Summary:
Morbidity and mortality of chronic obstructive pulmonary disease is associated
with severe exacerbations. In severely exacerbated patients, the courses of
disease are strongly varying. This might be due to the existence of different
exacerbation phenotypes and their respective respond to the chosen treatment.
As a marker for the responsiveness to inhaled corticosteroids, current
recommendations emphasize blood eosinophil cell counts. For the treatment of
moderate to severe exacerbations, the administration of systemic steroids is
recommended. Analyses from randomized clinical trials indicate a favorable
response to systemic corticosteroids in exacerbated patients with blood
eosinophils >2%, however data outside clinical trials are scarce.
We retrospectively evaluated the association between baseline eosinophil blood
count and both short- and long-term clinical outcomes, as well as different
inflammatory parameters and markers of disease severity in patients hospitalized
due to an exacerbation of their underlying chronic obstructive pulmonary disease.
We evaluated data from 1007 cases of patients who were admitted to the
University Medical Center Marburg between 01/2013 and 12/2018. All patients
had been diagnosed with an acute exacerbation of chronic obstructive pulmonary
disease. Patients were predominantly male (65%), had a median age of 74 years
and a median forced expiratory volume in one second of 1.03l (42.6% predicted).
Our analysis was based on a subgroup of 417 patients in whom a full blood cell
count was obtained at the day of admission. We compared the hospital length of
stay, inflammatory parameters and long-term outcome using established
thresholds for the eosinophil blood cell count (100 and 300/μl and 2%). For
patients that were re-hospitalized or died in our hospital during the observational
time period, Kaplan-Meier curves were used to evaluate the long-term outcome.
Patients with low eosinophils (< 2%, < 100/μl) had a longer median time in
hospital (length of hospital stay) as compared to patients with high eosinophils (<
2%: 9.31 vs. ≥ 2%: 7 days, and < 100/μl: 10 vs. 100-300/μl: 8 vs. > 300/μl: 7
days). The median C-reactive protein and more inflammatory markers
(Procalcitonin, Neutrophil-to-lymphocyte ratio, neutrophils, leucocytes and
fibrinogen) were higher in patients with low eosinophils as compared to the other
groups (< 2%: 22.7 vs. ≥ 2%: 9 mg/dl and < 100/μl: 25 vs. 100-300/μl: 13.5 vs. >
300/μl: 7.1 mg/dl). Time to re-hospitalization or time to death did not differ
between the strata of eosinophils.
To further reinforce the generalizability of our results and to prevent avoidable
influences, we did three subgroup analyses, excluding a) patients that had
received systemic steroids before blood collection, b) patients with radiological
signs of pneumonia and c) patients who did not receive any systemic steroids
either before their hospital stay and/or during admission. These restricted
analyses did not alter the results significantly. In an additional subgroup analysis,
we compared both short- and long-term outcome between patients with low
eosinophil blood counts and high parameters of inflammation (demonstrated by
C-reactive protein and Neutrophil-to-lymphocyte ratio) and those with high
eosinophils and low parameters of inflammation. Hospital length of stay was
significantly higher in patients with low eosinophils and high C-reactive protein/
Neutrophil-to-lymphocyte ratio. Time to re-hospitalization and time to death did
not differ significantly among the groups.
The shorter length of hospital stay and the lower levels of inflammation in
eosinophilic patients can be interpreted as an indication for the existence of
different exacerbation phenotypes. This could be an explanation for the better
responsiveness to steroid treatment in eosinophilic patients and the notion that a
more non-eosinophilic phenotype (which may include bacterial or viral infections)
may need a longer time to clinical improvement.
Our data confirms the results of other clinical studies and add to the growing body
of evidence that blood eosinophils may serve as a biomarker not only for inhaled
corticosteroid-responsiveness with regard to the prevention of exacerbations but
also for responsiveness towards systemic steroids during an acute exacerbation
of chronic obstructive pulmonary disease.