Introduction
Methods
Study subjects
Study design
Sample collection
Measurement of analytes
Data analysis
Results
Subject Characteristics
COPD non-smokers (N = 13) | COPD smokers (N = 8) | Control non-smokers (N = 12) | Control smokers (N = 9) | |
---|---|---|---|---|
Mean age (95% CI)
| 72.8 (69.4-76.3) | 62.3 (58.7 - 65.8) | 66.7 (62.4-70.9) | 56.4 (52.7-60.1) |
Female Gender
| 7 (54%) | 5 (63%) | 7 (58%) | 6 (67%) |
Mean BMI (95% CI)
| 28.3 (25.4-31.2) | 25.5 (20.9-30.2) | 25.8 (23.9-27.7) | 26.0 (24.5-27.6) |
Pack Years (95% CI)
| 44.5 (33.7-55.2) | 53.8 (44.5-63.0) | 0 | 29.3 (22.0-36.7) |
Post-bronchodilator FEV1% predicted
| 46 (39 - 53) | 44 (33 - 54) | 101 (92-111) | 102 (93-111) |
GOLD Stage II
| 6 (46%) | 3 (38%) | 0 | 0 |
GOLD Stage III
| 6 (46%) | 3 (38%) | 0 | 0 |
GOLD Stage IV
| 1 (8%) | 2 (25%) | 0 | 0 |
History of Chronic Bronchitis
| 7 (54%) | 8 (100%) | 0 (0%) | 3 (33%) |
Total lung capacity % predicted
| 122 (108 - 136) | 117 (106-127) | 103 (96-110) | 106 (99-114) |
Residual volume % predicted
| 172 (132 - 211) | 176 (150-201) | 93 (81-104) | 94 (81-108) |
Diffusion capacity (DLCO % predicted
| 64 (56 - 73) | 64 (50-78) | 86 (82-90) | 78 (71-84) |
Baseline Dyspnea Index Score (95% CI)
| 6.0 (4.7 - 7.4) | 6.5 (4.7 - 8.2) | 11.6 (11.2-11.9) | 10.9 (10.1-11.6) |
Use of inhaled corticosteroids
| 10 (77%) | 7 (88%) | 0 | 0 |
Serum Biomarker Results
Serum Protein | COPD non-smokers (N = 13) | COPD smokers (N = 8) | Control non-smokers (N = 12) | Control smokers (N = 9) | P value COPD vs controls |
---|---|---|---|---|---|
Eotaxin2 (pg/ml)
#
| 554.2 (352.5) | 465.6 (327.4) | 364.3 (158.3) | 475.5 (766.1) | 0.025 |
IP-10 (pg/ml)
#
| 170.2 (95.2) | 164.8 (126.4) | 125.8 (26.4) | 100.7 (44.3) | 0.22 |
TNF-R1 (pg/ml)
#
| 1489.4 (303.0) | 1312.1 (257.3) | 1430.9 (268.9) | 1442.7 (268.0) | 0.67 |
TNF-RII (pg/ml)
#
| 194.0 (118.8) | 268.4 (143.8) | 241.9 (116.2) | 235.9 (33.9) | 0.10 |
TIMP-2 (pg/ml)
#
| 25028.7 (5273.1) | 27639.6 (4570.7) | 30286.8 (4946.8) | 26514.6 (6425.1) | 0.046 |
HGF (pg/ml)
#
| 21112.5 (12544.1) | 19937.9 (10785.1) | 24076.2 (14625.4) | 25125.4 (9975.2) | 0.56 |
KGF (pg/ml)
#
| 82.1 (34.5) | 56.9 (26.0) | 65.3 (20.8) | 66.1 (15.7) | 0.94 |
MMP-13 (pg/ml)
#
| 1768.8 (2561.6) | 718.9 (450.6) | 774.5 (421.6) | 733.6 (328.7) | 0.58 |
