The Relationship Between Prognostic Nutritional Indexes and the Clinical Outcomes of Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Figures & data

Figure 1 Flowchart of the study participants.

Abbreviations: AECOPD, acute exacerbation of chronic obstructive pulmonary disease; ICU, intensive care unit.

Table 1 Baseline Characteristics of the Cohort Study Population by Prognostic Nutritional Index Tertiles

Characteristics	PNI Tertiles
	Low Tertile ≤ 40.8, n=127)	Middle Tertile (40.8–46.0, n=129)	High Tertile (>46.0, n=129)	P value
Age, years	74.9 ± 9.2	74.7 ± 8.2	73.1 ± 8.5	0.168
Male, n (%)	111 (87.4)	114 (88.4)	113 (87.6)	0.969
^aBMI, kg/m^2	20.0 ± 3.6	20.9 ± 4.3	21.1 ± 3.7	0.047
Smoking history, n (%)				0.342
Current-smoker	21 (16.7)	25 (19.4)	34 (26.4)
Previous smoker	85 (67.5)	84 (65.1)	73 (56.6)
Non-smoker	20 (15.9)	20 (15.5)	22 (17.1)
Drinking, n (%)	12 (9.7)	6 (4.7)	14 (10.9)	0.163
SBP, mmHg	134.8 ± 19.8	134.1 ± 20.3	135.9 ± 20.1	0.757
DBP, mmHg	78.8 ± 11.9	77.9 ± 12.6	77.3 ± 12.5	0.588
Comorbidities, n (%)
Coronary artery disease	20 (15.8)	23 (17.8)	23 (17.8)	0.878
Congestive heart failure	4 (3.2)	6 (4.7)	5 (3.9)	0.825
Arrhythmia	2 (1.6)	9 (7.0)	7 (5.4)	0.109
Chronic kidney disease	4 (3.2)	3 (2.3)	3 (2.3)	0.892
Diabetes	14 (11.0)	19 (14.7)	13 (10.1)	0.477
Hypertension	54 (42.5)	63 (48.8)	58 (45.0)	0.592
aCCI	4.0 (3.0–4.0)	4.0 (3.0–5.0)	4.0 (3.0–4.0)	0.470
Biochemistry
Leukocytes, ×10^9/L	8.7 ± 3.7	8.8 ± 4.2	10.2 ± 4.1	0.002
Lymphocytes, ×10^9/L	0.8 ± 0.4	1.2 ± 0.5	1.8 ± 0.7	<0.001
Neutrophils, ×10^9/L	7.1 ± 3.7	6.7 ± 4.1	7.4 ± 4.2	0.301
Monocytes, ×10^9/L	0.6 ± 0.4	0.7 ± 1.1	0.8 ± 0.3	<0.001
Eosinophils, ×10^9/L	0.0 (0.0–0.1)	0.1 (0.0–0.2)	0.2 (0.1–0.3)	<0.001
Platelet, ×10^9/L	215.2 ± 90.7	230.4 ± 102.9	246.3 ± 88.5	0.032
Red blood cell, ×10^12/L	4.4 ± 0.8	4.5 ± 0.8	4.8 ± 0.7	<0.001
Hemoglobin, g/L	126.7 ± 22.7	130.7 ± 20.1	139.4 ± 17.3	<0.001
NT-proBNP, pg/mL	495.1 (138.9–2151.5)	240.1 (93.6–1218.0)	102.1 (51.7–432.2)	<0.001
D-dimer, mg/L	1.0 (0.5–2.2)	0.6 (0.3–1.4)	0.5 (0.3–1.0)	0.014
Fibrinogen, g/L	4.2 ± 1.6	4.1 ± 1.4	3.9 ± 1.2	0.29
Cr, umol/L	86.1 ± 48.0	85.0 ± 36.3	86.0 ± 31.7	0.97
BUN, mmol/L	7.8 ± 4.5	6.9 ± 3.2	6.7 ± 2.6	0.046
TP, g/L	61.8 ± 6.5	67.2 ± 6.4	71.2 ± 6.5	<0.001
Albumin, g/L	32.5 ± 2.7	37.3 ± 2.4	40.9 ± 3.2	<0.001
Serum sodium, mmol/L	136.9 ± 5.3	137.2 ± 5.0	137.7 ± 4.4	0.435
Serum potassium, mmol/L	4.1 ± 0.6	4.1 ± 0.5	4.2 ± 0.6	0.098
Serum calcium, mmol/L	2.1 (2.0–2.2)	2.2 (2.11–2.3)	2.3 (2.2–2.3)	<0.001
^bTC, mmol/L	4.3 ± 1.2	4.6 ± 1.2	4.9 ± 1.1	0.014
TG, mmol/L	0.9 ± 0.5	1.0 ± 0.4	1.0 ± 0.5	0.535
HDL-c, mmol/L	1.2 ± 0.3	1.3 ± 0.3	1.3 ± 0.3	0.137
LDL-c, mmol/L	2.7 ± 0.8	2.8 ± 0.9	3.0 ± 0.8	0.021
CRP, mg/L	28.6 (8.0–72.4)	9.0 (2.6–28.5)	4.4 (2.0–19.6)	0.006
PCT, ng/mL	0.1 (0.1–0.2)	0.1 (0.0–0.1)	0.1 (0.0–0.1)	<0.001
LDH, IU/L	237.5 ± 139.3	224.3 ± 84.2	212.9 ± 68.0	0.196
pH	7.4 ± 0.1	7.4 ± 0.1	7.4 ± 0.1	0.927
PaO2, mmHg	82.5 ± 37.8	81.2 ± 26.6	85.1 ± 28.8	0.684
^cPaCO2, mmHg	60.5 ± 19.5	55.3 ± 19.6	50.1 ± 18.4	0.001
Length of stay, days	11.6 ± 13.0	9.3 ± 5.1	9.1 ± 6.1	0.039
Required NIMV, n (%)	39 (30.7)	25 (19.4)	13 (10.1)	<0.001
Worse outcome, n (%)	30 (23.6)	17 (13.2)	8 (6.2)	<0.001
Invasive ventilation	13 (10.2)	10 (7.7)	6 (4.6)	0.237
ICU admission	26 (20.5)	15 (11.6)	5 (3.9)	<0.001
Mortality	10 (7.9)	1 (0.8)	3 (2.3)	0.006

