Severe thinness is associated with mortality in patients with communityacquired pneumonia: a prospective observational study Jungyoup Lee MD, Kyuseok Kim MD, PhD, You Hwan Jo MD, PhD, Jae Hyuk Lee MD, PhD, Joonghee Kim MD, Heajin Chung MD, Ji Eun Hwang MD PII: DOI: Reference:

S0735-6757(14)00833-X doi: 10.1016/j.ajem.2014.11.019 YAJEM 54621

To appear in:

American Journal of Emergency Medicine

Received date: Accepted date:

21 October 2014 13 November 2014

Please cite this article as: Lee Jungyoup, Kim Kyuseok, Jo You Hwan, Lee Jae Hyuk, Kim Joonghee, Chung Heajin, Hwang Ji Eun, Severe thinness is associated with mortality in patients with community-acquired pneumonia: a prospective observational study, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.11.019

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Title of Manuscript

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Severe thinness is associated with mortality in patients with community-acquired

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pneumonia: a prospective observational study

Author List

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Jungyoup Leea, MD; Kyuseok Kima,*, MD,PhD; You Hwan Joa, MD,PhD; Jae Hyuk Leea, MD,PhD; Joonghee Kima, MD; Heajin Chunga, MD ; Ji Eun Hwanga, MD

Author Affiliations

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Department of Emergency Medicine, Seoul National University Bundang Hospital

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*Corresponding Author Kyuseok Kim, MD, PhD

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Department of Emergency Medicine, Seoul National University, Bundang Hospital, 300 Gumi-dong, Bundang-gu, Sungnam-si, Gyeonggi-do, 463-707, Republic of Korea Tel: +82-31-787-7572 Fax: +82-31-787-4055 E-mail: [email protected].

Running Title: Severe thinness is a mortality predictor in CAP Word Count: abstract 247, text 2025 Prior Presentations: no

ACCEPTED MANUSCRIPT Funding Sources: This study was partly supported by grant no.11-2014-061 from the

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SNUBH Research fund.

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Abstract Purpose

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This study aimed to investigate the probability of 30-day mortality based on body mass index (BMI) assessment combined with pneumonia severity index (PSI) in patients with community acquired pneumonia (CAP) and to determine whether being underweight is an

Basic procedures

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independent risk factor contributing to 30-day mortality.

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A prospectively collected database was analyzed retrospectively. Multivariable logistic

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regression analysis was performed to determine whether BMI is an independent predictor of mortality in patients with CAP by adjusting for PSI and other factors found significant in univariable analysis. Mortality-predictability of BMI and PSI was evaluated using area under the receiver-operating characteristic curve analyses.

Main findings A total of 1403 patients were assessed in this study. In multivariable regression analysis, severe thinness (BMI < 16 kg/m2), hypoalbuminemia (albumin < 3.3 mg/dL), and PSI IV and V were predictive factors for 30-day mortality in patients with CAP. In terms of mortality

ACCEPTED MANUSCRIPT prediction, the accuracy of PSI was 0.67 (95% CI, 0.63–0.71), as measured by the AUC. When hypoalbuminemia was combined with PSI, the predictive accuracy significantly

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increased to 0.71 (95% CI, 0.66–0.75, P = 0.02). The addition of severe thinness to PSI and

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hypoalbuminemia further increased the accuracy significantly to 0.74 (95% CI, 0.70–0.78) (P

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= 0.005).

Principal conclusions

Severe thinness (BMI < 16kg/m2) was associated with 30-day mortality in patients with CAP, showing improved prognostic performance when combined with PSI. We propose that

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physicians consider a patient’s nutritional state using BMI when predicting mortality in CAP.