GROα (pg/ml)
#
| 123.3 (61.4) | 93.4 (33.6) | 114.8 (53.0) | 113.6 (65.9) | 0.21 |
CRP (ug/ml)*
| 13.6 (11.4) | 7.8 (9.1) | 4.1 (3.2) | 4.4 (4.0) | 0.042 |
ENA-78 (ng/ml)*
| 2.3 (2.69) | 1.8 (0.6) | 2.5 (1.7) | 2.9 (1.9) | 0.13 |
IL-13(pg/ml)*
| 37.5 (7.0) | 46.8 (13.4) | 40.4 (10.3) | 37.9 (7.9) | 0.17 |
IL-18 (pg/ml)*
| 302.1 (165.4) | 329.0 (106.7) | 281.9 (170.9) | 256.3 (109.1) | 0.17 |
IL-6 (pg/ml)*
| 8.0 (7.1) | 6.4 (5.1) | 2.3 (0.7) | Below detection limits | 0.20 |
IL-8 (pg/ml)*
| 15.1 (12.1) | 11.4 (3.7) | 11.1 (3.4) | 11.5 (3.9) | 0.30 |
MCP-1 (pg/ml)*
| 279.1 (181.5) | 259.7 (101.1) | 182.3 (35.6) | 198.7 (42.4) | 0.16 |
Myeloperoxidase (ng/ml)*
| 523.7 (546.2) | 597.9 (298.9) | 379.6 (308.8) | 430.3 (248.9) | 0.031 |
TIMP-1 (ng/ml)*
| 162.7 (33.1) | 160.7 (21.2) | 162.3 (31.5) | 146.0 (33.2) | 0.61 |
VEGF (pg/ml)*
| 753.1 (217.9) | 999.5 (826.2) | 586.2 (192.1) | 674.5 (149.4) | 0.035 |
Serum Protein | Within-subject CV (%) (90% CI) | Between-subject CV (%) (90% CI) | Analytical variation (%) | Reference change value (%) |
---|---|---|---|---|
Eotaxin2
| 64 (55 - 77) | 65 (50 - 77) | 12.1 | 180.42 |
IP-10
| 49 (44 - 57) | 62 (50 - 67) | 12.2 | 139.87 |
TNF-R1
| 26 (20 - 33) | 20 (13 - 29) | 8.8 | 76.03 |
TNF-RII
| 50 (42 - 59) | 59 (40 - 68) | 8.6 | 140.53 |
TIMP-2
| 21 (17 - 26) | 20 (13 - 24) | 8.4 | 62.65 |
HGF
| 71 (59 - 84) | 56 (37 - 65) | 14.3 | 200.62 |
KGF
| 55 (46 - 62) | 46 (35 - 57) | 8.3 | 154.08 |
MMP-13
| 88 (74 - 103) | 151 (57 - 172) | 11.0 | 245.66 |
GROα
| 32 (26 - 37) | 48 (28 - 56) | 8.2 | 91.50 |
CRP
| 53 (40 - 69) | 94 (67 - 122) | 6.05 | 147.76 |
ENA-78
| 16 (13 - 19) | 101 (31 - 120) | 4.32 | 45.91 |
IL-13
| 19 (18 - 23) | 26 (19 - 30) | 3.25 | 53.39 |
IL-18
| 21 (17 - 23) | 46 (31 - 54) | 3.46 | 58.95 |
IL-6
| 34 (24 - 49) | 95 (64 - 111) | 3.73 | 94.74 |
IL-8
| 30 (20 - 38) | 66 (36 - 79) | 3.83 | 83.77 |
MCP-1
| 17 (14 - 20) | 56 (35 - 70) | 3.95 | 48.34 |
Myeloperoxidase
| 36 (31 - 41) | 83 (47 - 103) | 5.39 | 100.83 |
TIMP-1
| 16 (14 - 18) | 18 (13 - 21) | 5.89 | 47.23 |
VEGF
| 19 (14 - 27) | 63 (28 - 79) | 4.98 | 54.41 |
Median coefficient of variation for all proteins
| 32 | 59 | 6.05 | 91.05 |
Serum Biomarker | Post-bronchodilator FEV1 | Diffusion capacity (% predicted) | Baseline dyspnea index score |
