Bronchodilators use in patients with COPD

Figures & data

Table 1 Demographic characteristics of bronchodilator initiators at baseline

	Bronchodilator initiators (N=4,387)
Age on the index dates, mean (SD)	61.18 (15.86)
Male, %	73.03
Years of index dates, %
2001–2003	47.71
2004–2006	27.70
2007–2010	24.60
Comorbidities, %
Hypertension	29.82
Hypertensive heart and renal disease	14.75
Ischemic heart disease/angina	18.37
Myocardial infarction	1.19
Coronary revascularization	0.75
Cardiac dysrhythmia	8.96
Atrial fibrillation	2.17
Congestive heart failure	5.65
Cerebrovascular disease	10.78
Ischemic/hemorrhagic stroke	8.00
Transient ischemic attack	1.69
Diabetes mellitus	15.14
Pneumonia, influenza, and acute bronchitis	35.74
Rheumatoid arthritis/osteoarthritis	18.28
Any cancer (except lung cancer)	6.38
Lung cancer	2.26
Depressive disorder	4.65
Resource utilization
Hospitalization, %	27.42
Hospitalization due to COPD episodes, %	6.86
Hospitalization due to cardiovascular episodesa, %	13.20
Number of outpatient visits, mean (SD)	24.38 (19.83)
Number of outpatient visits due to COPD episodes, mean (SD)	1.05 (2.49)
Number of outpatient visits due to cardiovascular episodesa, mean (SD)	4.43 (7.65)

Notes:

a Cardiovascular episodes included hypertension, hypertensive heart/renal disease, ischemic heart disease/angina, myocardial infarction, coronary revascularization, cardiac dysrhythmia, atrial fibrillation, congestive heart failure, cerebrovascular disease, ischemic/hemorrhagic stroke, and transient ischemic attack.

Figure 1 Flowchart of study cohort assembly.

Notes: ^aBronchodilators included oral and inhaled forms: 1) oral forms: xanthines and beta-2 agonists, 2) inhaled forms: short-acting beta-2 agonists (SABAs), short-acting muscarinic antagonists (SAMAs), long-acting beta-2 agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and fixed dose combinations of LABA and inhaled corticosteroids (ICS) (LABA/ICS FDCs).
Abbreviation: FDC, fixed dose combination.

Table 2 Number and proportion of bronchodilator prescriptions over 1 year in total bronchodilator initiators and stratified by the years of index dates

	Total initiators	Years of index dates
		2001–2003	2004–2006	2007–2010
Number of total bronchodilator prescriptions	21,235	11,162	5,712	4,451
Pattern of bronchodilator treatments
By medication classesa, %
Oral xanthines	62.63	65.70	61.71	56.12
Oral beta-2 agonists	47.54	50.07	47.99	40.62
SABAs	9.84	8.14	10.21	13.61
SAMAs	8.78	8.68	8.05	9.98
LABAs	1.14	2.02	0.26	0.04
LABA/ICS FDCs	4.41	2.54	4.69	8.76
LAMAs	2.23	0.01	2.12	7.93
By regimensb, %
Oral bronchodilators alone	80.79	83.77	81.92	71.89
Oral and inhaled bronchodilators in combination	7.82	4.80	7.39	15.95
Inhaled bronchodilators alone	11.39	11.43	10.70	12.15
Number of inhaled bronchodilator prescriptions	4,096	1,812	1,033	1,251
Pattern of inhaled bronchodilator treatments
By regimensb, %
Short-acting bronchodilators alone	61.62	71.85	61.76	46.68
Short-acting and long-acting bronchodilators in combination	31.23	21.03	30.78	46.36
Long-acting bronchodilators alone	7.15	7.12	7.45	6.95

Notes:

a Proportions added up to more than 100% because patients may receive multiple bronchodilators during the 1-year follow-up period.

b Proportions may not be equal to 100% due to rounding.

Abbreviations: FDCs, fixed dose combinations; LABAs, long-acting beta-2 agonists; LAMAs, long-acting muscarinic antagonists; SABAs, short-acting beta agonists; SAMAs, short-acting muscarinic antagonists; ICS, inhaled cortiocsteroids.

