Emphysema extent on computed tomography is a highly specific index in diagnosing persistent airflow limitation: a real-world study in China

Figures & data

Figure 1 The flow chart of patient selection.

Abbreviation: CT, computed tomography.

Table 1 Demographic features of the derivation, internal validation, and external validation groups

	Group 1.1 (derivation)	Group 1.2 (internal validation)	Group 2 (external validation)
Number	671	479	1,250
Male	347 (51.7)	255 (53.2)	644 (51.5)
Age (years)	59 (50–65)	59 (51–65)	61 (53–69)
Height (cm)	165 (160–171)	165 (160–171)	165 (158–171)
Weight (kg)	63 (55–71)	65 (58–72)	62 (55–70)
BMI (kg/m^2)	23.4±3.4	23.6±3.6	23.2±3.4
FVC (L)	2.71 (2.19–3.32)	2.70 (2.23–3.35)	2.49 (1.98–3.14)
FEV1 (L)	2.18 (1.63–2.70)	2.11 (1.61–2.69)	2.04 (1.62–2.60)
FEV1/FVC (%)	82.1 (72.2–89.5)	81.1 (69.6–89.7)	84.3 (76.5–91.3)
RV/TLC (%)	46.7±9.2	47.2±9.1	46.5±8.4
TLC-SB	4.60±0.99	4.63±1.02	4.46±0.99
DLCO SB	5.44±1.88	5.46±1.89	5.12±1.77
DLCO/VA	1.29 (1.08–1.46)	1.28 (1.06–1.48)	1.21 (1.01–1.40)
FEV1 % pred	85.1 (66.4–97.5)	84.7 (65.0–96.3)	83.4 (67.9–95.7)
FVC% pred	83.4±17.5	83.0±17.3	80.3±17.5
TLC-SB% pred	79.9±12.1	79.9±12.3	79.1±12.2
DLCO SB% pred	67.3±17.3	66.4±18.7	63.0±17.5
DLCO/VA% pred	87.8 (76.2–99.2)	88.7 (75.1–99.5)	82.0 (70.7–93.4)
FEV1 (L) post-bronchodilation	2.31±0.86	2.27±0.81	NA
FEV1/FVC (%) post-bronchodilation	84.1 (73.9–91.0)	83.2 (72.0–90.2)	NA
FEV1%pred post-bronchodilation	89.1 (72.2–100.5)	87.5 (70.8–99.2)	NA
FEV1/FVC <70% post-bronchodilation	131 (19.5)	106 (22.1)	NA
FEV1/FVC <70%	147 (21.9)	117 (24.4)	180 (14.4)
Positive in bronchodilation test	87 (13)	63 (13.2)	NA
LAA% (−950 HU)	0.30 (0.07–0.69)	0.30 (0.05–0.73)	0.24 (0.06–0.55)
Perc 15 (HU)	−889 (−906 to −868)	−889 (−906 to −867)	−875 (−896 to −849)

Abbreviations: BMI, body mass index; DLCO, diffusion capacity for carbon monoxide of the lung; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; LAA%, percentage of the lung volume occupied by low attenuation areas; Perc n, percentile of the histogram of attenuation values; RV, residual volume; TLC, total lung capacity; TLC-SB, the single-breath diffusing capacity of the lung for CO; DLCO SB, diffusion capacity for carbon monoxide of the lung, using single-breath method; DLCO/VA, diffusion capacity for carbon monoxide of the lung per liters of alveolar.

Figure 2 The emphysema extent of patients in Group 1 (including derivation group and internal validation group).

Notes: (A) LAA%; (B) Perc n.
Abbreviations: LAA%, percentage of the lung volume occupied by low attenuation areas; Perc n, percentile of the histogram of attenuation values.

Figure 3 The correlation between post-bronchodilator FEV₁/FVC and emphysema extent.

