Clinical impacts of the classification by 2017 GOLD guideline comparing previous ones on outcomes of COPD in real-world cohorts

Figures & data

Table 1 Baseline characteristics of study population

Variables	Total population (N=1,880)	KOCOSS (n=1,500)	KOLD (n=236)	SNUH airway registry (n=144)	P-value
Age	69.2±8.9 (n=1,662)	69.3±9.3 (n=1,294)	67.9±7.4	70.2±7.9 (n=132)	0.028
Sex, male (%)	1,629/1,734 (93.9%) (n=1,734)	1,273/1,368 (93.1%)	216/222 (97.3%)	140/144 (97.2%)	0.009
Smoking pack-years	44.5±25.4 (n=1,736)	44.2±24.9 (n=1,365)	45.0±26.8	45.9±25.6 (n=135)	0.721
Body mass index	22.8±3.3 (n=1,876)	22.9±3.4 (n=1,500)	22.8±3.2 (n=232)	22.1±3.3 (n=143)	0.041
FEV1 (% pred)	56.6±18.6	56.5±18.5	55.8±17.9	58.7±20.5	0.309
Post-BDR FEV1/FVC	49.0±11.7	49.4±11.7	47.6±11.2	46.7±12.5	0.006
Positive BDR (>12% and 200 mL)	68/1,870 (3.6%) (n=1,870)	49/1,498 (3.3%)	19/236 (8.1%)	0/135 (0%)	<0.001
mMRC	1.5±0.9 (n=1,842)	1.5±0.9	1.5±1.1	1.7±0.9	0.004
CAT total	15.0±7.9 (n=1,670)	15.4±7.9	9.6±7.6	14.5±6.4	<0.001
SGRQ total	33.2±18.7 (n=1,825)	33.9±18.8	29.4±18.8	31.3±16.5	0.002
Medication for COPD at baseline
LAMA	937/1,671 (56.1%)	864/1,292 (66.9%)	71/235 (30.2%)	2/144 (1.4%)	<0.001
LABA	237/1,353 (14.9%)	233/1,211 (19.2%)	4/235 (1.7%)	0/144 (0%)	<0.001
LAMA/LABA	96/412 (23.3%)	33/33 (100.0%)	63/235 (26.8%)	0/144 (0%)	<0.001
ICS/LABA	616/1,617 (38.1%)	568/1,238 (45.9%)	4/235 (1.7%)	42/144 (29.2%)	<0.001
Roflumilast	76/1,545 (4.9%)	74/1,092 (6.4%)	2/235 (0.9%)	0/144 (0%)	<0.001
Total moderate-to-severe exacerbation rate in the year prior to enrollment	0.5±1.5 (n=1,873)	0.5±1.4 (n=1,498)	0.7±2.2 (n=235)	0.2±0.7 (n=140)	0.004

Note: Continuous variables are presented as mean value ± SD.

Abbreviations: BDR, bronchodilator response; CAT, COPD Assessment Test; ICS, inhaled corticosteroid; KOCOSS, Korean COPD Subtype Study; KOLD, The Korean Obstructive Lung Disease Cohort Study; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; SGRQ, St George’s Respiratory Questionnaire; SNUH registry, Seoul National University airway registry.

Figure 1 Patient selection flow.

Abbreviations: CAT, COPD Assessment Test; KOCOSS, Korean COPD Subtype Study; KOLD, The Korean Obstructive Lung Disease Cohort Study; SNUH registry, Seoul National University airway registry.

Table 2 Comparison of patients’ distribution between GOLD 2007, GOLD 2013, and GOLD 2017

Total (N=1,880)			GOLD 2013				GOLD 2017
			(A)	(B)	(C)	(D)	(A)	(B)	(C)	(D)
			335 (17.8%)	701 (37.5%)	124 (6.6%)	720 (38.1%)	418 (22.2%)	1,150 (61.2%)	41 (2.2%)	271 (14.4%)
GOLD 2007	I	197 (10.5%)	65 (19.4%)	116 (16.6%)	4 (3.2%)	12 (1.7%)	65 (15.6%)	116 (10.1%)	4 (9.8%)	12 (4.4%)
	II	974 (51.8%)	270 (80.6%)	585 (83.5%)	28 (22.6%)	91 (12.6%)	270 (64.6%)	585 (50.9%)	28 (68.3%)	91 (33.6%)
	III	592 (31.5%)	0	0	86 (69.4%)	506 (70.3%)	78 (18.7%)	380 (33.0%)	8 (19.5%)	126 (46.5%)
	IV	117 (6.2%)	0	0	6 (4.8%)	111 (15.4%)	5 (1.2%)	69 (6.0%)	1 (2.4%)	42 (14.4%)

Note: Data are presented as number of patients (percent).

Figure 2 Changes in distribution of COPD patients with new GOLD 2017 classification.

