Quality of life and adherence to inhaled corticosteroids and tiotropium in COPD are related

Figures & data

Table 1 Descriptive demographics for the study population at baseline who use ICS

Characteristics	Overall N=635	Optimal ≥75%–≤125% N=361	Suboptimal 50%–<75% N=120	Underuse <50% N=61	Overuse >125% N=93	P-value
Age in years, mean (SD)	67.1 (9.7)	67.5 (9.7)	66.4 (9.7)	65.6 (11.0)	67.4 (8.9)	0.414
Sex, number of males (%)	377 (59.4)	221 (61.2)	68 (56.7)	34 (55.7)	54 (58.1)	0.735
Smoking status, N (%)
Current smoker	176 (27.7)	91 (25.2)	27 (22.5)	23 (37.7)	35 (37.6)	0.016
Exsmoker	459 (72.3)	270 (74.8)	93 (77.5)	38 (62.3)	58 (62.4)
Pack-years, N (%)	38.3 (22.6)	38.4 (22.7)	39.8 (23.2)	36.6 (23.4)	36.8 (21.3)	0.743
Lung function*
FEV1 in liters, mean (SD)	1.4 (0.6)	1.4 (0.5)	1.4 (0.6)	1.4 (0.7)	1.2 (0.5)	0.047c
FEV1 predicted, mean (SD)	51.2 (18.4)	51.1 (18.0)	53.1 (19.6)	53.1 (20.3)	47.7 (16.9)	0.151
FEV1/VC ratio, mean (SD)	43.5 (13.3)	42.4 (12.6)	45.6 (13.8)	47.9 (16.1)	42.4 (12.6)	0.005b
COPD stage, N (%)**
GOLD I	38 (6.1)	23 (6.4)	6 (5.1)	4 (6.8)	5 (5.4)	0.498
GOLD II	270 (43.0)	154 (43.0)	58 (49.2)	26 (44.1)	32 (34.4)
GOLD III	254 (40.4)	147 (41.1)	38 (32.2)	23 (39.0)	46 (49.5)
GOLD IV	66 (10.5)	34 (9.5)	16 (13.6)	6 (10.2)	10 (10.8)
BMI, N (%)***
<22.0	101 (16.2)	48 (13.6)	22 (18.5)	13 (21.3)	18 (19.4)
≥22.0–<30	356 (57.0)	218 (61.9)	62 (52.1)	27 (44.3)	49 (52.7)	0.132
≥30.0	168 (26.9)	86 (24.4)	35 (29.4)	21 (34.4)	26 (28.0)
Exacerbations in the past year, N (%)
<2	407 (64.2)	235 (65.3)	72 (60.0)	47 (77.0)	53 (57.0)	0.055
≥2	227 (35.8)	125 (34.7)	48 (40.0)	14 (23.0)	40 (43.0)
≥1 Hospital admission, N (%)	93 (14.7)	39 (10.8)	30 (25.0)	10 (16.4)	14 (15.1)	0.002a
Comorbidities, N (%)
Heart failure	100 (15.8)	57 (15.8)	17 (14.2)	8 (13.1)	18 (19.4)	0.692
Ischemic heart disease	26 (4.1)	14 (3.9)	7 (5.8)	2 (3.3)	3 (3.2)	0.743
Diabetes mellitus	36 (5.7)	18 (5.0)	8 (6.7)	3 (4.9)	7 (7.5)	0.756
mMRC score, mean (SD)	1.80 (1.3)	1.69 (1.3)	1.99 (1.3)	1.96 (1.2)	1.93 (1.3)	0.073

Notes: After Holm–Bonferroni correction, there was a significant difference between optimal and

a suboptimal;

b underuse;

c between suboptimal and overuse.

* One missing lung function.

** Seven missing COPD stages.

*** Ten missing BMIs.

Abbreviations: ICS, inhaled corticosteroids; SD, standard deviation; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; VC, vital capacity; mMRC, modified Medical Research Council; BMI, body mass index.