Table 3 Number and proportion of bronchodilator prescriptions over 1 year stratified by physician specialists

	Family medicine	Internal medicine except chest	Chest	Others
Number of total bronchodilator prescriptions	1,671	6,458	9,228	3,968
Pattern of bronchodilator treatments
By medication classesa, %
Oral xanthines	55.60	63.84	71.26	43.55
Oral beta-2 agonists	57.27	47.09	40.78	59.90
SABAs	5.63	7.77	11.00	12.27
SAMAs	2.69	5.36	12.35	8.62
LABAs	0.00	0.79	2.05	0.08
LABA/ICS FDCs	0.66	1.87	8.33	1.01
LAMAs	0.06	1.25	4.14	0.28
By regimensb, %
Oral bronchodilators alone	92.40	87.40	71.65	86.42
Oral and inhaled bronchodilators in combination	3.77	5.62	9.89	8.29
Inhaled bronchodilators alone	3.83	6.98	18.45	5.29
Number of inhaled bronchodilator prescriptions	127	814	2,616	539
Pattern of inhaled bronchodilator treatments
By regimensb, %
Short-acting bronchodilators alone	90.55	70.88	51.49	89.98
Short-acting and long-acting bronchodilators in combination	9.45	24.32	39.37	7.24
Long-acting bronchodilators alone	0.00	4.79	9.14	2.78

Notes:

a Proportions add up to more than 100% because patients may receive multiple bronchodilators during the 1-year follow-up period.

b Proportions may not be equal to 100% due to rounding.

Abbreviations: FDCs, fixed dose combinations; LABAs, long-acting beta-2 agonists; LAMAs, long-acting muscarinic antagonists; SABAs, short-acting beta agonists; SAMAs, short-acting muscarinic antagonists; ICS, inhaled corticosteroids.

Table 4 Number and proportion of bronchodilator prescriptions over 1 year stratified by hospital accreditation levels

	Primary care clinics	District hospitals	Metropolitan hospitals	Medical centers
Number of total bronchodilator prescriptions	4,188	4,448	6,668	6,021
Pattern of bronchodilator treatments
By medication classesa, %
Oral xanthines	43.46	64.14	67.41	69.56
Oral beta-2 agonists	67.77	47.98	43.21	37.95
SABAs	2.55	10.39	11.41	12.76
SAMAs	1.10	6.25	10.36	14.25
LABAs	0.00	0.36	1.14	2.51
LABA/ICS FDCs	1.19	2.34	4.66	7.91
LAMAs	1.03	1.33	1.92	4.07
By regimensb, %
Oral bronchodilators alone	95.06	84.42	79.45	69.67
Oral and inhaled bronchodilators in combination	2.27	6.65	8.01	12.34
Inhaled bronchodilators alone	2.67	8.93	12.54	17.99
Number of inhaled bronchodilator prescriptions	207	693	1,370	1,826
Pattern of inhaled bronchodilator treatments
By regimensb, %
Short-acting bronchodilators alone	56.04	75.76	64.01	55.09
Short-acting and long-acting bronchodilators in combination	40.10	17.89	27.96	37.73
Long-acting bronchodilators alone	3.86	6.35	8.03	7.17

Notes:

a Proportions add up to more than 100% because patients may receive multiple bronchodilators during the 1-year follow-up period.

b Proportions may not be equal to 100% due to rounding.

Abbreviations: FDCs, fixed dose combinations; LABAs, long-acting beta-2 agonists; LAMAs, long-acting muscarinic antagonists; SABAs, short-acting beta agonists; SAMAs, short-acting muscarinic antagonists; ICS, inhaled corticosteroids.

Table S1 Anatomical Therapeutic Chemical (ATC) classification system codes used to identify bronchodilator initiators

Medication class	Therapeutic chemicals	ATC codes	Marketing year in Taiwan
Oral bronchodilators
Oral beta-2 agonists	Salbutamol	R03CC02	1974
Oral beta-2 agonists	Terbutaline	R03CC03	1979
Oral beta-2 agonists	Fenoterol	R03CC04	1979
Oral beta-2 agonists	Hexoprenaline	R03CC05	1982
Oral beta-2 agonists	Procaterol	R03CC08	1985
Oral beta-2 agonists	Trimetoquinol	R03CC09	1975
Oral beta-2 agonists	Bambuterol	R03CC12	1993
Oral beta-2 agonists	Clenbuterol	R03CC13	1988
Oral beta-2 agonists	Formoterol	R03CC91	1993
Oral xanthines	Theophylline	R03DA04	1972
Oral xanthines	Aminophylline	R03DA05	1970
Inhaled short-acting bronchodilators
SABAs	Salbutamol	R03AC02	1989
SABAs	Terbutaline	R03AC03	1989
SABAs	Fenoterol	R03AC04	1992
SABAs	Hexoprenaline	R03AC06	1995
SAMAs	Ipratropium	R03BB01	1981
SABA/SAMA FDCsa	Fenoterol/Ipratropium	R03AK03	1986
SABA/SAMA FDCsa	Salbutamol/Ipratropium	R03AK04	2000
Inhaled long-acting bronchodilators
LABAs	Salmeterol	R03AC12	1996
LABAs	Formoterol	R03AC13	2000
LABAs	Procaterol	R03AC16	1989
LABAs	Indacaterol	R03AC18	2010
LAMAs	Tiotropium	R03BB04	2003
LABA/ICS FDCs	Salmeterol/Fluticasone	R03AK06	2001
LABA/ICS FDCs	Formoterol/Budesonide	R03AK07	2001

Notes:

a Prescriptions with SABA/SAMA FDCs were simultaneously assigned into use of SABAs and use of SAMAs.