Notes: (A) Distribution of patients by GOLD classification. (B) Comparison of subgroup proportion of GOLD 2013 and 2017 classifications.

Table 3 Comparison of baseline clinical characteristics between patients in group B of GOLD 2013 and patients newly migrated to group B by GOLD 2017 classification

	Group (B) in GOLD 2013 (n=701)	Group (B) newly migrated in 2017; group B′ (n=449)	P-value
Age	69.8±9.1 (n=629)	68.3±8.0 (n=387)	0.008
Sex, male (%)	601/650 (92.5%)	390/404 (96.5%)	0.007
Smoking pack-years	43.7±24.3 (n=642)	44.8±25.9 (n=421)	0.490
Body mass index	23.5±3.1 (n=698)	21.8±3.4 (n=448)	<0.001
FEV1(% pred)	67.9±14.0	38.1±7.5	<0.001
Post-BDR FEV1/FVC	54.6±9.2	39.3±9.2	<0.001
Positive BDR (>12% and 200 mL)	23/697 (3.3%)	14/446 (3.1%)	0.881
mMRC	1.5±0.8 (n=684)	1.9±0.9 (n=44)	<0.001
CAT total	16.4±6.1 (n=664)	18.2±6.9 (n=402)	<0.001
SGRQ total	32.6±15.6 (n=677)	39.7±19.1 (n=439)	<0.001
Medication for COPD at baseline
LAMA	337/614 (54.9%)	242/406 (59.6%)	0.136
LABA	108/599 (18.0%)	42/381 (11.0%)	0.003
LAMA/LABA	26/118 (22.0%)	17/94 (18.1%)	0.478
ICS/LABA	186/600 (31.0%)	207/402 (51.5%)	<0.001
Roflumilast	5/572 (0.9%)	35/381 (9.2%)	<0.001
Total moderate-to-severe exacerbation rate in the year prior to enrollment	0.07±0.26	0.09±0.29	0.221

Note: Continuous variables were presented as mean value ± SD.

Abbreviations: BDR, bronchodilator response; CAT, COPD Assessment Test; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; SGRQ, St George’s Respiratory Questionnaire.

Table 4 Comparison of group shifting among GOLD classification systems in 1-year follow-up

GOLD classification	Group at enrollment	Group in 1-year follow-up	Difference	P for trend
GOLD 2013
Group (A)	335 (17.8%)	234 (21.4%)	3.6	<0.001
Group (B)	701 (37.3%)	424 (38.7%)	1.4
Group (C)	124 (6.6%)	72 (6.6%)	0
Group (D)	720 (38.3%)	337 (30.8%)	−7.5
GOLD 2017
Group (A)	418 (22.2%)	276 (25.2%)	3.0	<0.001
Group (B)	1,150 (61.2%)	6,408 (58.4%)	−2.8
Group (C)	41 (2.2%)	30 (2.7%)	0.5
Group (D)	2,714 (14.4%)	121 (11.0%)	−3.4
Reclassified GOLD 2017 with combined group
Group (A)	418 (22.2%)	276 (25.2%)	3.0	<0.001
Group (B)	1,150 (61.2%)	640 (58.4%)	−2.78
Group (C+D)	312 (16.6%)	151 (13.8%)	−2.8

Table 5 Univariate and multivariate analyses for impact of GOLD classifications on the risk of AECOPD in 1-year follow-up period

GOLD classification	Univariate analysis		Multivariate analysisa
	OR (95% CI)	P-value	OR (95% CI)	P-value
GOLD 2007
Stage I	Reference		Reference
Stage II	2.3 (1.2–4.2)	0.010	2.1 (1.0–4.3)	0.043
Stage III	3.6 (1.9–6.8)	<0.001	3.9 (1.9–8.1)	<0.001
Stage IV	3.8 (1.8–8.0)	0.001	4.4 (1.9–10.7)	0.001
GOLD 2013
Group (A)	Reference		Reference
Group (B)	2.0 (1.2–3.1)	0.005	2.5 (1.4–4.4)	0.001
Group (C)	2.0 (1.1–3.7)	0.032	2.3 (1.1–4.8)	0.033
Group (D)	4.0 (2.6–638)	<0.001	5.8 (3.4–10.1)	<0.001
GOLD 2017
Group (A)	Reference		Reference
Group (B)	2.0 (1.4–2.9)	<0.001	2.4 (1.5–3.6)	<0.001
Group (C)	1.7 (0.7–4.1)	0.234	1.0 (0.3–3.8)	0.997
Group (D)	4.5 (2.9–6.9)	<0.001	5.9 (3.5–10.0)	<0.001
GOLD combined group
Group (A)	Reference		Reference
Group (B)	2.0 (1.4–2.9)	<0.001	2.4 (1.5–3.6)	<0.001
Group (C+D)	4.0 (2.6–6.1)	<0.001	5.0 (3.0–8.3)	<0.001

Note:

a Adjusted for age, sex, body mass index, and pack-years.

