Supplementary Table 3: Impact of disease symptoms and duration of illness on the humanistic burden in patients with
symptomatic COPD
Study name
Al Moamary 2012 [4]
Boros 2012 [7]
Cai 2013* [55]
Outcomes
Study group(s)
Cough: Yes
Cough: No
Shortness of breath: Yes
CAT score
Shortness of breath: No
Wheezing: Yes
Wheezing: No
Cough: Yes
Cough: No
Shortness of breath: Yes
CRQ-SAS: Dyspnoea
score
Shortness of breath: No
Wheezing: Yes
Wheezing: No
Cough: Yes
Cough: No
Shortness of breath: Yes
CRQ-SAS: Emotion score
Shortness of breath: No
Wheezing: Yes
Wheezing: No
Cough: Yes
Cough: No
Shortness of breath: Yes
CRQ-SAS: Fatigue score
Shortness of breath: No
Wheezing: Yes
Wheezing: No
Cough: Yes
Cough: No
Shortness of breath: Yes
CRQ-SAS: Mastery score
Shortness of breath: No
Wheezing: Yes
Wheezing: No
Patients with a history of exacerbations
VAS score
Patients without a history of exacerbations
Overall COPD; Both NT and EM symptoms
CAT score
Overall COPD; Either NT or EM symptoms
Overall COPD; Neither NT nor EM symptoms
Overall COPD; Both NT and EM symptoms
mMRC score
Overall COPD; Either NT or EM symptoms
Overall COPD; Neither NT nor EM symptoms
Study size (N)
Mean (SD)
Median (SE) [range] 95%CI
66
54
96
24
45
75
66
54
96
24
45
75
66
54
96
24
45
75
66
54
96
24
45
75
66
54
96
24
45
75
318
246
188
318
246
188
21.5 (7.5)
19.2 (7.7)
21.3 (7.5)
17 (7.5)
20.7 (8.2)
20.3 (7.4)
4.6 (1.7)
4.5 (1.5)
4.5 (1.6)
5.1 (1.5)
4.6 (1.7)
4.6 (1.5)
4.5 (1.3)
4.8 (1.2)
4.6 (1.2)
4.9 (1.1)
4.5 (1.3)
4.7 (1.1)
4.1 (1.4)
4.4 (1.2)
4.2 (1.3)
4.3 (1.3)
4 (1.4)
4.4 (1.2)
4.8 (1.6)
4.9 (1.3)
4.7 (1.5)
5.3 (1.3)
4.7 (1.6)
4.9 (1.4)
56.7 (18.9)
64.3 (21.6)
21.6
13.8
9.1
1.8
1.1
0.8
p=0.022 vs. control
p<0.01 for all groups
p<0.01 for all groups
Study name
Outcomes
SF-12: PCS score
SF-12: MCS score
CAT score
SF-12: PCS score
HEED study (Jones 2012)
[31]
SGRQ: Total score
Study group(s)
Overall COPD; Both NT and EM symptoms
Overall COPD; Either NT or EM symptoms
Overall COPD; Neither NT nor EM symptoms
Overall COPD; Both NT and EM symptoms
Overall COPD; Either NT or EM symptoms
Overall COPD; Neither NT nor EM symptoms
MRC 0
MRC 1
MRC 2
MRC 3
MRC 4
Group A: patients with low risk, less symptoms and CAT ≥10
Group B: patients with low risk, more symptoms and CAT ≥10
Group C: patients with high risk, less symptoms and CAT ≥10
Group D: patients with high risk, more symptoms and CAT ≥10
Group A: patients with low risk, less symptoms and mMRC ≥2
Group B: patients with low risk, more symptoms and mMRC ≥2
Group C: patients with high risk, less symptoms and mMRC ≥2
Group D: patients with high risk, more symptoms and mMRC ≥2
Group A: patients with low risk, less symptoms and mMRC ≥1
Group B: patients with low risk, more symptoms and mMRC ≥1
Group C: patients with high risk, less symptoms and mMRC ≥1
Group D: patients with high risk, more symptoms and mMRC ≥1
MRC 0
MRC 1
MRC 2
MRC 3
MRC 4
Group A: patients with low risk, less symptoms and CAT ≥10
Group B: patients with low risk, more symptoms and CAT ≥10
Group C: patients with high risk, less symptoms and CAT ≥10
Group D: patients with high risk, more symptoms and CAT ≥10