Notes: Normally distributed data are presented as the mean ± SD, non-normally distributed data are presented as median (IQR) and categorical variables are presented as n (%). ^aBMI, was available for 312 subjects (89 with low tertile, 109 with middle tertile and 114 with high tertileI); ^bTC was available for 247 subjects (78 with low tertile, 83 with middle tertile and 86 with high tertileI); ^cP_aCO₂ was available for 281 subjects (93 with low tertile, 95 with middle tertile and 93 with high tertileI).

Abbreviations: PNI, prognostic nutritional index; SBP, systolic blood pressure; DBP, Diastole blood pressure; BMI, body mass index; aCCI, age-adjusted Charlson Comorbidity Index; NT-proBNP, N-terminal probrain natriuretic peptide; Cr, creatinine; BUN, blood urea nitrogen; TP, total protein; TC, total cholesterol; TG, triglyceride; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; PCT, procalcitonin; CRP, C-reactive protein; LDH, lactic dehydrogenase; NIMV, noninvasive mechanical ventilation; PaO₂, partial pressure of oxygen in arterial blood; PaCO₂, partial pressure of carbon dioxide in arterial blood; ICU, intensive care unit.

Table 2 Univariate Analysis for Adverse Hospitalization Outcomes

	Statistics	OR (95% CI)	P value
Age, years	74.2 ± 8.7	1.01 (0.98, 1.04)	0.5568
Sex			0.3119
Female	47 (12.2)	Ref
Male	338 (87.8)	0.67 (0.30, 1.47)
BMI, kg/m^2	20.7 ± 3.9	0.98 (0.88, 1.10)	0.7566
Smoking history, n (%)
Current-smoker	80 (20.8)	Ref
Previous smoker	242 (63.0)	1.47 (0.68, 3.19)	0.3304
Non-smoker	62 (16.2)	1.17 (0.42, 3.23)	0.7636
Drinking, n (%)			0.208
No	352 (91.7)	Ref
Yes	32 (8.3)	1.77 (0.73, 4.33)
SBP, mmHg	134.9 ± 20.0	1.00 (0.99, 1.01)	0.9477
DBP, mmHg	78.0 ± 12.3	0.97 (0.95, 0.99)	0.0151
Hypertension, n (%)			0.7699
No	210 (54.6)	Ref
Yes	175 (45.5)	0.92 (0.52, 1.63)
Diabetes, n (%)			0.2786
No	339 (88.1)	Ref
Yes	46 (11.9)	1.55 (0.70, 3.42)
Coronary artery disease, n (%)			0.0444
No	319 (82.9)	Ref
