Characteristics of Patients with Chronic Obstructive Pulmonary Disease Treated with Long-Acting Bronchodilators in a Real-World Setting in Singapore: A Single-Center Observational Study

Figures & data

Figure 1 Study design for (A) the main analysis and (B) the sensitivity analysis.

Abbreviations: LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist.

Figure 2 Patient enrollment in (A) the main analysis and (B) the sensitivity analysis.

Abbreviations: CGH, Changi General Hospital; COPD, chronic obstructive pulmonary disease; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist.

Table 1 Baseline Characteristics

Characteristic	Main Analysis				Sensitivity Analysis
	All (N=261)	LAMA (N=73)	LAMA+LABA (N=188)	P-value	All (N=159)	LAMA (N=40)	LAMA+LABA (N=119)	P-value
Age, years, mean (SD)	72 (9.7)	72 (11.0)	72 (9.1)	0.96	71 (9.5)	71 (10.9)	72 (9.0)	0.61
Male, n (%)	239 (91.6)	66 (90.4)	173 (92.0)	0.68	147 (92.5)	37 (92.5)	110 (92.4)	0.99
Ethnicity, n (%)
Chinese	159 (60.9)	44 (60.3)	115 (61.2)	0.84	95 (59.7)	27 (67.5)	68 (57.1)	0.40
Malay	62 (23.8)	17 (23.3)	45 (23.9)		40 (25.2)	6 (15.0)	34 (28.6)
Indian	16 (6.1)	6 (8.2)	10 (5.3)		10 (6.3)	3 (7.5)	7 (5.9)
Other races	24 (9.2)	6 (8.2)	18 (9.6)		14 (8.8)	4 (10.0)	10 (8.4)
Smoking history,^a n (%)
Former smoker	96 (42.1)	25 (39.7)	71 (43.0)	0.78	54 (41.2)	14 (46.7)	40 (39.6)	0.34
Current smoker	115 (50.4)	34 (54.0)	81 (49.1)		66 (50.4)	15 (50.0)	51 (50.5)
Non-smoker	17 (7.5)	4 (6.3)	13 (7.9)		11 (8.4)	1 (3.3)	10 (9.9)
Unknown	33 (12.6)	10 (13.6)	23 (12.2)		28 (17.6)	10 (25.0)	18 (15.1)
BMI, median,^a kg/m^2 (IQR)	21.7 (19.0–25.1)	22.6 (20.2–26.3)	21.0 (18.6–24.3)	0.028	21.8 (19.7–25.1)	22.7 (20.6–27.0)	21.6 (19.5–24.3)	0.026
Known, n (%)	202 (77.4)	50 (68.5)	152 (80.9)		119 (74.8)	23 (57.5)	96 (80.7)
Unknown, n (%)	59 (22.6)	23 (31.5)	36 (19.1)		40 (25.2)	17 (42.5)	23 (19.3)
Moderate-to-severe exacerbation history^b
Baseline period, mean	0.51	0.38	0.56	0.058	0.66	0.35	0.76	0.009
≥1 in baseline period, n (%)	115 (44.1)	26 (35.6)	89 (47.3)	0.09	75 (47.2)	12 (30.0)	63 (52.9)	0.012
CAT score, median (IQR)	10 (6–15)	8 (4–12)	12 (8–17)	0.008	9 (6–14)	6 (2–11)	10 (7–14)	0.005
Known, n (%)	127 (48.7)	36 (49.3)	91 (48.4)		82 (51.6)	19 (47.5)	63 (52.9)
Unknown, n (%)	134 (51.3)	37 (50.7)	97 (51.6)		77 (48.4)	21 (52.5)	56 (47.1)
Lung function^a
Pre-bronchodilator FEV1, median, L (IQR)	1.49 (1.04–1.85)	1.68 (1.36–2.02)	1.31 (0.99–1.73)	0.001	1.37 (1.01–1.78)	1.64 (1.17–2.04)	1.31 (1.00–1.75)	0.09
Pre-bronchodilator FEV1, mean, L (95% CI)	1.49 (1.40–1.59)	1.73 (1.56–1.92)	1.41 (1.30–1.52)		1.46 (1.34–1.58)	1.64 (1.37–1.93)	1.41 (1.28–1.54)
Pre-bronchodilator FEV1% predicted, median (IQR)	61 (50–80)	73 (59–92)	59 (46–75)	<0.001	63 (49–80)	72 (54–93)	60 (47–77)	0.13
Pre-bronchodilator FEV1% predicted, mean (95% CI)	66 (62–70)	77 (70–85)	62 (58–66)		65 (61–70)	73 (61–84)	63 (58–68)
Known, n (%)	152 (58.2)	38 (52.1)	114 (60.6)		93 (58.5)	20 (50.0)	73 (61.3)
Unknown, n (%)	109 (41.8)	35 (47.9)	74 (39.4)		66 (41.5)	20 (50.0)	46 (38.7)
GOLD spirometric grade, n (%)
Grade 1 (FEV1 ≥80%)	40 (26.3)	16 (42.1)	24 (21.1)	0.022	24 (25.8)	7 (35.0)	17 (23.3)	0.58
Grade 2 (FEV1 ≥50–<80%)	75 (49.3)	19 (50.0)	56 (49.1)		42 (45.2)	9 (45.0)	33 (45.2)
Grade 3 (FEV1 ≥30–<50%)	33 (21.7)	3 (7.9)	30 (26.3)		24 (25.8)	4 (20.0)	20 (27.4)
Grade 4 (FEV1 <30%)	4 (2.6)	0 (0.0)	4 (3.5)		3 (3.2)	0 (0.0)	3 (4.1)
Unknown, n (%)	109 (41.7)	35 (47.9)	74 (39.3)		66 (41.5)	20 (50.0)	46 (38.6)
Blood eosinophil count, 10^9 cells/L, median (IQR)	0.100 (0.050–0.300)	0.125 (0.050–0.400)	0.100 (0.050–0.300)	0.15	0.100 (0.050–0.300)	0.125 (0.050–0.400)	0.100 (0.050–0.300)	0.42
Known, n (%)	242 (92.7)	66 (90.4)	176 (93.6)		152 (95.6)	38 (95.0)	114 (95.8)
Unknown, n (%)	19 (7.3)	7 (9.6)	12 (6.4)		7 (4.4)	2 (5.0)	5 (4.2)