---|---|---|---|
CRP
| 0.13 | 0.02 | 0.03 |
Myeloperoxidase
| 0.03 | 0.009 | 0.008 |
VEGF
| 0.05 | 0.004 | 0.003 |
Sputum Biomarker Results
Sputum Protein | COPD non-smokers | COPD smokers | Control non-smokers | Control smokers | P value COPD vs controls |
---|---|---|---|---|---|
Eotaxin2 (pg/mg)
#
| 1244.2 (1638.6) | 808.9 (349.6) | 297.8 (279.1) | 1159.5 (1477.7) | 0.16 |
HGF (ng/mg)
#
| 19.2 (15.4) | 18.0 (17.0) | 7.6 (5.9) | 23.3 (20.9) | 0.61 |
IP-10 (pg/mg)
#
| 1015.3 (814.8) | 605.8 (393.0) | 395.7 (272.9) | 480.6 (988.8) | 0.94 |
KGF (pg/mg)
#
| 771.5 (747.7) | 881.4 (851.5) | 549.9 (516.4) | 1490.1 (1256.2) | 0.67 |
MMP-13 (ng/mg)
#
| 29.5 (25.8) | 30.9 (23.8) | 15.1 (11.7) | 45.8 (38.7) | 0.99 |
TNF-RI (pg/mg)
#
| 2459.5 (1548.9) | 2635.7 (2280.7) | 1390.2 (1241.6) | 3671.3 (2806.4) | 0.77 |
GROα (ng/mg)
#
| 54.9 (63.8) | 23.3 (18.3) | 7.6 (9.6) | 15.7 (14.6) | 0.007 |
TIMP2 (ng/mg)
#
| 21.1 (9.2) | 18.6 (17.0) | 5.8 (5.9) | 11.8 (14.4) | 0.09 |
TNF-RII (pg/mg)
#
| 169.1 (113.9) | 255.9 (367.0) | 46.7 (42.1) | 130.4 (129.8) | 0.04 |
α2 macroglobulin (mg/mg)*
| 0.008 (0.006) | 0.004 (0.002) | 0.005 (0.003) | 0.06 (0.07) | 0.09 |
ENA-78 (ng/mg)*
| 3.7 (4.1) | 1.9 (1.7) | 1.4 (1.6) | 1.2 (0.8) | 0.36 |
IL-13 (pg/mg)*
| 21.3 (31.2) | 9.3 (7.1) | 8.6 (1.9) | 5.7 (1.7) | 0.92 |
IL-15 (ng/mg)*
| 0.17 (0.32) | 0.11 (0.10) | 0.08 (0.03) | 0.04 (0.02) | 0.47 |
IL-18 (pg/mg)*
| 160.4 (189.8) | 118.9 (74.4) | 58.4 (39.1) | 100.8 (53.2) | 0.32 |
IL-1β (pg/mg)*
| 142.6 (170.7) | 404.3 (701.8) | 22.8 (12.3) | 53.2 (23.1) | 0.06 |
IL-1RA (ng/mg)*
| 87.3 (53.1) | 107.6 (87.4) | 60.7 (36.1) | 130.0 (72.1) | 0.64 |
IL-6 (pg/mg)*
| 156.5 (182.3) | 214.4 (194.7) | 13.3 (7.9) | 100.8 (88.4) | 0.00005 |
IL-8 (ng/mg)*
| 13.6 (9.0) | 32.7 (35.2) | 3.5 (3.0) | 9.0 (8.8) | 0.005 |
MCP-1 (pg/mg)*
| 845.2 (1285.2) | 692.2 (957.0) | 71.3 (54.6) | 237.2 (318.6) | 0.01 |
MMP-2 (ng/mg)*
| 55.3 (37.9) | 41.3 (20.4) | 60.1 (71.6) | 42.3 (20.5) | 0.06 |
TIMP-1 (ng/mg)*
| 206.6 (71.5) | 193.4 (68.9) | 75.5 (70.5) | 112.3 (83.5) | 0.004 |
VEGF(pg/mg)*
| 2653.0 (659.6) | 2845.7 (1013.8) | 1200.4 (706.5) | 1733.6 (819.8) | 0.006 |
Sputum Protein | Within-subject CV (%) (90% CI) | Between-subject CV (%) (90% CI) | Analytical variation (%) | Reference change value (%) |
