The hemoglobin-albumin-lymphocyte-platelet (HALP) score as a prognostic factor in patients with pneumonia aged 75 years and older

Introduction

Background

In general, studies of pneumonia are conducted by pneumonia type. These include community-acquired pneumonia (CAP), aspiration pneumonia (AP), and healthcare-associated pneumonia (HCAP). The incidence of pneumonia increases with age, and the same applies to AP. Older adult patients with pneumonia include those with all pneumonia types.

CAP is the most commonly reported; however, only 1/7 of the reported cases are associated with AP. Therefore, few studies have been published on the prognosis of older adults with pneumonia, including those with AP. Several prognostic factors, including the Sequential Organ Failure Assessment (SOFA) score, confusion, uremia, respiratory rate, blood pressure, and age ≥65 years (CURB-65) score, albumin level, and neutrophil-lymphocyte ratio (NLR), are being studied for these pneumonia types.

Rationale and knowledge gap

Hypoalbuminemia is a well-known factor for prognosis in all pneumonia types, but the cutoff value varies from 2.5 to 3.2 depending on reports, and no clear threshold has been established. CURB65 has generally been established as a prognostic indicator for CAP, but it is reportedly not a good indicator for AP (1); therefore, whether the findings of studies on CAP can be applied directly to pneumonia in older adult patients remains unclear. The World Health Organization (WHO) defines people aged ≥65 years as older adults, and many other reports on pneumonia in older adults also refer to people aged ≥65 years. Conversely, the WHO’s 2021 report on life expectancy shows that the global average is 71.4 years, while in Japan it is 84.5 years (2), a difference of >10 years. In terms of government systems in Japan, people aged ≥75 years are treated as late-stage older adults. In cancer research and other fields, people aged ≥75 years are often treated as older adults. We defined older adults as those aged ≥75 years for our study.

Common conditions in older adults include AP and a decline in activities of daily living (ADL) caused by longer periods of hospitalization. In some cases, poor nutrition after discharge from hospital for pneumonia treatment can lead to death. In studies on pneumonia prognosis, in-hospital death and 30-day mortality are most often used as evaluation indices, but these short-term mortality indicators may not adequately reflect the actual prognosis in older adults. No standard time period has been established for the mortality rate when considering the prognosis.

The hemoglobin-albumin-lymphocyte-platelet (HALP) score has been used as an immunonutritional biomarker predicting prognosis in patients with several malignancies (3). The HALP score is calculated as HALP score = hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L) and was originally developed by Chen et al. (4) to predict prognosis in patients with gastric carcinoma. In a recent review of the HALP score (3), the average score was reported as 31.2 when combining reports on various carcinomas. We believe that the HALP score, which includes albumin and lymphocyte levels and is a simple index that can be easily calculated, can be applied to predict the prognosis of pneumonia in older adults.

Objective

In this study, we investigated the usefulness of the HALP score as a prognostic factor for patients aged ≥75 years with pneumonia, including AP, using 90-day mortality as an indicator, with a cut-off value of 30, based on the values used in recent cancer prognosis studies. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1093/rc).

Methods

Study design

We conducted a retrospective study of 280 patients aged ≥75 years who had been diagnosed with pneumonia and were hospitalized at Koto Hospital, Tokyo, between January 2021 and December 2022. We collected information on various markers, including clinical data, age; sex; length of hospital stay; speech therapy intervention; use of dentures; comorbidities, such as diabetes, dementia, and other diseases; smoking history; oral intake of proton pump inhibitors (PPIs); oral food intake at discharge; laboratory data; and clinical outcomes, such as in-hospital death, 30-day mortality, and 90-day mortality, from the medical records of our 200-bed hospital, which has no intensive care unit (ICU). Some patients were discharged to their homes, whereas others were transferred to another hospital or nursing home. Survival data after discharge were collected where available. If a patient was hospitalized more than twice during the study period, only the first hospitalization period was included in the analysis. If information on patient follow-up after discharge or laboratory findings was missing, the missing values were not imputed. When calculating survival time, the last date of survival during outpatient visits, or for long-term survivors, the last follow-up date, December 31, 2023, was used.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. It was approved by the Institutional Review Board of Koto Hospital (No. 2024-1, approved on January 19, 2024), and approval for an opt-out consent method was obtained for this retrospective study.

Statistical analysis

Ninety-day mortality was defined as death within 90 days of admission. A logistic regression model was used to perform uni- and multivariate analyses of risk factors for 90-day mortality with odds ratios (ORs) and 95% confidence intervals (CIs). The factors included in the multivariate analyses were based on the existing literature. All statistical analyses were performed using JMP Pro software (version 18.0, SAS Institute Inc., Tokyo, Japan), and P<0.05 was considered statistically significant.