Yes	66 (17.1)	0.34 (0.12, 0.97)
Arrhythmia, n (%)			0.6944
No	367 (95.3)	Ref
Yes	18 (4.7)	0.74 (0.17, 3.31)
Congestive heart failure, n (%)			0.5217
No	370 (96.1)	Ref
Yes	15 (3.9)	1.53 (0.42, 5.60)
Chronic kidney disease, n (%)			0.6033
No	375 (97.4)	Ref
Yes	10 (2.6)	1.52 (0.31, 7.35)
aCCI	4.0 ± 1.0	1.13 (0.85, 1.50)	0.4011
Leukocytes, ×10^9/L	9.2 ± 4.1	1.04 (0.97, 1.11)	0.2888
Lymphocytes, ×10^9/L	1.3 ± 0.7	0.43 (0.25, 0.73)	0.0018
Neutrophils, ×10^9/L	7.0 ± 4.0	1.06 (1.00, 1.13)	0.0666
Monocytes, ×10^9/L	0.7 ± 0.7	0.69 (0.29, 1.66)	0.4069
Eosinophils, ×10^9/L	0.2 ± 0.2	0.12 (0.01, 0.94)	0.0441
Platelet, ×10^9/L	230.7 ± 94.9	1.00 (0.99, 1.00)	0.0336
Red blood cell, ×10^12/L	4.5 ± 0.8	0.62 (0.42, 0.90)	0.0131
Hemoglobin, g/L	132.2 ± 20.8	0.98 (0.97, 0.99)	0.0029
NT-proBNP, pg/mL	1400.5 ± 3762.8	1.00 (1.00, 1.00)	0.1177
D-dimer, mg/L	1.6 ± 3.6	1.09 (1.02, 1.17)	0.0124
Fibrinogen, g/L	4.1 ± 1.5	0.85 (0.68, 1.06)	0.1427
Cr, umol/L	85.7 ± 39.1	1.00 (0.99, 1.01)	0.7112
BUN, mmol/L	7.1 ± 3.5	1.15 (1.08, 1.23)	<0.0001
TP, g/L	66.8 ± 7.5	0.99 (0.95, 1.03)	0.675
Albumin, g/L	36.9 ± 4.4	0.91 (0.85, 0.97)	0.006
Serum sodium, mmol/L	137.3 ± 4.9	1.03 (0.97, 1.10)	0.278
Serum potassium, mmol/L	4.2 ± 0.6	2.40 (1.48, 3.89)	0.0004
Serum calcium, mmol/L	2.3 ± 2.8	0.03 (0.00, 0.26)	0.0021
TC, mmol/L	4.6 ± 1.2	0.66 (0.47, 0.93)	0.0169
TG, mmol/L	1.0 ± 0.5	1.01 (0.47, 2.18)	0.9737
HDL-c, mmol/L	1.2 ± 0.3	0.77 (0.24, 2.41)	0.6473
LDL-c, mmol/L	2.8 ± 0.8	0.63 (0.39, 1.02)	0.0619
CRP, mg/L	38.0 ± 59.6	1.00 (1.00, 1.01)	0.5021
PCT, ng/mL	0.2 ± 0.8	0.97 (0.66, 1.42)	0.8765
LDH, IU/L	224.7 ± 101.3	1.00 (1.00, 1.00)	0.537
pH	7.4 ± 0.1	0.00 (0.00, 0.00)	<0.0001
PaO2, mmHg	82.9 ± 31.3	1.00 (0.98, 1.01)	0.4053
PaCO2, mmHg	55.3 ± 19.6	1.05 (1.04, 1.07)	<0.0001
Length of stay, days	10.0 ± 8.8	1.15 (1.10, 1.21)	<0.0001
Required NIMV, n (%)			<0.0001
No	308 (80.0)	Ref
Yes	77 (20.0)	7.23 (3.91, 13.35)
PNI	43.4 ± 6.1	0.91 (0.87, 0.96)	0.0003