Abbreviations: FDCs, fixed dose combinations; ICS, inhaled corticosteroids; LABAs, long-acting beta-2 agonists; LAMAs, long-acting muscarinic antagonists; SABAs, short-acting beta agonists; SAMAs, short-acting muscarinic antagonists.

Table S2 International Classification of Diseases, 9th Revision, Clinical modification (ICD-9-CM) diagnostic codes used to identify comorbidities among bronchodilator initiators at baseline

Comorbidities	ICD-9-CM codes
Hypertension	401
Hypertensive heart/renal disease	402–404
Ischemic heart disease/angina	411, 413, 414
Myocardial infarction	410, 412
Coronary revascularizationa	68023A, 68023B, 68024A, 68024B, 68025A, 68025B, 83064A1, 97901K, 97902A, 97903B, 97906K, 97907A, 97908B, 97911K, 97912A, 97913B, 97916K, 97917A, 97918B, 33076A, 33076B, 33077A, 33077B, 33078A, 33078B, 97511K, 97512A, 97513B, 97516K, 97517A, 97518B, 97521K, 97522A, 97523B
Cardiac dysrhythmia	427
Atrial fibrillation	427.3
Congestive heart failure	428
Cerebrovascular disease	433, 434, 436–438
Ischemic/hemorrhagic stroke	430–434, 436
Transient ischemic attack	435
Peripheral vascular disease	440.21, 443
Diabetes mellitus	250
Pneumonia, influenza, and acute bronchitis	480–487, 466
Rheumatoid arthritis/osteoarthritis	710, 714, 715, 720
Any cancer (except lung cancer)	140–161, 163–208
Lung cancer	162
Depressive disorder	296.2, 296.3, 298.0, 300.4, 309.0, 309.1, 293.83, 296.90, 309.28, 296.82, 311

Notes:

a Based on National Health Insurance service claims codes (http://www.nhi.gov.tw/query/query2.aspx?menu=20&menu_id=710&webdata_id=3633&WD_ID=900 accessed October, 2013).

Table S3 Device types of inhaled bronchodilators over 1 year in total bronchodilator initiators and stratified by the years of index dates

	Total initiators	Years of index dates
		2001–2003	2004–2006	2007–2010
Number of inhaled bronchodilator prescriptions	4,096	1,812	1,033	1,251
By devicesa, %
Nebulizers	22.73	17.05	24.78	29.26
Metered dose inhalers	55.44	69.37	51.31	38.69
Dry powder inhalers	30.10	20.86	32.91	41.17

Notes:

a Proportions added up to more than 100% because patients may receive multiple inhaled bronchodilators during the 1-year follow-up period.

Table S4 Use of bronchodilators and the association with hospitalization in the follow-up 1 year

	Total initiators (n=4,387)	Patients hospitalized (n=1,289)	Patients without hospitalization (n=3,098)	ORa (95% CI)
Use of bronchodilators, mean (SD)
Any bronchodilators	4.86 (5.14)	6.30 (6.14)	4.26 (4.54)	1.05 (1.03–1.06)
Oral bronchodilators	4.48 (4.96)	5.69 (5.89)	3.98 (4.43)	1.04 (1.03–1.06)
Oral xanthines	3.04 (4.20)	3.97 (5.07)	2.66 (3.72)	1.05 (1.03–1.06)
Oral beta-2 agonists	2.31 (3.67)	2.76 (4.14)	2.12 (3.44)	1.03 (1.01–1.05)
Inhaled bronchodilator	0.93 (2.28)	1.31 (2.79)	0.78 (2.03)	1.07 (1.03–1.09)
Short-acting	0.64 (1.76)	1.05 (2.34)	0.47 (1.43)	1.12 (1.08–1.17)
Long-acting	0.36 (1.52)	0.33 (1.50)	0.37 (1.52)	0.98 (0.94–1.03)
LABAs	0.06 (0.53)	0.05 (0.50)	0.06 (0.54)	1.03 (0.90–1.17)
LABA/ICS FDCs	0.21 (0.11)	0.20 (1.11)	0.22 (1.11)	0.98 (0.90–1.17)
LAMAs	0.11 (0.93)	0.11 (0.89)	0.11 (0.95)	0.98 (0.91–1.06)

Notes:

a Adjusted for age, male sex, index years, and comorbidities and resource utilization at baseline.

Abbreviations: CI, confidence interval; FDCs, fixed dose combinations; ICS, inhaled corticosteroids; LABAs, long-acting beta-2 agonists; LAMAs, long-acting muscarinic antagonists; OR, odds ratio.