Notes: (A) LAA% using the threshold of −950 HU; (B) Perc 15 (HU).
Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; LAA%, percentage of the lung volume occupied by low attenuation areas; Perc n, percentile of the histogram of attenuation values.

Figure 4 The AUCs of different emphysema indexes in diagnosing persistent airflow limitation.

Notes: (A) LAA% using different thresholds (HU); (B) Perc n.
Abbreviations: AUC, area under the ROC curve; LAA%, percentage of the lung volume occupied by low attenuation areas; Perc n, percentile of the histogram of attenuation values; ROC, receiver-operating characteristic.

Table 2 Diagnostic values of the emphysema extent in diagnosing persistent airflow limitation using different cut point in groups 1–4

Rule	A	B	C	D	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Kappa
A: Group 1
LAA% (−950 HU) >0.84%
Group 1.1	77	63	54	477	58.8	88.3	55.0	89.8	0.83
Group 1.2	65	45	41	328	61.3	87.9	59.1	88.9	0.82
LAA% (−950 HU) >0.90%
Group 1.1	73	53	58	487	55.7	90.2	57.9	89.4	0.83
Group 1.2	62	39	44	334	58.5	89.5	61.4	88.4	0.83
LAA% (−950 HU) >1.4%
Group 1.1	58	26	73	514	44.3	95.2	69.0	87.6	0.85
Group 1.2	50	16	56	357	47.2	95.7	75.8	86.4	0.85
LAA% (−950 HU) >3.0%
Group 1.1	43	5	88	535	32.8	99.1	89.6	85.9	0.86
Group 1.2	33	4	73	369	31.1	98.9	89.2	83.5	0.84
Perc 15 <−907 HU
Group 1.1	73	76	58	464	55.7	85.9	49.0	88.9	0.8
Group 1.2	63	52	43	321	59.4	86.1	54.8	88.2	0.8
Perc 15 <−910 HU
Group 1.1	63	53	68	487	48.1	90.2	54.3	87.7	0.82
Group 1.2	60	32	46	341	56.6	91.4	65.2	88.1	0.84
Perc 15 <−915 HU
Group 1.1	54	23	77	517	41.2	95.7	70.1	87.0	0.85
Group 1.2	49	19	57	354	46.2	94.9	72.1	86.1	0.84
Perc 15 <−928 HU
Group 1.1	33	4	98	536	25.2	99.3	89.2	84.5	0.85
Group 1.2	24	0	82	373	22.6	100.0	100.0	82.0	0.83
LAA% (−930 HU) >1.4%
Group 1.1	103	142	28	398	78.6	73.7	42.0	93.4	0.75
Group 1.2	86	97	20	276	81.1	74.0	47.0	93.2	0.76
LAA% (−930 HU) >3.4%
Group 1.1	76	53	55	487	58.0	90.2	58.9	89.9	0.84
Group 1.2	72	34	34	339	67.9	90.9	67.9	90.9	0.86
LAA% (−930 HU) >5.2%
Group 1.1	65	26	66	514	49.6	95.2	71.4	88.6	0.86
Group 1.2	56	20	50	353	52.8	94.6	73.7	87.6	0.85
LAA% (−930 HU) >13%
Group 1.1	38	5	93	535	29.0	99.1	88.4	85.2	0.85
Group 1.2	25	1	81	372	23.6	99.7	96.2	82.1	0.83
Perc 3 <−922 HU
Group 1.1	96	124	35	416	73.3	77.0	43.6	92.2	0.76
Group 1.2	85	78	21	295	80.2	79.1	52.1	93.4	0.79
Perc 3 <−931 HU
Group 1.1	75	52	56	488	57.3	90.4	59.1	89.7	0.84
Group 1.2	70	32	36	341	66.0	91.4	68.6	90.5	0.86
