Categorization of COPD patients in Turkey via GOLD 2013 strategy document: ALPHABET study

Figures & data

Table 1 Patient characteristics within GOLD categories

	GOLD A	GOLD B	GOLD C	GOLD D	Total
Reported, n (%)	661 (41.1)	335 (20.8)	212 (13.2)	402 (25.0)	1,610 (100.0)
Age (year)
Mean (SD)	61.0 (10.0)	65.2 (10.0)	60.9 (8.9)	64.0 (9.6)	62.6 (9.9)
Median (IQR, min–max)	62.0 (15.0; 40–87)	66.0 (15; 40–92)	61.0 (12.5; 41–87)	64.0 (14.0; 40–90)	63.0 (14.0; 40–92)
Adjusted* for age, %	44.3	24.3	12.1	19.3	100.0
Sex, n (%)
Male	550 (83.2)	290 (86.6)	188 (88.7)	351 (87.3)	1,379 (85.7)
Female	111 (16.8)	45 (13.4)	24 (11.3)	51 (12.7)	231 (14.3)
Adjusted* for sex, %	44.0	20.3	12.0	23.8	100.0
COPD duration (year)
Mean (SD)	5.3 (5.9)	7.3 (6.1)	5.6 (5.3)	7.9 (6.0)	6.4 (6.0)
Median (IQR, min–max)	3.0 (7.0; 0–50)	5.0 (7.0; 0–30)	4.0 (6.0; 0–33)	7.0 (7.0; 0–44)	5.0 (8.0; 0–50)
Smoking status, n (%)
Active smoker	238 (36.0)	96 (28.7)	70 (33.0)	103 (25.6)	507 (31.5)
Ex-smoker	423 (64.0)	239 (71.3)	142 (67.0)	299 (74.4)	1,103 (68.5)
Concomitant disease, n (%)	343 (51.9)	212 (63.3)	111 (52.4)	254 (63.2)	920 (57.1)
Cardiovascular diseasea	241 (36.5)	154 (46.0)	72 (34.0)	177 (44.0)	644 (40.0)
Musculoskeletal diseaseb	10 (1.5)	9 (2.7)	3 (1.4)	13 (3.2)	35 (2.2)
Psychiatric diseasec	15 (2.3)	9 (2.7)	7 (3.3)	15 (3.7)	46 (2.9)
Diabetes mellitus	73 (11.0)	43 (12.8)	20 (9.4)	49 (12.2)	185 (11.5)
Others	13 (2.0)	7 (2.1)	1 (0.5)	3 (0.7)	24 (1.5)

Notes:

* Results were adjusted for 2013 Turkish population older than 18. Patients with

a any ischemic heart disease, heart failure, hypertension or atrial fibrillation,

b skeletal muscle dysfunction or osteoporosis,

c depression or anxiety.

Abbreviations: IQR, interquartile range; min, minimum; max, maximum; n, patient number; SD, standard deviation; GOLD, Global Initiative for Chronic Obstructive Lung Disease.

Table 2 Qualitative assessment of patient treatment (first-line, over, under) within GOLD categories

Selected protocol, n (%)	GOLD A (n=661)	GOLD B (n=335)	GOLD C (n=212)	GOLD D (n=402)	Total (n=1,610)
First-line treatment	40 (6.1)	29 (8.7)	39 (18.4)	319 (79.4)	427 (26.5)
Alternative treatment	94 (14.2)	21 (6.3)	4 (1.9)	12 (3.0)	131 (8.1)
Possible alternative treatment	0 (0.0)	7 (2.1)	9 (4.2)	9 (2.2)	25 (1.6)
All*	3 (0.5)	4 (1.2)	5 (2.4)	54 (13.4)	66 (4.1)
Over-treatment	496 (75.0)	265 (79.1)	150 (70.8)	0 (0.0)	911 (56.6)
Under-treatment	28 (4.2)	9 (2.7)	5 (2.4)	8 (2.0)	50 (3.1)

Notes:

* First-line/alternative/possible alternative treatment. Results are given n (% in GOLD sub-category).

Abbreviations: n, patient number; GOLD, Global Initiative for Chronic Obstructive Lung Disease.

