Use of the Relationship between Absolute Lymphocyte Count and CD4 Count to Improve Earlier Consideration of Pneumocystis Pneumonia in HIV-positive Emergency Department Patients with Pneumonia

doi:10.1016/j.jemermed.2012.05.001

The Journal of Emergency Medicine

Volume 44, Issue 1, January 2013, Pages 28-35

https://doi.org/10.1016/j.jemermed.2012.05.001 Get rights and content

Abstract

Background

The ability to accurately assess the level of immunosuppression in HIV+ patients in the emergency department (ED) is often limited and can affect management of these patients.

Objective

To evaluate the relationship between the absolute lymphocyte count (ALC) and CD4 count in HIV patients admitted through the ED with pneumonia and how utilization of this relationship may affect early consideration and evaluation of Pneumocystis jiroveci pneumonia (PCP).

Methods

Retrospective multicenter 5-year study of HIV+ patients with an ICD-9 diagnosis of pneumonia. Included patients had an ALC measured on ED presentation and a CD4 count measured in < 24 h. A receiver operator curve (ROC), decision plot analysis, and McNemar test of proportions were used to characterize the relationship between study variables.

Results

Six hundred eighty six patients were enrolled, 23.2% (95% confidence interval [CI] 20.2–26.1) were diagnosed with PCP. The geometric mean CD4 count and ALC were 81 and 1089, respectively. The correlation between ALC and CD4 was r = 0.60 (95% CI 0.55–65, p < 0.01). The ROC was 0.78 (0.75–0.82). An ALC < 1700 cells/mm³ had a sensitivity of 84% (95% CI 80–87) and specificity of 55% (95% CI 48–70) for a CD4 < 200 cells/mm³. An ALC threshold of 1700 cells/mm³ would have identified 86% of patients with PCP but falsely identified 2.5 patients without PCP for every one accurately identified.

Conclusion

The ALC threshold of 1700 cells/mm³ retains significant discriminatory value and would moderately improve identification of patients with a CD4 < 200 cells/mm³ but is not likely to be reliable as the sole method of early recognition and evaluation of PCP.

Introduction

Since 2006, the Centers for Disease Control and Prevention have recommended routine screening for HIV infection among all patients aged 13–64, unless the prevalence of undiagnosed HIV in the local population is less than 0.1% (1). Current research estimates the prevalence of known HIV infection to be as high as 3% in some urban areas, with the rate of undiagnosed HIV among emergency department (ED) patients ranging from 0.7 to 16% 2, 3, 4, 5. Management of HIV patients in the ED is challenging because differential diagnoses and treatment options depend on the level of immune suppression. In the absence of a recently documented CD4 count, the emergency physician’s ability to accurately assess the level of immunosuppression in HIV-infected patients is limited. This clinical uncertainty may result in failures to provide empiric treatment with trimethoprim-sulfamethoxazole (TMP-SMX) or in delayed diagnostic evaluation for Pneumocystis jiroveci pneumonia (PCP). The CD4 count is an important predictor of susceptibility to opportunistic infection (OI) in HIV patients, with a CD4 count < 200 cells/mm³, indicating an increased risk for opportunistic infections (6). However, the rapid determination of the CD4 count is not available in the earliest phases of care.

Several studies have demonstrated that the absolute lymphocyte count (ALC) is a good predictor of the CD4 count but until recently these studies were primarily based on outpatient populations, mixed inpatient and outpatient populations, or on populations in resource-poor regions of the world 7, 8, 9, 10, 11, 12, 13, 14. We recently found that ALC may be a good predictor of CD4 count in an unselected cohort of HIV patients admitted through the ED (15). However, all of these prior studies have examined general patient cohorts without targeting specific acute illnesses. As a result, prior research is limited by a spectrum bias that makes the accuracy and impact of this relationship more difficult to predict.

We sought to examine if the absolute lymphocyte count would correlate well with the CD4 count in HIV-positive ED patients with pneumonia. Additionally, we evaluated the ability of the ALC to serve as a proxy for the CD4 in identifying the need for early empiric therapy or evaluation for PCP.