---|---|---|---|---|
Eotaxin2
| 70 (53 - 95) | 88 (50 - 104) | 12.1 | 196.77 |
HGF
| 58 (44 - 76) | 66 (46 - 79) | 14.3 | 165.47 |
IP-10
| 62 (45 - 82) | 54 (32 - 73) | 12.2 | 175.03 |
KGF
| 49 (33 - 70) | 90 (58 - 126) | 8.3 | 137.66 |
MMP-13
| 54 (36 - 72) | 69 (43 - 89) | 11.0 | 152.65 |
TNF-RI
| 46 (36 - 54) | 56 (40 - 65) | 8.8 | 129.73 |
GROα
| 78 (56 - 100) | 89 (52 - 106) | 8.2 | 217.25 |
TIMP2
| 81 (57- 101) | 57 (38 - 77) | 8.4 | 225.57 |
TNF-RII
| 69 (49 - 89) | 104 (65 - 126) | 8.6 | 192.61 |
α2 macroglobulin
| 57 (33 - 75) | 70 (47 - 84) | 6.43 | 158.89 |
ENA-78
| 61 (49 - 74) | 88 (60 - 104) | 4.32 | 169.39 |
IL-13
| 30 (23 - 37) | 101 (32 - 116) | 3.25 | 83.59 |
IL-15
| 62 (48 - 76) | 121 (64- 149) | 3.96 | 172.09 |
IL-18
| 55 (43 - 66) | 63 (32 - 73) | 3.46 | 152.65 |
IL-1β
| 61 (44 - 77) | 160 (113 - 210) | 4.58 | 169.45 |
IL-1RA
| 58 (46 - 69) | 55 (37 - 68) | 5.86 | 161.48 |
IL-6
| 50 (36 - 68) | 99 (59 - 118) | 3.73 | 138.88 |
IL-8
| 60 (47 - 82) | 88 (70 - 106) | 3.83 | 166.54 |
MCP-1
| 86 (70 - 99) | 146 (84 - 182) | 3.95 | 238.47 |
MMP-2
| 57 (39 - 81) | 70 (38 - 82) | 3.33 | 158.16 |
TIMP-1
| 54 (33- 73) | 38 (27 - 46) | 5.89 | 150.47 |
VEGF
| 42 (32 - 55) | 24 (15 - 31) | 4.98 | 117.15 |
Median coefficient of variation for all proteins
| 58 | 79 | 5.88 | 163.47 |
Sputum Biomarker | Post-bronchodilator FEV1 | Residual Volume (% predicted) | Diffusion capacity (% predicted) | Baseline dyspnea index score |
---|---|---|---|---|
IL-6
| 0.0009 | 0.007 | 0.01 | 0.0007 |
IL-8
| 0.03 | 0.24 | 0.34 | 0.037 |
TIMP-1
| 0.004 | 0.01 | 0.07 | 0.009 |
VEGF
| 0.03 | 0.01 | 0.15 | 0.04 |
Sputum Protein | Spearman's correlation coefficient (Rho) | P value |
---|---|---|
Eotaxin2
| 0.70 | 0.0005 |
HGF
| 0.59 | 0.003 |
IP-10
| 0.57 | 0.005 |
KGF
| 0.37 | 0.07 |
MMP-13
| 0.58 | 0.004 |
TNF-RI
| 0.64 | 0.002 |
GROα
| 0.65 | 0.001 |
TIMP2
| 0.69 | 0.0006 |
TNF-RII
| 0.67 | 0.0009 |
α2 macroglobulin
| 0.51 | 0.01 |
ENA-78
| 0.44 | 0.03 |
IL-13
| -0.26 | 0.19 |
IL-15
| -0.18 | 0.37 |
IL-18
| 0.54 | 0.007 |
IL-1β
| 0.69 | 0.0006 |
IL-1RA
| 0.39 | 0.05 |
IL-6
| 0.64 | 0.001 |
IL-8
| 0.70 | 0.0005 |
MCP-1
| 0.69 | 0.0006 |
MMP-2
| 0.26 | 0.20 |
TIMP-1
| 0.55 | 0.006 |
VEGF
| 0.61 | 0.002 |