Group A: patients with low risk, less symptoms and mMRC ≥2
Group B: patients with low risk, more symptoms and mMRC ≥2
Group C: patients with high risk, less symptoms and mMRC ≥2
Group D: patients with high risk, more symptoms and mMRC ≥2
Group A: patients with low risk, less symptoms and mMRC ≥1
Group B: patients with low risk, more symptoms and mMRC ≥1
Group C: patients with high risk, less symptoms and mMRC ≥1
Group D: patients with high risk, more symptoms and mMRC ≥1
MRC 0
Study size (N)
Mean (SD)
173
146
118
173
146
118
344
604
427
271
79
147
348
165
1150
372
124
666
653
338
681
415
264
75
147
348
165
1150
372
124
666
653
313
38.1 (9.1)
40.7 (9.7)
45.3 (9.5)
49.5 (10.7)
54 (9.2)
52.9 (11)
11.7 (6.8)
15.7 (7)
20.5 (7.5)
23.5 (7.4)
27.3 (8.3)
46.7 (7.8)
38.7 (8.3)
45.1 (7.6)
35.1 (8.3)
43.2 (8.1)
34.8 (8)
40.3 (8)
32.3 (7.7)
45.7
38.9
43.4
35.2
44.5 (8.1)
39.8 (7.7)
35 (3.4)
30.5 (7.2)
26.1 (7.5)
19.5 (9.7)
41.6 (15.8)
24.2 (10.9)
51.9 (17.1)
30.5 (15.4)
48.3 (16.5)
38.6 (15.9)
58.1 (16.4)
24.7
40
31.8
51.1
28.5 (15.1)
Median (SE) [range] 95%CI
p<0.01 for all groups
95%CI: 45.4, 47.9
95%CI: 37.9, 39.6
95%CI: 43.9, 46.3
95%CI: 34.7, 35.6
95%CI: 42.3, 44
95%CI: 33.3, 36.2
95%CI: 39.7, 41
95%CI: 31.7, 32.9
95%CI: 44.4, 47
95%CI: 38, 39.8
95%CI: 42.3, 44.6
95%CI: 34.7, 35.7
95%CI: 17.8, 21.3
95%CI: 39.8, 43.3
95%CI: 22.5, 26
95%CI: 50.8, 52.9
95%CI: 28.8, 32.2
95%CI: 45.2, 51.4
95%CI: 37.3, 39.9
95%CI: 56.7, 59.4
95%CI: 22.3, 27.1
95%CI: 38.1, 41.9
95%CI: 29.5, 34
95%CI: 50, 52.2
-
Study name
Outcomes
FACIT-F score
Hens 2008 [26]
VAS score
SGRQ: Total score
SGRQ: Symptoms score
Jove 2012 [32]
SGRQ: Impact score
SGRQ: Activity score
Study group(s)
MRC 1
MRC 2
MRC 3
MRC 4
Group A: patients with low risk, less symptoms and CAT ≥10
Group B: patients with low risk, more symptoms and CAT ≥10
Group C: patients with high risk, less symptoms and CAT ≥10
Group D: patients with high risk, more symptoms and CAT ≥10
Group A: patients with low risk, less symptoms and mMRC ≥2
Group B: patients with low risk, more symptoms and mMRC ≥2
Group C: patients with high risk, less symptoms and mMRC ≥2
Group D: patients with high risk, more symptoms and mMRC ≥2
Group A: patients with low risk, less symptoms and mMRC ≥1
Group B: patients with low risk, more symptoms and mMRC ≥1
Group C: patients with high risk, less symptoms and mMRC ≥1
Group D: patients with high risk, more symptoms and mMRC ≥1
Nasal symptoms: Nasal obstruction
Nasal symptoms: Nasal discharge
Nasal symptoms: Headache
Nasal symptoms: Sneezing
Nasal symptoms: Itchy nose or eyes
Overall COPD: MRC 0
Overall COPD: MRC 1
Overall COPD: MRC 2
Overall COPD: MRC 3
Overall COPD: MRC 4
Overall COPD: MRC 0
Overall COPD: MRC 1
Overall COPD: MRC 2
Overall COPD: MRC 3
Overall COPD: MRC 4
Overall COPD: MRC 0
Overall COPD: MRC 1
Overall COPD: MRC 2
Overall COPD: MRC 3
Overall COPD: MRC 4
Overall COPD: MRC 0
Overall COPD: MRC 1
Overall COPD: MRC 2
Overall COPD: MRC 3
Overall COPD: MRC 4
Study size (N)
Mean (SD)
Median (SE) [range] 95%CI
610
388
243
73
147
348
165
1150
372
124
666
653
31
31
31
31
31
8
27
38
28
6
8
27
38
28
6
8
27
38
28
6
8
27
38
28
6
39.4 (15.5)
50.5 (15.8)
61.1 (13.8)