Abbreviation: AECOPD, acute exacerbation of COPD.

Figure 3 Associations between GOLD classifications and prospective total moderate-to-severe annual exacerbation rate.

Note: ^aAdjusted for age, sex, body mass index, and pack-years.
Abbreviation: IRR, incidence rate ratio.

Table 6 Associations between GOLD classifications and symptomatic score (SGRQ and CAT) changesa in 1-year follow-up

GOLD classification	Total SGRQ score	P-value	Total CAT score	P-value
GOLD 2007
Stage I	−4.8 (14.3) (n=96)	0.105	−1.1 (6.7) (n=66)	0.085
Stage II	−1.5 (13.4) (n=611)		−0.8 (6.4) (n=507)
Stage III	−0.6 (16.3) (n=404)		0.1 (7.2) (n=340)
Stage IV	−1.1 (20.7) (n=81)		−1.8 (7.4) (n=70)
GOLD 2013
Group (A)	0.6 (9.5) (n= 183)	0.017	1.7 (4.7) (n= 121)	<0.001
Group (B)	−2.8 (14.9) (n=447)		−1.6 (6.8) (n=393)
Group (C)	1.8 (13.8) (n=86)		3.3 (6.1) (n=66)
Group (D)	−1.5 (16.9) (n=488)		−0.9 (7.0) (n=415)
GOLD 2017
Group (A)	1.0 (11.1) (n=243)	0.023	2.3 (5.4) (n=166)	<0.001
Group (B)	−1.8 (16.1) (n=749)		−1.2 (7.0) (n=655)
Group (C)	0.6 (10.9) (n=26)		2.5 (4.9) (n=21)
Group (D)	−3.1 (15.3) (n=186)		−1.3 (6.6) (n= 153)
Reclassified GOLD 2017 with combined group
Group (A)	1.0 (11.1) (n=243)	0.017	2.3 (5.4) (n=166)	<0.001
Group (B)	−1.8 (15.9) (n=7,495)		−1.2 (7.0) (n=655)
Group (C+D)	−2.6 (15.4) (n=212)		−0.8 (6.6) (n= 174)

Note:

a Mean change (SD).

Abbreviations: CAT, COPD Assessment Test; GOLD, global initiative for chronic obstructive lung disease; SGRQ, St George’s Respiratory Questionnaire.

Table 7 Associations between GOLD classifications and prospective total moderate-to-severe annual exacerbation rate

GOLD classification	Univariate analysis		Multivariate analysisa
	IRR (95% CI)	P-value	IRR (95% CI)	P-value
GOLD 2007
Stage I	Reference		Reference
Stage II	2.3 (1.3–4.1)	0.0069	2.0 (1.0–3.8)	0.036
Stage III	2.9 (1.6–5.4)	<0.001	2.3 (1.2–4.6)	0.014
Stage IV	3.8 (1.8–7.9)	<0.001	3.2 (1.4–7.3)	0.006
GOLD 2013
Group (A)	Reference		Reference
Group (B)	2.8 (1.7–4.4)	<0.001	3.1 (1.8–5.2)	<0.001
Group (C)	2.3 (1.3–4.3)	0.008	2.0 (1.0–4.2)	0.052
Group (D)	4.6 (2.9–7.2)	<0.001	5.1 (3.0–8.4)	<0.001
GOLD 2017
Group (A)	Reference		Reference
Group (B)	2.5 (1.6–3.4)	<0.001	2.4 (1.6–3.5)	<0.001
Group (C)	2.3 (1.0–5.3)	0.060	1.0 (0.3–3.6)	0.997
Group (D)	5.1 (3.3–7.9)	<0.001	5.3 (3.3–8.6)	<0.001
Reclassified GOLD 2017 with combined group
Group (A)	Reference		Reference
Group (B)	2.3 (1.6–3.4)	<0.001	2.5 (1.6–3.7)	<0.001
Group (C+D)	4.7 (3.1–7.2)	<0.001	4.8 (3.0–7.7)	<0.001

Note:

a Adjusted for age, sex, body mass index, and pack-years.

Abbreviation: IRR, incidence rate ratio.

Figure S1 Changes in COPD classifications.

Abbreviations: CAT, COPD Assessment Test; GOLD, global initiative for chronic obstructive lung disease.

