Critical Error Frequency and the Impact of Training with Inhalers Commonly used for Maintenance Treatment in Chronic Obstructive Pulmonary Disease

Figures & data

Table 1 Single and Combination DPI Groups Enrolled in the Study

	Single-Inhaler Treatment Groups						Dual Inhaler Treatment Groups
Inhaled Medication Class	ICS/LABA			LAMA or LAMA/LABA			ICS/LABA plus LAMA
Primary DPI	ELLIPTA	Turbuhaler	DISKUS	ELLIPTA	HandiHaler	Breezhaler	ELLIPTA	Turbuhaler	DISKUS
	FF/VI	BUD/FOR	FP/SAL	UMEC/VI or UMEC	TIO	IND/GLY or GLY	FF/VI	BUD/FOR	FP/SAL
	(n=50)	(n=50)	(n=50)	(n=51)	(n=50)	(n=49)	(n=50)	(n=50)	(n=50)
Secondary DPI							ELLIPTA UMEC or HandiHaler TIO

Abbreviations: BUD, budesonide; DPI, dry-powder inhaler; FF, fluticasone furoate; FOR, formoterol; FP, fluticasone propionate; GLY, glycopyrronium; ICS, inhaled corticosteroid; IND, indacaterol; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; SAL, salmeterol; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

Table 2 Patient Demographics and Clinical Characteristics (ITT Population and per Prescribed Inhaler at Study Entry)

Characteristic	ELLIPTA FF/VI (n=50)	Turbuhaler BUD/FOR (n=50)	DISKUS FP/SAL (n=50)	ELLIPTA UMEC/VI or UMEC (n=51)	HandiHaler TIO (n=50)	Breezhaler IND/GLY or GLY (n=49)	ELLIPTA FF/VI plus LAMA (n=50)	Turbuhaler BUD/FOR plus LAMA (n=50)	DISKUS FP/SAL plus LAMA (n=50)	Total (ITT Population) (N=450)
Mean (SD) age, years	64.6 (10.24)	65.2 (11.43)	68.7 (10.67)	66.8 (8.93)	69.5 (9.95)	67.7 (10.01)	66.6 (8.44)	67.5 (8.21)	68.1 (9.16)	67.2 (9.75)
Male, n (%)	21 (42)	24 (48)	21 (42)	27 (53)	29 (58)	30 (61)	22 (44)	32 (64)	36 (72)	242 (54)
Mean (SD) BMI (kg/m^2)	27.1 (4.26)	28.1 (6.27)	27.0 (4.86)	28.0 (5.11)	25.7 (3.42)	25.9 (5.25)	26.8 (4.88)	26.8 (4.74)	27.8 (4.64)	27.0 (4.91)
Time since COPD diagnosis, n (%)
n	50	48	50	50	50	46	50	47	48	439
<6 months	0	0	0	0	0	1 (2)	1 (2)	0	0	2 (<1)
6 months to <10 years	34 (68)	30 (63)	26 (52)	34 (68)	37 (74)	32 (70)	29 (58)	34 (72)	26 (54)	282 (64)
10 years to <25 years	15 (30)	14 (29)	24 (48)	14 (28)	13 (26)	12 (26)	18 (36)	8 (17)	21 (44)	139 (32)
≥25 years	1 (2)	4 (8)	0	2 (4)	0	1 (2)	2 (4)	5 (11)	1 (2)	16 (4)
Number of moderate-to-severe COPD exacerbations in last 12 months, n (%)
0	36 (72)	40 (80)	37 (74)	39 (76)	38 (76)	31 (63)	26 (52)	29 (58)	24 (48)	300 (67)
1	12 (24)	7 (14)	7 (14)	7 (14)	11 (22)	13 (27)	15 (30)	8 (16)	13 (26)	93 (21)
≥2	2 (4)	3 (6)	6 (12)	5 (10)	1 (2)	5 (10)	9 (18)	13 (26)	13 (26)	57 (13)
Mean (SD) CAT score	14.7 (7.23)	15.8 (7.76)	17.5 (6.27)	16.7 (6.33)	16.0 (7.34)	16.7 (7.70)	18.2 (6.87)	17.3 (7.34)	16.9 (8.02)	16.6 (7.23)

