Efficacy and safety of tiotropium bromide inhalation in symptomatic patients with chronic obstructive pulmonary disease: A multicenter, prospective, and observational study

Figures & data

Figure 1. Flow chart of study design.

Table 1. Baseline demographic and clinical characteristics.

Characteristics	In total (n = 378)	Subgroup 1			Subgroup 2
		GOLD B (n = 242)	GOLD D (n = 136)	*P value	TBI (n = 110)	Dual (n = 72)	Triple(n = 137)	Quadruple (n = 59)	#P value
Demography
Age, years	64.24 (63.10, 65.38)	63.63 (62.21, 65.05)	65.34 (63.41, 67.26)	0.157	62.74 (60.56, 64.92)	59.58 (57.03, 62.14)	68.58 (66.88, 70.29)	62.66 (59.86, 65.46)	<0.001
Male patients (%)	273 (72.2)	168 (69.4)	105 (77.2)	0.105	73 (66.4)	57 (79.2)	103 (75.2)	40 (67.8)	0.189
Smokers and ex-smokers (%)	247 (65.3)	152 (62.8)	95 (69.9)	0.167	67 (60.1)	55 (76.4)	86 (62.7)	39 (66.1)	0.155
Comorbidities
Total (%)	126 (33.3)	76 (31.4)	50 (36.8)	0.289	29 (26.4)	15 (20.8)	52 (38.0)	30 (50.8)	0.001
Cardiovascular diseases (%)	100 (26.5)	57 (23.6)	43 (31.6)	0.088	14 (12.8)	15 (20.8)	45 (32.8)	26 (44.1)	<0.001
Diabetes (%)	32 (8.5)	22 (9.1)	10 (7.4)	0.560	10 (9.0)	2 (2.8)	9 (6.6)	11 (18.6)	0.009
Bronchodilators utilization in the last year before enrollment
Total (%)	255 (67.5)	160 (66.1)	95 (69.9)	0.457	47 (42.8)	49 (68.1)	110 (80.3)	49 (83.1)	<0.001
Salmeterol/Fluticasone (%)	118 (31.2)	61 (25.2)	57 (41.9)	0.001	12 (10.0)	10 (13.9)	70 (51.0)	33 (55.9)	<0.001
Budesonide/Formoterol (%)	39 (10.3)	27 (11.2)	12 (8.8)	0.474	1 (0.9)	0 (0.0)	24 (17.5)	14 (11.9)	<0.001
Theophylline (%)	155 (41.0)	98 (40.5)	57 (41.9)	0.788	32 (29.1)	47 (65.3)	34 (24.8)	42 (71.1)	<0.001
CT scans
Emphysema	244 (64.6)	154 (63.6)	90 (66.2)	0.268	48 (42.8)	40 (55.6)	107 (78.1)	50 (84.7)	0.001
Non-emphysema	62 (16.4)	45 (18.6)	17 (12.5)		21 (19.1)	22 (30.6)	14 (0.1)	5 (8.5)
Not assigned	72 (19.0)	43 (17.8)	29 (21.3)		42 (38.2)	10 (13.9)	16 (11.7)	4 (6.8)

This table demonstrates the baseline information of participants in the study. The results were described as mean (95% confidence interval), or numbers (percentage). *P values indicatethe statistical differences between GOLD B group and GOLD D group while #P values suggestthe statistical differences among TBI group (patients had received TQSL alone during the follow-up), Dual group (patients had received TQSL + Theophylline during the follow-up), Triple group (patients had used TQSL + LABA + ICS during the follow-up), and Quadruple group (patients had used TQSL + LABA + ICS + Theophylline during the follow-up). GOLD B: patients with 0 or 1 moderate or severe exacerbations (not leading to hospital admission); GOLD D: patients with ≥ 2 moderate or severe exacerbations, or ≥ 1 leading to hospital admission.

Table 2. Main outcomes in patients with COPD.