Results

In total, 351 patients with a diagnosis of bacterial pneumonia were hospitalized within the 2-year period. Of these, 280 patients aged ≥75 years were included in our study. Fifty-four patients died in the hospital, 226 patients were discharged from the hospital, and the status after 90 days of 54 patients was unknown, because of dropout from follow-up or a lack of information after hospital transfer.

The characteristics of the study population are shown in Table 1. The median age was 85 years, 181/280 (64.6%) were male, the median hospitalization period was 19 days, and 139/280 patients (49.6%) underwent speech therapy intervention. The comorbidities included (in order of frequency) hypertension, dementia, diabetes, dialysis, and Parkinson’s disease. The median laboratory test results for the albumin concentration, HALP score, and NLR were 3.0 g/dL, 14.7, and 9.5, respectively. The hospital death, 30-day mortality, and 90-day mortality rates were 19.2%, 15.4%, and 36.2%, respectively. Figure 1 shows the survival curves of all patients. According to the survival curve, survival declined quickly immediately after hospitalization, but at around 90 days, the rate of decline slowed, and gradual decline was subsequently observed.

Figure 1 Ninety-day mortality by age group.

Univariate logistic regression analysis was used to identify factors affecting 90-day mortality. Male sex, a low albumin level (<2.8 g/dL), low HALP score (<30), and high NLR (>10) were associated with a higher risk of mortality (Table 2). However, no other factors, such as comorbidities, speech therapy intervention, or PPI intake, affected 90-day mortality.

Multivariate logistic regression analysis of several risk factors selected based on the existing literature revealed that male sex and low HALP scores were risk factors for 90-day mortality. Age was not a risk factor for mortality among patients aged ≥75 years. The 90-day mortality of each 5-year age group was approximately 30%, with no significant between-group differences (Figure 1).

Discussion

Key findings

Clinical pneumonia research is usually conducted based on the pneumonia type. However, the older adults with pneumonia group presents unique challenges in that it includes those with all pneumonia types. Not only is it difficult to perform a swallowing assessment in older adult patients upon admission, but there is also the possibility of silent aspiration. Moreover, CAP and AP may occur simultaneously. In practice, distinguishing patients with AP from those with CAP on admission is not always easy. In this study, older adults were evaluated comprehensively in line with real-world clinical practice.

This was a retrospective study, and no common criteria for speech therapy intervention had been established at the hospital; it was performed at the discretion of each physician. Approximately half of total patients, who underwent speech therapy, were suspected of having AP. A report from Japan showed that the incidence of AP was 38.4% in patients aged >70 years (5). The proportion of patients with AP in our study was similar to that reported previously. Regarding severity, this study did not include severely ill patients, as our hospital has 200 beds and no ICU facilities.

An important consideration is determining the appropriate timeframe for assessing mortality in older adults.

We searched for reports in PubMed that examined mortality within 1 year that had the word “pneumonia” in the title and contained the keywords “elderly”, and “not coronavirus disease (COVID)”. The highest number of reports was 859 for 30-day mortality (combined with 28-day mortality), followed by 132 for 90-day mortality, 112 for 365-day mortality, 25 for 60-day mortality, and 17 for 180-day mortality.

In the current study, the in-hospital mortality rate was 19.2%, which was higher than the 30-day mortality rate of 15.4%, indicating that in-hospital deaths occurred after 30 days of hospitalization and that the 30-day in-hospital mortality rate was not an appropriate outcome measure. However, when considering long-term prognosis, it is expected that in older adults, if the time since admission is too long, the proportion of deaths due to factors other than pneumonia, such as life expectancy or comorbidities, will increase. According to a paper analyzing the 1-year mortality of patients with pneumonia aged >75, an increase in frailty may have a greater impact on the mortality rate for AP than the diagnosis of aspiration (6). It is not yet clear when during the course of the disease the prognosis should be evaluated, and when the impact of death due to a decline in ADL triggered by pneumonia should be assessed. However, the survival curve (Figure 2) for all patients showed that the survival rate decreased almost linearly from immediately after hospitalization, slowed down around 90 days, and continued to decline slowly thereafter. It may indicate that the direct impact of pneumonia on mortality continues up to 90 days after onset. Therefore, if we are assessing long-term prognosis, 90 days or later after onset would be appropriate.

Figure 2 Survival curve of all patients.

