Clinical variables impacting on the estimation of utilities in chronic obstructive pulmonary disease

Figures & data

Table 1 Characteristics of the study population

Characteristic	Statistics
Age, years, mean (SD)	67.9 (9.7)
Sex, male, n (%)	296 (85.5)
Current smoker, n (%)	68 (19.7)
Former smoker, n (%)	278 (80.3)
Pack-years, mean (SD)	54.2 (33.2)
Time from diagnosis, years, mean (SD)	7.6 (5.8)
BMI, kg/m^2, mean (SD)	28.0 (5.4)
Post-bronchodilator lung function, mean (SD)
FVC, mL	2,619.3 (781.8)
FVC, %	72.5 (18.7)
FEV1, mL	1,272 (506.0)
FEV1, %	46.2 (15.5)
FEV1/FVC, %	48.5 (11.6)
Positive post-bronchodilator test, n (%)	41 (15.9)
Severity of COPDa, n (%)
GOLD II (moderate)	135 (39.0)
GOLD III (severe)	145 (41.9)
GOLD IV (very severe)	66 (19.1)
Comorbidities (the most prevalent), n (%)
Cardiovascular diseaseb	94 (27.1)
Diabetes	57 (16.4)
Malignant neoplasias	43 (12.4)
Charlson index, mean (SD)	1.0 (1.4)
At least one exacerbation in the previous year, n (%)	202 (58.4)
Exacerbations in the previous year, mean (SD)	1.3 (1.5)
At least one admission in the previous year, n (%)	62 (17.9)
Admissions in the previous year, mean (SD)	0.3 (0.6)
Treatment, n (%)
Short-acting anticholinergic agents	22 (6.4)
Long-acting anticholinergic agents	305 (88.2)
Short-acting beta-adrenoceptor agonists	132 (38.2)
Long-acting beta-adrenoceptor agonists	321 (92.8)
Inhaled corticosteroids	266 (76.9)
Theophyllines	21 (6.1)
Phosphodiesterase IV inhibitors	46 (13.3)
Mucolytics	36 (10.4)
Leukotriene antagonist	4 (1.2)
Oral corticosteroid	2 (0.6)
Respiratory rehabilitation	42 (12.1)
Oxygen therapy	93 (26.9)
CAT total score, mean (SD)	16.2 (7.8)
Impact on CAT impairment, n (%)
Mild (0–10)	74 (21.4)
Moderate (10–20)	163 (47.1)
Severe (20–30)	87 (25.1)
Very severe (30–40)	22 (6.4)
mMRC total score	1.8 (1.1)
Dyspnea degree according to mMRC, n (%)
0	26 (7.5)
1	129 (37.3)
2	95 (27.5)
3	69 (19.9)
4	27 (7.8)
Utility values
Mean (SD)	0.73 (0.29)
Median (IQR)	0.81 (0.26)
Minimum	−0.482
Maximum	1

Notes:

a COPD moderate: FEV₁/FVC <0.70 and 50%≤ FEV₁ <80%; COPD severe: FEV₁/FVC <0.70 and 30%≤ FEV₁ <50%; COPD very severe: FEV₁/FVC <0.70 and FEV₁ <30%.

b Cardiovascular diseases are myocardial infarction, congestive heart failure, peripheral vascular disease, and cerebrovascular disease.

Abbreviations: BMI, body mass index; CAT, COPD Assessment Test; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global initiative for chronic Obstructive Lung Disease; IQR, interquartile range; mMRC, modified Medical Research Council Dyspnea Scale; SD, standard deviation; COPD, chronic obstructive pulmonary disease.

Table 2 Bivariate analysis: association between study variables and utility values

Variable	n (%)	Median (IQR)	P-value
Age (years)			0.3
≤65	136 (39.3)	0.80 (0.33)
>65	210 (60.7)	0.81 (0.25)
Sex			0.002
Male	296 (85.5)	0.82 (0.25)
Female	50 (14.5)	0.74 (0.44)
Smoking status			0.9
Former smokers	278 (80.3)	0.81 (0.25)
Current smokers	68 (19.7)	0.81 (0.27)
Pack-years			0.07
≤50	203 (58.7)	0.82 (0.20)
>50	143 (41.3)	0.80 (0.30)
Time from diagnosis (years)			0.07
≤8	218 (63.0)	0.82 (0.31)
>8	128 (37.0)	0.80 (0.25)
BMIa			0.4
Underweight	6 (1.7)	0.69 (0.51)
Normal	98 (28.3)	0.80 (0.31)
Overweight	141 (40.8)	0.82 (0.25)
Obese	101 (29.2)	0.81 (0.38)
Comorbidities
Cardiovascular diseasesb
No	252 (72.8)	0.82 (0.25)	0.2
Yes	94 (27.2)	0.78 (0.30)
Diabetes			0.8
No	289 (83.5)	0.81 (0.25)
Yes	57 (16.5)	0.81 (0.38)
Hematological malignancies			0.8
No	303 (87.6)	0.81 (0.27)
Yes	43 (12.4)	0.80 (0.16)
Charlson index			0.2
0	165 (47.7)	0.82 (0.25)
1	77 (22.3)	0.82 (0.40)
2	62 (17.9)	0.74 (0.26)
3+	42 (12.1)	0.81 (0.31)
FEV1 predictedc			<0.001
Moderate	135 (39.0)	0.87 (0.22)
Severe	145 (41.9)	0.80 (0.26)
Very severe	66 (19.1)	0.66 (0.42)
Positive bronchodilator test			0.02
No	217 (84.1)	0.81 (0.27)
Yes	41 (15.9)	0.89 (0.20)
Exacerbations in the previous year			<0.001
No	144 (41.6)	0.87 (0.25)
Yes	202 (58.4)	0.78 (0.31)
Exacerbations in the previous year			<0.001
<2	235 (67.9)	0.84 (0.29)
2+	111 (32.1)	0.74 (0.54)
CAT total score			<0.001
0–10	74 (21.4)	1.00 (0.13)
10–20	163 (47.1)	0.84 (0.18)
20–30	87 (25.1)	0.65 (0.45)
30–40	22 (6.4)	0.28 (0.46)
mMRC total score			<0.001
<2	155 (44.8)	0.91 (0.19)
2+	191 (55.2)	0.71 (0.33)

