Infectious Disease

Lymphopenia “unbiased predictor of mortality” in pneumonia

February 25, 2021

2 min read

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Primary care patients with low lymphocytes “years prior” to developing pneumonia were at increased risk of death, researchers of a retrospective cohort study wrote in the British Journal of General Practice.

“Many studies show that lymphopenia is associated with poor outcomes during or at the beginning of an infection.” Fergus Hamilton, from the Infection Science Division at the North Bristol National Health Service Trust, and colleagues wrote. “Research into the mechanisms and therapeutic implications of this phenomenon has been the subject of recent reviews and remains largely unexplained.”

Reference: Hamilton F, et al. Br J Gen Pract. 2021; doi: 10.3399 / bjgp20X713981.

The researchers analyzed the relationship between mortality and lymphocyte counts in a cohort of 40,909 primary care patients in the United Kingdom diagnosed with pneumonia. In the entire cohort, 35,690 patients never had a lymphocyte test.

“Participants who did not have blood tests were generally slightly older than other participants, but with a lower rate of all comorbidities,” wrote Hamilton and colleagues. “Notably, patients who never had a lymphocyte test had a significant 1-year mortality of 52.1%, suggesting that the group tested was significantly different from the untested.”

The researchers used a time-to-event approach to analyze the data. The median time between the test and pneumonia diagnosis was 677 days. The data were adjusted for age, possible causes of lymphopenia, gender, and social factors. The primary outcome was 28-day all-cause mortality and the secondary outcome was 1-year mortality after diagnosis of pneumonia.

Hamilton and colleagues wrote that when the patients’ lymphocyte counts were rated as 0-1 × 109 cells / L, their 28-day and 1-year mortality were 14% and 41%, respectively. When classified as 1-2 × 109 cells / L, the 28-day and 1-year mortality rates were 9.2% and 29%, respectively; when categorized as 2-3 × 10 9 cells / l, the rates were 6.5% and 22%, respectively; if the categorization was greater than 3 × 109 cells / l, the rates were 6.1% and 20%, respectively; and when the lymphocyte count was never tested, the rates were 25% and 52%, respectively. According to the researchers, the associations with “increased risk of death” remained consistent after multivariable analysis.

“Lymphopenia is an independent predictor of mortality from pneumonia in primary care,” wrote Hamilton and colleagues. “Even low-normal lymphopenia (1-2 × 109 cells / l) is associated with an increase in short- and long-term mortality compared to higher numbers.”

According to Hamilton and colleagues, the results could be the first of their kind among a cohort of primary care patients.

“The vast majority of patients with respiratory infections are present in primary care and risk stratification is critical here,” they wrote.

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Ryan Maves, MD, FACP, FIDSA)

Ryan Maves, MD, FACP, FIDSA

As a population-based study, Hamilton and colleagues’ paper is subject to numerous potential confounders. Nevertheless, the relationship between lymphopenia and mortality from pneumonia is consistent with other observational studies.

For example, the neutrophil-to-lymphocyte ratio (NLR) is a well-established prognostic marker in acutely ill hospital patients, with high NLRs (and thus low lymphocyte counts) being associated with mortality. Similarly, lymphopenia has been linked to an increased risk of pneumonia mortality in people living with HIV / AIDS.

The Hamilton study is unique in that it focuses on a broad primary care population. As an easy to determine risk parameter for respiratory diseases, future research could determine whether patients with lymphopenia benefit from targeted prevention strategies such as pneumococcal, influenza and coronavirus vaccinations.

Ryan Maves, MD, FACP, FIDSA

Director of Education, Naval Medical Center, San Diego
Hospital Doctor, Scripps Mercy Hospital, San Diego
Member of the US military

Disclosure: Maves does not report any relevant information. The views expressed here are his and do not necessarily reflect the official views of either the U.S. Department of the Navy, the Department of Defense, or the U.S. Government.

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