Lymphopenia ‘independent predictor of mortality’ in pneumonia
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Primary care patients with a low lymphocyte count “years before” developing pneumonia were at an increased risk for dying, researchers of a retrospective cohort study wrote in the British Journal of General Practice.
“Many studies show that lymphopenia during, or at the start of, infection is associated with poor outcomes,” Fergus Hamilton, of the division of infection sciences at the North Bristol National Health Service Trust, and colleagues wrote. “Exploring the mechanisms and therapeutic implications of this phenomenon has been the subject of recent reviews and remains largely unexplained.”
The researchers analyzed the relationship between mortality and lymphocyte count in a cohort of 40,909 primary care patients in the United Kingdom who were diagnosed with pneumonia. Among the entire cohort, 35,690 patients never had a lymphocyte test.
“Participants who had no blood tests recorded were generally slightly older than other participants, but with lower rates of all comorbidities,” Hamilton and colleagues wrote. “Remarkably, patients who had never had a lymphocyte test had a significant 1-year mortality of 52.1%, suggesting the tested group is significantly different to the non-tested one.”
The researchers used a time-to-event approach to analyze the data. The median time between test and pneumonia diagnosis was 677 days. The data were adjusted for age, potential causes of lymphopenia, sex and social factors. The primary outcome was 28-day, all-cause mortality, and the secondary outcome was 1-year mortality following pneumonia diagnosis.
Hamilton and colleagues wrote that when patients’ lymphocyte count was categorized as 0-1 × 109 cells/L, their 28-day and 1-year mortality was 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 × 109 cells/L, the rates were 6.5% and 22%, respectively; when categorized as 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. The associations with “increased hazard of death” remained consistent after multivariable analysis, according to the researchers.
“Lymphopenia is an independent predictor of mortality in primary care pneumonia,” Hamilton and colleagues wrote. “Even low–normal lymphopenia (1-2 × 109 cells/L) is associated with an increase in short- and long-term mortality compared with higher counts.”
The findings may be the first of their kind among a cohort of primary care patients, according to Hamilton and colleagues.
“The vast majority of patients with respiratory tract infection present to primary care, and risk stratification here is critical,” they wrote.
Perspective
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As a population‐based study, the paper by Hamilton and colleagues is subject to numerous potential confounders. Despite these, however, the linkage they describe between lymphopenia and mortality in pneumonia is consistent with other observational studies.
For example, the neutrophil‐lymphocyte ratio (NLR) is a well‐established prognostic marker in acutely ill hospitalized patients, with high NLRs (and thus low lymphocyte counts) being linked to mortality. Similarly, lymphopenia is associated with increased risk for pneumonia mortality in persons living with HIV/AIDS.
The Hamilton study is unique in that it focuses on a broad primary care population. As an easily obtained risk parameter for respiratory disease, future research could determine whether patients with lymphopenia benefit from targeted prevention strategies, such as pneumococcal, influenza, and coronavirus vaccination.
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