Discussion
In this multicenter cross-sectional study, we enrolled 598 AECOPD patients. At last, 111 patients (26%) with LHS <7 days (Normal LHS, N-LHS), 218 patients (51%) with LHS 7-10 days (Mild Prolonged LHS, MP-LHS), and 100 patients (23%) with LHS ≥11 days (Severe Prolonged LHS, SP-LHS) were included. Then, the significant differences in 11 factors, including age, the rates of CAP, hypertension, and CCP, WBC, NS, NS%, lymphocytes%, ESR, PH, and ALB were identified among 3 groups by univariate analysis. Since collinearity among WBC, NS%, and NS were observed, WBC and NS% were excluded in multiple logistics regression. Subsequently, multiple logistics regression revealed that the rates of hypertension and CCP were independently associated with LHS in AECOPD patients.
COPD is one of the leading causes of morbidity and mortality worldwide [24,27]. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), the prevalence of COPD was 11.7% (95% CI 8.4% to 15.0%), indicating globally about 384 million people suffering from COPD [28]. AECOPD is also one of the major causes of admission in COPD patients [29,30]. Mounting evidence showed that LHS was independently associated with the severity, cost burden, in-hospital mortality, and re-admission rates in COPD [2,5,9,15,31,32]. Some studies reported that comorbidities were independently associated with LHS in AECOPD patients [7,8]. In a retrospective study, Wang Y et al. showed that heart failure, diabetes, stroke, increased PaCO2, and reduced albumin (ALB) were the independent risk factors for prolonged LHS in AECOPD patients [8]. Meanwhile, in a longitudinal retrospective observational study, Inabnit LS et al. revealed that LHS significantly correlated with the number of comorbidities in COPD patients [7]. Furthermore, they also noticed that congestive heart failure (CHF), fluid and electrolyte disorders, and renal failure were associated with 28%, 20%, and 50% greater LHS in COPD patients, respectively. However, the variables, obtained in these studies, were not comprehensive. Hence, some potentially important risk factors and predictors probably were not included. Furthermore, until now, the risk factors associated with prolonged LHS weren’t well explored in Chinese AECOPD patients. Therefore, comprehensive data, including demographic data, underlying diseases, comorbidities, symptoms, lung function (GOLD stages), laboratory parameters, and CT scan, were collected in our study.
Simultaneously, an acknowledged definition of prolonged LHS was still in controversy. The varied definitions of prolonged LHS in COPD were used in different studies [8,20,33]. In a retrospective longitudinal study, the COPD patients, registered by London general practitioners and patients admitted to the emergency room with COPD from 2006 to 2010, were screened [33]. It was found that the average LHS was 7 days in COPD patients. Meanwhile, in a prospective study in the Hospital Clinic of Barcelona, 7 days also was used as the cut-off of prolonged LHS in AECOPD patients [20]. However, in another retrospective study, 11 days was used to define the prolonged LHS in AECOPD patients [8]. Therefore, two thresholds of prolonged LHS, both 7 days and 11 days were considered in the current study. Subsequently, multiple logistics regression identified that the rates of hypertension and CCP were independently associated with prolonged LHS in AECOPD patients.
Some studies identified the close relationship between COPD and hypertension [34,35]. In a retrospective cohort study, 314 AECOPD patients in Swiss were screened [34]. They found that new or worsening hypertension was an independent risk factor for re-exacerbation in AECOPD patients. Meanwhile, in a cross-sectional study, the association between COPD and comorbidities (presented by Charlson comorbidity scores) was explored [35]. The results revealed that Charlson comorbidity scores in COPD patients were higher than in non-COPD patients. Meanwhile, more than 40% of COPD patients were combined with cardiovascular diseases, hypertension, and hyperlipidemia. Several studies found that low-grade systemic inflammation contributed substantially to the pathogenesis of both hypertension and COPD [36-38]. Barnes PJ et al. showed that arterial constriction resulted from COPD-induced airway inflammation, lung hyperinflation, systemic inflammation, endothelial dysfunction, and oxidative stress was essential for hypertension in COPD patients [38]. Furthermore, several studies also revealed the benefits of blood pressure control in AECOPD combined with hypertension [39,40]. It was found that the angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) treatments were negatively associated with LHS in AECOPD combined with hypertension [39]. In a retrospective national cohort study, Mortensen EM et al. showed that ARBs and ACE inhibitors were associated with decreased mortality in hospitalized AECOPD combined with hypertension [40].
Additionally, the impact of CCP on COPD prognosis wasn’t well explored. To our knowledge, this was the first multiple center’s cross-sectional study to explore whether CCP was associated with LHS in AECOPD patients. CCP was defined as the right ventricle hypertrophy resulting from diseases affecting the function and/or structure of the lungs except when these pulmonary alterations are the result of diseases that primarily affect the left side of the heart [25,26]. In this study, the diagnosis of CCP was based on the findings of clinical presentations, echocardiography, and electrocardiogram (ECG) [25,26]. In advanced COPD, endothelial dysfunction, pulmonary arterioles constriction, and vascular remodeling, featured by intimal hyperplasia and vascular smooth muscle hypertrophy/hyperplasia, were induced by hypoxia and persistent chronic pulmonary inflammation, eventually leading to pulmonary hypertension (PH) [22,41,42]. In chronic pulmonary diseases, such as COPD and idiopathic pulmonary fibrosis, PH, and CCP were considered to be a single disease in different stages [25,26]. Progressive PH could cause right ventricular hypertrophy and eventually lead to right cardiac failure. Lung disease associated PH was defined as mean pulmonary arterial pressure (mPAP) greater than 20mmHg at rest [43]. Additionally, it was found that the diameter of the pulmonary artery was independently associated with acute exacerbation in COPD [44]. Then, in the current study, our results first time identified that CCP was an independent risk factor for prolonged LHS in AECOPD patients.
To our knowledge, this was the first multicenter cross-sectional study to explore the risk factor for prolonged LHS in AECOPD in the Chinese population. Meanwhile, two thresholds of prolonged LHS, 7 days and 11 days, were considered, making our data more convincible, which was one of the major strengths of this study. Additionally, comprehensive data, such as demographic data, underlying diseases, comorbidities, symptoms, lung function, and laboratory data, were collected. Particularly, a chest CT scan was performed on each patient, which effectively promoted the diagnosis accuracy and reduced confounders. The major limitation of our study included that the study was only performed in tertiary general hospitals in China. The results probably couldn’t generalize to primary health care. Meanwhile, only Chinses AECOPD patients were included. Then, the results should be replicated in other ethnic groups in the future.