Abbreviations: BMI, body mass index; BUD, budesonide; CAT, COPD Assessment Test; COPD, chronic obstructive pulmonary disease; FF, fluticasone furoate; FOR, formoterol; FP, fluticasone propionate; GLY, glycopyrronium; IND, indacaterol; ITT, intent-to-treat; LAMA, long-acting muscarinic antagonist; SAL, salmeterol; SD, standard deviation; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

Table 3 Percentage of Patients Making ≥1 Critical Error with their Prescribed DPI(s) at V1

DPI Group	Patients Making ≥1 Critical Error, n (%)	Patients Making No Critical Errors, n (%)	OR vs ELLIPTA (95% CI; P-value)
			Pre-Specified Analyses^a	Post-Hoc Sensitivity Analyses^b
ICS/LABA
ELLIPTA FF/VI (n=50)	5 (10)	45 (90)	‒	‒
Turbuhaler BUD/FOR (n=50)	20 (40)	30 (60)	4.66 (1.58–13.69; 0.005)	5.56 (1.93–16.01; 0.001)
DISKUS FP/SAL (n=50)	13 (26)	37 (74)	2.48 (0.80–7.63; 0.114)	2.98 (1.00^c–8.88; 0.050)
LAMA/LABA or LAMA only
ELLIPTA UMEC or UMEC/VI (n=51)	5 (10)	46 (90)	‒	‒
HandiHaler TIO (n=50)	17 (34)	33 (66)	3.49 (1.16–10.55; 0.026)	4.42 (1.52–12.83; 0.006)
Breezhaler IND/GLY or GLY (n=49)	16 (33)	33 (67)	3.94 (1.35–11.53; 0.012)	4.17 (1.42–12.18; 0.009)
ELLIPTA FF/VI alone vs ELLIPTA FF/VI plus LAMA (errors in primary DPI)
ELLIPTA FF/VI (n=50)	5 (10)	45 (90)	‒	‒
ELLIPTA FF/VI plus LAMA (n=50)	6 (12)	44 (88)	1.22 (0.36–4.15; 0.746)	1.21 (0.36–4.10; 0.761)
ELLIPTA FF/VI alone vs ELLIPTA FF/VI plus LAMA (errors in both DPIs considered)
ELLIPTA FF/VI (n=50)	5 (10)	45 (90)	‒	‒
ELLIPTA FF/VI plus LAMA (n=50)	11 (22)	39 (78)	2.50 (0.82–7.66; 0.108)	2.41 (0.79–7.33; 0.122)
ELLIPTA FF/VI alone vs any ICS/LABA plus LAMA combination (errors in primary DPI)
ELLIPTA FF/VI (n=50)	5 (10)	45 (90)	‒	‒
ELLIPTA FF/VI plus LAMA, and Turbuhaler BUD/FOR plus LAMA, and DISKUS FP/SAL plus LAMA (n=150)	38 (25)	112 (75)	2.29 (0.85–6.16; 0.100)	2.64 (0.99–7.02; 0.051)
Turbuhaler BUD/FOR plus Handihaler TIO, and DISKUS FP/SAL plus Handihaler TIO (n=99)	32 (32)	67 (68)	3.19 (1.13–9.00; 0.028)	3.96 (1.47–10.65; 0.006)
ELLIPTA FF/VI alone vs any ICS/LABA plus LAMA combination (errors in both DPIs considered)
ELLIPTA FF/VI (n=50)	5 (10)	45 (90)	‒	–
ELLIPTA FF/VI plus LAMA, and Turbuhaler BUD/FOR plus LAMA, and DISKUS FP/SAL plus LAMA (n=150)	61 (41)	89 (59)	4.89 (1.85–12.90; 0.001)	5.48 (2.11–14.28; <0.001)
Turbuhaler BUD/FOR plus Handihaler TIO, and DISKUS FP/SAL plus Handihaler TIO (n=99)	50 (51)	49 (49)	7.01 (2.51–19.54; <0.001)	8.43 (3.17–22.39; <0.001)
ELLIPTA FF/VI alone or plus LAMA vs other ICS/LABA DPIs alone or plus LAMA (errors in primary DPI)
ELLIPTA FF/VI, and ELLIPTA FF/VI plus LAMA (n=100)	11 (11)	89 (89)	‒	‒
Turbuhaler BUD/FOR, and Turbuhaler BUD/FOR plus LAMA (n=100)	39 (39)	61 (61)	3.99 (1.81–8.83; <0.001)	4.86 (2.34–10.08; <0.001)
DISKUS FP/SAL, and DISKUS FP/SAL plus LAMA (n=100)	26 (26)	74 (74)	2.18 (0.94–5.06; 0.069)	2.71 (1.27–5.76; 0.010)
ELLIPTA FF/VI alone or plus LAMA vs other ICS/LABA DPIs alone or plus LAMA (errors in both DPIs considered)
ELLIPTA FF/VI, and ELLIPTA FF/VI plus LAMA (n=100)	16 (16)	84 (84)	‒	‒
Turbuhaler BUD/FOR, and Turbuhaler BUD/FOR plus LAMA (n=100)	47 (47)	53 (53)	3.94 (1.86–8.34; <0.001)	4.73 (2.39–9.36; <0.001)
DISKUS FP/SAL, and DISKUS FP/SAL plus LAMA (n=100)	36 (36)	64 (64)	2.39 (1.09–5.26; 0.030)	2.96 (1.47–5.94; 0.002)

