The importance of inhaler devices: the choice of inhaler device may lead to suboptimal adherence in COPD patients

Figures & data

Figure 1 Percentage of persistent patients at the third, sixth, 12th, and 18th months.

Abbreviations: pMDI, pressurized metered-dose inhaler; DPI, dry powder inhaler.

Figure 2 Medication persistence.

Abbreviations: pMDI, pressurized metered-dose inhaler; DPI, dry powder inhaler.

Figure 3 Percentage of adherent patients by each inhaler device (n=1,263).

Notes: Nonpersistent patient = patient who discontinued their therapy before the 18th month, persistent + nonadherent patient = patient who did not discontinue therapy but was <90% of the MPR, and adherent patient = patient who did not discontinue their therapy but was >90% of the MPR.
Abbreviations: pMDI, pressurized metered-dose inhaler; DPI, dry powder inhaler; MPR, medication possession ratio.

Table 1 Characteristics of COPD patients according to the type of inhaler device: DPI or pMDI

Characteristics	pMDI (n=492)	DPI (n=771)	Total (n=1,263)	P-value
Male (%)	38.95	61.04	83.45	0.735
Age, mean (SD) (years)	70.54 (10.37)	70.66 (9.91)	70.61	0.326
39–50	5.28	3.50	4.20	–
51–61	12.40	13.75	13.22	–
62–71	33.54	32.68	33.02	–
72–83	40.04	40.73	40.46	–
84–97	8.74	9.34	9.11	–
Retired status (%)	87.2	89.23	88.44	0.966
Time since COPD was diagnosed, mean (SD) (years)	15.0 (5.19)	15.44 (5.04)	15.38 (5.10)	0.994
Severity of COPD (%)
Mild	17.89	14.79	15.99	–
Moderate	77.85	80.80	79.65	–
Severe	4.27	4.41	4.35	–
FEV1, mean (SD)	76.6 (9.9)	79.1 (9.9)	79.2 (9.9)	0.256
ICS/LABA FDC (%)
Formoterol/beclomethasone	24.59	17.12	20.03	–
Formoterol/budesonide	0.0	51.88	31.67	–
Salmeterol/fluticasone	75.41	31.00	48.30	–
Exacerbations (%) (binary on whether patients suffered an exacerbation or not)	36.99	42.15	40.14	0.068
Moderate	31.5	36.96	34.84	<0.001
Acute	16.06	14.92	15.36	0.630
Comorbidities (%)
Obesity	38.62	40.86	39.98	0.650
Smoking	21.14	19.58	20.19	0.743
Alcoholism	6.91	6.10	6.41	0.891
Cerebrovascular disease	34.15	35.80	35.15	0.948
Hypertension	59.35	60.57	60.10	0.650
Diabetes	28.66	28.40	28.50	0.732
Dyslipidemia	52.44	49.68	50.75	0.518
Osteoarthritis	8.40	6.28	7.17	0.099
Arthritis	20.42	21.16	20.73	0.714
Stroke	23.78	25.42	24.78	0.510
Ischemic heart disease	16.06	15.30	15.60	0.948
Failures	25.20	27.11	26.37	0.987
Dementia	6.50	6.87	6.73	0.964
Depression	24.19	26.72	25.73	0.855
Neoplasm	16.26	17.12	16.79	0.846
Other medication to treat COPD (%)	84.76	84.95	84.88	–
Oral corticosteroids	8.54	8.17	8.31	0.856
Systemic antibiotics	2.7	7.0	5.9	<0.05
SABA	80.3	80.4	80.3	0.862
Short-acting anticholinergic	57.72	55.12	56.14	0.364
Number of visits to doctor, mean (SD)	18.99 (13.28)	21.99 (14.24)	20.82 (13.94)	<0.001
Average cost per month, mean (SD) (Euros)	64.95 (43.54)	62.75 (44.10)	63.60 (43.88)	0.3852
Mean of total health care cost per patient, mean (SD) (Euros)	1,920.99 (1,427.22)	2,013 (1,716.5)	1,977 (1,716.5)	0.3527

Note: Patients’ characteristics who visited their primary care center between January 2007 and June 2014.

Abbreviations: DPI, dry powder inhaler; pMDI, pressurized metered-dose inhaler; SD, standard deviation; FEV₁, forced expiratory volume in 1 second; ICS/LABA, inhaled corticosteroids and long-acting β₂-agonist; FDC, fixed-dose combination; COPD, chronic obstructive pulmonary disease; SABA, short-acting β₂-agonist.

