Blood Urea Nitrogen to Serum Albumin Ratio: A Good Predictor of In-Hospital and 90-Day All-Cause Mortality in Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Zixiong Zeng; Xiaocui Ke; Shan Gong; Xin Huang; Qin Liu; Xiaoying Huang; Juan Cheng; Yuqun Li; Liping Wei

BMC Pulm Med. 2022;22(476)

Abstract and Introduction

Abstract

Background: Previous studies on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have found that those who died in hospital had higher blood urea nitrogen levels and a worse nutritional status compared to survivors. However, the association between the blood urea nitrogen to serum albumin ratio (BUN/ALB ratio) and in-hospital and short-term prognosis in patients with AECOPD remains unclear. The aim of this study was to explore the usefulness of BUN/ALB ratio in AECOPD as an objective predictor for in-hospital and 90-day all-cause mortality.

Methods: We recorded the laboratory and clinical data in patients with AECOPD on admission. By drawing the ROC curve for the patients, we obtained the cut-off point for the BUN/ALB ratio for in-hospital death. Multivariate logistic regression was used for analyses of the factors of in-hospital mortality and multivariate Cox regression was used to analyze the factors of 90-day all-cause mortality.

Results: A total of 362 patients were recruited and 319 patients were finally analyzed. Twenty-three patients died during hospitalization and the fatality rate was 7.2%. Furthermore, 14 patients died by the 90-day follow-up. Compared with in-hospital survivors, patients who died in hospital were older (80.78 ± 6.58 vs. 75.09 ± 9.73 years old, P = 0.001), had a higher prevalence of congestive heart failure(69.6% vs. 27.4%, P < 0.001), had a higher BUN/ALB ratio [0.329 (0.250–0.399) vs. 0.145 (0.111–0.210), P < 0.001], had higher neutrophil counts [10.27 (7.21–14.04) vs. 6.58 (4.58–9.04), P < 0.001], higher blood urea nitrogen levels [10.86 (7.10–12.25) vs. 5.35 (4.14–7.40), P < 0.001], a lower albumin level (32.58 ± 3.72 vs. 36.26 ± 4.53, P < 0.001) and a lower lymphocyte count [0.85 (0.58–1.21) vs. 1.22 (0.86–1.72), P = 0.001]. The ROC curve showed that the area under the curve (AUC) of BUN/ALB ratio for in-hospital death was 0.87, (95%CI 0.81–0.93, P < 0.001), the best cut-off point value to discriminate survivors from non-survivors in hospital was 0.249, the sensitivity was 78.3%, the specificity was 86.5%, and Youden's index was 0.648. Having a BUN/ALB ratio ≥ 0.249 was an independent risk factor for both in-hospital and 90-day all-cause mortality after adjustment for relative risk (RR; RR = 15.08, 95% CI 3.80–59.78, P < 0.001 for a multivariate logistic regression analysis) and hazard ratio (HR; HR = 5.34, 95% CI 1.62–17.57, P = 0.006 for a multivariate Cox regression analysis).

Conclusion: An elevated BUN/ALB ratio was a strong and independent predictor of in-hospital and 90-day all-cause mortality in patients with AECOPD.

Introduction

Chronic obstructive pulmonary disease (COPD), a complex multi-component disease with chronic systemic inflammation, is a common cause of death around the world.^[1,2] Acute exacerbations in COPD (AECOPD) are key events and they negatively influence the health status of patients, rates of hospitalization, readmission, and disease progression.^[3,4] However, effective methods to identify hospitalized patients with AECOPD with poor outcomes are still lacking. It is vital for clinicians to pay more attention to evaluating the severity and prognosis of patients with AECOPD in advance. Some severity scoring systems had been developed to assist with predicting the outcomes for AECOPD, such as the APACHE II score, DECAF score and SAPS II score.^[5–7] Although these scoring systems have shown great potential for accurately predicting AECOPD prognoses,^[6,8,9] not all patients cooperate with clinicians' investigations; for example, patients with dementia or the elderly. In addition, the subjectivity of some clinicians may affect the scoring system.^[10]

Based on previous studies, many blood biomarkers have been reported to predict the prognoses and indicate the severity of AECOPD, such as C-reactive protein and procalcitonin.^[11,12] Previous studies have found that non-survivors had higher blood urea nitrogen (BUN) levels and poorer nutritional status than survivors.^[13–15] Therefore, we hypothesized that patients with AECOPD with a higher BUN/ALB ratio have an inverse relationship with poorer outcomes of COPD exacerbation. However, to our knowledge, there is no study that has explored the association between BUN/ALB ratio and in-hospital mortality and the short-term prognosis in patients with AECOPD. Accordingly, the objective of our study was to ascertain the prognostic role of BUN/ALB ratio for in-hospital and 90-day all-cause mortality in AECOPD.