Table S1 Comparison of demographical and clinical characteristics between Class A in GOLD 2013 and 2017

	Class (A) in GOLD 2013(n=335)	Class (A) migrated in 2017 (C→A; n=83)	P-value
Age	68.5±9.1 (n=292)	69.0±9.2 (n=78)	0.584
Sex, male (%)	308/320 (96.3%)	73/79 (92.4%)	0.140
Smoking pack-years	43.6±23.3 (n=312)	47.8±30.4 (n=70)	0.201
Body mass index	23.6±3.1 (n=334)	22.1 ±3.6	<0.001
Baseline FEV1 (% pred)	68.7± 13.2	40.6±6.3	<0.001
Baseline FEV1/FVC	55.5±8.7	41.1±9.4	<0.001
Positive bronchodilator response (>12% and 200 mL)	15/334 (4.5%)	7/82 (8.5%)	0.166
mMRC	0.7±0.5	0.8±0.4	0.046
Baseline cat total	5.7±2.5	5.8±2.4	0.789
Baseline Sgrq total	18.9± 12.0	22.7± 13.4	0.012
Initial LAMA use	118/293 (40.3%)	40/73 (54.8%)	0.025
Initial LABA use	45/275 (16.4%)	10/70 (14.3%)	0.672
Initial LAMA/LABA use	28/112 (25.0%)	8/29 (27.6%)	0.776
Initial ICS/LABA	60/271 (22.1%)	22/69 (20.3%)	0.091
Initial roflumilast use	3/266 (1.1%)	3/67 (4.5%)	0.098
Total moderate-to-severe exacerbation rate in the year prior to enrollment	0.2±0.7	0.5± 1.0	0.028

Note:Continuous variables were presented as mean value ± SD.

Abbreviations: CAT, COPD Assessment Test; GOLD, global initiative for chronic obstructive lung disease; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; SGRQ, St George's Respiratory Questionnaire.

Table S2 Comparison of group shifting among GOLD classification systems in 1-year follow-up

Group at enrollment	Group in 1 year
	By GOLD 2013
	Group (A)	Group (B)	Group (C)	Group (D)	Group without airflow limitation
Group (A)	96 (41.0%)	35 (8.3%)	13 (18.1%)	9 (5.6%)	8 (27.6%)
Group (B)	79 (33.8%)	237 (56.2%)	11 (15.3%)	58 (14.7%)	11 (37.9%)
Group (C)	16 (6.8%)	18 (4.3%)	25 (34.7%)	14 (18.2%)	4 (13.8%)
Group (D)	43 (18.4%)	132 (31.3%)	23 (31.9%)	256 (55.7%)	6 (20.7%)
	By GOLD 2017
	Group (A)	Group (B)	Group (C)	Group (D)	Group without airflow limitation
Group (A)	128 (46.4%)	59 (9.2%)	12 (40.0%)	6 (5.0%)	10 (34.5%)
Group (B)	128 (46.0%)	462 (72.2%)	10 (33.3%)	74 (61.2%)	14 (48.3%)
Group (C)	7 (2.5%)	11 (1.7%)	3 (10.0%)	0 (0%)	2 (6.9%)
Group (D)	14 (5.1%)	108 (16.9%)	5 (16.7%)	41 (33.9%)	3 (10.3%)
	By reclassified GOLD 2017 with combined group
	Group (A)	Group (B)	Group (C+D)	Group without airflow limitation
Group (A)	128 (46.4%)	59 (9.2%)	18 (11.9%)	10 (34.5%)
Group (B)	127 (46.0%)	462 (72.2%)	84 (55.6%)	14 (48.3%)
Group (C+D)	21 (7.3%)	119 (18.6%)	49 (32.5%)	5 (17.2%)

Table S3 Comparison of patients’ distribution between GOLD 2007, GOLD 2013, and GOLD 2017

Total (N=1,880)			GOLD 2013				GOLD 2017
			(A)	(B)	(C3)	(D3)	(A)	(B)	(C)	(D)
			335 (17.8%)	704 (37.5%)	124 (6.6%)	720 (38.1%)	418 (22.2%)	1,157 (61.5%)	41 (2.2%)	271 (14.4%)
GOLD 2007	I	197 (10.5%)	65 (19.4%)	116 (16.6%)	4 (3.2%)	12 (1.7%)	65 (15.6%)	117 (10.1%)	4^C2 (9.8%)	12^D2 (4.6%)
	II	974 (51.8%)	270 (80.6%)	587 (83.5%)	27 (22.6%)	91 (12.6%)	270 (64.6%)	587 (50.7%)	28^C2 (68.3%)	91^D2 (33.7%)
	III	592 (31.5%)	0	0	86 (69.4%)	506 (70.3%)	78^C1 (18.7%)	380^D1 (33.1%)	8^C3 (19.5%)	124^D3 (47.0%)
	IV	117 (6.2%)	0	0	6 (4.8%)	111 (15.4%)	5^C1 (1.2%)	69^D1 (6.1%)	1^C3 (2.4%)	429^D3 (14.4%)

Notes: C1, C2, C3, D1, D2, D3: classified by GOLD 2013; C1, D1: by FEV₁; C2, D2: by exacerbation; C3, D3: by both.