Table 3 Treatment specifics within GOLD categories

All treatments	GOLD A (n=661)	GOLD B (n=335)	GOLD C (n=212)	GOLD D (n=402)	Total (n=1,610)
LABA	2.1	0.6	0.0	0.0	0.7
LAMA	10.0	8.7	2.4	3.2	6.1
LABA + LAMA	4.4	6.9	1.9	2.0	3.8
LABA + ICS	20.9	17.6	18.4	10.7	16.9
LABA + LAMA + ICS	49.5	61.2	70.3	78.9	65.0
LABA + PDE4-I	0.2	0.0	0.0	0.0	0.1
LAMA + PDE4-I	0.0	0.0	0.0	0.0	0.0
LABA + ICS + PDE4-I	0.2	0.3	0.5	1.0	0.5
SABA – SAMA	8.6	2.1	4.2	2.2	4.3
Others*	4.2	2.7	2.4	2.0	2.8
Total	100.0	100.0	100.0	100.0	100.0
Excluding PDE4-I
LABA	2.3	0.6	0.0	0.0	1.1
LAMA	10.0	8.7	2.4	3.2	7.0
LABA + LAMA	4.4	6.9	1.9	2.0	3.8
LABA + ICS	21.0	17.9	18.9	11.7	17.8
LABA + LAMA + ICS	49.5	61.2	70.3	78.9	62.0
SABA – SAMA	8.6	2.1	4.2	2.2	5.1
Others*	4.2	2.7	2.4	1.9	3.1
Total	100.0	100.0	100.0	100.0	100.0

Notes: Data are expressed as percent (%). Gray columns indicate inconsistency between reported and calculated values indicating less than recommended (light gray) or inappropriate (dark gray) use of selected treatment. Values in total column were calculated by arithmetic mean of results in each GOLD group.

* ICS monotherapy and no treatment were coded as others.

Abbreviations: SABA, short-acting beta-2 agonist; LABA, long acting beta-2 agonist, SAMA, short-acting muscarinic antagonist; LAMA, long-acting muscarinic antagonist; ICS, inhaled corticosteroid; PDE4-I, PDE4 inhibitors; GOLD, Global Initiative for Chronic Obstructive Lung Disease.

Table 4 Risk and symptom determinations by GOLD categories

		Total (n=1,610)	GOLD A (n=661)		GOLD B (n=335)	GOLD C (n=212)	GOLD D (n=402)
Symptom evaluation
mMRC per se		1,290 (80.1)	530 (41.1)		294 (22.8)	178 (13.8)	288 (22.3)
CAT per se		21 (1.3)	5 (23.8)		10 (47.6)	1 (4.8)	5 (23.8)
Both methods		299 (18.6)	126 (42.1)		31 (10.4)	33 (11.0)	109 (36.5)
Consistency of methods1		mMRC 0–1		mMRC ≥2		Total
CAT < 10		151 (95.0)		2(1.4)		153 (51.2)
CAT ≥ 10		8 (5.0)		138 (98.6)		146 (48.8)
Total		159 (100.0)		140 (100.0)		299 (100.0)
Kappa test		Coefficient: 0.993; P<0.0001
Exacerbation risk
FEV1 predicted classification		289 (18.9)	112 (38.8)		61 (21.1)	45 (15.6)	71 (24.6)
Exacerbation history		837 (52.0)	431 (51.5)		205 (24.5)	63 (7.5)	138 (16.5)
FEV1 classification + exacerbation history		484 (30.1)	118 (24.4)		69 (14.3)	104 (21.5)	193 (39.9)
Hospitalization within past 12 months	Yes	319 (19.8)	33 (10.3)		80 (25.1)	42 (13.2)	164 (51.4)
	No	1,286 (79.9)	623 (48.4)		255 (19.8)	170 (13.2)	238 (18.5)
	Missing	5	–		–	–	–
Consistency of methods2		FEV1 group 1–2		FEV1 group 3–4		Total
Exacerbation number 0–1		159 (88.8)		185 (60.7)		344 (71.1)
Exacerbation number ≥2		20 (11.2)		120 (39.3)		140 (28.9)
Total		179 (100.0)		305 (100.0)		484 (100.0)
Kappa test		Coefficient: 0.237; P<0.0001

Notes: Data are expressed as n (%). Only for patients for whom both methods of either symptom evaluation or exacerbation risk were used

1 n=299,

2 n=484.