Perc 3 <−937 HU
Group 1.1	64	24	67	516	48.9	95.6	72.7	88.5	0.86
Group 1.2	54	16	52	357	50.9	95.7	77.1	87.3	0.86
Perc 3 <−951 HU
Group 1.1	39	4	92	536	29.8	99.3	90.7	85.4	0.86
Group 1.2	28	4	78	369	26.4	98.9	87.5	82.6	0.83
B: Group 2
LAA% (−950 HU) >0.84%	86	113	94	957	47.8	89.4	43.2	91.1	0.83
LAA% (−950 HU) >0.90%	83	99	97	971	46.1	90.7	45.6	90.9	0.84
LAA% (−950 HU) >1.4%	69	55	111	1,015	38.3	94.9	55.6	90.1	0.87
LAA% (−950 HU) >3.0%	44	11	136	1,059	24.4	99.0	80.0	88.6	0.88
Perc 15 <−907 HU	77	84	103	986	42.8	92.1	47.8	90.5	0.85
Perc 15 <−910 HU	73	61	107	1,009	40.6	94.3	54.5	90.4	0.87
Perc 15 <−915 HU	64	37	116	1,033	35.6	96.5	63.4	89.9	0.88
Perc 15 <−928 HU	35	4	145	1,066	19.4	99.6	89.7	88.0	0.88
LAA% (−930 HU) >1.4%	112	215	68	855	62.2	79.9	34.3	92.6	0.77
LAA% (−930 HU) >3.4%	86	77	94	993	47.8	92.8	52.8	91.4	0.86
LAA% (−930 HU) >5.2%	75	40	105	1,030	41.7	96.3	65.2	90.7	0.88
LAA% (−930 HU) >13%	39	5	141	1,065	21.7	99.5	88.6	88.3	0.88
Perc 3 <−922 HU	108	165	72	905	60.0	84.6	39.6	92.6	0.81
Perc 3 <−931 HU	85	72	95	998	47.2	93.3	54.1	91.3	0.87
Perc 3 <−937 HU	70	38	110	1,032	38.9	96.4	64.8	90.4	0.88
Perc 3 <−951 HU	44	10	136	1,060	24.4	99.1	81.5	88.6	0.88
C: Group 3
LAA% (−950 HU) >0.84%	2	3	3	32	40.0	91.4	40.0	91.4	0.85
LAA% (−950 HU) >0.90%	2	3	3	32	40.0	91.4	40.0	91.4	0.85
LAA% (−950 HU) >1.4%	2	2	3	33	40.0	94.3	50.0	91.7	0.88
LAA% (−950 HU) >3.0%	1	0	4	35	20.0	100.0	100.0	89.7	0.90
Perc 15 <−907 HU	2	1	3	34	40.0	97.1	66.7	91.9	0.90
Perc 15 <−910 HU	2	1	3	34	40.0	97.1	66.7	91.9	0.90
Perc 15 <−915 HU	2	0	3	35	40.0	100.0	100.0	92.1	0.93
Perc 15 <−928 HU	0	0	5	35	0.0	100.0	NA	87.5	0.88
LAA% (−930 HU) >1.4%	2	6	3	29	40.0	82.9	25.0	90.6	0.78
LAA% (−930 HU) >3.4%	2	2	3	33	40.0	94.3	50.0	91.7	0.88
LAA% (−930 HU) >5.2%	2	1	3	34	40.0	97.1	66.7	91.9	0.90
LAA% (−930 HU) >13%	0	0	5	35	0.0	100.0	NA	87.5	0.88
Perc 3 <−922 HU	2	4	3	31	40.0	88.6	33.3	91.2	0.83
Perc 3 <−931 HU	2	2	3	33	40.0	94.3	50.0	91.7	0.88
Perc 3 <−937 HU	2	1	3	34	40.0	97.1	66.7	91.9	0.90
Perc 3 <−951 HU	1	0	4	35	20.0	100.0	100.0	89.7	0.90
D: Group 4
LAA% (−950 HU) >0.84%
With lung infiltration	48	38	40	233	54.5	86.0	55.8	85.3	0.78
With bronchiectasis	19	8	7	34	73.1	81.0	70.4	82.9	0.78
With mass in lung	11	10	4	52	73.3	83.9	52.4	92.9	0.82
With nodule in lung	78	56	55	470	58.6	89.4	58.2	89.5	0.83
With interstitial lung disease	18	14	4	49	81.8	77.8	56.3	92.5	0.79
With pneumothorax	1	1	0	5	100	83.3	50.0	100	0.86
Post-thoracic surgery	1	7	5	21	16.7	75.0	12.5	80.8	0.65
