Figures
- FIGURE 1
Flow diagram of the inclusion process. FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; TIE: Tools Identifying Exacerbations in COPD study; AECOPD: acute exacerbation of COPD.
- FIGURE 2
Baseline a) blood neutrophil-to-lymphocyte ratio (NLR) and b) blood eosinophils in 460 subjects with COPD, stratified by the occurrence of any exacerbation the previous year.
- FIGURE 3
Longitudinal stability of blood neutrophil-to-lymphocyte ratio (NLR) in 386 subjects with COPD. The diagram at the left shows the proportion of subjects with high and low neutrophil-to-lymphocyte ratio at baseline visit. The diagrams in the middle show the respective proportion at year 1, and the diagrams at the right show the respective proportion at year 2.
- FIGURE 4
Longitudinal stability of blood eosinophil levels in 386 subjects with COPD. The diagram at the left shows the proportion of subjects with high, intermediate and low blood eosinophils (B-Eos) at baseline visit. The diagrams in the middle show the respective proportion at year 1, and the diagrams at the right show the respective proportion at year 2.
- FIGURE 5
Longitudinal stability of a) blood neutrophil-to-lymphocyte ratio (NLR) and b) blood eosinophils measured at three yearly visits in 377 subjects with COPD, stratified by the occurrence of any acute exacerbation of COPD during the 3-year study period.
Tables
- TABLE 1
Characteristics of subjects included in analyses of the association between blood cells and acute exacerbations of COPD, categorised by baseline blood cells
Total NLR B-Eos (cells·µL−1) <3.00 ≥3.00 <150 ≥150–<300 ≥300 Subjects n 466 345# 117# 176# 159# 127# Recruited from Secondary care 55 (11.8) 33 (9.6) 22 (18.8) 26 (14.8) 19 (11.9) 10 (7.9) Primary care 411 (88.2) 312 (90.4) 95 (81.2) 150 (85.2) 140 (88.1) 117 (92.1) Age 68.7±7.5 68.1±7.6 70.1±7.0 68.7±7.7 68.2±6.9 69.0±7.8 Female 268 (57.5) 198 (57.4) 67 (57.3) 98 (55.7) 106 (66.7) 61 (48.0) Current smoker 122 (26.2) 94 (27.2) 27 (23.1) 40 (22.7) 46 (28.9) 35 (27.6) BMI (kg m−2) 27.0±4.9 26.8±4.7 27.4±5.4 26.7±4.9 27.3±4.9 26.9±4.8 CAT score 11.0 (7.0–16.0) 10.0 (6.0–16.0) 12.0 (8.0–20.0) 11.0 (6.5–18.0) 11.0 (8.0–16.0) 10.0 (6.0–16.0) ≥1 AECOPD previous year 177 (38.1) 117 (34.1) 59 (50.4) 65 (36.9) 61 (38.6) 50 (39.7) FEV1 % pred 57.6±17.1 58.8±15.9 54.4±19.6 56.3±18.2 57.7±16.4 59.6±16.1 FEV1 grades GOLD grade 1 45 (9.7) 33 (9.6) 12 (10.3) 17 (9.7) 18 (11.3) 10 (7.9) GOLD grade 2 265 (56.9) 212 (61.4) 52 (44.4) 95 (54.0) 86 (54.1) 83 (65.4) GOLD grade 3 130 (27.9) 89 (25.8) 38 (32.5) 52 (29.5) 45 (28.3) 30 (23.6) GOLD grade 4 26 (5.6) 11 (3.2) 15 (12.8) 12 (6.8) 10 (6.3) 4 (3.1) Asthma 152 (32.7) 107 (31.1) 43 (36.8) 54 (30.7) 55 (34.8) 41 (32.3) Chronic bronchitis 155 (33.3) 113 (32.8) 41 (35.0) 57 (32.4) 39 (24.7) 58 (45.7) Coronary heart disease 47 (10.1) 33 (9.6) 14 (12.0) 15 (8.5) 14 (8.8) 18 (14.2) Heart failure 22 (4.7) 13 (3.8) 9 (7.7) 7 (4.0) 8 (5.0) 7 (5.5) Depression or anxiety 104 (22.4) 76 (22.2) 27 (23.1) 37 (21.1) 40 (25.3) 26 (20.5) ICS, current use 264 (57.6) 189 (55.6) 72 (63.2) 99 (56.6) 89 (58.2) 73 (57.9) LABA, current use 250 (53.6) 178 (51.6) 69 (59.0) 93 (52.8) 93 (58.5) 61 (48.0) LAMA, current use 292 (62.7) 209 (60.6) 81 (69.2) 107 (60.8) 103 (64.8) 80 (63.0) Long-term oxygen, current use 9 (1.9) 7 (2.0) 2 (1.7) 5 (2.8) 4 (2.5) 0 (0.0) B-leukocytes 7.5 (6.5–8.9) 7.3 (6.3–8.6) 8.4 (7.1–10.2) 7.1 (6.1–8.4) 7.6 (6.5–9.0) 7.9 (7.0–9.6) B-Eos 0.2 (0.1–0.3) 0.2 (0.1–0.3) 0.2 (0.1–0.3) 0.1 (0.1–0.1) 0.2 (0.2–0.2) 0.4 (0.3–0.4) B-Eos categories <150 176 (38.1) 122 (35.4) 54 (46.2) 