Clinical Characterization and Treatment Patterns for the Frequent Exacerbator Phenotype in Chronic Obstructive Pulmonary Disease with Severe or Very Severe Airflow Limitation

Figures & data

Table 1. Patients characteristics across clinical phenotypes.

	Mean (SD) or N (%)
	All patients	Partial bronchodilator			Unclassified
Characteristics	(N = 743)	response (N = 35)	Emphysema (N = 119)	Bronchitis (N = 5)	(N = 584)	p-value
Age	71 (7.6)	70.4 (7.3)	68.5 (7.7)	68.8 (9.0)	71.5 (7.5)	<0.01
Men	581 (78.2)	25 (71.4)	92 (77.3)	1 (20.0)	463 (79.3)	<0.01
Smoking habit	681 (91.7)	30 (85.7)	117 (98.3)	5 (100.0)	529 (90.6)	0,02
Body mass index	26.5 (5.3)	26.2 (6.4)	24.8 (4.0)	27.6 (11.2)	26.9 (5.4)	<0.01
Forced expiratory volume (1 second)%	38.6 (8.3)	40.8 (6.6)	36 (8.9)	42.6 (3.9)	39 (8.2)	<0.01
Forced expiratory volume (1 second)% < 30%	134 (18)	3 (8.6)	30 (25.2)	0 (0)	101 (17.3)	0,06
Total lung capacity (L)	5.9 (0.9)	6.0 (1.1)	6.0 (0.8)	4.8 (0.7)	5.9 (0.9)	<0.01
Hyperinflation^a	119 (16)	16 (45.7)	32 (26.9)	1 (20)	70 (12)	<0.01
Outpatient setting	513 (69)	35 (100)	66 (55.5)	2 (40)	410 (70.2)	<0.01
Number of co-morbidities	1.71 (1.31)	1.3 (0.96)	1.9 (1.44)	3 (2.45)	1.68 (1.29)	<0.01
Hypertension	489 (65.8)	25 (71.4)	71 (59.7)	4 (80.0)	389 (66.6)	0,38
Heart failure	146 (19.7)	4 (11.4)	30 (25.2)	3 (60.0)	109 (18.7)	0,03
Coronary artery disease	130 (17.5)	4 (11.4)	26 (21.9)	0 (0.0)	100 (17.1)	0,31
Arrhythmia	36 (4.9)	1 (2.9)	4 (3.4)	1 (20.0)	30 (5.1)	0,33
Other cardiovascular disorders	54 (7.3)	0 (0.0)	16 (13.5)	2 (40.0)	36 (6.2)	<0.01
Diabetes	145 (19.5)	3 (8.6)	21 (17.7)	2 (40.0)	119 (20.4)	0,21
Metabolic syndrome	61 (8.2)	0 (0.0)	10 (8.4)	1 (20.0)	50 (8.6)	0,25
Psychiatric conditions	111 (14.9)	4 (11.4)	24 (20.1)	1 (20.0)	82 (14)	0,34
Chronic kidney disease	35 (4.7)	2 (5.7)	4 (3.4)	1 (20.0)	28 (4.8)	0,37
Osteoporosis	60 (8.1)	2 (5.71)	18 (15.1)	0 (0.0)	39 (6.7)	0,02
≥3 Exacerbations yearly	292 (39.3)	10 (28.57)	54 (45.4)	2 (40.0)	226 (38.7)	0,31
Treatment regimens						<0.01
Steroids and bronchodilators	486 (61.1)	13 (37.1)	74 (62.2)	3 (60.0)	364 (62.3)
LAB and SAB^c	10 (1.4)	0 (0.0)	0 (0.0)	0 (0.0)	10 (1.7)
Double SAB^c	1 (0.1)	0 (0.0)	1 (0.8)	0 (0.0)	1 (0.1)
Double LAB^b	63 (8.4)	0 (0.0)	14 (11.8)	0 (0.0)	49 (8.4)
Single SAB^c	8 (1.1)	0 (0.0)	2 (1.7)	1 (20.0)	5 (0.9)
Single LAB^b	92 (12.4)	2 (5.7)	6 (5.0)	0 (0.0)	84 (14.4)
Steroids alone	24 (3.2)	20 (57.1)	1 (0.8)	0 (0.0)	3 (0.5)
No steroids or bronchodilators	91 (12.3)	0 (0.0)	22 (18.5)	1 (20.0)	68 (11.6)
Other treatments	139 (18.7)	6 (17.1)	26 (21.9)	1 (20.0)	106 (18.2)	0.83
Systemic steroids	116 (17.4)	23 (65.7)	28 (28.0)	0 (0.0)	65 (12.4)	<0.01
N° of prescription medications	2.8 (1.4)	1.9 (1.2)	3.3 (1.4)	2.0 (0.0)	2.8 (1.4)	<0.01

Absolute (n) and relative (%) frequencies are reported for categorical variables. Means and standard deviations are reported for continuous variables.

