Blood urea nitrogen(BUN) is the nitrogen component in urea, the final product of metabolism, which originates from the liver and is excreted by the kidney[22].Based on previous research findings[14, 15],and compared with survivors,a higher blood urea nitrogen level was found in those died in hospital.In this research, our results also showed that the non-survivor group had a higher BUN level than the survivor group during hospitalization.Thus,we believe that elevated BUN levels reflect the severity of the disease.In addition,BUN had been proved that had a certain predictive effect on the prognosis of the diseases[23, 24].And from (Fig. 2),we observed that BUN levels could predict the hospitalization outcome of the hospitalized AECOPD patients(AUC = 0.85,95%CI:0.77–0.92, P < 0.001).This was similar to previous findings which indicated that elevated BUN levels were associated with the prognosis of some diseases.And a study performed by Beier K et al also observed that among critically ill patients,an elevated blood urea nitrogen was associated with increased mortality[25].
COPD is often combined with digestion and absorption dysfunction and high energy consumption, causing the COPD patients to suffer from malnutrition.Not only malnutrition but also the systemic inflammatory response contribute to decrease the albumin levels in serum,leading to a poor prognosis in COPD patients[26, 27].In our cohort,we observed that those died during the hospitalization had lower albumin levels than the survivors,which was similar to the results of others[16].In clinical work,we had better pay more attention to the nutritional status of AECOPD patients.
Many studies had reported the prognostic value of the BUN/ALB ratio in some respiratory diseases.Motoi Ugajin et al[26]conducted a prospective study with 175 patients previously found that elevated BUN/ALB ratio was a simple but independent predictor of mortality and severity of community-acquired pneumonia.The BUN/ALB ratio could reflect the severity of the patients with pneumonia.For aspiration pneumonia patients,Ry u et al [28]demonstrated that the BUN/ALB ratio was associated with increased 28-day mortality.In addition,Fang J et al [29]concluded that the BUN/ALB ratio could be a useful prognostic tool to predict mortality in critically ill patients with acute pulmonary embolism.In our prospective cohort study,we firstly investigated the association between the BUN/ALB ratio and in-hospital and 90-day all-cause mortality.Interestingly,after adjusting the confounding factors,we found that the BUN/ALB ratio ≥ 0.249 was a strong and an independent risk factor of in-hospital(RR = 15.08,95%CI:3.80-59.78, P < 0.001) and 90-day all-cause mortality(HR = 5.34,95%CI:1.62–17.57, P= 0.006) in AECOPD patients.Therefore,we considered that our study might be seen as a supplement to the BUN/ALB ratio as a prognostic factor for respiratory diseases.And stratified by BUN/ALB ratio levels,we observed that those with a high BUN/ALB ratio level had increased in-hospital(30.5vs.1.9%, P < 0.001) and 90-day all-cause(17.1vs.2.7%, P < 0.001) mortality.All this indicated that higher BUN/ALB ratio levels mean AECOPD patients with higher BUN levels and lower albumin levels in serum.Thus,a higher BUN/ALB ratio level often reflects the severity and increased mortality of AECOPD.Many factors might explain the association between a high BUN/ALB ratio level and in-hospital and 90-day mortality in AECOPD patients.First,once patients with COPD suffered acute exacerbations,they are usually combined with infection[17]and the inflammatory response will accelerate the process of proteolysis and the BUN levels elevated due to lower albumin levels in patients.Second,congestive heart failure is a common comorbidity in COPD[17].Because of the decreased cardiac outputs, the renin angiotensin aldosterone system (RAAS) and sympathetic nervous system were activated.Meanwhile,angiotensin and adrenergic stimulation cause renal vasoconstriction and decrease GFR and renal blood flow.This process can enhance the reabsorption of the urea,causing the BUN levels elevated[30].In our cohort,we found that the BUN/ALB ratio ≥ 0.249 group had more AECOPD patients with renal dysfunction than the BUN/ALB ratio < 0.249 group(62.7% vs.43.8%, P = 0.009).We considered that renal dysfunction might lead to urea excretion obstruction.Specifically,reabsorption of the urea will be enhanced.However,in this study,we did not find renal dysfunction was associated with in-hospital mortality of AECOPD(RR = 0.32,95%CI:0.09–1.13, P = 0.076),which was inconsistent with previous studies[31, 32].We considered that our small sample size or different statistical methods might be the reasons for the different results.
