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.