Abbreviations: SBP, systolic blood pressure; DBP, Diastole blood pressure; BMI, body mass index; aCCI, age-adjusted Charlson Comorbidity Index; NT-proBNP, N-terminal probrain natriuretic peptide; Cr, creatinine; BUN, blood urea nitrogen; TP, total protein; TC, total cholesterol; TG, triglyceride; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; PCT, procalcitonin; CRP, C-reactive protein; LDH, lactic dehydrogenase; NIMV, noninvasive mechanical ventilation; PaO₂, partial pressure of oxygen in arterial blood; PaCO₂, partial pressure of carbon dioxide in arterial blood; PNI, prognostic nutritional index.

Table 3 Unadjusted and Adjusted Logistic Regression Models of PNI and Adverse Hospitalization Outcomes

Adverse Hospitalization Outcomes	Crude Model	P value	Model 1	P value	Model 2	P value
	OR (95% CI)		OR (95% CI)		OR (95% CI)
PNI	0.91 (0.89, 0.93)	<0.0001	0.90 (0.88, 0.92)	<0.0001	0.94 (0.91, 0.97)	<0.0001
PNI
Low tertile	1.00 (Ref)		1.00 (Ref)		1.00 (Ref)
Middle tertile	0.49 (0.26, 0.94)	0.033	0.47 (0.24, 0.91)	0.0253	0.76 (0.31, 1.88)	0.5511
High tertile	0.21 (0.09, 0.49)	0.0002	0.20 (0.09, 0.47)	0.0002	0.37 (0.10, 1.34)	0.1292
P for trend	<0.0001		<0.0001		0.002

Notes: Model 1 adjusted for sex, age, BMI and smoking status; Model 2 further adjusted for comorbidities (including diabetes, hypertension, arrhythmia, congestive heart failure, chronic kidney disease and coronary artery disease), leukocytes, platelets, eosinophils, hemoglobin, blood urea nitrogen, serum sodium, serum potassium, serum calcium, total cholesterol, NT-proBNP, pH, PaCO₂, and required NIMV. Among the patients, 72 were missing BMI, accounting for approximately 18.9% of the total patients; 134 patients were missing TC, accounting for approximately 35.0% of the total patients. Multiple imputation was used for the models with BMI and TC, and the results are presented after multiple imputation.

Abbreviations: PNI, prognostic nutritional index; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; BMI, body mass index; NT-proBNP, N-terminal probrain natriuretic peptide; NIMV, noninvasive mechanical ventilation; PaCO₂, partial pressure of carbon dioxide in arterial blood; OR, odd ratios; CI, confidence intervals.

Table 4 The Results of the Two-Piecewise Linear Regression Model

	OR	95% CI	P value
Fitting model by standard linear regression	0.96	0.92 to 0.99	0.0108
Fitting model by two-piecewise linear regression
The inflection point of PNI
<42	0.87	0.82 to 0.92	<0.0001
≥42	1.05	0.99 to 1.11	0.0799
P for the log-likelihood ratio test	<0.001

Effect: Adverse hospitalization outcomes Cause: Prognostic nutritional index; Adjusted: Sex, age, BMI, smoking status, comorbidities (including hypertension, diabetes, arrhythmia, congestive heart failure, chronic kidney disease and coronary artery disease), leukocytes, platelets, eosinophils, hemoglobin, blood urea nitrogen, serum sodium, serum potassium, serum calcium, total cholesterol, NT-proBNP, pH, PaCO₂, and required NIMV.