73.3 (14.5)
45.8
35.3
44.5
31.3
40.5
31.8
38
27.9
42.4
36.5
40.4
31.8
1.65
2.09
2
1.89
1.78
22.3 (13.2)
33.9 (11.9)
44.8 (14.2)
58.1 (13.3)
73 (15.4)
31.7 (18.2)
42.2 (19.3)
52.8 (19.2)
54.4 (19.2)
72.6 (15.9)
14.9 (9.8)
23 (12.3)
36.5 (17.1)
46 (14.7)
62.4 (20.5)
30.4 (22.5)
44.5 (14.6)
60.8 (16.4)
78.3 (16.1)
88.4 (11.3)
95%CI: 44.9, 46.6
95%CI: 34.2, 36.4
95%CI: 43.4, 45.6
95%CI: 30.7, 32
95%CI: 39.6, 41.5
95%CI: 29.9, 33.7
95%CI: 37.3, 38.7
95%CI: 27, 28.8
95%CI: 41.1, 43.8
95%CI: 35.4, 37.6
95%CI: 39.1, 41.7
95%CI: 31.1, 32.5
(0.47)
(0.49)
(0.52)
(0.43)
(0.45)
p=0.001 for all MRC grades
p=0.001 for all MRC grades
p=0.001 for all MRC grades
p=0.001 for all MRC grades
Study name
Outcomes
BDQ score
Mollaoglu 2011[25]
VAS-F: Fatigue score
VAS-F: Energy score
Study group(s)
Dyspnoea: Mild
Dyspnoea: Moderate
Dyspnoea: Severe
Fatigue: Mild
Fatigue: Moderate
Fatigue: Severe
Cough: Mild
Cough: Moderate
Cough: Severe
Sputum: Mild
Sputum: Moderate
Sputum: Severe
Disability: None
Disability: Mild
Disability: Moderate
Disability: Severe
Dyspnoea: Mild
Dyspnoea: Moderate
Dyspnoea: Severe
Fatigue: Mild
Fatigue: Moderate
Fatigue: Severe
Cough: Mild
Cough: Moderate
Cough: Severe
Sputum: Mild
Sputum: Moderate
Sputum: Severe
Disability: None
Disability: Mild
Disability: Moderate
Disability: Severe
Dyspnoea: Mild
Dyspnoea: Moderate
Dyspnoea: Severe
Fatigue: Mild
Fatigue: Moderate
Fatigue: Severe
Cough: Mild
Cough: Moderate
Cough: Severe
Study size (N)
Mean (SD)
Median (SE) [range] 95%CI
18
39
41
20
38
40
27
41
30
32
35
31
18
39
41
20
18
39
41
20
38
40
27
41
30
32
35
31
18
39
41
20
38
40
27
41
30
13.16 (3.54)
13.25 (4.51)
16.68 (4.2)
10.57 (1.9)
13.9 (4.35)
15.98 (4.54)
12.21 (4.13)
14.43 (4.35)
16.93 (4.06)
11.84 (4.08)
15 (4.12)
16.84 (4.11)
13.16 (3.54)
13.25 (4.51)
16.68 (4.2)
10.57 (1.9)
74.21 (20.43)
79.2 (22.08)
86.2 (19.85)
56.29 (12.93)
78.46 (21.91)
88.16 (17.62)
73.25 (20.02)
82.05 (22.9)
87.03 (17.08)
72.88 (23.43)
82.38 (18.82)
85.42 (19.55)
49.9 (35)
50 (34.1)
77.6 (18.47)
85.77 (19.26)
21.74 (8.33)
18.05 (9.37)
15.49 (9.96)
24.71 (7.43)
19.08 (9)
14.95 (9.87)
20.68 (8.65)
18.62 (10.29)
13.63 (8.33)
-
Study name
Outcomes
OLIN-COPD study
(Stridsman 2013) [59]
FACIT-F score
Punekar 2007 [33]
EQ-5D score
SF-36: MCS score
SAPALDIA 2008 [8]
SF-36: PCS score
Voll-Aanerud 2008 [27]
SF-12: PCS score
Study group(s)
Sputum: Mild
Sputum: Moderate
Sputum: Severe
Disability: None
Disability: Mild
Disability: Moderate
Disability: Severe
COPD Patients: with respiratory symptoms
COPD patients: with respiratory symptoms Gold stage I
COPD patients: with respiratory symptoms Gold stage II
COPD patients: with respiratory symptoms Gold stage III/IV
PCP: No symptom
PCP: Day-time symptoms only
PCP: Night-time symptoms only
PCP: Day-time and Night-time symptoms only
RS: No symptom
RS: Day-time symptoms only
RS: Night-time symptoms only
RS: Day-time and Night-time symptoms only
PCP: Breathlessness after exercising heavily (MRC dyspnoea)
PCP: Breathlessness when hurrying on level ground (MRC
dyspnoea)
PCP: Walk slower than most people of same age (MRC dyspnoea)
PCP: Have to stop for breath even when walking on level ground
