Burden of Disease Among Exacerbating Patients with COPD Treated with Triple Therapy in Spain

Figures & data

Figure 1 Patient flow according to STROBE guide.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 1 Sociodemographic and Clinical Variables of COPD and Impact on the Quality of Life of Patients with Exacerbating COPD Treated with Triple Therapy

Variables	Total Sample N=306 (100.0%)	Eosinophils <150 Cells/µL N=149 (48.7%)	Eosinophils ≥ 150 Cells/µL N=157 (51.3%)	P-value^a
Sociodemographic variables
Age (years)
Mean (SD)	69.9 (9.2)	70.5 (9.0)	69.3 (9.4)	0.310
Sex - n (%)
Male	236 (77.1%)	114 (76.5%)	122 (77.7%)	0.910
Clinical features
BMI (kg/m^2)
Mean (SD)	27.5 (5.5)	27.4 (5.9)	27.6 (5.0)	0.465
Smoking – n (%)
Former smoker^b	243 (79.4%)	115 (77.2%)	128 (81.5%)	0.424
Current smoker	63 (20.6%)	34 (22.8%)	29 (18.5%)
Number of packs-year
Mean (SD)	54.8 (31.7)	54.6 (32.1)	55.0 (31.3)	0.936
Comorbidities – n (%)
Diabetes without target organ involvement	51 (16.7%)	20 (13.4%)	31 (19.7%)	0.184
Congestive heart failure	41 (13.4%)	21 (14.1%)	20 (12.7%)	0.857
Myocardial infarction	39 (12.7%)	18 (12.1%)	21 (13.4%)	0.866
Malignancies	28 (9.1%)	15 (10.1%)	13 (8.3%)	0.731
Kidney disease	27 (8.8%)	8 (5.4%)	19 (12.1%)	0.061
Peripheral vascular disease	23 (7.5%)	10 (6.7%)	13 (8.3%)	0.762
Other^c	74 (24.2%)	41 (27.5%)	33 (21.0%)	0.185
COPD features
Time from diagnosis (years)^d
Median (IQR)	8.0 [5.0–12.0]	8.0 [5.0–13.0]	8.0 [5.0–11.0]	0.565
Modified dyspnoea scale score (mMRC) - n (%)
Grade 0	8 (2.6%)	2 (1.3%)	6 (3.8%)	0.036
Grade 1	61 (19.9%)	21 (14.1%)	40 (25.5%)
Grade 2	124 (40.5%)	65 (43.6%)	59 (37.6%)
Grade 3	85 (27.8%)	43 (28.9%)	42 (26.7%)
Grade 4	28 (9.2%)	18 (12.1%)	10 (6.4%)
Post-bronchodilator FEV1(% predicted)
Mean (SD)	44.5 (16.4)	42.7 (15.6)	46.3 (17.0)	0.098
Post-bronchodilator FEV1/FVC (%)
Mean (SD)	46.9 (12.1)	45.6 (11.2)	48.2 (12.9)	0.055
Eosinophils (cells/µL)
Mean (SD)	217.9 (384.9)	61.3 (51.5)	366.6 (491.4)	<0.001
Impact of COPD on quality of life
Total CAT score
Mean (SD)	17.4 (8.5)	17.7 (8.3)	17.1 (8.7)	0.512
Low impact (CAT score ≤10)– n (%)	73 (24.0%)	30 (20.3%)	43 (27.6%)	0.328
Moderate impact (CAT score >10 and ≤20)– n (%)	121 (39.8%)	66 (44.6%)	55 (35.3%)
High impact (CAT score >20 and ≤30)– n (%)	82 (27.0%)	39 (26.3%)	43 (27.6%)
Very high impact (CAT score ≥30)– n (%)	28 (9.2%)	13 (8.8%)	15 (9.6%)
Utilities (EQ-5D-5L)
Mean (SD)	0.6 (0.3)	0.6 (0.3)	0.7 (0.3)	0.270
Number of exacerbations (patient/year)
Total exacerbations
Mean (SD)	2.5 (1.4)	2.5 (1.6)	2.5 (1.3)	0.421
Moderate exacerbations
Mean (SD)	1.5 (1.4)	1.2 (1.4)	1.7 (1.5)	0.001
Severe exacerbations
Mean (SD)	1.0 (1.1)	1.3 (1.2)	0.8 (0.9)	<0.001

Notes: ^a P-value between patients with eosinophils <150 cells/µL vs ≥ 150cells/µL. The chi-square test was used for dichotomous variables and the Mann–Whitney U-test for quantitative variables. ^b Ex-smoker: Former smoker who has not smoked for at least the last 6 months. ^c Others in the global population: Peptic ulcer (n-16), rheumatological disease (n-15), mild liver disease (n-14), cerebrovascular disease (n-10), diabetes with target organ involvement (n-7), acquired immunodeficiency syndrome (n- 4), moderate or severe liver disease (n- 3), hemiplegia or paraplegia (n-3), dementia (n-1), metastasis of solid tumours (n-1). ^d Until the inclusion visit.