Table 2 CCQ scores (range 1–6) per therapy adherence category for ICS users

CCQ Median (IQR)	Optimal N=332	Suboptimal N=111	Underuse N=53	Overuse N=83	P-value
CCQ-1	1.0 (0.0–2.0)	1.5 (0.0–2.0)	1.0 (0.0–3.0)	1.0 (0.0–3.0)	0.007a
CCQ-2	4.0 (2.0–6.0)	5.0 (3.0–6.0)	4.0 (2.0–6.0)	5.0 (3.0–6.0)	0.323
CCQ-3	0.0 (0.0–1.0)	0.0 (0.0–1.0)	0.0 (0.0–1.0)	0.0 (0.0–2.0)	0.015b
CCQ-4	0.0 (0.0–2.0)	0.0 (0.0–2.0)	0.0 (0.0–2.0)	0.0 (0.0–2.0)	0.399
CCQ-5	2.0 (1.0–3.0)	2.0 (1.0–3.0)	2.0 (1.0–3.0)	2.0 (2.0–3.0)	0.479
CCQ-6	2.0 (1.0–3.0)	2.0 (1.0–3.0)	2.0 (0.0–3.5)	2.0 (1.0–3.0)	0.589
CCQ-7	4.0 (2.0–5.0)	4.0 (2.0–6.0)	4.0 (3.0–6.0)	4.0 (3.0–6.0)	0.246
CCQ-8	2.5 (1.0–4.0)	3.0 (2.0–5.0)	3.0 (1.0–5.0)	3.0 (2.0–4.0)	0.083
CCQ-9	1.0 (0.0–3.0)	2.0 (0.0–4.0)	2.0 (0.0–3.0)	1.0 (0.0–3.0)	0.039a
CCQ-10	0.0 (0.0–2.0)	1.0 (0.0–3.0)	1.0 (0.0–2.0)	1.0 (0.0–3.0)	0.167
Domain 1 symptom*	2.45 (1.3)	2.52 (1.2)	2.47 (1.3)	2.56 (1.2)	0.868
Domain 2 function*	2.19 (1.5)	2.58 (1.6)	2.55 (1.4)	2.50 (1.6)	0.049c
Domain 3 mental	0.0 (0.0–1.0)	0.5 (0.0–1.5)	0.5 (0.0–1.5)	0.5 (0.0–2.0)	0.112
CCQ Total*	1.78 (1.0)	1.97 (1.1)	1.95 (0.9)	2.04 (1.1)	0.086

Notes:

* Mean (SD). After Holm–Bonferroni correction, there was a significant difference between optimal and

a suboptimal;

b overuse;

c no difference after correction.

Abbreviations: CCQ, Clinical COPD Questionnaire; ICS, inhaled corticosteroids; IQR, interquartile range; SD, standard deviation.

Table 3 EuroQol-5D scores (range 1–3) per therapy adherence category for ICS users

EuroQol-5D ICS	Optimal, n (%) N=337	Suboptimal, n (%) N=112	Underuse, n (%) N=53	Overuse, n (%) N=83	P-value
Mobility					0.383
1. I have no problems in walking about	114 (61.6)	32 (17.3)	16 (8.6)	23 (12.4)
2. I have some problems in walking about	219 (56.3)	76 (19.5)	37 (9.5)	57 (14.7)
3. I am confined to bed	4 (36.4)	4 (36.4)	0 (0.0)	3 (27.3)
Self-care					0.138
1. I have no problems with self-care	231 (61.3)	67 (17.8)	31 (8.2)	48 (12.7)
2. I have some problems with self-care	91 (53.5)	35 (20.6)	18 (10.6)	26 (15.3)
3. I am unable to wash or dress myself	15 (39.5)	10 (26.3)	4 (10.5)	9 (23.7)
Usual activities					0.375
1. I have no problems performing usual activities	144 (62.1)	39 (16.8)	17 (7.3)	32 (13.8)
2. I have some problems performing usual activities	164 (56.2)	56 (19.2)	30 (10.3)	42 (14.4)
3. I am unable to perform usual activities	29 (47.5)	17 (27.9)	6 (9.8)	9 (14.8)
Pain/discomfort					0.893
1. I have no pain or discomfort	159 (57.6)	51 (18.5)	22 (8.0)	44 (15.9)
2. I have moderate pain or discomfort	129 (57.3)	44 (19.6)	24 (10.7)	28 (12.4)
3. I have extreme pain or discomfort	49 (58.3)	17 (20.2)	7 (8.3)	11 (13.1)
Anxiety/depression					0.438
1. I am not anxious or depressed	252 (59.7)	79 (18.7)	33 (7.8)	58 (13.7)
2. I am moderately anxious or depressed	67 (50.8)	27 (20.5)	18 (13.6)	20 (15.2)
3. I am extremely anxious or depressed	17 (58.6)	5 (17.2)	2 (6.9)	5 (17.2)
Measuring scale (VAS)*	61.9 (16.3)	61.5 (15.6)	59.8 (14.4)	60.2 (14.9)	0.718