LAA% (−950 HU) >0.90%
With lung infiltration	45	32	43	239	51.1	88.2	58.4	84.8	0.79
With bronchiectasis	19	8	7	34	73.1	81.0	70.4	82.9	0.78
With mass in lung	10	7	5	55	66.7	88.7	58.8	91.7	0.84
With nodule in lung	76	47	57	479	57.1	91.1	61.8	89.4	0.84
With interstitial lung disease	17	12	5	51	77.3	81.0	58.6	91.1	0.80
With pneumothorax	1	1	0	5	100	83.3	50.0	100	0.86
Post-thoracic surgery	1	6	5	22	16.7	78.6	14.3	81.5	0.68
LAA% (−950 HU) >1.4%
With lung infiltration	33	9	55	262	37.5	96.7	78.6	82.6	0.82
With bronchiectasis	14	3	12	39	53.8	92.9	82.4	76.5	0.78
With mass in lung	8	2	7	60	53.3	96.8	80.0	89.6	0.88
With nodule in lung	65	24	68	502	48.9	95.4	73.0	88.1	0.86
With interstitial lung disease	17	9	5	54	77.3	85.7	65.4	91.5	0.84
With pneumothorax	1	1	0	5	100	83.3	50.0	100	0.86
Post-thoracic surgery	0	4	6	24	0.0	85.7	0.0	80.0	0.71
LAA% (−950 HU) >3.0%
With lung infiltration	22	2	66	269	25.0	99.3	91.7	80.3	0.81
With bronchiectasis	10	1	16	41	38.5	97.6	90.9	71.9	0.75
With mass in lung	5	0	10	62	33.3	100	100	86.1	0.87
With nodule in lung	40	5	93	521	30.1	99.0	88.9	84.9	0.85
With interstitial lung disease	16	4	6	59	72.7	93.7	80.0	90.8	0.88
With pneumothorax	0	0	1	6	0.0	100	NA	85.7	0.86
Post-thoracic surgery	0	3	6	25	0.0	89.3	0.0	80.6	0.74
Perc 15 <−907 HU
With lung infiltration	43	40	45	231	48.9	85.2	51.8	83.7	0.76
With bronchiectasis	17	9	9	33	65.4	78.6	65.4	78.6	0.74
With mass in lung	7	5	8	57	46.7	91.9	58.3	87.7	0.83
With nodule in lung	79	68	54	458	59.4	87.1	53.7	89.5	0.81
With interstitial lung disease	14	5	8	58	63.6	92.1	73.7	87.9	0.85
With pneumothorax	0	2	1	4	0.0	66.7	0.0	80.0	0.57
Post-thoracic surgery	0	3	6	25	0.0	89.3	0.0	80.6	0.74
Perc 15 <−910 HU
With lung infiltration	37	25	51	246	42.0	90.8	59.7	82.8	0.79
With bronchiectasis	15	4	11	38	57.7	90.5	78.9	77.6	0.78
With mass in lung	6	1	9	61	40.0	98.4	85.7	87.1	0.87
With nodule in lung	71	49	62	477	53.4	90.7	59.2	88.5	0.83
With interstitial lung disease	14	4	8	59	63.6	93.7	77.8	88.1	0.86
With pneumothorax	0	0	1	6	0.0	100	NA	85.7	0.86
Post-thoracic surgery	0	3	6	25	0.0	89.3	0.0	80.6	0.74
Perc 15 <−915 HU
With lung infiltration	28	16	60	255	31.8	94.1	63.6	81.0	0.79
With bronchiectasis	12	2	14	40	46.2	95.2	85.7	74.1	0.76
With mass in lung	6	1	9	61	40.0	98.4	85.7	87.1	0.87
With nodule in lung	55	22	78	504	41.4	95.8	71.4	86.6	0.85
With interstitial lung disease	14	2	8	61	63.6	96.8	87.5	88.4	0.88
With pneumothorax	0	0	1	6	0.0	100	NA	85.7	0.86
Post-thoracic surgery	0	2	6	26	0.0	92.9	0.0	81.3	0.76