Abbreviations: COPD, chronic obstructive pulmonary disease; BMI, body mass index; FVC, forced vital capacity; FEV₁, forced expiratory volume in the first second;SD, standard deviation; IQR, interquartile range.

Figure 2 Use of resources for COPD exacerbations (per patient) in patients with exacerbating COPD treated with triple therapy: total population and according to blood eosinophil levels (<150 cells/µL, ≥ 150 cells/µL).

Notes: ^a Statistical difference in hospital admission according to blood eosinophil levels (<150cells/µL, ≥ 150 cells/µL).

Abbreviations: COPD, chronic obstructive pulmonary disease; PC, primary care; SC, secondary care, ER, emergency room; SD, standard deviation.

Table 2 Use of Resources Due to Stable-Phase COPD (per Patient) in Patients with Exacerbating COPD Treated with Triple Therapy

Variables	Total Sample N=306 (100.0%)	Eosinophils <150 Cells/µL N=149 (48.7%)	Eosinophils ≥ 150 Cells/µL N=157 (51.3%)	P-value^a
Visits
Number of total visits
Mean (SD)	6.2 (4.2)	5.8 (3.8)	6.6 (4.5)	0.125
Number of PHC physician visits
Mean (SD)	3.7 (3.8)	3.3 (3.5)	4.1 (3.9)	0.037
Number of specialized medical visits ^b
Mean (SD)	2.5 (1.7)	2.5 (1.5)	2.5 (1.9)	0.492
Outpatient tests^c
Spirometries
Mean (SD)	1.3 (0.7)	1.3 (0.7)	1.4 (0.8)	0.348
Blood analyses
Mean (SD)	2.8 (3.8)	2.6 (3.4)	3.1 (4.2)	0.030
Chest X-rays
Mean (SD)	1.5 (1.8)	1.4 (1.5)	1.6 (2.1)	0.809
Bronchodilator tests
Mean (SD)	0.8 (0.8)	0.7 (0.7)	0.9 (0.8)	0.035
Arterial blood gases
Mean (SD)	1.0 (1.6)	1.0 (1.7)	0.9 (1.5)	0.188
Lung volumes and/or DLCO
Mean (SD)	0.02 (0.1)	0.03 (0.2)	0.01 (0.1)	0.374
6-minute walk test
Mean (SD)	0.3 (0.5)	0.2 (0.4)	0.3 (0.5)	0.535
Chest CT
Mean (SD)	0.2 (0.5)	0.3 (0.5)	0.2 (0.5)	0.875
FENO measurements
Mean (SD)	0.1 (0.4)	0.1 (0.4)	0.2 (0.5)	0.531
Non-pharmacological treatment
Influenza vaccination – n (%)	249 (81.4%)	119 (79.9%)	130 (82.8%)	0.608
Pneumococcal vaccination - n (%)	197 (64.4%)	94 (63.1%)	103 (65.6%)	0.734
Home oxygen – n (%)	102 (33.3%)	55 (36.9%)	47 (29.9%)	0.241
Respiratory rehabilitation – n (%)	22 (7.2%)	12 (8.0%)	10 (6.4%)	0.727
Non-invasive home ventilation - n (%)	20 (6.5%)	13 (8.7%)	7 (4.5%)	0.201
Drug treatment^d,e
LAMA – n (%)	217 (70.9%)	108 (72.5%)	109 (69.4%)	0.556
LABA/ICS – n (%)	214 (69.9%)	108 (72.5%)	106 (67.5%)	0.344
SABA – n (%)	122 (39.9%)	58 (38.9%)	64 (40.8%)	0.743
ICS – n (%)	94 (30.7%)	43 (28.9%)	51 (32.5%)	0.492
LABA/LAMA – n (%)	92 (30.1%)	42 (28.2%)	50 (31.8%)	0.485
Other airway agents – n (%)	43 (14.0%)	21 (14.1%)	22 (14.0%)	0.984

Notes: ^aP-value between patients with eosinophils <150 cells/µL vs ≥ 150 cells/µL. The chi-square test was used for dichotomous variables and the Mann–Whitney U-test for quantitative variables. ^bNot including inclusion visit. ^cOutpatient tests required by <5% of patients not shown. ^dTreatment prescribed in <10% of patients not shown. ^eCategories mutually non-exclusive.

Abbreviations: COPD, chronic obstructive pulmonary disease; PHC, primary healthcare; DLCO, lung diffusion capacity; CT, computed tomography; FE_NO, exhaled nitric oxide; SABA, short-acting inhaled adrenergic; LABA, long-acting β agonists; LAMA, long-acting muscarinic antagonist; ICS, inhaled corticosteroids; SD, standard deviation; IQR, interquartile range.

