Correlation of Leukocyte Count with Clinical Outcomes in

Report
Correlation of Leukocyte Count with Clinical Outcomes in Hospitalized Patients with
Community-Acquired Pneumonia: Results from Rapid Empiric Treatment with Oseltamivir
Study (RETOS)
Srinivas Uppatla, MD,1 Sridivya Peddapalli, MD,1 Cynthia Meza Ortiz, MD,1 Kelly Carrico, BS,1 Timothy Wiemken, PhD,1 Forest Arnold, DO, MSc.1
Division of Infectious Diseases.1
RESULTS (Cont’d)
ABSTRACT
INTRODUCTION (Cont’d)
RESULTS
Introduction: Community-acquired pneumonia (CAP) continues to be
a major health problem worldwide. Leukocytes are an important host
response factor against invading pathogens causing CAP. Patients
with elevated leukocyte count (leukocytosis) are expected to have
better clinical outcomes in comparison to patients with normal or low
leukocyte count (leukopenia). However, there is limited information
about leukocyte count and its correlation with clinical outcomes in
hospitalized patients with CAP. The objective of this study was to
correlate leukocyte count on admission with clinical outcomes in
hospitalized patients with CAP.
Patients with an elevated leukocyte count (leukocytosis) are expected to
have better clinical outcomes in comparison to patients with normal or low
leukocyte count (leukopenia). Lack of leukocytosis can be a manifestation
of lack of systemic inflammatory response, and may indicate abnormal
immune function and has been shown to predict mortality in CAP
patients.3
A total of 476 CAP patients were evaluated. Out of these,
315 (66%)
.
patients had leukocytosis, and 161 (34%) patients had no leukocytosis on
admission.
Methods: This was a secondary analysis of the RETOS database, an
on-going, randomized, prospective clinical trial to evaluate the impact
of rapid empiric treatment with oseltamivir on the outcomes of
hospitalized patients with lower respiratory tract infections (LRTIs).
All patients admitted to eight hospitals in Louisville, Kentucky from
December 2010 to March 2012 with a diagnosis of LRTI were invited
to participate in the study. Patients diagnosed with CAP were divided
into 2 groups based on their leukocyte count: 1. Leukocyte count
>10,000 and 2. Leukocyte count < 10,000. Logistic regression was
used to determine the effect of leukocyte count on 30-day mortality
while adjusting for the Pneumonia Severity Index.
Results: A total of 476 CAP patients were evaluated. Out of these,
315 (66%) patients had leukocytosis, and 161 (34%) patients had no
leukocytosis on admission. The results of the multivariable analysis
indicated a significant increase in mortality for patients with
leukopenia.
Conclusions: This study indicates that CAP patients with leukopenia
have higher 30-day mortality when compared to patients with normal
leukocyte count and leukocytosis. The finding of leukopenia in a
hospitalized patient with CAP should prompt an aggressive
management approach since these patients are at a higher risk for
mortality. Therapeutic interventions to increase white blood cell count
may need to be studied.
INTRODUCTION
Community-acquired pneumonia (CAP) continues to be a major health
problem worldwide. The annual incidence of CAP cases is 5.6 million
in the United States, and 1.2 million patients get hospitalized each
year. The inpatient mortality rate for hospitalized patients with CAP
has been documented to be as high as 5.8 %.1 Due to its high mortality
rate, early diagnosis of CAP is important for initiation of appropriate
therapy. Leukocyte count on admission is an important factor that is
used in the evaluation of CAP patients.
Leukocyte count is routinely used in the evaluation of patients with
lower respiratory tract infections (LRTIs) including CAP to help guide
the diagnosis and management.2 Leukocytes are an important host
response factor against invading pathogens causing CAP.
However, there is limited information about leukocyte count and its
correlation with clinical outcomes in hospitalized patients with CAP. The
objective of this study was to correlate leukocyte count on admission with
clinical outcomes in hospitalized patients with CAP
MATERIALS AND METHODS
Study design and study population
This was a secondary analysis of the RETOS database, an ongoing,
randomized, prospective clinical trial to evaluate the impact of rapid
empiric treatment with oseltamivir on the outcomes of hospitalized
patients with LRTIs. All patients admitted to eight hospitals in Louisville,
Kentucky from December 2010 to March 2012 with a diagnosis of LRTI
were invited to participate in the study. Although the database was created
to evaluate patients’ response to oseltamivir, it contains basic laboratory
values from which meaningful information can be derived.
