Quantitative CT analysis in patients with pulmonary emphysema: is lung function influenced by concomitant unspecific pulmonary fibrosis?

Figures & data

Table 1 Characteristics of study subjects

Mean age (years)	66 (SD 6.6; range 45–79)
Male/female sex	53/35 (♀ 43%)
Pack years (n=48)	49 (SD 22)
Forced expiratory volume in 1 second % pre BS (FEV1%, percent of predicted)	27.0 (SD 7.8, range 12–46)
Forced expiratory volume in 1 second % post BS (FEV1%, percent of predicted)	28.8 (SD 8.1, range 13–50)
Total lung capacity % pre BS (TLC, percent of predicted)	123.6 (SD 14.0, range 92–159)
Total lung capacity % post BS (TLC, percent of predicted)	121.8 (SD 14.0, range 87–158)
Residual volume % pre BS (RV, percent of predicted)	222.1 (SD 43.8, range 131–362)
Residual volume % post BS (RV, percent of predicted)	213.2 (SD 42.7, range 92–316)
Functional vital capacity % pre BS (FVC, percent of predicted)	65.1 (SD 15.7, range 36–120)
Functional vital capacity % post BS (FVC, percent of predicted)	69 (SD 15.8, range 38–112)
Diffusing capacity of the lung for carbon monoxide % (DLCO, percent of predicted, n=72)	28.0 (SD 15.9, range 3–95)
6 min walking test (n=75, in meters)	236 (SD 102.1, range 0–450)
St. George’s Respiratory Questionnaire (SGRQ) (n=76)	64.4 (SD 12.9, range 38–98)
COPD GOLD stage III	31 (35.2%)
COPD GOLD stage IV	57 (64.8%)

Abbreviations: FEV1%, forced expiratory volume in 1 second (percent of predicted); TLC, total lung capacity (percent of predicted); DLCO%, diffusing capacity of the lung for carbon monoxide (percent of predicted); RV%, residual volume (percent of predicted); pre/post BS, before and after application of bronchodilators; FVC, functional vital capacity; COPD, chronic obstructive pulmonary disease, SD, standard deviation.

Table 2 Detailed distribution of HAV and LAV divided into respective percentage and peel/core subgroups

	Total lung	Core lung	Peel lung
Mean distribution of HAV/LAV
%HAV inspiration	7.7 SD 1.5	6.0 SD 1.2	10.3 SD 2.0
%HAV expiration	10.5 SD 3.3	8.2 SD 2.7	13.4 SD 4.1
%LAV inspiration	30.7 SD 8.6	36.7 SD 10.1	21.7 SD 7.4
%LAV expiration	24.5 SD 9.4	29.8 SD 11.1	17.7 SD 8.7
Distribution of HAV
	HAV ≤7%	HAV =7–10	HAV >10
%HAV inspiration total	n=28 (31.8%)	n=54 (61.4%)	n=6 (6.8%)
%HAV inspiration core	n=76 (86.4%)	n=11 (12.5%)	n=1 (1.1%)
%HAV inspiration peel	n=0 (0%)	n=43 (48.9%)	n=45 (51.1%)
%HAV expiration total	n=5 (5.7%)	n=41 (46.6%)	n=42 (47.7%)
%HAV expiration core	n=30 (34.1%)	n=41 (46.6%)	n=17 (19.3%)
%HAV expiration peel	n=1 (1.1%)	n=9 (10.2%)	n=78 (88.6%)
Distribution of LAV
	LAV <25%	LAV =25–40%	LAV >40%
%LAV inspiration total	n=26 (29.6%)	n=50 (56.8%)	n=12 (13.6%)
%LAV inspiration core	n=9 (10.2%)	n=38 (43.2%)	n=41 (46.6%)
%LAV inspiration peel	n=56 (63.6%)	n=31 (35.2%)	n=1 (1.1%)
%LAV expiration total	n=44 (50%)	n=39 (44.3%)	n=5 (5.7%)
%LAV expiration core	n=32 (36.4%)	n=44 (50%)	n=12 (13.6%)
%LAV expiration peel	n=71 (80.7%)	n=16 (18.2%)	n=1 (1.1%)

Note: Distribution of HAV- and LAV subgroups, peel defined as volume within, core as volume without a subpleural margin of 2 cm.

Abbreviations: %LAV, percentage of low attenuation volume; %HAV, percentage of high attenuation volume.

Figure 1 Distribution of HAV and LAV in full IN and full EX.

Note: Calculated LAV was always higher than HAV.
Abbreviations: TOT, whole lung; CORE, central lung areas; PEEL, peripheral lung areas; HAV, high attenuation volume; LAV, low attenuation volume; IN, full inspiration; EX, full expiration.