Perc 15 <−928 HU
With lung infiltration	19	1	69	270	21.6	99.6	95.0	79.6	0.81
With bronchiectasis	8	1	18	41	30.8	97.6	88.9	69.5	0.72
With mass in lung	5	0	10	62	33.3	100	100	86.1	0.87
With nodule in lung	34	5	99	521	25.6	99.0	87.2	84.0	0.84
With interstitial lung disease	15	4	7	59	68.2	93.7	78.9	89.4	0.87
With pneumothorax	0	0	1	6	0.0	100	NA	85.7	0.86
Post-thoracic surgery	0	3	6	25	0.0	89.3	0.0	80.6	0.74
LAA% (−930 HU) >1.4%
With lung infiltration	64	78	24	193	72.7	71.2	45.1	88.9	0.72
With bronchiectasis	23	17	3	25	88.5	59.5	57.5	89.3	0.71
With mass in lung	11	15	4	47	73.3	75.8	42.3	92.2	0.75
With nodule in lung	109	132	24	394	82.0	74.9	45.2	94.3	0.76
With interstitial lung disease	18	18	4	45	81.8	71.4	50.0	91.8	0.74
With pneumothorax	1	2	0	4	100	66.7	33.3	100	0.71
Post-thoracic surgery	2	7	4	21	33.3	75.0	22.2	84.0	0.68
LAA% (−930 HU) >3.4%
With lung infiltration	49	28	39	243	55.7	89.7	63.6	86.2	0.81
With bronchiectasis	17	8	9	34	65.4	81.0	68.0	79.1	0.75
With mass in lung	10	4	5	58	66.7	93.5	71.4	92.1	0.88
With nodule in lung	85	53	48	473	63.9	89.9	61.6	90.8	0.85
With interstitial lung disease	17	11	5	52	77.3	82.5	60.7	91.2	0.81
With pneumothorax	1	1	0	5	100	83.3	50.0	100	0.86
Post-thoracic surgery	1	6	5	22	16.7	78.6	14.3	81.5	0.68
LAA% (−930 HU) >5.2%
With lung infiltration	38	17	50	254	43.2	93.7	69.1	83.6	0.81
With bronchiectasis	16	4	10	38	61.5	90.5	80.0	79.2	0.79
With mass in lung	6	1	9	61	40.0	98.4	85.7	87.1	0.87
With nodule in lung	71	24	62	502	53.4	95.4	74.7	89.0	0.87
With interstitial lung disease	16	5	6	58	72.7	92.1	76.2	90.6	0.87
With pneumothorax	0	0	1	6	0.0	100	NA	85.7	0.86
Post-thoracic surgery	0	3	6	25	0.0	89.3	0.0	80.6	0.74
LAA% (−930 HU) >13%
With lung infiltration	19	1	69	270	21.6	99.6	95.0	79.6	0.81
With bronchiectasis	9	0	17	42	34.6	100	100	71.2	0.75
With mass in lung	5	1	10	61	33.3	98.4	83.3	85.9	0.86
With nodule in lung	35	3	98	523	26.3	99.4	92.1	84.2	0.85
With interstitial lung disease	10	1	12	62	45.5	98.4	90.9	83.8	0.85
With pneumothorax	0	0	1	6	0.0	100	NA	85.7	0.86
Post-thoracic surgery	0	1	6	27	0.0	96.4	0.0	81.8	0.79
Perc 3 <−922 HU
With lung infiltration	60	59	28	212	68.2	78.2	50.4	88.3	0.76
With bronchiectasis	21	15	5	27	80.8	64.3	58.3	84.4	0.71
With mass in lung	11	12	4	50	73.3	80.6	47.8	92.6	0.79
With nodule in lung	103	114	30	412	77.4	78.3	47.5	93.2	0.78
With interstitial lung disease	17	16	5	47	77.3	74.6	51.5	90.4	0.75
With pneumothorax	1	2	0	4	100	66.7	33.3	100	0.71
