In the present study, we specifically examined the potential of plasma NT-proBNP to discriminate LV failure in AECB patients with no history of HF. Our results demonstrated NT-proBNP for LV failure in patients with AECB had a higher AUC, with a higher sensitivity and negative predictive value at an optimal cutoff value. The addition of NT-proBNP to clinical judgment would improve diagnostic accuracy for LV failure in patients with AECB. These data suggested that NT-proBNP still is a useful tool for identifying LV failure in patients with AECB.
HF is one of common complications in patients with AECB, and suspected as a cause of exacerbation in many such patients 
. As there is the pre-existence of basic symptoms such as dyspnea and wheezing in patients with CB and these symptoms are relatively non-specific 
, which makes clinical judgment very difficult. Thus, the physician should carefully discriminate whether worsening dyspnea is the result of deterioration of pulmonary disease and/or the onset of HF. which is critically important as it will greatly influence therapeutic decisions. However, as demostrated in our study, emergency physicians were either uncertain or missed the diagnosis of LV failure in a substantial proportion of those ultimately proven to have LV failure, or those ultimately proven to have no LV failure.
Natriuretic peptides have been used world wide in diagnosis or exclusion of acute HF 
, and the utility of natriuretic peptides in congestive heart failure management has been stressed in the last European Society of Cardiology guidelines 
. Thus, determining plasma NT-proBNP levels to identify LV failure may be appealing in patients with AECB. The analysis of this study is based upon an evaluation of the utility of plasma NT-proBNP measurement to offer a diagnostic service for patients with LV failure.
Our data demonstrated that NT-proBNP was a stronger predictor of LV failure in multivariate logistic regression analysis. Moreover, a diagnostic test with an AUC higher than 0.8 is commonly considered to be of clinical value. The greater AUC resulted from our study showed that NT-proBNP testing is useful for identifying LV failure in patients with AECB. In fact, our ROC analysis illustrated that using NT-proBNP test for identifying HF was more superior to clinical judgment alone, while adding the results of NT-proBNP to those of clinical judgment alone would significantly improve the diagnostic accuracy. These results were consistent with the previous (PRIDE) study by Januzzi JL et al.
. Importantly, the negative predictive values for LV failure were higher than 90.0% at the corresponding optimal cutoff values of NT-proBNP both in patients stratified by age and in all patients, suggesting that NT-proBNP is more useful as a “rule out” test in our study populations. As demonstrated by our study, addition of NT-proBNP to clinical judgment would help physicians to rule out more than half of the false LV failure patients. Similarly, Gariani et al.
assessed the diagnostic performance of BNP in detecting LV dysfunction in patients with no history of HF admitted for acute exacerbation of COPD. For a cutoff of 500 ng/L, they found a sensitivity of 62.0%, a specificity of 80.0%, a positive predictive value of 47.0% and a negative predictive value of 88.0%. In the present study, we assessed NT-proBNP instead of BNP and found NT-proBNP seemed to have more superior diagnostic performance to BNP. In addition, Abroug et al.
assessed the accuracy of NT-proBNP for the diagnosis of LV dysfunction in 148 selected patients with severe acute exacerbation of COPD. A cutoff of 1000 ng/L was accurate to rule out left-heart involvement with a sensitivity of 94%, a negative predictive value of 94%. Although these patients differed from our sample, and they tended to be 10 years younger on average as well as the symptoms of acute exacerbation presented more severe, the results of this study and ours are comparable.
Of note, the AUC of the NT-proBNP for detecting LV failure in our patients with AECB was somewhat lower than in previous studies of patients with suspected HF and patients with acute dyspnea attending the Emergency Department 
. The possible reasons were as followings. Firstly, our patients had higher pulmonary pressure. Numerous studies have shown that in primary or secondary pulmonary hypertension, there is a supraphysiologic secretion of natriuretic peptides. Nagaya and coworkers showed that atrial natriuretic protein and BNP levels each correlated with mean pulmonary artery pressure, right atrial pressure, right ventricular end-diastolic pressure, and pulmonary resistance 
. Secondly, there is the presenting feature of a wide range of other co-morbidities during exacerbation 
, while some of these co-morbidities, such as atrial fibrillation, renal dysfunction, may affect the natriuretic peptide levels 
. Consistent with these findings, our study showed that pulmonary pressure, atrial fibrillation and renal function had independent effects on plasma NT-proBNP levels. Thirdly, during acute exacerbation, hyperinflation of the lung is associated with decreased cardiac function and lead to an increase of plasma BNP levels 
. Because acute exacerbation is associated with a transient decrease in expiratory flow, which, in some cases, takes weeks to return to the baseline 
. The radical decreases in expiratory flow may lead to increased air-trapping and hyperinflation of the lung 
. In fact, our data showed that plasma NT-proBNP levels were elevated in patients with AECB, regardless of whether they have LV failure or not. This result was consistent with the recent subgroup analysis by Inoue Y et al.
, who found that plasma BNP level during exacerbations was significantly higher than during stable disease. Fifthly, most of patients with newly detected LV failure were probably seen in an early stage of HF, which makes it plausible that the concentrations of NT-proBNP are lower than in patients with established HF 
, because NT-proBNP production in the ventricles of the heart increases in response to increased intracardiac volume or pressure. Finally, although the distension of ventricular cardiomyocytes is generally considered the main mechanical stimulus, the production/secretion of BNP may be the result of a complex integration among mechanical, chemical, hemodynamic, humoral, ischemic, and inflammatory inputs 
. Of these factors, some pro-inflammatory cytokines may be important pathophysiological mechanisms active in AECB patients. It is these differences that may influence the overall diagnostic accuracy, especially the specificity, of the NT-proBNP for detecting HF.
The limitation to the present study is this observational study was done at a single centre. We must acknowledge that the optimal cutoffs and the diagnostic characteristics of NT-proBNP assessed in our study are dependent on the patient population studied and the “gold standard” used for diagnosis of LV failure, and they also may be influenced by the assay method because the diagnostic information provided by NT-proBNP measurement might be method-dependent 
. Another, the small sample size of our study limits the precision of our estimates. Therefore, one must be careful about generalizing the results to the entire population.
From our results, we concluded that, our results, along with other previous works, supported that NT-proBNP, readily available in most hospital settings, was of potential value for the identification of LV failure and confirmed a role of NT-proBNP measurement for ruling out LV failure in patients with AECB.