Notes:

* Mean (SD). Higher outcomes indicate more symptoms.

Abbreviations: ICS, inhaled corticosteroids; VAS, visual analogue scale (range 1–100); SD, standard deviation.

Table 4 Multinominal regression analysis of associated variables per therapy adherence category for ICS users

Variable	OR	95% CI	P-value
Suboptimal (≥50%–<75%)
N=112
FEV1 in liters	0.90	0.53–1.50	0.660
FEV1/VC ratio	1.03	1.00–1.05	0.024
CCQ-3	1.10	0.92–1.32	0.310
Smoker	0.78	0.46–1.32	0.351
Exsmoker	1.00
Hospital admission	2.67	1.48–4.80	0.001
No hospital admission	1.00
Underuse (<50%)
N=53
FEV1 in liters	0.62	0.31–1.26	0.186
FEV1/VC ratio	1.05	1.02–1.08	0.001
CCQ-3	0.94	0.71–1.23	0.645
Smoker	1.47	0.78–2.80	0.237
Exsmoker	1.00
Hospital admission	1.83	0.80–4.20	0.153
No hospital admission	1.00
Overuse (>125%)
N=83
FEV1 in liters	0.49	0.25–0.95	0.034
FEV1/VC ratio	1.02	0.99–1.04	0.221
CCQ-3	1.26	1.05–1.52	0.015
Smoker	1.73	1.02–2.91	0.040
Exsmoker	1.00
Hospital admission	1.43	0.69–2.93	0.336
No hospital admission	1.00

Abbreviations: ICS, inhaled corticosteroids; OR, odds ratio; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; CCQ, Clinical COPD Questionnaire; VC, vital capacity.

Table 5 Descriptive demographics for the study population at baseline who use tiotropium

Characteristics	Overall N=438	Good ≥75%–≤125% N=340	Suboptimal 50%–<75% N=48	Underuse <50% N=29	Overuse >125% N=21	P-value
Age in years, mean (SD)	65.5 (9.7)	65.9 (9.4)	64.4 (10.6)	62.9 (11.2)	65.8 (10.9)	0.366
Sex, number of men (%)	269 (61.4)	214 (62.9)	25 (52.1)	15 (51.7)	15 (71.4)	0.247
Smoking status, N (%)
Current smoker	130 (29.7)	99 (29.1)	10 (20.8)	13 (44.8)	8 (38.1)	0.124
Exsmoker	308 (70.3)	241 (70.9)	38 (79.2)	16 (55.2)	13 (61.9)
Pack-years, N (%)	39.3 (22.8)	37.8 (21.6)	44.5 (26.5)	42.4 (27.3)	45.2 (23.5)	0.138
Lung function
FEV1 in liters, mean (SD)	1.4 (0.6)	1.43 (0.6)	1.46 (0.5)	1.64 (0.7)	1.31 (0.6)	0.177
FEV1 predicted, mean (SD)	52.1 (17.9)	51.7 (17.6)	53.2 (16.7)	59.1 (21.6)	47.4 (17.9)	0.102
FEV1/VC ratio, mean (SD)	43.8 (13.1)	43.0 (12.6)	47.0 (13.4)	49.7 (16.6)	41.8 (12.2)	0.013a
COPD stage, N (%)*
GOLD I	29 (6.7)	21 (6.2)	2 (4.2)	4 (14.8)	2 (9.5)	0.617
GOLD II	191 (44.0)	148 (43.8)	24 (50)	13 (48.1)	6 (28.6)
GOLD III	175 (40.3)	139 (41.1)	17 (35.4)	8 (29.6)	11 (52.4)
GOLD IV	39 (9.0)	30 (8.9)	5 (10.4)	2 (7.4)	2 (9.5)
BMI**
<22.0	65 (15.1)	48 (14.4)	8 (16.7)	4 (13.8)	5 (23.8)	0.882
≥22.0–<30	254 (58.9)	198 (49.5)	26 (54.2)	19 (65.5)	11 (52.4)
≥30.0	112 (26.0)	87 (26.1)	14 (29.2)	6 (20.7)	5 (23.8)
Exacerbations in the past year, N (%)
<2	293 (66.9)	229 (67.4)	27 (56.3)	24 (82.8)	13 (61.9)	0.111
≥2	145 (33.1)	111 (32.6)	21 (43.8)	5 (17.2)	8 (38.1)
≥1 Hospital admission, N (%)	47 (10.7)	33 (9.7)	6 (12.5)	6 (20.7)	2 (9.5)	0.313
Comorbidities, N (%)
Heart failure	77 (17.6)	60 (17.6)	7 (14.6)	6 (20.7)	4 (19.0)	0.914
Ischemic heart disease	17 (3.9)	11 (3.2)	3 (6.3)	1 (3.4)	2 (9.5)	0.406
Diabetes mellitus	30 (6.8)	22 (6.5)	2 (4.2)	5 (17.2)	1 (4.8)	0.129
mMRC score, mean (SD)	1.69 (1.2)	1.60 (1.2)	1.87 (1.2)	2.12 (1.2)	2.16 (1.3)	0.041b