Variables		In total (n = 378)	Subgroup 1		Subgroup 2
			GOLD B (n = 242)	GOLD D (n = 136)	TBI (n = 110)	Dual (n = 72)	Triple(n = 137)	Quadruple (n = 59)
Primary Outcomes
FEV1, liters	Visit 0	1.33 (1.27, 1.39)	1.53 (1.45, 1.61)	0.97 (0.91, 1.02)	1.30 (1.19, 1.41)	1.30 (1.17, 1.43)	1.42 (1.31, 1.53)	1.20 (1.05, 1.35)
	Visit 2	1.61 (1.53, 1.68)	1.77 (1.67, 1.86)	1.32 (1.22, 1.41)	1.71 (1.58, 1.83)	1.49 (1.37, 1.61)	1.66 (1.53, 1.80)	1.41 (1.22, 1.60)
	P value	<0.001	<0.001	<0.001	<0.001	0.030	0.006	0.076
FVC, liters	Visit 0	2.47 (2.38, 2.56)	2.56 (2.44, 2.69)	2.31 (2.20, 2.42)	2.44 (2.28, 2.60)	2.50 (2.32, 2.68)	2.60 (2.44, 2.77)	2.19 (1.96, 2.42)
	Visit 2	2.56 (2.47, 2.64)	2.61 (2.49, 2.73)	2.47 (2.36, 2.58)	2.55 (2.42, 2.68)	2.62 (2.46, 2.78)	2.63 (2.46, 2.80)	2.34 (2.10, 2.58)
	P value	<0.001	0.611	0.036	0.290	0.305	0.850	0.356
FEV1/FVC	Visit 0	0.53 (0.52, 0.54)	0.60 (0.59, 0.61)	0.41 (0.40, 0.42)	0.53 (0.51, 0.55)	0.52 (0.50, 054)	0.53 (0.51, 0.55)	0.54 (0.51, 0.57)
	Visit 2	0.62 (0.60, 0.63)	0.67 (0.66, 0.68)	0.52 (0.50, 0.54)	0.66 (0.64, 0.68)	0.57 (0.55, 0.59)	0.61 (0.59, 0.63)	0.59 (0.56, 0.62)
	P value	<0.001	<0.001	<0.001	<0.001	0.001	<0.001	0.030
Other Outcomes
CAT scores	Visit 0	26.56 (25.84, 27.28)	25.97 (25.05, 26.88)	27.63 (26.47, 28.78)	28.05 (26.73, 29.38)	25.43 (23.88, 26.98)	25.77 (24.51, 27.03)	27.00 (25.24, 28.76)
	Visit 2	16.28 (15.78, 16.77)	16.31 (15.65, 16.96)	16.22 (15.46, 17.00)	16.29 (15.46, 17.13)	15.58 (14.66, 16.51)	15.96 (15.01, 16.92)	17.83 (16.52, 19.14)
	P value	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

This table demonstrates lung function parameters and CAT scores in patients at the baseline (visit 0) and post-treatment (visit 2). All results are described as mean (95% confidence interval). P value shows the statistical difference between visit 0 and visit 2 in each group.

Figure 2. This figure presents the changes of main lung function parameters between pre-treatment and post-treatment in different groups.

Table 3. AECOPD reported during 3-month follow-up.

Acute Exacerbations	In total (n = 378)	Subgroups		*P value	Subgroup 2				#P value
		GOLD B (n = 242)	GOLD D (n = 136)		TBI (n = 110)	Dual (n = 72)	Triple(n = 137)	Quadruple (n = 59)
The number of AEs during the last year prior enrollment, mean (95% CI)	1.11 (1.03, 1.19)	0.97 (0.87, 1.06)	1.36 (1.24, 1.49)	< 0.001	1.00 (0.86, 1.14)	0.85 (0.64, 1.05)	1.23 (1.12, 1.35)	1.34 (1.14, 1.54)	0.001
The number of AEs during the 3-month follow-up, mean (95% CI)	0.53 (0.46, 0.61)	0.48 (0.38, 0.57)	0.63 (0.51, 0.76)	0.045	0.59 (0.45, 0.73)	0.25 (0.16, 0.42)	0.65 (0.51, 0.79)	0.44 (0.26, 0.62)	0.009
The total number of AEs during the 3-month follow-up	202	115	86	< 0.001	65	21	89	27	< 0.001
First month (% total AEs)	108(53.5)	57 (49.6)	51 (59.3)		36 (55.4)	13 (61.9)	44 (49.4)	15 (25.4)
Second month (%total AEs)	78 (38.6)	47 (40.9)	30 (34.9)		28 (43.1)	6 (28.6)	36 (40.4)	7 (11.9)
Third month (% total AEs)	16 (7.9)	11 (9.6)	5 (5.8)		1 (1.5)	2 (9.5)	9 (10.1)	5 (8.5)
Subtotal (% total^&)	149 (39.4)	81 (33.5)	68 (50.0)	0.002	50 (45.5)	18 (25.0)	60 (43.8)	21 (35.6)	0.012

This table demonstrates the AECOPD reported during 3-month follow-up. The results were described as mean (95% confidence interval), or numbers (percentage). *P values indicatethe statistical differences between GOLD B and GOLD D group while #P values suggest the statistical differences among TBI, Dual, Triple, and Quadruple group. & shows the percentage of patients who had acute exacerbations during the 3-month treatment to the total number of patients in each group.

Table 4. Multiple linear regression analysis for FEV₁/FVC changes and CAT changes.

Parameters	FEV1/FVC changes		CAT changes
	β	p-value	β	p-value
Age	−0.062	0.169	0.025		0.486
Sex	0.029	0.611	−0.002		0.964
Smoking status	−0.044	0.432	0.023		0.607
Emphysema	−0.020	0.671	−0.020		0.575
Comorbidities	−0.097	0.031	−0.099		0.005
Medicine history	−0.015	0.743	−0.068		0.069
Concomitant medication	−0.280	<0.001	−0.085		0.020
FEV1/FVC at the baseline	−0.142	0.067	0.050		0.415
CAT scores at the baseline	0.376	<0.001	0.726		<0.001
AE frequency	0.031	0.548	0.008		0.873
GOLD ABCD Assessment	−0.003	0.971	0.085		0.161

Figure 3. This figure presents the changes of CAT scores between pre-treatment and post-treatment in different groups.