Abbreviations: mMRC, Medical Research Council dyspnea scale; CAT, COPD assessment test; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; n, patient number.

Table 5 Reported by re-classified GOLD categories

Reported category	Re-classified category1
	GOLD A	GOLD B	GOLD C	GOLD D	CNC	Total
GOLD A	629 (95.2)	5 (0.8)	8 (1.2)	15 (2.3)	4 (0.6)	661 (41.1)
GOLD B	8 (2.4)	281 (83.9)	8 (2.4)	37 (11)	1 (0.3)	335 (20.8)
GOLD C	9 (4.2)	7 (3.3)	185 (87.3)	11 (5.2)	0 (0)	212 (13.2)
GOLD D	2 (0.5)	14 (3.5)	2 (0.5)	384 (95.5)	0 (0)	402 (25.0)
Total	648 (40.2)	307 (19.1)	203 (12.6)	447 (27.8)	5 (0.3)	1,610 (100)
Test for association	Gamma test (coefficient: 0.282; P<0.0001)
Consistency2
Reported as milder	0 (0)	5 (1.6)	16 (7.9)	63 (14.1)	–	84 (5.2)
Reported as more severe	19 (2.9)	21 (6.8)	2 (1.0)	0 (0)	–	42 (2.6)
Reported in agreement	629 (97.1)	281 (91.5)	185 (91.1)	384 (85.9)	–	1,479 (92.1)
Total	648 (100)	307 (100)	203 (100)	447 (100)	–	1,605 (100)

Notes:

1 If more than one method was reported for symptom evaluation or exacerbation risk, worst result is used for classification; n (% in reported GOLD category).

2 GOLD category was considered to be reported correctly if it was the same as the re-classified category, while it was considered to be milder (preceding categories, ie, if “A” is reported for the re-classified “B”) or vice versa (latter categories, ie, if “C” or “D” is reported for the re-classified “B”) in case of differences.

Abbreviations: n, patient number; CNC, could not be classified due to missing data; GOLD, Global Initiative for Chronic Obstructive Lung Disease.

Table S1 Criteria used for consistency of selected treatment protocols with GOLD recommendations for treatment in each category