Section snippets

Design and Setting

This was a retrospective cohort study of consecutive HIV patients admitted through three urban emergency departments over a 5-year period. Patients were included if they were admitted to the hospital through the ED and had a known diagnosis of HIV, had an ALC measured in the ED, a CD4 count measured within 24 h of admission, and were discharged with an ICD-9 discharge diagnosis of pneumonia (ICD-9 136.3, 481–486). Patients were considered to have PCP if they were clinically diagnosed as such,

Results

A total of 2469 patients with known HIV infection were treated over the 5-year period. Of these patients, 686 unique patients had a hospital discharge diagnosis of acute bacterial pneumonia and met inclusion criteria during the study period. The mean age was 44.3 (± 9.7) years old. Slightly less than half of the patients (48.3%; 95% CI 44.5–52.0) were female, and a large majority (90.8%; 95% CI 88.7–93.0) were African-American. The overall prevalence of a CD4 < 200 cells/mm³ was 63.7% (95% CI

Discussion

In this study we examined ALC and CD4 counts in a population of ED patients with HIV admitted for acute pneumonia. To the best of our knowledge, this is the second study to examine the ALC–CD4 relationship specifically in ED patients and the first to do so in focused cohort of patients with pneumonia. The ALC retains significant discriminatory value in identifying a CD4 < 200 cells/mm³, though not as high as previously reported and an optimal level could not be identified such that a CD4 < 200

Conclusion

In HIV patients admitted from the ED with acute bacterial pneumonia, an ALC threshold of < 1700 cells/mm³ would moderately improve recognition of patients with a CD4 < 200 cells/mm³. However, the ALC–CD4 relationship was not strong enough to utilize this measure as the sole method for early recognition and evaluation of PCP without significant false positives. Further research utilizing this measure in conjunction with other clinical predictors may improve early recognition and evaluation of

Acknowledgment

The authors would like to acknowledge the support of Dr. Mark Smith, without whom none of this work would have been possible.

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It is not always possible to determine the immunological status of the patient at the ED, and even more so, if the patient is not followed up in the same hospital, which can give rise to diagnostic doubts on whether the etiology of pneumonia may or may not be caused by PCP. Because of this, Napoli et al.22 found that a total lymphocyte value of <1700 cells/mm is a predisposing factor, but not the only one to suffer an infection by PCP. Nowadays, LRTI by PCP is frequently seen in non-HIV immunodepressed patients, such as those with a transplanted solid organ, oncological patients and patients that suffer from connective tissue diseases.
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Data were collected on the first visit of HIV-infected patients at our ED due to a LRTI, (defined according to the criteria of the European Respiratory Society), between 1/1/2000 and 31/12/2010. A series of epidemiological and laboratory variables as well as the need for admission to the intensive care unit (ICU). LRTI etiology were also collected. The influence ofthe mentioned variables on 30-day mortality were analyzed.
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Se recogió únicamente el primer episodio del paciente que acude al SU por IRVB (definida según la European Respiratory Society). Se analizaron una serie de variables epidemiológicas y de laboratorio, así como la necesidad de ingreso en una unidad de cuidados intensivos (UCI). Se estudió la etiología de la IRVB y la incidencia. Finalmente se analizaron la influencia de las variables con la mortalidad a 30 días.
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Original ContributionsUse of the Relationship between Absolute Lymphocyte Count and CD4 Count to Improve Earlier Consideration of Pneumocystis Pneumonia in HIV-positive Emergency Department Patients with Pneumonia

Abstract

Background

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Design and Setting

Results

Discussion

Conclusion

Acknowledgment

Ann Emerg Med

Ann Emerg Med

Chest

Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings

MMWR Recomm Rep

Health department collaboration with emergency departments as a model for public health programs among at-risk populations

Public Health Rep

Detecting unsuspected HIV infection with a rapid whole-blood HIV test in an urban emergency department

J Acquir Immune Defic Syndr

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America

MMWR Recomm Rep

Correlation between total and CD4 lymphocyte counts in HIV infection: not making the good an enemy of the not so perfect

Int J STD AIDS

Total lymphocyte count as a predictor of absolute CD4+ count and CD4+ percentage in HIV-infected persons

JAMA

Relationship between total lymphocyte count (TLC) and CD4 count among peoples living with HIV, Southern Ethiopia: a retrospective evaluation

AIDS Res Ther

Total lymphocyte count of 1200 is not a sensitive predictor of CD4 lymphocyte count among patients with HIV disease in Kampala, Uganda

Afr Health Sci

Total lymphocyte count (TLC) is a useful tool for the timing of opportunistic infection prophylaxis in India and other resource-constrained countries

J Acquir Immune Defic Syndr

Is total lymphocyte count a reliable predictor of the CD4 lymphocyte cell count in resource-limited settings?

AIDS

Original Contributions
Use of the Relationship between Absolute Lymphocyte Count and CD4 Count to Improve Earlier Consideration of Pneumocystis Pneumonia in HIV-positive Emergency Department Patients with Pneumonia