Notes: ^aPre-specified analyses were performed with the covariate of time on primary DPI included in the logistic regression model; ^bPost-hoc sensitivity analyses excluded the covariate of time on primary DPI from the model due to confounding with DPI type (ELLIPTA and Breezhaler users were more likely to have used their inhaler for a shorter time than Turbuhaler, DISKUS and HandiHaler users); ^cRounded from 0.999.

Abbreviations: BUD, budesonide; CI, confidence interval; DPI, dry-powder inhaler; FF, fluticasone furoate; FOR, formoterol; FP, fluticasone propionate; GLY, glycopyrronium; ICS, inhaled corticosteroid; IND, indacaterol; LABA, long acting β₂-agonist; LAMA, long-acting muscarinic antagonist; OR, odds ratio; SAL, salmeterol; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol; V1, Visit 1.

Figure 1 Percentage of patients making ≥1 critical error with the primary DPI at V1. LAMA represents ELLIPTA UMEC or HandiHaler TIO.

Abbreviations: BUD, budesonide; DPI, dry-powder inhaler; FF, fluticasone furoate; FOR, formoterol; FP, fluticasone propionate; GLY, glycopyrronium; IND, indacaterol; LAMA, long-acting muscarinic antagonist; SAL, salmeterol; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol; V1, Visit 1.

Table 4 Percentage of Patients Making ≥1 Critical Error with their Prescribed DPI(s) at V2

