COPD) is a common and largely avoidable disease that is characterized by irreversible airway obstruction, predominantly due to inhaled noxae and particles. COPD was listed as the third leading cause of death by the World Health Organization in 2012 and has surpassed epidemiological estimations by the Global Burden of Disease Project, now causing over 3.1 million deaths per year [
Traditionally, the diagnosis of COPD is based on spirometric measurements of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), as specified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [
Chest computed tomography (CT) is currently not listed as an obligate diagnostic tool in patients with suspected COPD by GOLD [
Despite these benefits, CT has not become a recommended examination in newly diagnosed COPD yet since the clinical impact is not fully understood [
Several prior studies have correlated quantified chest CT measurements with functional lung parameters [
Thus, the aim of this prospective study was to investigate the correlation of functional lung parameters beyond FEV1 and FVC with quantified CT parameters acquired during maximum inspiration as well as maximum expiration.
The HIPAA compliant study protocol, which is in accordance with the Declaration of Helsinki, was approved by our local ethics committee (
We prospectively enrolled 49 patients with previously diagnosed COPD and a clinical indication for unenhanced chest CT in a single-center, all-comer approach. Written informed consent was obtained from all patients following a full explanation of the purpose of the study and of potential risks and discomforts associated with their participation.
All patients underwent spirometry and whole-body plethysmography (MasterScreen® Body, CareFusion, Höchberg, Germany) yielding the following parameters: vital capacity (VC), FEV1, Tiffeneau index (FEV1%VC), residual volume (RV), total lung capacity (TLC), ratio of residual volume to TLC (RV%TLC), and specific total airway resistance (sRtot). Except for FEV1%VC and RV%TLC, all values are given as percent of predicted, as calculated according to current ATS/ERS recommendations or GLI equations, respectively [
A noncontrast chest scan was performed in maximum inspiration and maximum expiration using a 3rd generation dual-source CT (Somatom FORCE, Siemens Healthineers, Forchheim, Germany) at 100 kVp with a dedicated tin filter for dose reduction [
Inspiratory and expiratory datasets were analyzed using dedicated semiautomatic software (SyngoViaVB10, Pulmo3D, Siemens Healthineers, Forchheim, Germany). Lung segmentation was automated and manually revised if necessary (Figure
Automatic detection of lung borders and lung parenchyma. Blue areas: low attenuation volume (LAV) with HU values below −950; red areas: high attenuation volume (HAV) with HU values above −200.
A total of 28 correlation pairs (four quantified CT parameters and seven lung function parameters) were analyzed for inspiratory, expiratory, and delta values. The Pearson product-moment correlation coefficient was calculated for each pair using JMP 11 (SAS, Cary, USA). The correlation coefficients of inspiratory and expiratory scans were compared by Pearson and Filon z test, using cocor Software [
The study population consisted of 46 patients (26 male) with previously diagnosed COPD. Twenty patients were active smokers at the date of examination. The remaining 26 patients had smoked in the past (Tables
Patient characteristics.
|
♂/♀ | Age, years (range) | Size, cm (range) | Weight, kg (range) | Smokers/ex-smokers |
---|---|---|---|---|---|
46 | 26/20 | 66 ± 10 (44–87) | 166 ± 7 (153–190) | 76 ± 18 (34–117) | 20/26 |
Lung function parameters.
Parameter | Mean | SD | Range |
---|---|---|---|
VC (%) | 70 | 23.3 | 22.2–128.6 |
FEV1 (%) | 49.4 | 20.8 | 16.1–100.4 |
FEV1%VC | 53.4 | 13 | 32.7–90.9 |
RV (%) | 210.9 | 81.9 | 35.3–405.7 |
TLC (%) | 125 | 31.6 | 54.4–205 |
RV%TLC | 65 | 14.8 | 16.4–87.6 |
sRtot (%) | 337.4 | 241 | 47.8–1054.8 |
VC: vital capacity; FEV1: forced expiratory volume in one second; FEV1%VC: Tiffeneau index; RV: residual volume; TLC: total lung capacity; sRtot: specific total airway resistance.
Quantified CT parameters.
Parameter | Mean | SD | Range | |||
---|---|---|---|---|---|---|
Inspiration | Expiration | Inspiration | Expiration | Inspiration | Expiration | |
Volume (ml) | 5421 | 4417 | 1441 | 1279 | 2528 to 8541 | 1859 to 7792 |
MLD (HU) | −840 | −803 | 48 | 66 | −915 to −715 | −910 to −663 |
FWHM (HU) | 94 | 123 | 32 | 43 | 27 to 230 | 71 to 231 |
LAV (%) | 12 | 9 | 15 | 14 | 0 to 50 | 0 to 50 |
MLD: mean lung density; FWHM: full width half max; LAV: low attenuation volume.