Strengths and limitations

This study has some limitations. First, the number of patients in the target group for this study for whom the HALP score could be calculated was small (n=164). This is because the calculation of the index requires an assessment of the lymphocyte count; however, if the patient is transported to the emergency room (ER) at night or on weekends, the blood cell count cannot be calculated, so the HALP score cannot be calculated. In this study, the HALP score was calculated based on the blood tests performed at admission. Therefore, many patients who were hospitalized through the ER, which tends to include relatively severe cases, were excluded. Thus, the study population may be biased toward patients with a mild disease. To address this issue, further studies are needed to clarify the natural course of the HALP score during hospitalization and evaluate whether the HALP score calculated within few days after admission can be used as a substitute. Second, our hospital is a medium-sized community hospital without an ICU, and although we were targeting inpatients, there were inevitably very few patients with severe pneumonia. Third, although 90-day mortality was used as the outcome, as the study did not evaluate the return to home (discharge to the same place as before hospitalization, including not only home but also a nursing home) as an observation item, it was not possible to evaluate whether 90-day mortality is a truly useful indicator that includes the ADL. Fourth, pneumonia severity was not evaluated.

Comparison with similar research

Prognostic factors

Factors such as age, sex, the albumin level, NLR, new early warning score (NEWS), procalcitonin level, pneumonia severity index (PSI), and others, or a combination of these factors, have been examined as prognostic factors for pneumonia, but the classification of pneumonia and the timing for determining mortality rates reported in the literature vary. Many reports suggest that low albumin levels are associated with a poor prognosis in CAP; however, the cutoff value varies from 2.85–3.2 g/dL (7,8). In AP, an albumin level <3.2 g/dL is thought to be a factor for in-hospital death and 28-day mortality (8). Furthermore, an albumin level of 2.75 is considered to be a good indicator of HCAP 30-day and 90-day mortality (9). However, a threshold albumin level has not been established. In this study, when we used an albumin level of 2.8 as the cutoff value, the OR was high at 5, but a similar tendency was observed at a cut-off value of 2.5 or 3.0. Therefore, establishing a clear threshold value for albumin as a prognostic factor is challenging.

The NLR is the ratio of the absolute neutrophil count to the absolute lymphocyte count, and as an easily measured indicator, it is attracting attention as a useful prognostic marker in various pathological conditions, including infectious and malignant diseases. In a recent review, a correlation with prognosis was reported for various carcinomas, and although the cutoff value varies depending on the report and type of carcinoma, it is generally around 3–4 (10). In pneumonia studies, the cutoff value differs from that for malignant diseases, with many reports for CAP setting it at 10–12. Conflicting reports have been published, such as those that correlate it with 30-day mortality (11), versus those that do not correlate it with in-hospital mortality or prognosis after 6 months (12). In a report on HCAP, a cutoff of 11.64 was used and no significant correlation with 30-day mortality was observed (9). However, in the current study, a cutoff of 10 was used and no significant association with 90-day mortality was observed.

The HALP score is calculated based on albumin and blood cell platelet lymphocytes; it is a composite indicator of nutritional status, immune status, and inflammation levels. The HALP score is reportedly associated with prognosis in various types of cancer (3); however, similar to the NLR, the cutoff value varies depending on the type of cancer. However, it is important to have a versatile cutoff value that can be used in actual clinical practice. To our knowledge, no previous reports have examined the HALP score in terms of the prognosis of pneumonia; therefore, this study may be the first to examine its usefulness in this context.

Explanations of findings

A significant correlation with 90-day mortality was observed and a significant difference was also observed in the subsequent survival curve. In summary, the results of the multivariate analysis showed that sex and a HALP score of 30 rather than age were associated with prognosis in patients with pneumonia aged ≥75 years. Because sex may predict general life expectancy, it can be excluded, and since calendar age has little effect on prognosis among older adults, an indicator such as the HALP score may be considered more useful.

Implications and actions needed

It is not possible to conclude from this study alone whether the HALP score with a cutoff value of 30 is useful for predicting the prognosis of pneumonia in older adults; further studies are required. These should include studies with larger sample sizes, e.g., by increasing the number of cases by examining the HALP score after hospitalization, investigating whether the data obtained within a few days of hospitalization can be used as a substitute, and expanding the target to include other conditions such as CAP and patients aged <75 years.

Conclusions

In older adult patients with pneumonia, the HALP score with a cutoff of 30 may be useful in predicting prognosis. However, further studies with larger sample sizes are required to validate our findings.

Acknowledgments

The authors would like to thank the staff of Koto Hospital for their contribution to data collection.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1093/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1093/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1093/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1093/coif). K.T. reports the grants from Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Taiho Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd.; payment or honoraria for lectures, presentations, or speaking engagements from Chugai Pharmaceutical Co., Ltd., AstraZeneca K. K., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K. K., Bristol-Myers K. K., Daiichi Sankyo Co., Ltd., Nippon Kayaku Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. K.T. is on the board of directors of both the Japanese Lung Cancer Society and the Japanese Respiratory Society. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Institutional Review Board of Koto Hospital (No. 2024-1, approved on 19 January 2024), and approval for an opt-out consent method was given for this retrospective study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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