Prescription Status and Clinical Outcomes of Methylxanthines and Leukotriene Receptor Antagonists in Mild-to-Moderate Chronic Obstructive Pulmonary Disease

Figures & data

Table 1 Baseline Characteristics of Study Population

	Total (N=2269)
Age, years	64.9 ± 10.0
Sex, male	1630 (71.8)
Body mass index, kg/m^2	23.6 ± 2.8
Smoking history
Never smoker	697 (30.7)
Current or ex-smoker	1572 (69.3)
Pack-years	21.0 ± 23.3
Previous pulmonary tuberculosis	285 (12.6)
Comorbidities
Hypertension	828 (36.5)
Diabetes mellitus	323 (14.2)
Asthma	191 (8.4)
Coronary heart disease	88 (3.9)
Depression	79 (3.5)
Stroke	64 (2.8)
Other allergic diseases	29 (1.3)
Baseline lung function test
FEV1, L	2.3 ± 0.6
FEV1, % predicted	78.8 ± 13.7
FVC, L	3.5 ± 0.9
FVC, % predicted	90.6 ± 13.6
FEV1/FVC ratio	0.6 ± 0.1
Severity of airflow limitation
FEV1% predicted ≥80	1037 (45.7)
65≤ FEV1% predicted <80	867 (38.2)
50≤ FEV1% predicted <65	365 (16.1)
EQ-5D index values	0.9 ± 0.2
Use of inhalers	139 (6.12)
LAMA	81 (3.6)
ICS/LABA	97 (4.3)
Use of oral methylxanthines/LTRA	279 (12.3)
Methylxanthines	255 (11.2)
LTRA	70 (3.1)

Note: Data are presented as n (%) or mean ± SD, unless otherwise stated.

Abbreviations: FEV₁, forced expiratory volume during the first second; FVC, forced volume vital capacity; EQ-5D, EuroQol-5 dimension; LAMA, long-acting anti-muscarinic agent; ICS/LABA, inhaled corticosteroid/long-acting β2-agonist; LTRA, leukotriene receptor antagonist.

Figure 1 Proportion of patients under medical treatments in the study population.

Abbreviations: LAMA, long-acting anti-muscarinic agent; ICS/LABA, inhaled corticosteroid/long-acting β2-agonist; LTRA, leukotriene receptor antagonist.

Table 2 Contributing Factors of Prescription of Oral Methylxanthines and LTRA in Mild-to-Moderate COPD

Dependent Variables	Methylxanthines		LTRA
	aOR (95% CI)*	P value	aOR (95% CI)*	P value
Age, years	1.02 (1.00–1.05)	0.075	1.01 (0.98–1.05)	0.472
Sex, male	1.64 (0.84–3.22)	0.149	0.65(0.27–1.56)	0.340
Body mass index, kg/m2	0.96 (0.89–1.04)	0.301	1.10 (0.99–1.22)	0.084
Smoking history
Never smoker	1 (ref)		1 (ref)
Current or ex-smoker	0.93 (0.48–1.78)	0.821	1.84 (0.77–4.42)	0.173
Comorbidities
Asthma	5.49 (1.61–18.7)	0.006	1.40 (0.5–3.92)	0.526
Allergic disease	2.38 (1.39–4.08)	0.002	1.93 (1.02–3.68)	0.045
Diabetes mellitus	0.72 (0.40–1.29)	0.271	0.60 (0.25–1.44)	0.256
Cardiovascular disease	0.91 (0.43–1.92)	0.796	1.06 (0.36–3.10)	0.921
Severity of airflow limitation
FEV1, % predicted ≥80	1 (ref)		1 (ref)
65≤ FEV1, % predicted <80	1.89 (1.17–3.05)	0.009	1.17 (0.56–2.46)	0.671
50≤ FEV1, % predicted <65	2.82(1.63–4.86)	<0.001	1.65 (0.79–3.45)	0.187
Quality of life
EQ-5D index values ≥0.9	1 (ref)		1 (ref)
EQ-5D index values <0.9	1.91 (1.24–2.93)	0.003	1.34(0.74–2.44)	0.338
Specialty of prescribing doctors
General practitioner vs specialist	9.32 (1.82–47.83)	0.008	0.43 (0.08–2.41)	0.335
Internal medicine vs non-internal medicine	25.78 (12.54–53.02)	<0.001	46.49 (9.5–227.63)	<0.001
Type of institution
2nd/3rd referral hospital	1 (ref)		1 (ref)
Private hospital	5.52 (3.04–10.04)	<0.001	0.92 (0.46–1.86)	0.821
Use of inhalers	0.94 (0.55–1.61)	0.828	4.87(2.53–9.40)	<0.001