Table 3 Results of multivariate and simple regression analysis before and after application of bronchodilators

	Before use of bronchodilators (n=88)					After use of bronchodilators (n=86)
	Multivariate analysis		R^2	Simple regression		Multivariate analysis		R^2	Simple regression
	HAV	LAV		LAV and FEV1%	p=	HAV	LAV		LAV and FEV1%	p=
FEV1% whole lung in inspiration	0.786	0.008	0.096	−0.309	0.003	0.616	0.022	0.078	−0.208	0.009
FEV1% core lung in inspiration	0.744	0.017	0.104	−0.323	0.002	0.945	0.026	0.085	−0.291	0.006
FEV1% peel lung in inspiration	0.213	0.106	0.054	0.233	0.029	0.167	0.148	0.048	−0.218	0.044
FEV1% whole lung in expiration	0.431	0.091	0.136	0.369	<0.001	0.052	0.196	0.132	−0.363	0.001
FEV1% core lung in expiration	0.376	0.015	0.143	0.377	<0.001	0.186	0.063	0.136	−0.377	<0.001
FEV1% peel lung in expiration	0.587	0.027	0.097	0.312	0.003	0.431	0.036	0.102	−0.320	0.003

Notes: Correlations of HAV and LAV with FEV1%. There is no significant correlation (p<0.05) of HAV and FEV1% for any of the datasets.

Abbreviations: FEV1%, forced expiratory volume in 1 second (percent of predicted); LAV, percentage of low attenuation volume; HAV, percentage of high attenuation volume; peel, peripheral lung (lung volume within a subpleural margin of 2 cm); core, central lung (lung volume without a subpleural margin of 2 cm).

Figure 2 Correlation of HAV andLAV with forced expiratory volume in 1 second, percent of predicted (FEV1%) in different lung volumes and breathhold series. All lung function tests were performed without prior bronchospasmolysis. In full expiration, more than 88% of the lung parenchyma in peripheral lung areas accounted for HAV (second row on the right). Even in this situation, solely LAV showed a significant negative correlation with FEV1% and HAV did not (LAV: r=−0.312, R²=0.097, p=0.027; HAV: p=0.587).

Abbreviations: Peel, peripheral volumes of lung tissue; Core, central volumes of lung tissue; LAV, percentage of low attenuation volume; HAV, percentage of high attenuation volume; IN, full inspiration; EX, full expiration.

Table 4 Subgroup analyses

Subgroup 1	Multivariate analysis		R^2	Simple, bivariate regression
	p-values for correlation for HAV	p-values for correlation for LAV		LAV, r	p=
n=25 patients with lowest FEV1% (9–24.7%)	0.308	0.025	0.176	−0.419	0.037
n=25 patients with highest FEV1% (35.7–51.6%)	0.961	0.976	<0.001	0.007	0.975
Subgroup 2	Difference between in-/expiration in lobe with highest HAV, Pearson´s r		R^2	p-value
HAV in lobe with highest HAV	0.023		<0.001	0.836
LAV in lobe with highest HAV	−0.112		0.013	0.312
	Difference between in-/expiration in lobe with lowest HAV, Pearson´s r		R^2	p-value
HAV in lobe with lowest HAV	−0.063		0.004	0.572
LAV in lobe with lowest HAV	0.313		0.098	0.004

Notes: In subgroups with highest and lowest HAV of total lung (subgroup 1) and for correlation of LAV and HAV with volume difference between in-/expiration (in lobes with highest and lowest HAV) only LAV seemed to correlate with the respective dependent variables.

Abbreviations: FEV1%, forced expiratory volume in 1 second (percent of predicted); LAV, percentage of low attenuation volume; HAV, percentage of high attenuation volume.

Table 5 Independent contributions of LAV and HAV

Variable	Standardized regression in multivariate analysis	p-values for covariables
FVC% pre BS	−0.067 (R^2=0.004)	LAV= 0.378 HAV= 0.540
FVC% post BS	−0.107 (R^2=0.011)	LAV= 0.426 HAV= 0.480
RV% pre BS	0.175 (R^2=0.031)	LAV= 0.295 HAV= 0.221
RV% pre BS	0.053 (R^2=0.053)	LAV= 0.981 HAV= 0.339
DLCO% (n=72)	−0.385 (R^2=0.148)	LAV= 0.001 HAV= 0.045 No correlation of LAV/HAV, p=0.573

Note: No correlation between LAV and HAV was found.

Abbreviations: FVC%, functional vital capacity (percent of predicted); RV%, residual volume (percent of predicted); DLCO%, diffusing capacity of the lung for carbon monoxide (percent of predicted); LAV, percentage of low attenuation volume; HAV, percentage of high attenuation volume; pre/post BS, before and after application of bronchodilators.

Figure 3 Correlation of LAV with volume difference between ex- and inspiration in pulmonary lobes with the highest and lowest percentage of HAV, respectively. Only with a low proportion of fibrotic patterns low attenuation volumes seem to statistically significantly reduce the volume difference (as a measure of elasticity or air trapping) in the affected lobe (see right functional graph); LAV´s Pearson´s r=0.313, R²=0.098, p=0.0004; HAV: p=0.572). In pulmonary lobes with high HAV, no significant correlation between LAV and the volume difference could be demonstrated. On the contrary, the relationship seems to at least tend to be inverse (see left functional graph); LAV´s Pearson´s r=−0.112, R²=0.013, p=0.312; HAV: p=0.836).

Abbreviations: LAV, percentage of low attenuation volume; HAV, percentage of high attenuation volume.