Notes:

a Underweight: <18.5 kg/m²; normal: 18.5–25 kg/m²; overweight: 25–30 kg/m²; and obese: ≥30 kg/m².

b Cardiovascular diseases are myocardial infarction, congestive heart failure, peripheral vascular disease, and cerebrovascular disease.

c Post-bronchodilator. COPD moderate: FEV₁/FVC <0.70 and 50%≤ FEV₁ <80%; COPD severe: FEV₁/FVC <0.70 and 30%≤ FEV₁ <50%; COPD very severe: FEV₁/FVC <0.70 and FEV₁ <30%.

Abbreviations: BMI, body mass index; CAT, COPD Assessment Test; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; IQR, interquartile range; mMRC, modified Medical Research Council Dyspnea Scale; COPD, chronic obstructive pulmonary disease.

Figure 1 Utilities by (A) FEV₁ (%) predicted post-bronchodilator, (B) exacerbations, (C) CAT score, and (D) mMRC score.

Note: The graphs show utilities ≥0.
Abbreviations: CAT, COPD Assessment Test; FEV₁, forced expiratory volume in 1 second; mMRC, modified Medical Research Council Dyspnea Scale.

Table 3 Factors associated with utility values in the univariate and multivariate linear regression analyses

Variable	Univariate (raw effects)			Multivariate (adjusted effects)
	Beta	95% CI	P-value	Beta	95% CI	P-value
Age	0.001	(−0.002, 0.004)	0.6
Sex (female vs male)	−0.147	(−0.233, −0.060)	<0.001	−0.084	(−0.154, −0.013)	0.02
Smoking status (current vs former)	0.001	(−0.077, 0.079)	0.9
Time diagnostic	−0.005	(−0.011, 0.0001)	0.056
BMIa (overweight is the reference group)
Underweight	−0.249	(−0.487, −0.010)	0.04
Normal	−0.049	(−0.124, 0.026)	0.2
Obese	−0.019	(−0.093, 0.056)	0.6
Cardiovascular diseases (yes vs no)	−0.041	(−0.110, 0.029)	0.3
Diabetes (yes vs no)	0.010	(−0.073, 0.093)	0.8
Hematological malignancies (yes vs no)	0.031	(−0.062, 0.125)	0.5
Charlson index (0 is the reference group)
1	−0.012	(−0.091, 0.068)	0.8
2	−0.041	(−0.127, 0.045)	0.3
3+	−0.002	(−0.102, 0.097)	0.9
FEV1 (%) predicted post-bronchodilator	0.006	(0.004, 0.008)	<0.001
Positive bronchodilator test	0.091	(−0.007, 0.189)	0.07
Number of exacerbations	−0.067	(−0.086, −0.048)	<0.001	−0.027	(−0.044, −0.010)	0.002
mMRC score (1 is the reference group)
0	0.034	(−0.065, 0.134)	0.5	0.011	(−0.088, 0.109)	0.8
2	−0.135	(−0.197, −0.072)	<0.001	−0.123	(−0.185, −0.061)	<0.001
3	−0.263	(−0.332, −0.193)	<0.001	−0.231	(−0.301, −0.161)	<0.001
4	−0.616	(−0.714, −0.518)	<0.001	−0.559	(−0.660, −0.458)	<0.001

Notes:

a Underweight: <18.5 kg/m²; normal weight: 18.5–25 kg/m²; overweight: 25–30 kg/m²; and obese: ≥30 kg/m².

Abbreviations: BMI, body mass index; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; mMRC, modified Medical Research Council Dyspnea Scale.

Table S1 Multivariate linear, Tobit, and CLAD regressions

Variable	Multivariate linear regression		Multivariate Tobit regression		Multivariate CLAD regression
	Beta	95% CI	Beta	95% CI	Beta	95% CIa
Sex (female vs male)	−0.084	(−0.154, −0.013)	−0.098	(−0.182, −0.013)	−0.062	(−0.130, −5·10^−4)
Number of exacerbations	−0.027	(−0.044, −0.010)	−0.030	(−0.051, −0.009)	−0.006	(−0.038, 0.0045)
mMRC score (1 is the reference group)
0	0.011	(−0.088, 0.109)	0.079	(−0.053, 0.212)	0.090	(0.0005, 0.113)
2	−0.123	(−0.185, −0.061)	−0.178	(−0.253, −0.102)	−0.094	(−0.158, −0.063)
3	−0.231	(−0.301, −0.161)	−0.298	(−0.383, −0.213)	−0.222	(−0.297, −0.177)
4	−0.559	(−0.660, −0.458)	−0.626	(−0.747, −0.505)	−0.632	(−0.812, −0.341)
Intercept	0.899	(0.855, 0.942)	0.976	(0.921, 1.031)	0.910	(0.886, 0.914)

Note:

a Bias-corrected and accelerated method for CI.

Abbreviations: CI, confidence interval; CLAD, censored least absolute deviations; mMRC, modified Medical Research Council.