DPI Group	Patients Making ≥1 Critical Error, n (%)	Patients Making No Critical Errors, n (%)	OR vs ELLIPTA (95% CI; P-value)
			Pre-Specified Analyses^a	Post-Hoc Sensitivity Analyses^b
ICS/LABA
ELLIPTA FF/VI (n=50)	0	50 (100)	‒	‒
Turbuhaler BUD/FOR (n=48)	4 (8)	44 (92)	7.35 (0.41–132.14; 0.176)	10.21 (0.52–200.90; 0.126)
DISKUS FP/SAL (n=45)	5 (11)	40 (89)	9.30 (0.53–164.47; 0.128)	13.72 (0.72–263.13; 0.082)
LAMA/LABA or LAMA only
ELLIPTA UMEC or UMEC/VI (n=50)	0	50 (100)	‒	‒
HandiHaler TIO (n=47)	10 (21)	37 (79)	20.45 (1.19–351.61; 0.038)	28.28 (1.56–512.53; 0.024)
Breezhaler IND/GLY or GLY (n=47)	8 (17)	39 (83)	18.78 (1.13–311.67; 0.041)	21.74 (1.18–399.54; 0.038)
ELLIPTA FF/VI alone vs ELLIPTA FF/VI plus LAMA (errors in primary DPI)
ELLIPTA FF/VI (n=50)	0	50 (100)	‒	‒
ELLIPTA FF/VI plus LAMA (n=49)	3 (6)	46 (94)	8.87 (0.48–162.78; 0.141)	7.60 (0.37–155.76; 0.188)
ELLIPTA FF/VI alone vs ELLIPTA FF/VI plus LAMA (errors in both DPIs considered)
ELLIPTA FF/VI (n=50)	0	50 (100)	‒	‒
ELLIPTA FF/VI plus LAMA (n=49)	4 (8)	45 (92)	12.15 (0.68–216.82; 0.090)	9.99 (0.51–196.44; 0.130)
ELLIPTA FF/VI alone vs any ICS/LABA plus LAMA combination (errors in primary DPI)
ELLIPTA FF/VI (n=50)	0	50 (100)	‒	‒
ELLIPTA FF/VI plus LAMA, and Turbuhaler BUD/FOR plus LAMA, and DISKUS FP/SAL plus LAMA (n=144)	12 (8)	132 (92)	7.78 (0.49–124.12; 0.147)	9.79 (0.55–173.30; 0.120)
Turbuhaler BUD/FOR plus Handihaler TIO, and DISKUS FP/SAL plus Handihaler TIO (n=94)	8 (9)	86 (91)	6.16 (0.37–103.65; 0.207)	10.21 (0.56–185.88; 0.117)
ELLIPTA FF/VI alone vs any ICS/LABA plus LAMA combination (errors both DPIs considered)
ELLIPTA FF/VI (n=50)	0	50 (100)	‒	‒
ELLIPTA FF/VI plus LAMA, and Turbuhaler BUD/FOR plus LAMA, and DISKUS FP/SAL plus LAMA (n=144)	18 (13)	126 (88)	11.91 (0.75–188.21; 0.079)	15.06 (0.87–262.04; 0.063)
Turbuhaler BUD/FOR plus Handihaler TIO, and DISKUS FP/SAL plus Handihaler TIO (n=94)	13 (14)	81 (86)	10.21 (0.62–167.57; 0.104)	17.21 (0.97–304.03; 0.052)
ELLIPTA FF/VI alone or plus LAMA vs other ICS/LABA DPIs alone or plus LAMA (errors in primary DPI)
ELLIPTA FF/VI, and ELLIPTA FF/VI plus LAMA (n=99)	3 (3)	96 (97)	‒	‒
Turbuhaler BUD/FOR, and Turbuhaler BUD/FOR plus LAMA (n=97)	7 (7)	90 (93)	2.09 (0.38–11.39; 0.395)	3.20 (0.60–17.14; 0.175)
DISKUS FP/SAL, and DISKUS FP/SAL plus LAMA (n=91)	11 (12)	80 (88)	3.25 (0.61–17.24; 0.166)	5.41 (1.06–27.61; 0.042)
ELLIPTA FF/VI alone or plus LAMA vs other ICS/LABA DPIs alone or plus LAMA (errors in both DPIs considered)
ELLIPTA FF/VI and ELLIPTA FF/VI plus LAMA (n=99)	4 (4)	95 (96)	‒	‒
Turbuhaler BUD/FOR and Turbuhaler BUD/FOR plus LAMA (n=97)	11 (11)	86 (89)	2.67 (0.52–13.69; 0.239)	4.27 (0.85–21.49; 0.078)
DISKUS FP/SAL and DISKUS FP/SAL plus LAMA (n=91)	12 (13)	79 (87)	2.93 (0.57–15.13; 0.200)	5.13 (1.03–25.55; 0.046)

Notes: ^aPre-specified analyses were performed with the covariate of time on primary DPI included in the logistic regression model; ^bPost-hoc sensitivity analyses excluded the covariate of time on primary DPI from the model due to confounding with DPI type (ELLIPTA and Breezhaler users were more likely to have used their inhaler for a shorter time than Turbuhaler, DISKUS and HandiHaler users).

Abbreviations: BUD, budesonide; CI, confidence interval; DPI, dry-powder inhaler; FF, fluticasone furoate; FOR, formoterol; FP, fluticasone propionate; GLY, glycopyrronium; ICS, inhaled corticosteroid; IND, indacaterol; LABA, long acting β₂-agonist; LAMA, long-acting muscarinic antagonist; OR, odds ratio; SAL, salmeterol; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol; V2, Visit 2.

Figure 2 Percentage of patients making ≥1 critical error with the primary DPI at V2, 6 weeks after training. LAMA represents ELLIPTA UMEC or HandiHaler TIO.

Abbreviations: BUD, budesonide; DPI, dry-powder inhaler; FF, fluticasone furoate; FOR, formoterol; FP, fluticasone propionate; GLY, glycopyrronium; IND, indacaterol; LAMA, long-acting muscarinic antagonist; SAL, salmeterol; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol; V2, Visit 2.