Notes: After Holm–Bonferroni correction, there was a significant difference between optimal and

a underuse;

b no difference after correction.

* Four missing COPD stages.

** Seven missing BMIs.

Abbreviations: SD, standard deviation; FEV₁, forced expiratory volume in 1 second; VC, vital capacity; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified Medical Research Council; BMI, body mass index.

Table 6 CCQ scores (range 1–6) per therapy adherence category for tiotropium users

CCQ Median (IQR)	Optimal N=320	Suboptimal N=45	Underuse N=26	Overuse N=19	P-value
CCQ-1	1.0 (0.0–2.0)	2.0 (0.0–2.5)	1.0 (0.0–4.0)	1.0 (0.0–3.0)	0.004a
CCQ-2	3.0 (2.0–6.0)	4.0 (2.0–6.0)	4.5 (2.75–6.0)	5.0 (3.0–6.0)	0.512
CCQ-3	0.0 (0.0–1.0)	0.0 (0.0–1.0)	1.0 (0.0–2.0)	0.0 (0.0–2.0)	0.003b
CCQ-4	0.0 (0.0–1.0)	0.0 (0.0–2.0)	0.5 (0.0–2.25)	0.0 (0.0–2.0)	0.225
CCQ-5	2.0 (1.0–3.0)	2.0 (1.0–3.0)	3.0 (1.75–4.0)	3.0 (2.0–5.0)	0.030d
CCQ-6	2.0 (0.0–3.0)	2.0 (0.5–3.0)	2.5 (1.0–5.0)	3.0 (2.0–5.0)	0.005c
CCQ-7	3.0 (2.0–5.0)	4.0 (2.0–6.0)	5.0 (2.75–6.0)	3.0 (3.0–5.0)	0.114
CCQ-8	2.0 (1.0–4.0)	3.0 (2.0–4.0)	3.0 (2.0–4.0)	3.0 (1.0–4.0)	0.316
CCQ-9	1.0 (0.0–2.0)	1.0 (0.0–3.0)	1.0 (0.0–3.25)	2.0 (0.0–5.0)	0.091
CCQ-10	0.0 (0.0–2.0)	1.0 (0.0–2.0)	1.0 (0.0–3.0)	0.0 (0.0–2.0)	0.154
Domain 1 symptom*	2.27 (1.2)	2.48 (1.3)	2.99 (1.6)	3.05 (1.4)	0.002b,c
Domain 2 function*	2.02 (1.4)	2.43 (1.4)	2.61 (1.7)	2.45 (1.5)	0.060
Domain 3 mental	0.0 (0.0–1.0)	0.5 (0.0–1.5)	1.0 (0.0–2.125)	0.0 (0.0–2.0)	0.064
CCQ Total*	1.64 (1.0)	1.93 (1.1)	2.28 (1.3)	2.23 (1.1)	0.001^2

Notes:

* Mean (SD). After Holm–Bonferroni correction there was a significant difference between optimal and

a suboptimal;

b underuse;

c overuse;

d no difference after correction.