Table 3 Total Costs per Patient Due to COPD During the Last 12 Months in Patients with Exacerbating COPD Treated with Triple Therapy^a

Variables	Total Sample N= 306 (100.0%)	Eosinophils <150 Cells/µL N= 149 (48.7%)	Eosinophils ≥ 150 Cells/µL N= 157 (51.3%)	P-value^b
Direct health costs due to exacerbations
Cost of resource use in exacerbations (moderate and severe)	3273.8 (4353.6)	4324.2 (5080.2)	2276.9 (3243.2)	<0.001
Cost of resource use in moderate exacerbations	155.8 (240.9)	120.8 (171.6)	189.1 (288.5)	0.005
Pharmacological cost	42.9 (152.9)	25.4 (37.8)	59.6 (209.3)	0.001
Cost of PC visits	28.2 (37.9)	24.3 (35.6)	32.0 (39.7)	0.060
Cost of SC visits	16.7 (50.6)	15.7 (50.5)	17.7 (50.8)	0.811
Cost of emergency visits	68.0 (148.3)	55.4 (138.8)	79.9 (156.3)	0.096
Cost of resource use in severe exacerbations	3117.9 (4372.5)	4203.4 (5100.6)	2087.7 (3240.8)	<0.001
Pharmacological cost	526.2 (1071.4)	663.6 (1131.3)	395.8 (997.4)	<0.001
Cost of hospital admissions	2491.7 (3489.1)	3360.8 (4189.3)	1667.0 (2397.0)	<0.001
Cost of ICU stay	99.9 (659.9)	179.0 (884.7)	24.9 (311.5)	0.015
Fixed health costs in stable phase
Total annual cost of resource use	2427.5 (1377.3)	2378.7 (1378.6)	2473.8 (1378.8)	0.312
Annual pharmacological cost	1037.7 (627.9)	965.2 (489.7)	1106.5 (730.5)	0.036
Annual cost of total visits	336.9 (195.6)	321.0 (172.4)	352.0 (214.8)	0.431
Annual cost of PC visits	121.2 (122.7)	107.9 (115.6)	133.8 (128.2)	0.037
Annual cost of SC visits	215.8 (146.9)	213.1 (128.6)	218.3 (162.8)	0.492
Annual cost of outpatient tests	522.9 (433.8)	493.9 (408.0)	550.3 (456.6)	0.153
Annual cost of spirometry	67.9 (37.7)	65.1 (36.9)	70.5 (38.4)	0.348
Annual cost of blood analyses	179.6 (243.2)	162.3 (218.4)	196.0 (264.4)	0.030
Annual cost of chest X-ray	39.9 (48.1)	37.3 (40.3)	42.3 (54.6)	0.809
Annual cost of bronchodilator testing	46.9 (45.1)	40.5 (39.8)	52.9 (48.9)	0.035
Annual cost of arterial blood gases	42.0 (70.8)	45.0 (74.8)	39.1 (66.9)	0.188
Annual cost of complete functional testing	53.7 (86.6)	53.0 (85.9)	54.3 (87.5)	0.889
Annual cost of 6-minute walk test	15.3 (27.3)	13.9 (25.2)	16.6 (29.1)	0.535
Annual cost of chest CT	46.0 (97.5)	48.5 (104.1)	43.6 (91.1)	0.875
Annual cost of FENO measurements	15.0 (44.8)	12.1 (36.6)	17.8 (51.3)	0.531
Annual cost of other tests	16.6 (61.1)	16.0 (53.4)	17.1 (67.7)	0.885
Annual cost of non-pharmacological treatment	530.0 (1020.0)	598.5 (1130.8)	465.0 (901.2)	0.544
Annual cost of home oxygen	289.9 (499.4)	310.4 (511.5)	270.5 (488.4)	0.322
Annual cost vaccinations	31.3 (20.2)	30.7 (20.5)	31.9 (19.8)	0.611
Annual cost respiratory rehabilitation	12.7 (70.1)	17.8 (92.9)	7.75 (36.9)	0.550
Annual cost of non-invasive home ventilation	156.2 (680.3)	196.4 (756.7)	118.1 (598.8)	0.199
Annual cost of other treatments	39.8 (193.0)	43.1 (206.9)	36.73 (179.4)	0.899
Total cost
Total annual cost	6720.7 (8061.3)	8381.7 (9862.5)	5144.4 (5443.9)	<0.001
Total direct health costs (exacerbations + stable phase)	5701.3 (4733.0)	6702.9 (5388.4)	4750.7 (3792.7)	<0.001
Total indirect costs	1019.5 (6066.1)	1678.9 (7820.5)	393.7 (3620.9)	0.369

Notes: ^aCosts in euros 2019. Mean (SD). ^bP-value between patients with eosinophils <150 cells/µL vs ≥ 150 cells/µL. The Mann–Whitney U-test was used.

Abbreviations: COPD, chronic obstructive pulmonary disease; PC, primary care; SC, secondary care; ICU, intensive care unit; CT, computed axial tomography; FE_NO,exhaled nitric oxide test; SD, standard deviation.

Figure 3 Distribution of total direct health costs per COPD patient in the last 12 months.