Post-thoracic surgery	1	8	5	20	16.7	71.4	11.1	80.0	0.62
Perc 3 <−931 HU
With lung infiltration	47	28	41	243	53.4	89.7	62.7	85.6	0.81
With bronchiectasis	17	8	9	34	65.4	81.0	68.0	79.1	0.75
With mass in lung	10	3	5	59	66.7	95.2	76.9	92.2	0.90
With nodule in lung	82	51	51	475	61.7	90.3	61.7	90.3	0.85
With interstitial lung disease	17	10	5	53	77.3	84.1	63.0	91.4	0.82
With pneumothorax	1	1	0	5	100	83.3	50.0	100	0.86
Post-thoracic surgery	1	5	5	23	16.7	82.1	16.7	82.1	0.71
Perc 3 <−937 HU
With lung infiltration	18	0	70	271	20.5	100	100	79.5	0.81
With bronchiectasis	9	0	17	42	34.6	100	100	71.2	0.75
With mass in lung	4	0	11	62	26.7	100	100	84.9	0.86
With nodule in lung	32	2	101	524	24.1	99.6	94.1	83.8	0.84
With interstitial lung disease	10	1	12	62	45.5	98.4	90.9	83.8	0.85
With pneumothorax	0	0	1	6	0.0	100	NA	85.7	0.86
Post-thoracic surgery	0	1	6	27	0.0	96.4	0.0	81.8	0.79
Perc 3 <−951 HU
With lung infiltration	38	15	50	256	43.2	94.5	71.7	83.7	0.82
With bronchiectasis	16	4	10	38	61.5	90.5	80.0	79.2	0.79
With mass in lung	7	1	8	61	46.7	98.4	87.5	88.4	0.88
With nodule in lung	72	25	61	501	54.1	95.2	74.2	89.1	0.87
With interstitial lung disease	17	5	5	58	77.3	92.1	77.3	92.1	0.88
With pneumothorax	0	0	1	6	0.0	100	NA	85.7	0.86
Post-thoracic surgery	0	3	6	25	0.0	89.3	0.0	80.6	0.74

Notes: A, true positives (with obvious emphysema and persistent airflow limitation); B, false positives (with obvious emphysema, but without persistent airflow limitation); C, false negatives (without obvious emphysema, but with persistent airflow limitation); D, true negatives (without obvious emphysema and persistent airflow limitation).

Abbreviations: LAA%, percentage of the lung volume occupied by low attenuation areas; NPV, negative predictive value; Perc n, percentile of the histogram of attenuation values; PPV, positive predictive value.

Figure 5 The ROC curve of emphysema indexes and predicting model in diagnosing consistent airflow limitation.

Notes: (A) Group 1.1 (derivation group); (B) Group 1.2 (internal validation group). LAA% (−950 HU) and LAA% (−930 HU) indicate the percentage of the lung volume occupied by low attenuation areas using the thresholds of −950 and −930 HU; Perc 3 and Perc 15 indicate percentile of the histogram of attenuation values.
Abbreviations: LAA%, percentage of the lung volume occupied by low attenuation areas; Perc n, percentile of the histogram of attenuation values; ROC, receiver-operating characteristic.