Abbreviations: CCQ, Clinical COPD Questionnaire; IQR, interquartile range; SD, standard deviation.

Table 7 EuroQol-5D scores (range 1–3) per therapy adherence category for tiotropium users

EuroQol-5D Tiotropium	Optimal, n (%) N=323	Suboptimal, n (%) N=45	Underuse, n (%) N=26	Overuse, n (%) N=19	P-value
Mobility					0.042
1. I have no problems in walking about	126 (85.1)	9 (6.1)	6 (4.1)	7 (4.7)
2. I have some problems in walking about	194 (74.6)	35 (13.5)	20 (7.1)	11 (4.1)
3. I am confined to bed	3 (60.0)	1 (20.0)	0 (0.0)	1 (20.0)
Self-care					0.086
1. I have no problems with self-care	239 (81.3)	30 (10.2)	15 (5.1)	10 (3.4)
2. I have some problems with self-care	72 (72.0)	13 (13.0)	8 (8.0)	7 (7.0)
3. I am unable to wash or dress myself	12 (63.2)	2 (10.5)	3 (15.8)	2 (10.5)
Usual activities					0.002
1. I have no problems performing usual activities	154 (85.1)	13 (7.2)	7 (3.9)	7 (3.9)
2. I have some problems performing usual activities	152 (76.4)	25 (12.6)	14 (7.0)	8 (4.0)
3. I am unable to perform usual activities	17 (51.5)	7 (21.2)	5 (15.2)	4 (12.1)
Pain/discomfort					0.165
1. I have no pain or discomfort	153 (78.9)	21 (10.8)	10 (5.2)	10 (5.2)
2. I have moderate pain or discomfort	136 (81.9)	15 (9.0)	9 (5.4)	6 (3.6)
3. I have extreme pain or discomfort	34 (64.2)	9 (17.0)	7 (13.2)	3 (5.7)
Anxiety/depression					0.003
1. I am not anxious or depressed	255 (82.5)	29 (9.4)	14 (4.5)	11 (3.6)
2. I am moderately anxious or depressed	59 (67.0)	13 (14.8)	10 (11.4)	6 (6.8)
3. I am extremely anxious or depressed	7 (50.0)	3 (21.4)	2 (14.3)	2 (14.3)
Measuring scale (VAS)*	64.2 (15.6)	60.7 (13.5)	57.9 (17.8)	60.5 (18.0)	0.115

Notes:

* Mean (SD). Higher outcomes indicate more symptoms.

Abbreviations: VAS, visual analogue scale (range 1–100); SD, standard deviation.

Table 8 Multinominal regression analysis of associated variables per therapy adherence category for tiotropium users

Variable	OR	95% CI	P-value
Suboptimal (≥50%–<75%)
N=45
FEV1/VC ratio	1.03	1.01–1.06	0.015
CCQ-question 3	1.06	0.81–1.39	0.661
Usual activities score 1	1.00	–	–
Usual activities score 2	1.68	0.79–3.57	0.181
Usual activities score 3	3.09	0.95–10.06	0.061*
Underuse (<50%)
N=26
FEV1/VC ratio	1.04	1.01–1.07	0.018
CCQ-question 3	1.32	0.93–1.87	0.119
Usual activities score 1	1.00	–	–
Usual activities score 3	3.07	0.71–13.22	0.133
Overuse (>125%)
N=19
FEV1/VC ratio	0.99	0.96–1.03	0.633
CCQ-question 3	1.46	1.07–2.00	0.043
Usual activities score 1	1.00	–	–
Usual activities score 2	0.81	0.26–2.48	0.711
Usual activities score 3	3.29	0.70–15.53	0.133

Notes: Higher scores on usual activities indicate more symptoms.

* P-value was 0.049 when building the multivariate model.

Abbreviations: OR, odds ratio; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; VC, vital capacity; CCQ, Clinical COPD Questionnaire.