Table 2 Univariate analysis of each potential confounders of adherence

Explanatory variables	Category	Adherence (n=1,263)
		Percentage points	Odds ratios	95% CI	P-value
Medical device DPI (baseline pMDI)		−7.85	0.72	0.583–0.8686	0.002
ICS/LABA FDC (baseline formoterol/beclometasone)	Formoterol/budesonide	−3.58	0.858	0.640–1.150	0.308
	Salmeterol/fluticasone	2.98	1.13	0.860–1.487	0.378
Therapy line (baseline first line)	Second line	16.55	1.96	1.363–2.814	0.000
	Third line	24.75	2.75	1.222–6.186	0.011
Age		−0.35	0.98	0.975–0.995	0.004
Sex (baseline men)		6.29	1.30	0.985–1.715	0.063
Retired status		−3.14	0.87	0.638–1.204	0.417
Obesity		4.61	1.21	0.985–1.493	0.069
Smoking		7.63	1.37	1.066–1.777	0.014
Stroke		−6.73	0.75	0.594–0.957	0.020
Cerebrovascular disease		−6.72	0.75	0.608–0.935	0.010
Hypertension		0.89	1.04	0.843–1.278	0.724
Diabetes		−1.80	0.93	0.738–1.164	0.517
Dislipemia		−1.89	0.92	0.753–1.133	0.448
Osteoarthritis		0.87	1.03	0.808–1.330	0.775
Arthritis		−0.31	0.98	0.654–1.489	0.951
Alcoholism		6.51	1.31	0.863–1.993	0.203
Ischemic cardiomyopathy		−0.83	0.96	0.730–1.277	0.807
Failures		2.89	1.12	0.895–1.421	0.306
Dementia		−9.18	0.68	0.446–1.309	0.075
Depression		−2.07	0.92	0.727–1.156	0.465
Neoplasm		3.93	1.17	0.896–1.548	0.239
Number of exacerbations		4.48	1.21	1.114–1.311	0.000
Number of severe exacerbations		−9.41	0.91	0.684–1.210	0.518
Number of mild/moderate exacerbations		5.77	1.28	1.165–1.403	0.000
Severity of COPD (baseline mild)	Moderate	4.80	1.23	0.930–1.619	0.148
	Severe	22.15	2.47	1.374–4.459	0.003
Time since COPD was diagnosed Other medication to treat COPD		−1.72	0.93	0.909–0.947	0.000
		5.66	1.27	1.181–1.375	0.000
	Oral corticosteroids	11.32	1.61	1.307–1.990	0.000
	Systemic antibiotics	14.83	1.87	1.444–2.430	0.000
	SABA	16.95	2.06	1.629–2.604	0.000
	Short acting anticholinergic	7.83	1.388	1.130–1.707	0.002
	Β2 Agonists (systemic)	6.82	1.33	0.903–1.956	0.149
Long acting anticholinergic agents		13.56	1.77	1.393–2.260	0.000
Cost		−0.25	0.98	0.986–0.991	0.000
Visits to doctor		0.41	1.017	1.009–1.25	0.000

Abbreviations: CI, confidence interval; DPI, dry powder inhaler; pMDI, pressurized metered-dose inhaler; ICS/LABA, inhaled corticosteroids and long-acting β₂-agonist; FDC, fixed-dose combination; COPD, chronic obstructive pulmonary disease; SABA, short-acting β₂-agonist.

