Changes in the airway lumen and surrounding parenchyma in chronic obstructive pulmonary disease

Figures & data

Figure 1 Computed tomography images of phantoms by high-resolution CT, ultrahigh-resolution CT, and ultrahigh-resolution CT with iDose⁴ (Philips Healthcare) software.

Abbreviations: Di, inner diameter; CT, computed tomography; UHR, ultrahigh-resolution.

Figure 2 Comparison of conventional view of ultrahigh-resolution CT, reconstructed longitudinal airway view, and perpendicular image of airway axis in two patients with chronic obstructive pulmonary disease. (A–C) Patient 1 and (D–F) patient 2.

Abbreviation: CT, computed tomography.

Figure 3 Definition of measurement area in computed tomography images of airways in patients with chronic obstructive pulmonary disease. (A) Longitudinal image of right B9a. Central zone (C) was defined as the point 2 cm from the entrance to the segmental bronchus; peripheral zone (P) was defined as the point 2 cm from the pleura; and middle zone (M) was defined as the point halfway between P and C. (B–D) Images exactly perpendicular to airway axis at each point (part B shows central zone; part C shows middle zone; and part D shows peripheral zone). The 3 cm circle indicates the selected airway. Within this circle, we measured the percentage of low attenuation area, number of bronchi, number of vessel structures, and the inner diameter of the center airway.

Abbreviation: HU, Hounsfield units.

Table 1 Comparison of 70 male patients with COPD and 15 male controlsa

Variable	Controls (n=15)	GOLD spirometric stages of COPD patients (n =70)
		Stage I (n=20)	Stage II (n=21)	Stage III (n=19)	Stage IV (n=10)	P-valueb
Age, years	65.7 (6.7)	70.8 (6.7)	70.6 (8.0)	72.4 (5.4)	70.2 (4.2)	NS
Never smoker	8	0	0	0	0
Smoking index	12.1 (16.1)	74.7 (38.1)	74.9 (37.6)	80.4 (26.8)	80.3 (34.3)	NS
Body mass index	23.3 (2.7)	21.2 (3.8)	21.5 (3.7)	20.3 (2.7)	18.5 (3.8)	NS
FVC, %c	96.5 (11.5)	101.5 (19.2)	84.6 (13.5)	74.7 (13.5)	59.5 (13.1)	NS
FEV1, %c	114.1 (15.7)	103.2 (14.8)d	60.8 (7.2)e	40.2 (5.2)e	26.3 (3.2)e	<0.0001
MEF75, %c	108.9 (19.9)	54.2 (19.5)e	17.9 (8.0)e	7.9 (3.8)e	4.7 (1.9)e	<0.0001
MEF50, %c	86.1 (18.6)	30.8 (10.3)e	11.9 (5.2)e	6.3 (2.2)e	4.2 (2.0)e	<0.0001
MEF25, %c	76.7 (21.2)	32.3 (14.5)e	17.4 (8.4)e	12.3 (5.1)e	7.7 (3.5)e	<0.0001

Notes:

a Values are shown as the mean (standard deviation) unless indicated otherwise;

b significance of difference among all groups was analyzed by analysis of variance;

c predicted;

d P<0.05 versus controls by the Tukey–Kramer multiple comparison test;

e P<0.001 versus controls by the Tukey–Kramer multiple comparison test.

Abbreviations: COPD, chronic obstructive pulmonary disease; FVC, forced vital capacity; FEV₁, forced expiratory volume in one second; GOLD, Global initiative for chronic Obstructive Lung Disease; MEF75, maximum expiratory flow at 75% FVC; MEF50, maximum expiratory flow at 50% FVC; MEF25, maximum expiratory flow at 25% FVC.

Figure 4 Computed tomography images of severe emphysema and airway lumen-obliterated emphysema. (A) Reconstructed image of longitudinal airway view of severe emphysema with little parenchyma around septum or vessels (arrows indicate the point where image B was reconstructed within 2 cm from pleura). (B) Reconstructed image of view exactly perpendicular image to airway axis at red line in panel A (arrows indicate the airway used for image reconstruction). Even in peripheral airway within 2 cm from the pleura airway lumens could be observed. Green line indicates the size of the airway. (C) Reconstructed image of longitudinal airway view of airway lumen-obliterated emphysema. The airway lumen is obliterated at the proximal levels of the bronchi (>2 cm apart from the surface of the lung), and subsegmental areas lacking parenchyma were observed. The obliterated bronchus could be traced into the air-trapped emphysematous area (arrows indicate the point where image D was reconstructed). (D) Reconstructed image of view exactly perpendicular to the long axis of the bronchus at the red line in panel C. Red circle indicates the airway which was used for image reconstruction.

Figure 5 Three cases of airway lumen-obliterated emphysema. (A, C and E) Reconstructed images of longitudinal airway view of airway lumen-obliterated emphysema. Red lines indicate the points where perpendicular images were reconstructed. (B, D and F) Reconstructed images of view exactly perpendicular image to airway axis at red lines in panel A, C, and E, respectively.