^a Hyperinflation defined as residual capacity/total lung capacity >0.35.

^b LAB, long-acting bronchodilator.

^c SAB, short-acting bronchodilator.

p-values relative to ANOVA or chi-square test where appropriate.

Table 2. Patients characteristics across GOLD stages of airflow limitation.

	Mean (SD) or N (%)
		GOLD classification of airflow limitation
Characteristics	All patients (N = 743)	Stage III (N = 609)	Stage IV (N = 134)	p-value
Age	71 (7.6)	71.6 (7.5)	68.3 (7.2)	<0.01
Men	581 (78.2)	470 (77.2)	110 (82.4)	0.15
Smoking habit	681 (91.7)	558 (91.6)	123 (91.8)	0.95
Body mass index	26.5 (5.3)	26.8 (5.19)	25.3 (5.6)	<0.01
FEV^1%	38.6 (8.3)	41.7 (5.48)	24.9 (4.0)	<.001
TLC (L)	5.9 (0.9)	5.84 (0.92)	6.1 (0.9)	0.03
Hyperinflation^a	119 (16)	99 (16.3)	20 (14.9)	0.7
Outpatient setting	513 (69)	25 (71.8)	76 (56.7)	<.001
Number of co-morbidities	1.71 (1.31)	1.7 (1.33)	1.6 (1.3)	0.14
Hypertension	489 (65.8)	412 (67.7)	77 (57.5)	0.02
Heart failure	146 (19.7)	119 (19.5)	27 (20.2)	0.87
Coronary artery disease	130 (17.5)	107 (17.6)	23 (17.2)	0.91
Arrhythmia	36 (4.9)	32 (5.3)	4 (3.0)	0.27
Other cardiovascular disorders	54 (7.3)	40 (6.6)	14 (10.5)	0.12
Diabetes	145 (19.5)	130 (21.4)	15 (11.2)	<0.01
Metabolic syndrome	61 (8.2)	55 (9)	6 (4.5)	0.08
Psychiatric conditions	111 (14.9)	85 (14)	26 (19.4)	0.11
Chronic kidney disease	35 (4.7)	32 (5.3)	3 (2.2)	0.14
Osteoporosis	60 (8.1)	47 (7.7)	13 (9.7)	0.45
≥3 Exacerbations yearly	292 (39.3)	230 (37.8)	62 (46.3)	0.07
Treatment regimens
Steroids and bronchodilators	486 (65.4)	393 (64.5)	93 (69.4)	0.28
LAB and SAB^c	10 (1.4)	10 (1.6)	0 (0.0)	0.14
Double SAB^c	4 (0.5)	4 (0.7)	0 (0.0)	0.34
Double LAB^b	67 (9)	54 (8.9)	13 (9.7)	0.76
Single SAB^c	11 (1.5)	9 (1.5)	2 (1.5)	0.98
Single LAB^b	92 (12.4)	80 (13.1)	12 (9)	0.18
Steroids alone	27 (3.6)	24 (3.9)	3 (2.2)	0.34
No steroids or bronchodilators	46 (6.2)	35 (5.8)	11 (8.2)	0.28
Other treatments	139 (18.7)	117 (19.2)	22 (16.4)	0.45
Systemic steroids	116 (17.4)	95 (17.5)	21 (17.4)	0.93
N° Drugs for patient	2.8 (1.4)	2.8 (1.4)	3.0 (1.4)	0.15

Absolute (n) and relative (%) frequencies are reported for categorical variables. Means and standard deviations are reported for continuous variables.

^a Hyperinflation defined as residual capacity/total lung capacity >0.35.

^b LAB, long-acting bronchodilator.

^c SAB, short-acting bronchodilator.

p-values relative to ANOVA o chi-square test where appropriate.

Figure 1. Unadjusted and casemix-adjusted prevalence of the unclassified phenotype across participating centers. Distribution of unclassified patients across centers: (A) Crude prevalence of patients without sufficient diagnostic testing for phenotypical characterization across centers. (B) Estimated casemix-adjusted prevalence of unclassified patients. We obtained predicted center-related probabilities from a random-intercept logistic regression model adjusted for age, sex, co-morbidities, FEV¹%, body mass index, smoking habit, and therapy regimens.

Figure 2. Casemix-adjusted prevalence of patients with three or more exacerbations in the previous year across participating centers. Points represent the estimated casemix-adjusted prevalence of patients with three or more exacerbations in the previous year at each center. We obtained predicted center-related probabilities from a random-intercept logistic regression model adjusted for age, sex, co-morbidities, FEV¹%, body mass index, smoking habit, and therapy regimens.