Table 3 Multivariate results of potential confounders of adherence

Explanatory variables (McFadden’s R^2=0.0711)	Adherence (n=1,263)
	Without active ingredients			Controlling for active ingredients
	Percentage points	Odd ratios	95% CI	Percentage points	Odd ratios	95% CI
Medical device DPI (baseline pMDI)	−9.95*	0.60*	0.481–0.750	−9.57*	0.61*	0.467–0.802
ICS/LABA FDC (baseline formoterol/beclometasone)
Formoterol/budesonide	–	–	–	2.07	1.11	0.798–1.556
Salmeterol/fluticasone	–	–	–	3.37	1.19	0.893–1.586
Severity of COPD (baseline mild)
Persistent moderate	11.22*	1.91**	1.323–2.766	11.65*	1.89*	1.311–2.741
Persistent severe	7.08	1.49	0.645–3.484	6.74	1.47	0.632–3.426
Time since COPD was diagnosed	−1.15*	0.942	0.917–0.968	−1.14*	0.94*	0.918–0.968
Therapy line
Second	10.13**	1.637**	1.125–2.380	10.21**	1.64**	1.130 – 2.390
Third	20.45**	2.624**	1.077–6.361	20.14**	2.58*	1.063–6.305
Age	−0.11	0.994	0.979–1.009	−0.12	0.99	0.978–1.009
Sex	4.02	1.23	0.161–0.921	0.41	1.23	0.923–1.644
Obesity	2.12	1.11	0.894–1.391	1.94	1.10	0.885–1.379
Smoking	4.63	1.268	0.958–1.677	4.50	1.260	0.952–1.667
Stroke	−3.34	0.842	0.588–1.206	−3.21	0.848	0.592–1.214
Cerebrovascular disease	−3.84	0.821	0.551–1.222	−3.85	0.821	0.551–1.222
Exacerbations	−6.20**	0.72**	0.529–1.001	−6.57**	0.714**	0.517–0.984
Mild/moderate exacerbations	10.22**	1.69**	1.188–2.400	10.62**	1.72**	1.210–2.457
Long-acting anticholinergic agent	2.77	1.15	0.838–1.584	2.73	1.150	0.836–1.582
Pharmacological cost	−0.21*	0.989*	0.986–0.992	−0.21**	0.989**	0.986–0.992
Visits to doctor	0.24**	1.012**	1.004–1.021	0.24**	1.012**	1.004–1.021

Notes:

* P<0.001 and

** P<0.05.

Abbreviations: CI, confidence interval; DPI, dry powder inhaler; pMDI, pressurized metered-dose inhaler; ICS/LABA, inhaled corticosteroids and long-acting β₂-agonist; FDC, fixed-dose combination; COPD, chronic obstructive pulmonary disease.

Table 4 Final specification: results of multivariable analysis examining the associations between inhaler devices for ICS/LABA FDC and adherence

Explanatory variables (McFadden’s R^2=0.2898)	Adherence (n=1,263)
	Percentage points	Odds ratio	95% CI
Medical device DPI (baseline pMDI)	−5.38*	0.71*	0.521–0.970
ICS/LABA FDC (baseline formoterol/beclomethasone)
Formoterol/budesonide	−0.38	0.97	0.661–1.440
Salmeterol/fluticasone	3.07	0.72	0.241–2.174
Severity of COPD (baseline moderate)
Mild	−9.81*	0.53*	0.300–0.960
Severe	−5.15	0.72	0.241–2.174
Time since COPD was diagnosed	−0.78*	0.95*	0.923–0.981
Therapy line (baseline first line)
Second line	−1.27	0.92	0.603–1.413
Third line	1.69	1.11	0.437–2.823
Sex (baseline men)	3.01	1.21	0.816–1.782
Age (as a continuous variable)	−1.23**	0.96**	0.887–0.966
Age groups (baseline 87–97)
39–51	−34.04**	0.99*	0.169–0.578
51–61	−29.69**	0.13*	0.036–0.501
61–71	−23.04**	0.212*	0.081–0.552
72–83	−16.62**	0.32**	0.173–0.599
Retired status	5.05	1.37	0.736–2.563
Number of comorbidities
2	−0.74	0.95	0.662–1.374
3	−10.96*	0.49*	0.282–0.864
Obesity	6.26	1.47	0.975–2.231
Smoking	14.52*	2.248*	1.105–5.587
Smoking men	−28.73**	0.167**	0.034–0.800
Hypertension	6.29*	1.48*	1.085–2.018
Diabetes	5.00	1.36	0.981–1.902
Acute exacerbation	−8.36*	0.59*	0.378–0.933
Moderate exacerbation	2.20	1.14	0.914–1.438
Long-acting anticholinergic agents	5.23	1.37	0.928–2.050
Other medication to treat COPD	2.44	1.16	0.995–1.362
Additional visit to the doctor Visits to doctor	2.15**	1.14**	1.122–1.165
Two times per month (on average)	−33.88**	0.11**	0.797–0.165
Three times per month (on average)	−67.25**	0.0028**	0.009–0.007
Average pharmacological cost per month	0.04	1.00	0.999–1.006

Notes:

* P<0.05 and

** P<0.001.

Abbreviations: ICS/LABA, inhaled corticosteroids and long-acting β₂-agonist; FDC, fixed-dose combination; CI, confidence interval; DPI, dry powder inhaler; pMDI, pressurized metered-dose inhaler; COPD, chronic obstructive pulmonary disease.