Abbreviations: PNI, prognostic nutritional index; BMI, body mass index; NT-proBNP, N-terminal probrain natriuretic peptide; NIMV, noninvasive mechanical ventilation; PaCO₂, partial pressure of carbon dioxide in arterial blood; OR, odd ratios; CI, confidence intervals.

Figure 2 The relationship between PNI and adverse hospitalization outcomes. A nonlinear relationship was observed between the PNI and the adverse hospitalization outcomes after adjusting for sex, age, BMI, smoking status, comorbidities (including hypertension, diabetes, arrhythmia, congestive heart failure, chronic kidney disease and coronary artery disease), leukocytes, PLT, Eos, Hb, BUN, TC, NT-proBNP, pH, PaCO₂, serum potassium, serum calcium, serum sodium, and required NIMV. The solid black line in the figure represents the best-fit line, and the black dotted lines are 95% confidence intervals.

Abbreviations: PNI, prognostic nutritional index; BMI, body mass index; PLT, platelet; Eos, eosinophils; Hb, hemoglobin; BUN, blood urea nitrogen; TC, total cholesterol; NT-proBNP, N-terminal probrain natriuretic peptide; PaCO₂, partial pressure of carbon dioxide in arterial blood; NIMV, noninvasive mechanical ventilation.

Table 5 Subgroup Analyses of the Association Between PNI and Adverse Hospitalization Outcomes of AECOPD Patients

Subgroup	Participants (n)	OR (95% CI)	P value	P for Interaction
Age, years				0.48
< 75	184	0.96 (0.87, 1.07)	0.508
≥ 75	193	1.01 (0.91, 1.13)	0.8144
Sex				0.29
Female	47	0.97 (0.88, 1.06)	0.5001
Male	338	1.06 (0.90, 1.26)	0.4649
BMI, kg/m^2				0.57
< 20.56	156	0.88 (0.72, 1.08)	0.2131
≥ 20.56	156	0.96 (0.72, 1.27)	0.7711
Smoking history				0.17
Current-smoker	80	0.83 (0.67, 1.03)	0.0962
Previous smoker	242	1.01 (0.92, 1.12)	0.7987
Non-smoker	62	1.03 (0.86, 1.23)	0.7476
Required NIMV				0.93
No	308	0.99 (0.90, 1.09)	0.8434
Yes	77	0.98 (0.86, 1.13)	0.8053
TC, mmol/L				0.37
< 4.6	120	1.07 (0.83, 1.38)	0.6143
≥ 4.6	127	1.24 (0.95, 1.62)	0.1089
Hemoglobin, g/L				0.45
< 135	190	0.96 (0.86, 1.06)	0.3992
≥ 135	195	1.01 (0.89, 1.14)	0.8572
PaCO2, mmHg				0.99
≤ 45	101	0.99 (0.90, 1.08)	0.7831
> 45	180	0.99 (0.81, 1.21)	0.9023

Notes: Model was adjusted for white blood cell count, platelet count, eosinophils, hemoglobin, blood urea nitrogen, serum sodium, serum potassium, serum calcium, total cholesterol, NT-proBNP, pH, PaCO₂, and required NIMV. All covariates were adjusted for with the exception of the stratification variable.

Abbreviations: PNI, prognostic nutritional index; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; BMI, body mass index; NT-proBNP, N-terminal probrain natriuretic peptide; NIMV, noninvasive mechanical ventilation; PaCO₂, partial pressure of carbon dioxide in arterial blood; OR, odd ratios; CI, confidence intervals.

Data Sharing Statement

The dataset used and analyzed during the current study can be accessed by reasonable request from the authors.