Regarding inspiratory, expiratory, and delta values, we were able to show statistically significant correlations between every quantified CT parameter and each lung function parameter in either of one of the analyses (inspiration, expiration, and delta values; Tables
Heat map of correlations for inspiratory values. MLD: mean lung density; FWHM: full width half max; LAV: low attenuation volume; VC: vital capacity; FEV1: forced expiratory volume in one second; FEV1%VC: Tiffeneau index; RV: residual volume; TLC: total lung capacity; sRtot: specific total airway resistance.
Heat map of correlations for expiratory values. MLD: mean lung density; FWHM: full width half max; LAV: low attenuation volume; VC: vital capacity; FEV1: forced expiratory volume in one second; FEV1%VC: Tiffeneau index; RV: residual volume; TLC: total lung capacity; sRtot: specific total airway resistance.
Heat map of correlations for delta values. MLD: mean lung density; FWHM: full width half max; LAV: low attenuation volume; VC: vital capacity; FEV1: forced expiratory volume in one second; FEV1%VC: Tiffeneau index; RV: residual volume; TLC: total lung capacity; sRtot: specific total airway resistance.
The fewest significant correlations were found when using data from the inspiratory acquisition (14 out of 28 correlated pairs; Table
The most significant correlations were found when using data from the expiratory acquisition (25 out of 28 correlated pairs; Table
Comparison between inspiratory and expiratory correlation coefficients.
Quantified CT parameter | Lung function parameter | Correlation inspiration | Correlation expiration |
|
|
---|---|---|---|---|---|
Volume | VC | 0.0577 | −0.2367 | 3.1409 | 0.0017 |
Volume | FEV1 | −0.1314 | −0.4643 | 3.631 | 0.0003 |
Volume | FEV1%VC | −0.3605 | −0.5225 | 1.8699 | 0.0615 |
Volume | RV | 0.3587 | 0.6466 | −3.3049 | 0.001 |
Volume | TLC | 0.3809 | 0.5503 | −1.9779 | 0.0479 |
Volume | RV%TLC | 0.1813 | 0.549 | −4.0252 | 0.0001 |
Volume | sRtot | 0.102 | 0.4345 | −3.6152 | 0.0003 |
MLD | VC | −0.0194 | 0.1563 | −1.9585 | 0.0502 |
MLD | FEV1 | 0.2186 | 0.4696 | −2.9337 | 0.0033 |
MLD | FEV1%VC | 0.4856 | 0.6376 | −2.005 | 0.045 |
MLD | RV | −0.4421 | −0.6362 | 2.4796 | 0.0132 |
MLD | TLC | −0.5098 | −0.6378 | 1.7201 | 0.0854 |
MLD | RV%TLC | −0.2924 | −0.6108 | 3.7492 | 0.0002 |
MLD | sRtot | −0.3061 | −0.5225 | 2.5933 | 0.0095 |
FWHM | VC | 0.0602 | 0.2715 | −1.8312 | 0.0671 |
FWHM | FEV1 | 0.0918 | 0.4228 | −2.9634 | 0.003 |
FWHM | FEV1%VC | 0.1818 | 0.403 | −1.9774 | 0.048 |
FWHM | RV | −0.1707 | −0.416 | 2.1972 | 0.028 |
FWHM | TLC | −0.1718 | −0.3402 | 1.4834 | 0.138 |
FWHM | RV%TLC | −0.0505 | −0.4579 | 3.6813 | 0.0002 |
FWHM | sRtot | −0.0756 | −0.3345 | 2.2735 | 0.023 |
LAV | VC | −0.2261 | −0.346 | 3.1849 | 0.0014 |
LAV | FEV1 | −0.3907 | −0.4465 | 1.5801 | 0.1141 |
LAV | FEV1%VC | −0.4002 | −0.336 | −1.7761 | 0.0757 |
LAV | RV | 0.5293 | 0.5748 | −1.3982 | 0.1621 |
LAV | TLC | 0.4354 | 0.405 | 0.8695 | 0.3846 |
LAV | RV%TLC | 0.4527 | 0.5015 | −1.4274 | 0.1535 |
LAV | sRtot | 0.5235 | 0.5602 | −1.1266 | 0.2599 |
MLD: mean lung density; FWHM: full width half max; LAV: low attenuation volume; VC: vital capacity; FEV1: forced expiratory volume in one second; FEV1%VC: Tiffeneau index; RV: residual volume; TLC: total lung capacity; sRtot: specific total airway resistance.