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Abstract and Introduction
Methods
Results
Discussion
Conclusion
References

Table 1. Characteristics of AECOPD patients according to in-hospital mortality
Characteristic	Non-survivors (n = 23)	Survivors (n = 296)	P value
Age, years	80.78 ± 6.58	75.09 ± 9.73	0.001
BMI, kg/m²	20.07 ± 3.97	21.05 ± 3.89	0.244
Sex, n (%)			0.308
Male	17 (73.9)	244 (82.4)
Female	6 (26.1)	52 (17.6)
Smoking status, n (%)			0.920
Never smoker	4 (17.4)	61 (20.6)
Current/ever smoker	19 (82.6)	235 (79.4)
Hospital stay, days	7.7 ± 4.6	8.0 ± 3.0	0.795
Exacerbations during preceding year, n (%)	15 (65.2)	127 (42.9)	0.038
GOLD stage, n (%)			0.771
I	1 (4.3)	20 (6.7)
II	11 (47.8)	110 (37.2)
III	8 (34.8)	116 (39.2)
IV	3 (13.0)	50 (16.9)
CHF, n (%)	16 (69.6)	81 (27.4)	< 0.001
RD, n (%)	10 (43.5)	141 (47.6)	0.701
Bronchiectasis, n (%)	4 (17.4)	91 (30.7)	0.238
Diabetes, n (%)	2 (8.7)	30 (10.1)	0.825
Hypertension, n (%)	13 (56.5)	163 (55.1)	0.893
CHD, n (%)	8 (34.8)	76 (25.7)	0.339
Neutrophil count, × 10⁹/L	10.27 (7.21–14.04)	6.58 (4.58–9.04)	< 0.001
Lymphocyte count, × 10⁹/L	0.85 (0.58–1.21)	1.22 (0.86–1.72)	0.001
PH	7.36 ± 0.15	7.40 ± 0.04	0.262
PaO₂, mmHg	85.1 ± 33.2	90.0 ± 25.2	0.382
PaCO₂, mmHg	50.7 ± 23.4	44.7 ± 10.2	0.231
BUN, mmol/L	10.86 (7.10–12.25)	5.35 (4.14–7.40)	< 0.001
ALB, g/L	32.58 ± 3.72	36.26 ± 4.53	< 0.001
BUN/ALB ratio	0.329 (0.250–0.399)	0.145 (0.111–0.210)	< 0.001

Variables are expressed as mean ± standard deviation (SD), medians (interquartile range, IQR) or percentages
GOLD Global Initiative for Chronic Obstructive Lung Disease, CHF congestive heart failure, RD renal dysfunction, CHD coronary heart disease, PaO₂ arterial oxygen tension, PaCO₂ arterial carbon dioxide tension, BUN blood urea nitrogen, ALB albumin, BUN/ALB ratio blood urea nitrogen to serum albumin ratio

Table 2. Comparison of the ROC curve analysis of BUN/ALB ratio, 1/ALB, and BUN for predicting in-hospital mortality
Parameters	AUC	95% CI	Cut-off value	Sensitivity,%	Specificity,%	Youden's index	P value
BUN/ALB ratio	0.87	0.81–0.93	0.249	78.3	86.5	0.648	< 0.001
1/ALB	0.73	0.64–0.82	0.028	82.6	56.1	0.387	< 0.001
BUN, mmol/L	0.85	0.77–0.92	9.06	69.6	87.8	0.574	< 0.001

AUC area under the curve, CI confidence interval

Table 3. Baseline characteristics stratified by BUN/ALB ratio
Characteristic	BUN/ALB ratio ≥ 0.249 (59)	BUN/ALB ratio < 0.249 (260)	P value
Hospitalization mortality (%)	30.5	1.9	< 0.001
Age, years	80.5 ± 8.3	74.4 ± 9.6	< 0.001
BMI, kg/m²	20.46 ± 3.83	21.10 ± 3.91	0.257
Sex, n (%)			0.518
Male	50 (84.7)	211 (81.2)
Female	9 (15.3)	49 (18.8)
Smoking status, n (%)			0.469
Never smoked	10 (16.9)	55 (21.2)
Current smoker/Ever smoked	49 (83.1)	205 (78.8)
Hospital stay, days	8.2 ± 4.2	7.9 ± 2.8	0.472
Exacerbations during preceding year, n (%)	27 (45.8)	115 (44.2)	0.831
GOLD stage, n (%)			0.485
I	3 (5.0)	18 (6.9)
II	27 (45.8)	94 (36.2)
III	22 (37.3)	102 (39.2)
IV	7 (11.9)	46 (17.7)
CHF, n (%)	26 (44.1)	71 (27.3)	0.012
RD, n (%)	37 (62.7)	114 (43.8)	0.009
Bronchiectasis, n (%)	16 (27.1)	79 (30.4)	0.620
Diabetes, n (%)	6 (10.2)	26 (10.0)	0.969
Hypertension, n (%)	40 (67.8)	136 (52.3)	0.031
CHD, n (%)	22 (37.3)	62 (23.8)	0.034
Neutrophil count, × 10⁹/L	10.27 (7.21–14.04)	6.58 (4.58–9.04)	0.001
Lymphocyte count, × 10⁹/L	0.85 (0.58–1.21)	1.22 (0.86–1.72)	< 0.001
PH	7.38 ± 0.09	7.40 ± 0.05	0.239
PaO₂, mmHg	90.7 ± 29.0	89.4 ± 25.2	0.732
PaCO₂, mmHg	44.9 ± 14.3	45.2 ± 11.0	0.870
BUN, mmol/L	10.86 (7.10–12.25)	5.35 (4.14–7.40)	< 0.001
ALB, g/L	32.69 ± 4.36	36.74 ± 4.28	< 0.001