Given that BUN/ALB ratio was associated with in-hospital and short-term prognosis in AECOPD patients.we recommend that BUN/ALB ratio should be gaining prominence in clinical work. Because how to quickly and accurately assess the severity of the AECOPD patients and give corresponding intervention measures to improve the outcome and prognosis is crucially important. BUN/ALB ratio,combined with BUN and ALB may play a better role in assessing the severity of AECOPD patients. In addition, the two laboratory indexes are easy to obtain, convenient to use, and are not affected by the evaluator's subjectivity,which is more realistic in the clinical work.
In this study,we also found that CHF was an independent risk factor for in-hospital mortality (RR = 4.36,95%CI:1.07–17.85, P = 0.040),which was consistent with previous findings that CHF was a significant and independent risk factor of all-cause mortality in COPD and had an influence on COPD course[33].Stratified by the BUN/ALB ratio,compared with the BUN/ALB ratio < 0.249 group,there were more patients with congestive heart failure in the BUN/ALB ratio ≥ 0.249 group(44.1%vs.27.3%, P = 0.012).And the pathophysiological mechanism behind the association between elevated BUN/ALB ratio levels and CHF had been previously described[26, 30].This might indicate that those combined with CHF have a higher BUN/ALB ratio level and we had better pay more attention to those with CHF for the adverse hospitalization outcomes.
Compared with COPD,the inflammation in AECOPD is amplified,causing a poor prognosis[34].In our study,we found that those died in hospital had a higher neutrophil count level than survivors(10.27(7.21, 14.04) vs.6.58(4.58, 9.04)×109/L, P < 0.001).Meanwhile,we also found that a higher neutrophil count was an independent predictor of in-hospital mortality in AECOPD patients after the adjustment in multivariate logistic regression (RR = 1.15,95%CI: 1.02–1.30, P = 0.020).More importantly,from Table 3,in BUN/ALB ratio ≥ 0.249 group,we observed that the neutrophil count levels were higher than those with a BUN/ALB ratio < 0.249.This indicated that the systemic inflammatory response contributed to decrease the albumin levels in serum and increase the BUN levels[26].As indicated above,a higher neutrophil count level might mean adverse hospital outcomes of AECOPD patients.
Here are several limitations in our study.First, this study was a single-center study with a small sample size, especially a small number of patients who died in hospital.However,to the best of our knowledge,this study was the largest prospective cohort study that we know of that was applied to investigate the prognostic of BUN/ALB ratio in AECOPD.Second,although it was the first study to reveal the relationship between BUN/ALB ratio and in-hospital and 90-day all-cause mortality of AECOPD patients, which still lacks previous studies as references. Meanwhile, in the present study,we did not analyze the effect of therapeutic interventions on BUN levels of AECOPD patients during hospitalization, which may influence the results. We also did not exclude the patients combined with chronic kidney disease.As renal dysfunction is common in AECOPD,its inclusion in the cohort might made our study closer to a real-world study.Third,AECOPD patients often have severe hypoxia in admission, they may have been given oxygen treatment in outpatient department before the first blood drawing.To some extent,it may influence the results of our study. Fourth,previous studies[26, 28]suggested that BUN/ALB ratio is associated with pneumonia.However,in clinical work,it is difficult for us to accurately distinguish AECOPD from COPD combined with community-acquired pneumonia (CAP) although we only recruited the patients discharged from hospital with AECOPD as the primary reason for hospitalization.At last,in our study,we only explore the short-term prognosis and we do not know the association between the BUN/ALB ratio and long-term mortality. Thus,the results of this study still need to be further verified by large-sample,multicenter prospective studies in the future.