As seen in Figure
Our study found significant correlations for quantified CT parameters and functional lung parameters beyond the commonly used FEV1 and VC. The additional scan performed in end-expiration showed overall stronger correlations compared to the inspiratory scan. These findings were consistent for both static and dynamic lung function parameters.
Every quantified CT parameter significantly correlated with the functional lung parameters in all of the three different analyses. Nevertheless, there was a strong difference in the extent and the number of significant correlations between the inspiratory, expiratory, and delta of the quantified CT parameters.
Stronger correlations were found between static parameters of lung volume, such as TLC and RV, as compared to the dynamic parameters FEV1, FEV1%VC, and sRtot. This finding could be reasonably expected, as the acquisitions were also static and provided predominantly anatomic information. Likewise, LAV correlated with these static parameters on all three analyses (i.e., there was no additive value of the expiratory scan or delta values), which can be expected, given the LAV was relatively fixed between inspiratory and expiratory acquisitions.
Our findings align with the 2015 Fleischner Society statement on CT-definable subtypes of COPD, in which they noted the potential additive information of end-expiratory acquisitions in patients with COPD [
TLC% and inspiratory volume showed only a weak correlation (0.38), despite the fact, that both parameters should measure the same volume. Beyond the weak correlation, the absolute values differed. One reason for this difference is the quantification process of the CT images. The software automatically ads a distance of 1 cm between the quantified lung volume and pleura to eliminate errors occurring through pleural irregularities. This led to a reduced total lung volume in the qCT when compared to lung function tests. Further, total lung volume was acquired in supine position in qCT rather than sitting TLC in body plethysmography. As shown previously, posture has an effect on measured lung volumes and thereby might have strengthened the named difference [
Our study has several limitations that must be considered. First, we did not perform spirometric triggering during CT. Thereby, we cannot verify that all patients strictly followed the breathing commands. There was a mean volume difference of 1 liter between maximal inspiration and expiration, and we believe that our data are representative of functional inspiration and expiration. Second, since we only included patients with clinical indications for unenhanced chest CT, severe stages of COPD might be overrepresented in our cohort. Third, the number of subjects included in our study was rather small.
The strength of our study is the systematic evaluation of expiratory values, stand-alone delta values, and their respective correlations with lung function testing. As mentioned before, previous studies have correlated qCT parameters and lung function tests. But they did not take the expiratory and stand-alone delta values into account as we did in this work. Moreover, we focused on lung function parameters acquired by body plethysmography, which has advantages compared to traditional spirometry: While RV and TLC cannot be measured by spirometry, both are altered in COPD due to the loss of elastic recoil, airway closure, and hyperinflation of the lung [
Overall, our study confirms three major presumptions. First, quantified CT parameters correlate with lung function parameters beyond the commonly used FEV1 and VC. Second, a single acquisition in maximum inspiration alone is an incomplete approach for comparison of quantified CT parameters and functional lung parameters in COPD. Again, from a pathophysiological standpoint, these findings are related to the fact that COPD, as an
Consequently, the additional acquisition of an expiratory scan does not only provide a wider range of significant correlations with lung function parameters itself but also allows the calculation of the delta values. This does not only leads to more significant correlations to functional lung parameters but might also be important for future phenotyping of COPD with combined quantified CT and pulmonary function tests. Thereby, the expiratory and the delta values contain additional information and should be considered as mandatory correlation parameters in future studies.
An abstract containing preliminary analyses of the underlying data has been presented at the 2017 Annual European Congress of Radiology (C-2635, March 1 to 5) in Vienna, Austria.
The authors declare that they have no conflicts of interest.
Joshua Gawlitza, Frederik Trinkmann, and Thomas Henzler conceived and designed the study. Andreas Fischer, Nils Vogler, Ibrahim Akin, Hans Scheffel, John W. Nance, Claudia Henzler, and Joachim Saur drafted the work. Martin Borggrefe and Stefan O. Schoenberg provided the final approval.
Figure E1: correlations of mean lung density (MLD) and forced expiratory volume in one second (FEV1) for inspiratory, expiratory, and calculated delta values. Figure E2: voxel-density histogram from a qCT. Table E1: correlation of quantified CT and lung function parameters for inspiration scan. Table E2: correlation of quantified CT and body plethysmography parameters for expiration scan. Table E3: correlation of quantified CT and body plethysmography parameters for delta values.