(MRC dyspnoea)
PCP: Too breathless to leave house (MRC dyspnoea)
RS: Breathlessness after exercising heavily (MRC dyspnoea)
RS: Breathlessness when hurrying on level ground (MRC
dyspnoea)
RS: Walk slower than most people of same age (MRC dyspnoea)
RS: Have to stop for breath even when walking on level ground
(MRC dyspnoea)
RS: Too breathless to leave house (MRC dyspnoea)
Stage 1 COPD; No symptom
Stage 1 COPD; With symptom
Stage 2-4 COPD; No symptom
Stage 2-4 COPD; With symptom
Stage 1 COPD; No symptom
Stage 1 COPD; With symptom
Stage 2-4 COPD; No symptom
Stage 2-4 COPD; With symptom
No of respiratory symptom: 1
Study size (N)
Mean (SD)
Median (SE) [range] 95%CI
32
35
31
426
203
196
27
-
22.75 (9.04)
16.24 (9.19)
14.23 (8.78)
37 (16.97)
28 (14.14)
19.47 (7.02)
15.77 (9.71)
40.5 (9.7)
41.6 (9.1)
40.2 (9.5)
34 (12.8)
0.85
0.69
0.73
0.59
0.81
0.72
0.69
0.56
0.88
42 [IQR: 35, 49]
44 [IQR: 35, 49]
42 [IQR:35, 48]
37 [IQR: 24, 46]
95%CI: 0.83, 0.86
95%CI: 0.68, 0.72
95%CI: 0.65, 0.81
95%CI: 0.56, 0.61
95%CI: 0.79, 0.84
95%CI: 0.69, 0.74
95%CI: 0.58, 0.8
95%CI: 0.53, 0.59
95%CI: 0.86, 0.9
-
0.79
95%CI: 0.77, 0.81
-
0.71
95%CI: 0.68, 0.74
-
0.59
95%CI: 0.57, 0.62
-
0.17
0.88
95%CI: 0.11, 0.24
95%CI: 0.85, 0.9
-
0.79
95%CI: 0.77, 0.81
-
0.73
95%CI: 0.7, 0.76
-
0.6
95%CI: 0.58, 0.63
295
224
30
61
295
224
30
61
486
0.29
52.5 (7.6)
48.9 (10.1)
53.9 (6.3)
50.5 (9.8)
51.2 (8.2)
48.7 (10.8)
51.4 (4.4)
44.2 (12.1)
49.6 (8.8)
95%CI: 0.22, 0.35
-
Study name
Outcomes
Study group(s)
Study size (N)
Mean (SD)
Median (SE) [range] 95%CI
No of respiratory symptom: 2
313
48.2 (9.7)
No of respiratory symptom: 3
188
45.1 (10.4)
No of respiratory symptom: 4
127
42.1 (11.9)
No of respiratory symptom: 5
59
38.1 (11.4)
No of respiratory symptom: 6
31
34.7 (10.2)
Morning cough
583
45.6 (10.9)
Chronic cough
288
43.6 (11.6)
Phlegm cough
554
46.2 (10.8)
Wheeze
529
46.1 (10.6)
Dyspnoea attacks
349
43.1 (11.9)
Dyspnoea grade 2
378
39.7 (11.9)
No of respiratory symptom: 1
486
50.9 (8.5)
No of respiratory symptom: 2
313
48.8 (9.6)
No of respiratory symptom: 3
188
48.9 (10.6)
No of respiratory symptom: 4
127
47.2 (10.2)
No of respiratory symptom: 5
59
43.5 (10.4)
No of respiratory symptom: 6
31
44.2 (9.8)
SF-12: MCS score
Morning cough
583
48.5 (9.8)
Chronic cough
288
46.8 (10.9)
Phlegm cough
554
48.6 (10)
Wheeze
529
48.5 (9.9)
Dyspnoea attacks
349
47.1 (9.9)
Dyspnoea grade 2
378
47.3 (10.1)
*Represents primary studies which include secondary studies from which data was extracted and evaluated.
BDQ Brief Disability Questionnaire, CAT COPD Assessment Test, CI confidence interval, COPD chronic obstructive pulmonary disease, EM early morning, EQ-5D European Quality of Life Questionnaire5 Dimensional, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, MCS Mental Component Summary, mMRC modified Medical Research Council, MRC Medical Research Council, NT
night time, PCP primary care physician, PCS Physical Component Summary, RS respiratory specialist, SD standard deviation, SE standard error, SF Short Form survey, SGRQ St. George’s Respiratory
Questionnaire, VAS Visual Analogue Scale, VAS-F Visual Analogue Scale-Fatigue, vs. versus