Eosinophilic and non-eosinophilic COPD patients with chronic respiratory failure: neutrophil-to-lymphocyte ratio as an exacerbation marker

Figures & data

Figure 1 Flowchart of patient enrollment.

Abbreviations: ALS, amyotrophic lateral sclerosis; CBC, complete blood count; CRF, chronic respiratory failure; CRP, C-reactive protein; ILD, interstitial lung disease; OHS, obesity hypoventilation syndrome.

Figure 2 Flowchart of MEMs in COPD patients with CRF.

Notes: Exacerbation and stable groups were defined by using MEMs. Patients were grouped into two according to NLR cutoff value and evaluated for the presence of PBE.
Abbreviations: CRF, chronic respiratory failure; CRP, C-reactive protein; MEM, modified exacerbation model; NLR, neutrophil-to-lymphocyte ratio; PBE, peripheral blood eosinophilia; WBC, white blood cell.

Table 1 Characteristics of COPD patients with CRF

Variables	N	Values
Gender, male (n, %)	636	60
Age, median (IQR) (years)	1,066	67 (60–75)
BMI, median (IQR) (kg/m^2)	728	26 (21–33)
Cigarette, median (IQR) (pack/year)	223	45 (33–70)
LTOT (n, %)	392	65
Home noninvasive ventilation (n, %)	266	44
ABGs
pH, mean ± SD	423	7.39±0.04
PaCO2, mean ± SD (mmHg)	423	49±8
PaO2/FiO2, median (IQR)	395	300 (265–357)
HCO3, median (IQR) (mmol)	423	29 (27–32)
SaO2, mean ± SD (%)	399	92±5
Spirometry values
FEV1, median (IQR) (mL)	355	730 (570–970)
FEV1, median (IQR) (%)	345	31 (23–43)
FVC, median (IQR) (mL)	355	1,320 (1,005–1,730)
FVC, median (IQR) (%)	355	43 (32–53)
FEV1/FVC, median (IQR) (%)	355	57 (49–65)
CBC
Leukocyte, mean ± SD (×10^9/L)	1,066	8.42±2.76
Neutrophil, mean ± SD (×10^9/L)	1,066	5.7±2.5
Neutrophil, mean ± SD (%)	1,066	66±10
Lymphocyte, median (IQR) (×10^9/L)	1,066	1.78 (1.39–2.23)
Lymphocyte, mean ± SD (%)	1,066	23±8
Eosinophil, median (IQR) (×10^9/L)	1,066	0.15 (0.09–0.23)
Eosinophil, median (IQR) (%)	1,066	2.02 (1.23–3.10)
Erythrocyte, mean ± SD (×10^12/L)	1,066	4.67±0.72
Hemoglobin, mean ± SD (g/dL)	1,066	13.2±2.1
Hct, mean ± SD (%)	1,066	41±6
MCV, mean ± SD (fL)	1,066	87±7
Platelet, mean ± SD (×10^9/L)	1,062	247±92
NLR, median (IQR)	1,066	2.90 (2.12–3.99)
CRP, median (IQR) (mg/dL)	1,042	9.9 (3.6–17.7)

Abbreviations: ABG, arterial blood gas; BMI, body mass index; CBC, complete blood count; CRF, chronic respiratory failure; CRP, C-reactive protein; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; Hct, hematocrit; IQR, interquartile range; LTOT, long-term oxygen therapy; MVC, mean corpuscular volume; NLR, neutrophil-to-lymphocyte ratio; PLT, platelet.

Table 2 Patient distribution in MEMs

Models	Attack, N (%)	Stable, N (%)
Exacerbation model A	73 (7)	993 (93)
Exacerbation model B	173 (16)	893 (84)
Exacerbation model C	192 (18)	874 (82)
Exacerbation model D	218 (20)	848 (80)

Notes: Model A: WBC ≥12,000/mm³, CRP >10 mg/dL for attack group; WBC <12,000/mm³, CRP <10 mg/dL for stable group. Model B: WBC ≥10,000/mm³, CRP >10 mg/dL for attack group; WBC <10,000/mm³, CRP <10 mg/dL for stable group. Model C: WBC ≥10,000/mm³, CRP >8 mg/dL for attack group; WBC <10,000/mm³, CRP <8 mg/dL for stable group. Model D: WBC ≥10,000/mm³, CRP >5 mg/dL for attack group; WBC ≥10,000/mm³, CRP >5 mg/dL for stable group.