Variables are expressed as mean ± standard deviation (SD), medians (interquartile range, IQR) or percentages.
CHF congestive heart failure, RD renal dysfunction, CHD coronary heart disease, PaO₂ arterial oxygen tension, PaCO₂ arterial carbon dioxide tension, BUN blood urea nitrogen, ALB albumin

Table 4. Univariate and multivariate logistic regression analyses of factors affecting in-hospital mortality
Variable	Univariate analysis		Multivariate analysis
Variable	RR (95% CI)	P value	RR (95% CI)	P value
Age (per increase of 5-year)	1.47 (1.11–1.96)	0.008	0.95 (0.60–1.51)	0.836
BMI (per increase of 1 point)	0.94 (0.84–1.05)	0.243	0.90 (0.76–1.06)	0.201
Sex (female vs. male)	0.60 (0.23–1.61)	0.312	0.35 (0.05–2.19)	0.259
Smoking status (never smoker vs. current/ever smoker)	1.23 (0.41–3.76)	0.713	3.09 (0.40–23.70)	0.277
Exacerbations during preceding year (yes vs. no)	2.50 (1.03–6.07)	0.044	2.93 (0.74–11.59)	0.127
GOLD stage (per increase to next stage)	0.87 (0.52–1.45)	0.590
CHF (yes vs. no)	6.07 (2.41–15.29)	< 0.001	4.36 (1.07–17.85)	0.040
RD (yes vs. no)	0.85 (0.36–1.99)	0.701	0.32 (0.09–1.13)	0.076
Bronchiectasis (yes vs. no)	0.47 (0.16–1.43)	0.186
Diabetes (yes vs. no)	0.84 (0.19–3.78)	0.825
Hypertension (yes vs. no)	1.06 (0.45–2.50)	0.893
CHD (yes vs. no)	1.54 (0.63–3.79)	0.343
Neutrophil count(per increase of 1 × 10⁹/L)	1.16 (1.08–1.24)	< 0.001	1.15 (1.02–1.30)	0.020
Lymphocyte count(per increase of 1 × 10⁹/L)	0.24 (0.09–0.59)	0.002	0.36 (0.09–1.47)	0.154
PH
(PH < 7.35 vs. 7.35 ≤ PH ≤ 7.45)	5.08 (1.78–14.48)	0.002	8.87 (1.62–48.55)	0.012
(PH > 7.45 vs. 7.35 ≤ PH ≤ 7.45)	7.31 (2.51–21.32)	< 0.001	4.04 (0.87–18.81)	0.075
PaO₂ (≥ 60 vs. < 60 mmHg)	4.56 (1.51–13.77)	0.007	4.86 (0.89–26.67)	0.069
PaCO₂ (≥ 50 vs. < 50 mmHg)	1.88 (0.74–4.77)	0.187
BUN/ALB ratio (≥ 0.249 vs. < 0.249)	22.39 (7.88–63.62)	< 0.001	15.08 (3.80–59.78)	< 0.001

Table 5. The influence of BUN/ALB ratio on 90-day all-cause mortality by multivariate Cox proportional hazards analysis
Variable	Model 1		Model 2		Model 3
Variable	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
BUN/ALB ratio (≥ 0.249 vs. < 0.249)	6.62 (2.32–18.88)	< 0.001	4.08 (1.32–12.58)	0.014	5.34 (1.62–17.57)	0.006
Age (per increase of 5-year)			1.71 (1.13–2.59)	0.012	2.30 (1.32–4.01)	0.003
BMI (per increase of 1 point)			0.98 (0.85–1.12)	0.730	1.02 (0.89–1.18)	0.751
Sex (male vs. female)			0.64 (0.18–2.35)	0.505	0.46 (0.10–2.05)	0.305
Smoking status (current/ever smoker vs. never smoker)			0.92 (0.25–3.36)	0.904	1.20 (0.27–5.23)	0.812
Exacerbations during preceding year (yes vs. no)					1.46 (0.48–4.44)	0.509
GOLD stage (per increase to next stage)					3.01 (1.07–8.41)	0.036
PaCO₂ (≥ 50 vs. < 50 mmHg)					2.03 (0.46–8.92)	0.349
CHF (yes vs. no)					0.83 (0.23–3.00)	0.779
RD (yes vs. no)					0.46 (0.14–1.47)	0.191
Bronchiectasis (yes vs. no)					0.64 (0.16–2.57)	0.533
Diabetes (yes vs. no)					2.05 (0.37–11.29)	0.411
Hypertension (yes vs. no)					0.75 (0.19–2.99)	0.686
CHD (yes vs. no)					2.72 (0.82–9.08)	0.104