Figure 6 Percentage of low attenuation area, number of airways, number of vessels and airway inner diameter in patients with chronic obstructive pulmonary disease grouped by GOLD stage and compared with controls. Bar graphs show summaries of lung structures in the 3 cm circle around the selected bronchus measured in right B1 to B10 bronchi. Means and standard error bars are shown. The peripheral zone was defined as the point 2 cm from the pleura; the central zone was defined as the point 2 cm from the entrance to the segmental bronchus; the middle zone was designated as the point half-way between the peripheral and central zone. Analysis of variance was used to determine the overall difference among groups, and the Tukey–Kramer multiple comparison test was used to compare groups. Significances between the controls (normal) and each GOLD airflow limitation stage (I–IV) are shown. Asterisks indicate *P<0.05, **P<0.01, and ***P<0.001 compared with controls.

Abbreviations: GOLD, Global initiative for chronic Obstructive Lung Disease; %LAA, percentage of low attenuation area.

Figure 7 Segmental low attenuation area by GOLD stage and percentages of airway lumen-obliterated emphysema by GOLD stage. (Left panels) The segmental low attenuation area (LAA) is a mean of the LAA in the peripheral, middle, and central zones of each bronchus. Analysis of variance with the Tukey–Kramer multiple comparison test was used to compare groups. Asterisks indicate *P<0.05; **P<0.01; and ***P<0.001 compared with controls. (Right panels) The percentage of airway lumen-obliterated emphysema in each segment (part A) and according to GOLD airflow limitation stages (part B) were significantly different with the Kruskal–Wallis test.

Abbreviations: GOLD, Global initiative for chronic Obstructive Lung Disease; N, normal controls; I, stage I; II, stage II; III, stage III; and IV, stage IV.

Table 2 Relationships between airway dimensions and pulmonary function in COPD

Variable	FEV1, %a, rb	P-value	MEF75, %a, rb	P-value	MEF50, %a, rb	P-value	MEF25, %a, rb	P-value
%LAA
Peripheral zone	−0.68	<0.0001	−0.706	<0.0001	−0.681	<0.0001	−0.593	<0.0001
Middle zone	−0.601	<0.0001	−0.675	<0.0001	−0.673	<0.0001	−0.581	<0.0001
Central zone	−0.494	<0.0001	−0.54	<0.0001	−0.533	<0.0001	−0.454	<0.0001
Total zone	−0.621	<0.0001	−0.673	<0.0001	−0.661	<0.0001	−0.57	<0.0001
Airways, n
Peripheral zone	0.618	<0.0001	0.687	<0.0001	0.74	<0.0001	0.722	<0.0001
Middle zone	0.56	<0.0001	0.663	<0.0001	0.708	<0.0001	0.68	<0.0001
Central zone	0.074	NS	0.07	NS	0.054	NS	0.091	NS
Total zone	0.599	<0.0001	0.682	<0.0001	0.724	<0.0001	0.713	<0.0001
Vessels, No
Peripheral zone	0.47	<0.0001	0.583	<0.0001	0.625	<0.0001	0.599	<0.0001
Middle zone	0.524	<0.0001	0.613	<0.0001	0.63	<0.0001	0.571	<0.0001
Central zone	0.466	<0.0001	0.537	<0.0001	0.547	<0.0001	0.499	<0.0001
Total zone	0.524	<0.0001	0.624	<0.0001	0.649	<0.0001	0.602	<0.0001
Airway inner diameter, mm
Peripheral zone	0.614	<0.0001	0.612	<0.0001	0.569	<0.0001	0.542	<0.0001
Middle zone	0.667	<0.0001	0.649	<0.0001	0.614	<0.0001	0.561	<0.0001
Central zone	0.466	<0.0001	0.659	<0.0001	0.606	<0.0001	0.537	<0.0001
Total zone	0.723	<0.0001	0.71	<0.0001	0.563	<0.0001	0.603	<0.0001

Notes:

a Predicted;

b Pearson correlation coefficients (r) are expressed for spirometric parameters and their relationship to the area of emphysema (%LAA), number of airways, number of vessels, and airway inner diameter of 3 mm circles. Around the airway at the peripheral zone (2 cm from the pleura), the central zone (2 cm from the entrance to the segmental bronchus), and the middle zone (half-way point between the central and peripheral zones). The averages of image parameters of right B1 to right B10 are used.

Abbreviations: FEV₁, forced expiratory volume in one second; %LAA, percentage of low attenuation area; MEF25, maximum expiratory flow at 25% forced vital capacity; MEF50, maximum expiratory flow at 50% forced vital capacity; MEF75, maximum expiratory flow at 75% forced vital capacity; NS, not statistically significant.

Table 3 Standard regression coefficients and correlation coefficient (r values) of stepwise multiple regression analysis for PFTs

		SRC		SRC		SRC	r	P-value
FEV1, %a	PNa	0.183	MLAA	−0.328	TDi	0.491	0.816	<0.0001
MEF75, %a	PNa	0.274	MLAA	−0.396	TDi	0.399	0.859	<0.0001
MEF50, %a	PNa	0.435	MLAA	−0.384	CDi	0.268	0.862	<0.0001
MEF25, %a	PNa	0.462	MLAA	−0.282	TDi	0.226	0.796	<0.0001

Note:

a Predicted.

Abbreviations: PFTs, pulmonary function tests; SRC, standard regression coefficient; MLAA, low attenuation area at middle zone (%); PNa, airway numbers at peripheral zone; TDi, total zone airway diameter (mm); CDi, airway diameter at central zone (mm); MEF75, maximum expiratory flow at 75% forced vital capacity; MEF50, maximum expiratory flow at 50% forced vital capacity; MEF25, maximum expiratory flow at 25% forced vital capacity.