Treatment protocol	GOLD A	GOLD B	GOLD C	GOLD D
ICS	Over-treatment	Over-treatment	Under-treatment	Under-treatment
LABA	Alternative	First-line	Under-treatment	Under-treatment
LABA + ICS	Over-treatment	Over-treatment	First-line	First-line
LABA + ICS + PDE4-I	Over-treatment	Over-treatment	Over-treatment	Alternative
LABA + ICS + Theophylline	Over-treatment	Over-treatment	First-line/alternative/possible alternative	First-line/alternative/possible alternative
LABA + LAMA	Over-treatment	Alternative	Alternative	Alternative
LABA + LAMA + ICS	Over-treatment	Over-treatment	Over-treatment	First-line
LABA + LAMA + ICS + PDE4-I	Over-treatment	Over-treatment	Over-treatment	Over-treatment
LABA + LAMA + ICS + Theophylline	Over-treatment	Over-treatment	Over-treatment	First-line/alternative/possible alternative
LABA + LAMA + Theophylline	Over-treatment	First-line/alternative/possible alternative	First-line/alternative/possible alternative	First-line/alternative/possible alternative
LABA + PDE4-I	Over-treatment	Over-treatment	Alternative	Under-treatment
LAMA	Alternative	First-line	First-line	First-line
LAMA + Theophylline	First-line/alternative/possible alternative	First-line/alternative/possible alternative	First-line/alternative/possible alternative	First-line/alternative/possible alternative
No drug	Under-treatment	Under-treatment	Under-treatment	Under-treatment
SABA	First-line	Possible alternative	Possible alternative	Possible alternative
SABA + ICS	Over-treatment	Over-treatment	Under-treatment	Under-treatment
SABA + LABA	Alternative	First-line	Under-treatment	Under-treatment
SABA + LABA + ICS	Over-treatment	Over-treatment	First-line	First-line
SABA + LABA + ICS + Theophylline	Over-treatment	Over-treatment	First-line/alternative/possible alternative	First-line/alternative/possible alternative
SABA + LABA + LAMA	Over-treatment	Alternative	Alternative	Alternative
SABA + LABA + LAMA + ICS	Over-treatment	Over-treatment	Over-treatment	First-line
SABA + LABA + LAMA + ICS + Theophylline	Over-treatment	Over-treatment	Over-treatment	First-line/alternative/possible alternative
SABA + LABA + LAMA + Theophylline	Over-treatment	First-line/alternative/possible alternative	First-line/alternative/possible alternative	First-line/alternative/possible alternative
SABA + LAMA	Alternative	First-line	First-line	First-line
SABA + LAMA + Theophylline	First-line/alternative/possible alternative	First-line/alternative/possible alternative	First-line/alternative/possible alternative	First-line/alternative/possible alternative
SABA + SAMA	Alternative	Possible alternative	Possible alternative	Possible alternative
SABA + SAMA + ICS	Over-treatment	Over-treatment	Under-treatment	Under-treatment
SABA + SAMA + ICS + Theophylline	Over-treatment	Over-treatment	Under-treatment	Under-treatment
SABA + SAMA + LABA	Alternative	First-line	Under-treatment	Under-treatment
SABA + SAMA + LABA + ICS	Over-treatment	Over-treatment	First-line	First-line
SABA + SAMA + LABA + ICS + Theophylline	Over-treatment	Over-treatment	First-line/alternative/possible alternative	First-line/alternative/possible alternative
SABA + SAMA + LABA + LAMA	Over-treatment	Alternative	Alternative	Alternative
SABA + SAMA + LABA + LAMA + ICS	Over-treatment	Over-treatment	Over-treatment	First-line
SABA + SAMA + LABA + LAMA + ICS + Theophylline	Over-treatment	Over-treatment	Over-treatment	First-line/alternative/possible alternative
SABA + SAMA + LABA + LAMA + Theophylline	Over-treatment	First-line/alternative/possible alternative	First-line/alternative/possible alternative	First-line/alternative/possible alternative
SABA + SAMA + LAMA	Alternative	First-line	First-line	First-line
SABA + SAMA + LAMA + PDE4-I	Over-treatment	Over-treatment	Alternative	Alternative
SABA + SAMA + LAMA + Theophylline	First-line/alternative/possible alternative	First-line/alternative/possible alternative	First-line/alternative/possible alternative	First-line/alternative/possible alternative
SABA + SAMA + Theophylline	First-line/alternative/possible alternative	Possible alternative	Possible alternative	Possible alternative
SAMA	First-line	Possible alternative	Possible alternative	Possible alternative
SAMA + LABA	Alternative	First-line	Under-treatment	Under-treatment
SAMA + LABA + ICS	Over-treatment	Over-treatment	First-line	First-line
SAMA + LABA + ICS + PDE4-I	Over-treatment	Over-treatment	Over-treatment	Alternative
SAMA + LABA + ICS + Theophylline	Over-treatment	Over-treatment	First-line/alternative/possible alternative	First-line/alternative/possible alternative
SAMA + LABA + LAMA	Over-treatment	Alternative	Alternative	Alternative
SAMA + LABA + LAMA + ICS	Over-treatment	Over-treatment	Over-treatment	First-line
SAMA + LABA + LAMA + ICS + Theophylline	Over-treatment	Over-treatment	Over-treatment	First-line/alternative/possible alternative
SAMA + LAMA	Alternative	First-line	First-line	First-line

Abbreviations: SABA, short-acting beta-2 agonist; LABA, long-acting beta-2 agonist; SAMA, short-acting muscarinic antagonist; LAMA, long-acting muscarinic antagonist; ICS, inhaled corticosteroid; PDE4-I, PDE4 inhibitors; GOLD, Global Initiative for Chronic Obstructive Lung Disease.