Factors Associated with the Non-Exacerbator Phenotype of Chronic Obstructive Pulmonary Disease

Figures & data

Figure 1 Flow chart describing the selection and data collection within the study.

Abbreviation: COPD, chronic obstructive lung disease.

Table 1 Patient Characteristics

Variables	Patients with Exacerbations	Patients without Exacerbations	p-value
	n (%)	n (%)
	n=463 (34)	n=891 (66)
Sex
Male	190 (41)	408 (46)	0.095
Female	273 (59)	483 (54)	Ref
Age groups
<65	126 (28)	246 (28)	Ref
65–69	132 (29)	253 (28)	0.904
>70	205 (44)	392 (44)	0.881
BMI groups^a
<22	99 (22)	138 (16)	0.003
22–30	242 (53)	531 (61)	Ref
>30	113 (25)	204 (23)	0.165
COPD stage (FEV1%pred)
Stage 1 (≥80)	76 (16)	273 (31)	<0.001
Stage 2 (50–79)	184 (40)	395 (44)	<0.001
Stage 3 (30–49)	121 (26)	184 (21)	<0.001
Stage 4 (<30)	82 (18)	39 (4)	Ref
CAT <10^b	565 (66)	399 (90)	<0.001
Daily smoking^c
Never	22 (5)	32 (4)	Ref
Ex	304 (67)	564 (64)	0.395
Occasional	33 (7)	46 (5)	0.906
Current	93 (21)	232 (27)	0.075
Educational level^d
Low	281 (62)	495 (56)	Ref
High	175 (38)	383 (44)	0.065
COPD maintenance treatment
No inhaled maintenance treatment	64 (14)	335 (38)	<0.001
LAMA or LABA	78 (17)	183 (21)	<0.001
LAMA and LABA	30 (7)	33 (4)	0.820
ICS in any form	291 (63)	340 (38)	Ref
Chronic bronchitis	40 (9)	40 (5)	0.003
Heart failure	75 (16)	71 (8)	<0.001
Ischemic heart disease	87 (19)	123 (14)	0.017
Atrial fibrillation	56 (12)	70 (8)	0.011
Depression or anxiety^e	122 (27)	191 (22)	0.033

Notes: ^aMissing data n=27; ^bmissing data n=59. ^cMissing data n=28; ^dmissing data n=20; ^emissing data n=27; patient characteristics in total and distributed by presence of exacerbations or not. Statistically significant differences are presented in bold text.

Abbreviations: BMI, body mass index; COPD, chronic obstructive lung disease; FEV1%pred, forced expiratory volume in one second % of predicted; CAT, COPD assessment test; Re, reference category.

Table 2 Associations with the Non-Exacerbator COPD Phenotype

Variables	Unadjusted OR CI (95%)	p-value	Adjusted OR CI (95%)	p-value
Male sex	1.21 (0.97–1.52)	0.095	0.81 (0.60–1.09)	0.159
Age groups
<65	Ref		Ref
65–69	0.98 (0.73–1.33)	0.904	1.28 (0.90–1.81)	0.170
≥70	0.98 (0.75–1.29)	0.881	1.28 (0.92–1.80)	0.144
Current daily smoking	1.40 (1.06–1.83)	0.017	1.41 (1.02–1.94)	0.036
Level of education	1.24 (0.99–1.57)	0.066	1.21 (0.93–1.59)	0.158
BMI groups
<22	0.64 (0.47–0.86)	0.003	0.68 (0.48–0.97)	0.032
22–30	Ref		Ref
≥ 30	0.82 (0.63–1.08)	0.165	0.89 (0.65–1.22)	0.477
COPD stage (FEV1%pred)
Stage 1 (≥80)	7.55 (4.78–11.9)	<0.001	5.72 (3.30–9.92)	<0.001
Stage 2 (50–79)	4.51 (2.97–6.87)	<0.001	3.42 (2.13–5.51)	<0.001
Stage 3 (30–49)	3.20 (2.05–4.99)	<0.001	2.38 (1.46–3.88)	<0.001
Stage 4 (<30)	Ref		Ref
CAT <10	4.49 (3.20–6.30)	<0.001	3.35 (2.34–4.80)	<0.001
Chronic bronchitis	0.50 (0.32–0.78)	0.003	0.47 (0.28–0.79)	0.004
Heart failure	0.45 (0.32–0.63)	<0.001	0.66 (0.42–1.03)	0.064
Ischemic heart disease	0.69 (0.51–0.94)	0.017	0.76 (0.53–1.08)	0.122
Atrial fibrillation	0.62 (0.43–0.90)	0.011	0.86 (0.54–1.37)	0.515
Depression or anxiety	0.78 (0.61–1.00)	0.052	0.75 (0.57–1.00)	0.051

Notes: Results from multivariable analysis including all variables in the left column. The analyses were adjusted for sex, age, smoking, level of education, BMI, COPD stage, CAT, chronic bronchitis, heart failure, ischemic heart disease, atrial fibrillation and depression/anxiety. Statistically significant differences are presented in bold text.

Abbreviations: BMI, body mass index; CAT, COPD assessment test; CI, confidence interval; COPD, chronic obstructive lung disease; FEV1%pred, forced expiratory volume in one second % of predicted; OR, odds ratio; Ref, reference category.

Figure 2 The non-exacerbator phenotype by severity of COPD proportions of patients with no exacerbations in every COPD stage.

Abbreviation: COPD, chronic obstructive lung disease.

Figure 3 Factors associated with having no exacerbations in COPD results from multivariable analysis, adjusted for sex, age, smoking, level of education, BMI, COPD stage, CAT, chronic bronchitis, heart failure, ischemic heart disease, atrial fibrillation and depression/anxiety.

Abbreviations: BMI, body mass index; CAT, COPD assessment test; CB, Chronic bronchitis; HF, Heart failure.

Table 3 Differences by Sex

Variables	Men		Women		p for Interaction
	Adjusted OR CI (95%)	p-value	Adjusted OR CI (95%)	p-value
BMI groups
<22	1.27 (0.69–2.33)	0.445	0.47 (0.30–0.73)	<0.001	0.033
22–30	1	Ref	Ref		Ref
≥ 30	1.23 (0.74–2.02)	0.426	0.66 (0.43–1.01)	0.054	0.046
COPD stage
Stage 1	13.7 (4.31–43.3)	<0.001	3.28 (1.43–7.56)	0.005	0.048
Stage 2	8.19 (2.58–26.0)	<0.001	2.58 (1.48–4.50)	<0.001	0.080
Stage 3	4.44 (1.34–14.7)	0.015	2.06 (1.17–3.64)	0.012	0.243
Stage 4	Ref		Ref		Ref
Heart failure	0.44 (0.23 to 0.83)	0.012	1.03 (0.54 to 1.99)	0.923	0.030

Notes: Multivariate analysis stratified by sex and with the results of the interaction analysis. The analyses were adjusted for sex, age, smoking, level of education, BMI, COPD stage, CAT, chronic bronchitis, heart failure, ischemic heart disease, atrial fibrillation and depression/anxiety, and the multiplicative interaction variable of sex and respective independent variable. Statistically significant differences are presented in bold text.

Abbreviations: OR, odds ratio; CI, confidence interval; BMI, body mass index; CAT, COPD Assessment Test, COPD, chronic obstructive lung disease; Ref, reference category.