Notes: ^aMost recent values before index date; ^bModerate-to-severe COPD-related exacerbations were defined as an inpatient hospitalization or emergency department visit with a COPD exacerbation diagnosis code in the primary diagnosis.

Abbreviations: BMI, body mass index; CAT, COPD Assessment Test; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IQR, interquartile range; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; SD, standard deviation.

Table 2 Prevalence of Comorbidities^a in the Study Population

	Main Analysis				Sensitivity Analysis
	All (N=261)	LAMA (N=73)	LAMA+LABA (N=188)	P value	All (N=159)	LAMA (N=40)	LAMA+LABA (N=119)	P value
Comorbidities, n (%)
Hypertension, uncomplicated	110 (42.1)	32 (43.8)	78 (41.5)	0.73	67 (42.1)	18 (45.0)	49 (41.2)	0.67
Hyperlipidemia	62 (23.8)	19 (26.0)	43 (22.9)	0.59	42 (26.4)	11 (32.5)	31 (26.1)	0.86
Ischemic heart disease	96 (36.4)	26 (35.6)	69 (36.7)	0.87	54 (34.0)	13 (32.5)	41 (34.5)	0.82
Heart failure	47 (18.0)	13 (17.8)	34 (18.1)	0.96	26 (16.4)	5 (12.5)	21 (17.6)	0.45
Diabetes, complicated	57 (21.8)	19 (26.0)	38 (20.2)	0.31	37 (23.3)	8 (20.0)	29 (24.4)	0.57
Diabetes, uncomplicated	27 (10.3)	7 (9.6)	20 (10.6)	0.80	18 (11.3)	3 (7.5)	15 (12.6)	0.38
Anxiety/depression	9 (3.4)	2 (2.7)	7 (3.7)	0.70	4 (2.5)	0 (0.0)	4 (3.4)	0.24
Chronic kidney disease	42 (16.1)	10 (13.7)	32 (17.0)	0.51	25 (15.7)	4 (10.0)	21 (17.6)	0.25
Asthma	15 (5.7)	4 (5.5)	11 (5.9)	0.91	10 (6.3)	3 (7.5)	7 (5.9)	0.72
Stroke/TIA	2 (0.8)	1 (1.4)	1 (0.5)	0.49	1 (0.6)	0 (0.0)	1 (0.8)	0.56
Bronchiectasis	24 (9.2)	5 (6.8)	19 (10.1)	0.41	17 (10.7)	3 (7.5)	14 (11.8)	0.45
Atrial fibrillation/arrhythmias	53 (20.3)	15 (20.5)	38 (20.2)	0.95	37 (23.3)	9 (22.5)	28 (23.5)	0.89
Pulmonary tuberculosis	4 (1.5)	1 (1.4)	3 (1.6)	0.89	4 (2.5)	1 (2.5)	3 (2.5)	0.99
Obstructive sleep apnea	7 (2.7)	1 (1.4)	6 (3.2)	0.41	5 (3.1)	1 (2.5)	4 (3.4)	0.79
Elixhauser comorbidity index, median (IQR)	8 (3–17)	8 (3–17)	8 (3–16)	0.40	8 (3–16)	7 (3–17)	8 (3–15)	0.66

Notes: ^aOnly comorbidities with ≥2% prevalence are shown.

Abbreviations: IQR, interquartile range; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; TIA, transient ischemic attack.

Table 3 Proportion of Patients with Clinical Worsening, a Moderate-to-Severe Exacerbation or a Change in Treatment by Index Maintenance Therapy

Patients, n (%)	Main Analysis			Sensitivity Analysis
	Overall (N=261)	LAMA (N=73)	LAMA+LABA (N=188)	Overall (N=159)	LAMA (N=40)	LAMA+LABA (N=119)
Clinical worsening^a	124 (47.5)	38 (52.0)	86 (45.7)	77 (48.4)	18 (45.0)	59 (49.6)
≥1 moderate-to-severe exacerbation	89 (34.1)	17 (23.3)	72 (38.3)	57 (35.8)	8 (20.0)	49 (41.2)
Change in treatment	31 (11.9)	19 (26.0)	12 (6.4)	18 (11.3)	9 (22.5)	9 (7.6)
≥1 moderate-to-severe exacerbation and  change in treatment^b	4 (1.5)	2 (2.7)	2 (1.1)	2 (1.3)	1 (2.5)	1 (0.8)

Notes: ^aClinical worsening was analyzed based on the first event (ie, a first moderate-to-severe exacerbation or a first change in treatment by index maintenance therapy, whichever occurred first). ^bOccurred on the same day.

Abbreviations: LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist.

Figure 3 Kaplan–Meier curves of time-to-clinical worsening for (A) the main analysis and (B) the sensitivity analysis.

Abbreviations: LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist.