Evaluation of BODE index and its relationship with systemic inflammation mediated by proinflammatory biomarkers in patients with COPD

Figures & data

Table 1 Baseline characteristics of the COPD patients and smoker controls

Characteristics	COPD subjects (n=290)	Smoker controls (n=80)	P-value
Age (years)	58.3±16.1	47.2±11.0	<0.001
Male/female	254/36	65/15	–
Smoking (years)	38.7	16.4	<0.001
Pack-years	38.6±17.4	17.4±9.5	<0.001
BMI (kg/m^2)	22.4±6.2	22.8±4.6	0.42
FEV1 (% predicted)	54.3±12.8	102.8±16.3	<0.001
FEV1/FVC (%)	45.8±11.6	79.2±5.4	<0.001
FEV1 reversibility (%)	10.7±13.7	4.5±5.8	<0.001
FVC (%)	86.4±18.6	110.4±13.5	<0.001
6-minute walking distance (m)	329±122	510±133	<0.001
BODE index score	5.20±3.9	0 (0–1)	<0.001
Quartile 1 (0–2)	193 (66.5%)	80 (100%)	–
Quartile 2 (3–4)	41 (14.1%)	0	<0.001
Quartile 3 (5–6)	36 (12.4%)	0	–
Quartile 4 (7–10)	20 (6.8%)	0	–
mMRC score	1.8±1.3	0.8±0.2	<0.001
Inflammatory variables
TNF-α (pg/mL)	4.09±1.38	3.76±1.39	<0.001
IL-6 (pg/mL)	1.56±0.98	1.16±0.73	<0.001
CRP (pg/mL)	4.52±2.26	2.88±1.12	<0.001

Note: Values are expressed as mean (standard deviation) or as percentage. P-value’s were calculated via unpaired Student’s t-test.

Abbreviations: BMI, body mass index; BODE, BMI (B), airflow obstruction (O) as measured by the postbronchodilator FEV1 (percentage of predicted value), dyspnea (D) assessed by the mMRC score, and exercise tolerance (E) measured by 6-minute walking distance; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; IL-6, interleukin 6; mMRC, modified Medical Research Council scale; TNF-α, tumor necrosis factor alpha.

Table 2 Baseline characteristics of COPD according to different stages of GOLD

Parameter	GOLD II (n=147)	GOLD III (n=104)	GOLD IV (n=39)	P-value
Age	53.08±9.12	56.22±10.45	58.28±10.05	0.005
BMI	20.74±2.27	21.37±2.70	21.69±2.30	0.0002
Pack-years	24.80±8.45	25.31±8.75	30.10±10.68	<0.001
FEV1 (%)	62.15±6.90	41.03±6.23	27.25±2.57	<0.001
FVC	71.91±9.84	56.06±8.29	42.19±6.83	<0.001
FEV1/FVC%	60.68±4.7	49.63±7.05	38.50±5.43	<0.001
6MWT	235.35±59.59	221.94±63.59	190.47±47.83	<0.001
mMRC score	1.7±1.2	2.1±1.1	2.5±1.4	<0.001
TNF-α (pg/mL)	4.14±1.33	4.25±1.31	4.45±1.57	0.005
CRP (pg/mL)	4.29±1.21	4.80±1.25	4.62±1.32	0.04
IL-6 (pg/mL)	1.04±0.50	1.92±1.00	2.36±1.14	0.002
BODE index	2.09±1.59	5.96±1.34	7.24±1.62	<0.001

Note: Values are expressed as mean (standard deviation) or as percentage. P-value’s were calculated via ANOVA.

Abbreviations: 6MWT, 6-minute walking test; BMI, body mass index; BODE, BMI (B), airflow obstruction (O) as measured by the postbronchodilator FEV1 (percentage of predicted value), dyspnea (D) assessed by the mMRC score, and exercise tolerance (E) measured by 6-minute walking distance; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IL-6, interleukin 6; mMRC, modified Medical Research Council scale; TNF-α, tumor necrosis factor alpha.

Figure 1 Distribution of inflammatory biomarkers (IL-6, CRP, and TNF-α) stratified by GOLD stage in COPD patients.

Abbreviations: COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IL-6, interleukin 6; TNF-α, tumor necrosis factor alpha.

Table 3 Comparison of clinical variables and inflammatory biomarkers according to different quartiles of BODE index in COPD patients

Parameters	Quartile 1	Quartile II	Quartile III–1V	P-value
Age (years)	52.06±7.14	57.32±8.12	64.16±11.23	0.004
Pack-years	23.12±7.47	27.32±6.45	31.45±8.91	0.001
BMI (kg/m^2)	24.3±3.5	22.4±4.5	20±3.2	0.001
FEV1 (% predicted)	60.8±13.4	47.4±13.1	38.8±7.76	<0.001
FEV1/FVC (%)	52.7±11.0	44.9±10.6	36.6±9.6	<0.001
FEV1 reversibility (%)	10.2±10.5	8.2±12.4	8.4±11.4	0.008
mMRC score	1.1±0.6	1.8±0.7	2.2±0.6	<0.001
6MWD (m)	412±85.0	316±65.0	194±54.0	<0.001
CRP (pg/mL)	3.46±2.12	3.94±2.75	4.78±2.87	0.0002
IL-6 (pg/mL)	1.21±0.83	1.97±1.04	2.88±1.82	<0.001
TNF-α (pg/mL)	3.94±2.02	4.21±1.87	4.72±2.07	0.005

Notes: Values are mean (SD) depending on the distribution. Comparison between groups was done by ANOVA.

Abbreviations: 6MWD, 6-minute walking distance; ANOVA, analysis of variance; BMI, body mass index; BODE, BMI (B), airflow obstruction (O) as measured by the postbronchodilator FEV1 (percentage of predicted value), dyspnea (D) assessed by the mMRC score, and exercise tolerance (E) measured by 6MWD; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; IL-6, interleukin 6; mMRC, modified Medical Research Council scale; SD, standard deviation; TNF-α, tumor necrosis factor alpha.

Figure 2 Relationship between BODE index score and GOLD stage in COPD patients.

Abbreviations: BODE, body mass index (B), airflow obstruction (O) as measured by the postbronchodilator forced expiratory volume in 1 second (percentage of predicted value), dyspnea (D) assessed by the modified Medical Research Council scale score, and exercise tolerance (E) measured by 6-minute walking distance; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease.

Table 4 Correlations between BMI, 6MWT, mMRC, BODE index, and inflammatory biomarkers in COPD patients

Biomarkers	BMI	mMRC	6MWT	BODE index
TNF-α (pg/mL)	r=−0.030	r=0.214**	r=−0.126	r=0.251
	P=0.669	P=0.002	P=0.073	P=<0.001*
CRP (pg/mL)	r=0.095	r=0.252**	r=−0.069	r=0.169
	P=0.179	P=0.007	P=0.331	P=0.016*
IL-6 (pg/mL)	r=0.104	r=0.068**	r=0.201*	r=0.530*
	P=0.139	P=0.001	P=0.004	P=0.001
BMI (kg/m^2)	1	r=0.164*	r=−0.013	r=−0.151**
		P=0.002	P=0.081	P=0.032

Notes:

* Correlation is significant at the 0.01 level (two-tailed).

** Correlation is significant at the 0.05 level.

Abbreviations: 6MWT, 6-minute walking test; BMI, body mass index; BODE, BMI (B), airflow obstruction (O) as measured by the postbronchodilator forced expiratory volume in 1 second (percentage of predicted value), dyspnea (D) assessed by the mMRC score, and exercise tolerance (E) measured by 6-minute walking distance; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; IL-6, interleukin 6; mMRC, modified Medical Research Council scale; TNF-α, tumor necrosis factor alpha.

Table 5 Correlation between pulmonary function parameters and inflammatory biomarkers in COPD patients

Biomarkers	FEV1	FEV1/FVC	FVC
TNF-α (pg/mL)	r=−0.183**	r=−0.123	r=−0.209**
	P=0.009	P=0.081	P=0.003
CRP (pg/mL)	r=−0.210**	r=−0.186**	r=−0.139*
	P=0.003	P=0.008	P=0.048
IL-6 (pg/mL)	r=−0.580*	r=−0.460**	r=−0.523**
	P=0.001	P=0.001	P=0.001

Notes:

* Correlation is significant at the 0.01 level.

** Correlation is significant at the 0.05 level.

Abbreviations: COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; IL-6, interleukin 6; TNF-α, tumor necrosis factor alpha.

Figure 3 Relationship of serum concentrations of the inflammatory biomarkers studied with the BODE index and 6-minute walk test in COPD patients.

Note:R = Pearson’s linear bivariate correlation coefficient.

Abbreviations: 6MWT, 6-minute walking test; BODE, body mass index (B), airflow obstruction (O) as measured by the postbronchodilator forced expiratory volume in 1 second (percentage of predicted value), dyspnea (D) assessed by the modified Medical Research Council scale score, and exercise tolerance (E) measured by 6-minute walking distance; CRP, C-reactive protein; IL, interleukin; TNF-α, tumor necrosis factor alpha.

Figure 4 Correlation between serum biomarkers and FEV1% in COPD patients and smoker controls (A, B, C: COPD patients; D, E, F: smoker controls).

Abbreviations: COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; FEV1, forced expiratory volume in 1 second; IL-6, interleukin 6; TNF-α, tumor necrosis factor alpha.