Notes: Data are presented as n (%) or mean ± SD, unless otherwise stated. *Adjusted with age, sex, smoking history, and FEV₁% predicted.

Table 3 Hospital Utilization According to Use of Oral Methylxanthines and/or LTRA in Mild-to-Moderate COPD

Variables	Methylxanthines and/or LTRA User (n=279)	Methylxanthines and/or LTRA Non-User (n=1990)	P-value
Frequency of acute exacerbation, times/yr	0.4 ± 0.30	0.2 ± 0.15	<0.001
Total OPD visit	12.9 ± 20.20	4.9 ± 8.82	<0.001
OPD visit, times/yr	2.2 ± 3.37	0.8 ± 1.47	<0.001
ER visit, times/yr	0.2 ± 0.14	0.2 ± 0.06	0.044
Hospitalization, times/yr	0.3 ± 0.29	0.2 ± 0.15	<0.001
ICU, times/yr	0.2 ± 0.07	0.2 ± 0.0	0.083
Total used days	21.2 ± 27.92	13.2 ± 19.16	<0.001
Cost/year, USD	346,315.0 ± 671,806.1	370,182.0 ± 632,665.0	0.324

Abbreviations: OPD, outpatient department; ER, emergency room; ICU, intensive care unit; USD, United States dollar; yr, year.

Table 4 Dependent Factors for Annual Frequency of Acute Exacerbation in Patients with COPD

Variable	Univariate		Multivariate
	β ± SE	P-value	β ± SE	P-value
Age (years)	0.004 ± 0.002	0.032	0.001 ± 0.002	0.633
Male	0.005 ± 0.029	0.864	−0.004 ± 0.052	0.933
FEV1, %	−0.067 ± 0.024	0.005	−0.057 ± 0.037	0.126
Methylxanthines and/or LTRA use	0.122 ± 0.028	<0.001	0.053 ± 0.031	0.088
Current smoker	0.022 ± 0.029	0.445	0.046 ± 0.041	0.261
Use of inhalers	0.175 ± 0.032	<0.001	0.136 ± 0.035	<0.001
EQ-5D index	−0.033 ± 0.071	0.642	0.004 ± 0.069	0.959

Abbreviations: FEV₁, forced expiratory volume during the first second; LTRA, leukotriene receptor antagonist; EQ-5D, EuroQol-5 dimension.

Table 5 Dependent Factors for Annual Cost of Hospital Utilization in Mild-to-Moderate COPD

Variable	Univariate		Multivariate
	β ± SE	P value	β ± SE	P value
Age (years)	6427.3 ± 3126.2	0.040	5590.2 ± 365,835.8	0.125
Male	−42,299.1 ± 59,713.3	0.479	−89,850.4 ± 3637.6	0.393
FEV1, %	−93,114.3 ± 48,634.2	0.056	−27,653.4 ± 105,063.8	0.706
Methylxanthines and/or LTRA use	−23,867.0 ± 55,958.6	0.670	−107,942.0 ± 73,207.8	0.074
Current smoker	−396.4 ± 59,318.9	0.995	97,904.0 ± 60,241.2	0.265
Use of inhalers	197,035.9 ± 63,622.4	0.002	238,300.0 ± 87,799.2	<0.001
EQ-5D index	−229,727.0 ±152,189.9	0.132	−174,776.0 ± 68,257.7	0.264

Abbreviations: FEV₁, forced expiratory volume during the first second; LTRA, leukotriene receptor antagonist; EQ-5D, EuroQol-5 dimension.