176 (100.0) 0 (0.0) 0 (0.0) ≥150–<300 159 (34.4) 125 (36.2) 34 (29.1) 0 (0.0) 159 (100.0) 0 (0.0) ≥300 127 (27.5) 98 (28.4) 29 (24.8) 0 (0.0) 0 (0.0) 127 (100.0) B-neutrophils 4.6 (3.7–5.6) 4.2 (3.4–4.9) 6.0 (5.0–7.2) 4.6 (3.6–5.4) 4.4 (3.5–5.6) 4.7 (3.8–5.8) B-lymphocytes 2.0 (1.6–2.5) 2.2 (1.8–2.6) 1.5 (1.2–1.8) 1.8 (1.5–2.3) 2.1 (1.6–2.6) 2.0 (1.7–2.6) NLR 2.2 (1.7–3.0) 2.0 (1.5–2.4) 3.9 (3.4–4.9) 2.4 (1.9–3.2) 2.1 (1.6–2.8) 2.2 (1.6–2.9) NLR ≥3.00 117 (25.3) 0 (0.0) 117 (100.0) 54 (30.7) 34 (21.4) 29 (22.8) Thrombocytes 267±69 266±68 268±72 257±70 273±65 271±71 Data presented as n (%) for categorical and binary variables and mean±sd or median (interquartile range) for quantitative variables, unless otherwise stated. NLR: blood neutrophil-to-lymphocyte ratio; B-Eos: blood eosinophils; BMI: body mass index; CAT: COPD Assessment Test; AECOPD: acute exacerbation of COPD; FEV1: forced expiratory volume in 1 s; GOLD: Global initiative for Obstructive Lung Disease; ICS: inhaled corticosteroids; LABA: long-acting β2-agonists; LAMA: long-acting muscarinic antagonists. #: sum of strata (n=462) does not equal total population (n=466) due to missing blood cell data.
- TABLE 2
Mixed-effects single variable logistic regression models on the association of neutrophil-to-lymphocyte ratio and blood eosinophils to risk of acute exacerbation of COPD the following year
OR (95% CI) NLR, continuous variable Entire study population 1.48 (1.21–1.81) No AECOPD previous year 1.23 (0.88–1.72) ≥1 AECOPD previous year 1.64 (1.14–2.36) NLR ≥3.00 versus <3.00 Entire study population 1.61 (0.91–2.84) No AECOPD previous year 0.89 (0.36–2.22) ≥1 AECOPD previous year 2.88 (1.00–8.25) B-Eos, continuous variable# Entire study population 1.02 (0.86–1.19) No AECOPD previous year 1.10 (0.87–1.37) ≥1 AECOPD previous year 0.96 (0.72–1.28) B-Eos ≥300 versus <300 cells·µL−1 Entire study population 1.47 (0.83–2.63) No AECOPD previous year 2.10 (0.84–5.15) ≥1 AECOPD previous year 1.15 (0.40–3.28) Models were calculated for the entire study population, and for observations where the subjects had and had not had an acute exacerbation the previous year, respectively. Each row represents a separate model. NLR: blood neutrophil-to-lymphocyte ratio; AECOPD: acute exacerbation of COPD; B-Eos: blood eosinophils. #: per 100 cells·µL−1 increase.
- TABLE 3
Mixed-effects multivariable logistic regression models on the association of neutrophil-to-lymphocyte ratio and blood eosinophils with the risk of acute exacerbation of COPD the following year
Models with NLR only# Models with B-Eos only# Models combining NLR and B-Eos¶ aOR (95% CI) aOR (95% CI) aOR (95% CI) NLR, continuous variable 1.20 (1.04–1.38) x 1.22 (1.06–1.40) NLR ≥3.00 versus <3.00 1.13 (0.76–1.68) x 1.13 (0.76–1.67) B-Eos, continuous variable+ x 1.08 (0.98–1.20) 1.10 (0.997–1.22) B-Eos ≥300 versus <300 x 1.54 (1.06–2.24) 1.54 (1.06–2.24) x indicates predictor not analysed. Models adjusted for ≥1 acute exacerbation of COPD preceding year, COPD Assessment Test score, body mass index, current smoking, current inhaled corticosteroid use, forced expiratory volume in 1 s, sex and age. Complete estimates for all predictors are shown in supplementary table S7. NLR: blood neutrophil-to-lymphocyte ratio; B-Eos: blood eosinophils; aOR: adjusted odds ratio. #: each aOR represents a separate model; ¶: two models, one for the two continuous variables and one for the two dichotomous; +: per 100 cells·µL−1 increase
Supplementary Material
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Supplementary material 00471-2021.SUPPLEMENT