Baseline characteristics and clinical outcomes of patients with CAP are
shown in Table 1. Results of the multivariable analysis are shown in
Figure 1.
The trend, although clinically significant for patients with leukopenia did not
reach statistical significance overall (P=0.75).
This analysis indicated that patients with leukopenia were at a higher risk
for mortality than patients with a normal leukocyte count or leukocytosis.
Figure 1: Graph depicting correlation of Percent mortality at 30
Days in CAP patients and WBC count
Table 1: Demographic characteristics of CAP patients in the
study
CONCLUSIONS
Leukocyte count
>10000
n=315 (66%)
Leukocyte count
<10000
n=161 (34%)
P-value
62 (18-91)
61 (22-99)
0.542
120 (38)
62 (39)
0.999
25 (8)
6 (4)
0.115
COPD
141 (45)
75 (47)
0.770
CHF
82 (26)
48 (30)
0.386
Cerebrovascular
accident
29 (9)
20 (12)
0.270
Liver Disease
21 (7)
14 (9)
0.459
Patients diagnosed with CAP were divided into two groups based on their
leukocyte count:
 Leukocyte count >10,000 cells/ µL
 Leukocyte count <10,000 cells/ µL
Renal Disease
60 (19)
29 (18)
0.805
Diabetes
104 (33)
63 (39)
0.189
Altered Mental Status
25 (8)
12 (7)
0.999
Statistical analysis:
Baseline patient characteristics and clinical outcomes were compared
between patients with leukocytosis and no leukocytosis using the Chi
squared test for categorical variables and the Mann-Whitney U-test for
continuous variables.
ICU Admission
54 (17)
22 (14)
0.357
Multilobar Infiltrates
107 (34)
46 (29)
0.255
Study definition:
CAP was defined as the presence of new pulmonary infiltrate on the chest
radiograph at the time of hospitalization that was associated with at least
one of the following:
- New or increased cough
- An abnormal temperature (<35.6°C or >37°C)
- Leukocytosis (leukocyte count >10,500 cells/ µL), leukopenia (leukocyte
count < 4,500 cells/µL), or left shift (>5% immature neutrophils).
To evaluate the adjusted effect of leukocyte count on 30-day mortality, a
logistic regression model was constructed. This model considered the
continuous leukocyte count as the primary predictor variable, 30-day
mortality as the outcome, and the pneumonia severity index as a
confounding variable. P-values of ≤0.05 were considered statistically
significant. SAS v9.2 and R v2.14.0 were used for all analyses.
Variable
Age, Median (Range)
Female Gender
Nursing Home Resident
-This study indicates that CAP patients with leukopenia trend
towards higher 30-day mortality when compared to patients with
normal leukocyte count and leukocytosis.
-The finding of leukopenia in a hospitalized patient with CAP should
prompt an aggressive management approach since these patients
are at a higher risk for mortality.
-Therapeutic interventions to increase white blood cell count may
need to be studied.
-In our study, we also found a significant number of CAP patients who
did not have leukocytosis on admission. Hence, absence of
leukocytosis on admission should not deter physicians from fully
evaluating patients with a chest radiograph and ordering appropriate
microbiologic tests when patients present with signs and symptoms
consistent with pneumonia.
REFERENCES
Clinical Outcomes
Time to Clinical Stability
3 (0-8)
2.5 (0-8)
0.056
Length of Stay
4 (0-36)
4 (0-29)
0.339
9 (3)
7 (4)
0.425
In-Hospital Mortality
Mortality at 30 Days
18 (6)
10 (7)
0.835
1. Bartlett JG, Dowell SF, Mandell LA, et al. Practice guidelines for the
management of community-acquired pneumonia in adults. Infectious
Diseases Society of America. Clin Infect Dis 2000; 31:347-82
2. Furer V, Raveh D, Picard E, Goldberg S, Izbicki G. Absence of
leukocytosis in bacteraemic pneumococcal pneumonia. Prim Care
Respir J 2011; 20(3):276-281
3. Ahkee S, Srinath L, Ramirez J. Community-acquired pneumonia in
the elderly: association of mortality with lack of fever and
leukocytosis. South Med J 1997; 90:296–298

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