Abbreviations: CRP, C-reactive protein; MEM, modified exacerbation model; WBC, white blood cell.

Table 3 The sensitivity and specificity of NLR ≥3.54 value in MEMs

	Specificity (%)	Sensitivity (%)	PPV	NPV
Model A	69	78	0.15	0.84
Model B	71	63	0.29	0.41
Model C	72	61	0.31	0.68
Model D	71	58	0.34	0.65

Notes: Model A: WBC ≥12,000/mm³, CRP >10 mg/dL for attack group; WBC <12,000/mm³, CRP <10 mg/dL for stable group. Model B: WBC ≥10,000/mm³, CRP >10 mg/dL for attack group; WBC <10,000/mm³, CRP <10 mg/dL for stable group. Model C: WBC ≥10,000/mm³, CRP >8 mg/dL for attack group; WBC <10,000/mm³, CRP <8 mg/dL for stable group. Model D: WBC ≥10,000/mm³, CRP >5 mg/dL for attack group; WBC ≥10,000/mm³, CRP >5 mg/dL for stable group.

Abbreviations: CRP, C-reactive protein; MEM, modified exacerbation model; NLR, neutrophil-to-lymphocyte ratio; NPV, negative predictive value; PPV, positive predictive value; WBC, white blood cell.

Figure 3 ROC curves, the optimal cutoff value, sensitivity, and specificity of NLR for MEMs (models A, B, C, D).

Notes: ROC-AUC was used to asses “patients’ NLR value” in all four attack models. NLR cutoff value was found according to ROC curves. (A) The cutoff value, sensitivity, and specificity of NLR for exacerbation model A. (B) The cutoff value, sensitivity, and specificity of NLR for exacerbation model B. (C) The cutoff value, sensitivity, and specificity of NLR for exacerbation model C. (D) The cutoff value, sensitivity, and specificity of NLR for exacerbation model D. Diagonal segments are produced by ties.
Abbreviations: AUC, area under the curve; MEM, modified exacerbation model; NLR, neutrophil-to-lymphocyte ratio; ROC, receiver operating characteristic.

Table 4 Ratio of the COPD patients with CRF according to the NLR and peripheral blood eosinophil count in MEMs

	Model A		Model B		Model C		Model D
	Attack, N (%)	Stable, N (%)	Attack, N (%)	Stable, N (%)	Attack, N (%)	Stable, N (%)	Attack, N (%)	Stable, N (%)
Non-eosinophilic <2%
NLR ≥3.54	54 (78)	300 (32)	106 (66)	248 (29)	113 (63)	241 (29)	122 (60)	232 (29)
NLR <3.54	15 (22)	649 (68)	55 (34)	609 (71)	66 (37)	598 (71)	82 (40)	582 (72)
Eosinophilic ≥2%
NLR <3.54	1 (25)	35 (80)	9 (75)	27 (75)	9 (69)	27 (77)	10 (71)	26 (76)
NLR ≥3.54	3 (75)	9 (20)	3 (25)	9 (25)	4 (31)	8 (23)	4 (29)	8 (24)

Notes: Model A: WBC ≥12,000/mm³, CRP >10 mg/dL for attack group; WBC <12,000/mm³, CRP <10 mg/dL for stable group. Model B: WBC ≥10,000/mm³, CRP >10 mg/dL for attack group, WBC <10,000/mm³, CRP <10 mg/dL for stable group. Model C: WBC ≥10,000/mm³, CRP>8 mg/dL for attack group; WBC <10,000/mm³, CRP <8 mg/dL for stable group. Model D: WBC ≥10,000/mm³, CRP >5 mg/dL for attack group; WBC ≥10,000/mm³, CRP >5 mg/dL for stable group. Eosinophilic, peripheral blood eosinophil count ≥2%; non-eosinophilic, peripheral blood eosinophil count <2%.

Abbreviations: CRF, chronic respiratory failure; CRP, C-reactive protein; MEM, modified exacerbation model; NLR, neutrophil-to-lymphocyte ratio; WBC, white blood cell.