3.2 Treatment and medical costs in different groups
Referring to the treatment, the proportions of antibiotic and joint
antibiotic use were higher in non-eosinophilic AECOPD patients, but the
use of short-term steroids showed no difference between these two
groups. Interestingly, lengths of stay (LOS) in eosinophilic AECOPD were
shorter than those in non-eosinophilic AECOPD among elderly patients,
but it showed no difference in middle-aged patients. Besides, the
overall hospital costs (OHC) and daily hospital costs (DHC) was lower in
elderly eosinophilic AECOPD patients. (Table 2).
3.3 Association between eosinophilic exacerbation and clinical remission
Compared to patients with non-eosinophilic exacerbation, patients with
eosinophilic exacerbation had an higher probability of clinical
remission at the time point of 7 (p =0.020), 10(p =0.002)
and, 14 (p =0.003), 21 (p< 0.001), and 28 days
(p =0.003) (Table 3). Figure 2 shows and the changes of cumulative
remission rates along with hospital days, with the horizontal axis
(x-axis) representing time in days and the vertical axis (y-axis) the
cumulative proportion of clinical remission at the different time
points. The higher rate of clinical remission was observed in
eosinophilic
AECOPD patients at most of the time point when comparing with
non-eosinophilic patients (Figure 2a).
In elderly patients, the Cox proportional hazards model showed that
eosinophilic exacerbation was significantly associated with in-hospital
clinical stability and eosinophilic exacerbation tended to have a higher
rate of clinical remission compared to non-eosinophilic exacerbation at
7 (p =0.003), 10 (p =0.040), 14 (p =0.003), 21
(p= 0.020), and 28 (p =0.010) day time points. In contrast,
no statistically significant differences were observed at all time
points (all p >0.05) in the middle-aged patients
(Table 3 and Figure 2b, 2c).
4. Discussion
Earlier and accurate individual risk assessment of patients is important
for successful disease
management[27]. Despite recent
technical progress in diagnosis and treatment, the management of AECOPD
remains difficult; thus, it is necessary to identify clinically
meaningful predictors for successful
management[28]. This retrospective
study investigated the relationship between eosinophils and clinical
remission of AECOPD and demonstrated several new findings. First, we
observed a lower medical cost in eosinophilic AECOPD patients. Second,
subgroup analysis stratified by age groups revealed a higher rate of
clinical remission observed among elderly but not in middle-aged
eosinophilic patients. In the baseline analysis, we found that
neutrophils, hs-CRP level, and OHC in eosinophilic cases were lower and
hospital time was shorter than those in non-eosinophilic cases. These
findings are consistent with those of previous studies despite different
clinical settings, enrollment criteria, and definitions of disease
severity and exacerbation[17,
26, 29].
Our findings of statistically significant differences in LOS and OHC
between groups was consistent with those of a previous study
[30]. Furthermore, the Cox
proportional hazards model used to assess and explore the risk of
eosinophilic exacerbation to in-hospital remission of AECOPD patients,
showed that eosinophilic group tended to show higher rates of clinical
remission at all time points (7, 10, 14, 21, and 28 day time points). In
the subgroup analysis assessing the association between eosinophilic
exacerbation and remission, eosinophilic exacerbation group in elderly
patients showed a higher clinical remission rate at all time points. In
contrast to these findings in elderly patients, no significant
differences in middle-aged patients were observed.
Eosinophilic exacerbation is associated with eosinophilic airway
inflammation which was associated with T-helper cell type 2 (Th2)
inflammation. Increasing evidence in recent years has shown that
eosinophilic airway inflammation might play an important role in
COPD[31]. Subsequent infiltration of
eosinophils in the airways of COPD patients regulates the immunoglobulin
E (IgE)-dependent mechanism, which is considered as an important part of
Th2 cell cytokine production
process[32], with an irregular
Th1/Th2 ratio and interleukin-17/IgE ratio that may be caused by
imbalanced Th2 cell production[33].
Previous clinical trials have explored the relationship between blood
eosinophil counts over time and in-hospital management
outcomes[16]. Eosinophilia has been
observed both in COPD and AECOPD patients and represents a novel
pathological mechanism of a special clinical phenotype in COPD.
Moreover, eosinophilic exacerbation also affects COPD outcomes. Previous
studies reported an association between COPD patients with persistently
increased blood eosinophil counts and better outcomes; furthermore,
evidence from randomized clinical trials has shown that patient blood
eosinophil counts are crucial for predicting a good response to
corticosteroid administration[34,
35]. Corticosteroid treatment at the
time of an exacerbation may yield better interventional outcomes with
shorter LOS and better treatment
responses[36]. In the current study,
with the similar rate of steroids use, elderly patients with
eosinophilic AECOPD gained higher clinical remission rate than
non-eosinophilic elderly patients, which implied that steroids acted
better in elderly eosinophilic patients, highlighting the value of
steroids in AECOPD patients.
Age is always listed as a risk factor for COPD; elderly patients are
often accompanied by other typical comorbidities that negatively impact
prognosis and health status, and the number of comorbidities is
associated with the risk of COPD
exacerbation[11,
37]. However, although COPD is common
in older people, whether there is difference between elderly patients
and middle-aged patients in terms of eosinophilic phenotype-related COPD
outcomes remains unclear. Previous study reported the value of blood
eosinophilia for predicting clinical remission of AECOPD by setting 10
days as the observation time point; due to the design and information
collected by the study, observing the association at more set time
points or adjusting for age were not possible. In this study, we were
able to further demonstrate this phenomenon by setting more observation
time points (at 7, 10, 14, 21, and 28 days in hospital), and patients
were divided into different age groups, which would make the difference
between middle-aged and elderly patients more visible. We found a
significant difference in clinical remission between elderly patients
and middle-aged adults over all the observation time points.
The current study has some limitations. First, although 703 patients
were enrolled, this study was a single-center retrospective study.
Further multi-center prospective studies evaluating the value of blood
esinophils are needed. Second, patient follow-up after discharge was not
performed in this study, as the data were collected from electronic
medical records, and readmissions and other follow-up-related
information of these patients could not be identified. To better
understand the relationship between eosinophils and elderly ages,
additional eosinophilic phenotype-related clinical and basic studies
focusing on AECOPD at different ages might be performed
5. Conclusion:
In this study, the eosinophilic phenotype was associated with better
clinical remission at 7, 10, 14, 21, and 28 days in the hospital among
elderly but not middle-aged patients with AECOPD. Early identification
of this special phenotype in elderly patients may be valuable in better
personalized management for AECOPD.