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Keywords: pneumonia; BMI; thinness; mortality; prediction

Abbreviations: AUC, area under the receiver-operating characteristic curve; BMI, body mass index; CAP, community-acquired pneumonia; ED, emergency department; ICU, intensive care unit; HR, heart rate; PSI, pneumonia severity index; SBP, systolic blood pressure

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1. INTRODUCTION

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality

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worldwide, and many organizations have attempted to improve the results of current treatment options [1,2]. To improve the treatment outcome of patients with CAP, factors that increase mortality and morbidity resulting from CAP need to be identified. The pneumonia severity index (PSI) is widely used to predict mortality in patients with pneumonia and, in our

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experience, is the factor on which the decision to admit and discharge patients with CAP is

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based [3,4]. Nutrition is one of the most important clinical factors influencing mortality and morbidity resulting from infectious disease [5-9]. However, the PSI does not include any

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clinical factor on malnutrition. A previous study showed that mortality predictability

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increases when hypoalbuminemia is factored into PSI [10]. Body mass index (BMI) is widely used to define baseline nutritional status in adults [11]. Several studies showed that being underweight is associated with mortality in patients with pneumonia [12-14]. However, these previous studies did not sufficiently consider nutritional factors that may influence mortality in pneumonia patients. Furthermore, it is unclear whether factoring of being underweight increases the predictability of mortality when combined with a severity scale such as PSI [3]. The primary objectives of this study were to investigate 30-day mortality predictability of BMI assessment in patients with CAP and to determine whether being underweight combined with PSI and other clinical factors is an independent risk factor for 30-day mortality. The secondary objectives were to investigate the association of BMI, intensive care unit (ICU)

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admission rates and length of hospital stay among patients with CAP.

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2. METHODS

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2.1. Study Design and Setting

All patients presenting with pneumonia who were admitted to our emergency department

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(ED) since 2008 have been registered in a prospectively collected pneumonia database [4,10,15]. We extracted and retrospectively analyzed information from this database. The study hospital is a 950-bed tertiary academic hospital with an annual ED census of 80000. This study was approved by the institutional review board of the study hospital, and the

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requirement for patient consent was waived.

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2.2. Data Collection and Follow Up

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The pneumonia database has 130 variables, including demographic factors, clinical factors, laboratory data, and therapeutic results. Vital signs and BMI were recorded at the triage stage in the ED. Initial laboratory data after ED admission were recorded. We extracted data on the following clinical factors: age, sex, BMI, diabetes mellitus (DM), hypertension (HTN), chronic obstructive pulmonary disease (COPD), heart failure, cerebrovascular disease, liver disease, neoplastic disease, renal disease, systolic blood pressure (SBP), heart rate (HR), respiratory rate (RR), body temperature (BT), white blood cell (WBC) count, hematocrit, platelet count, and the levels of glucose, albumin, blood urea nitrogen (BUN), creatinine, sodium, and C-reactive protein (CRP). In terms of therapeutic results, we investigated the 30day mortality, intensive care unit (ICU) admission and length of hospital stay (days). Patients

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2.3. Inclusion and Exclusion Criteria

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or obtained additional information from patients by phone or personal interview.

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Eligible patients were older than 15 years of age and were hospitalized between November 2009 and September 2013, following a diagnosis of CAP. Patients who were discharged from the ED, transferred to another hospital, or diagnosed with hospital-acquired pneumonia (HAP) or health care-associated pneumonia (HCAP) were excluded. HAP was defined as pneumonia

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that occurred more than 48 hours after hospitalization [16-18]. Patients who were hospitalized in an acute care hospital for more than 2 days within 90 days of the infection,

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resided in a nursing home or long-term care facility, attended a hemodialysis clinic, recently

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received intravenous antibiotics or chemotherapy, or sought wound care within 30 days of

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the infection were classified as having HCAP [16,18-20].

2.4. BMI Classification BMI was calculated as weight (kg)/height (m)2. BMI groups were defined according to the basic criteria of the World Health Organization (WHO) guidelines with a modified cutoff value for the definition of overweight and obese patients in an Asian population (underweight, 30

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cycles/min, BT>40 °C or BT250 mg/dL, albumin 65 years,

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univariable analysis, the following variables were found to differ between BMI groups: age DM, HTN, heart failure, cerebrovascular disease, renal failure, SBP < 90

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mmHg, HR > 125 beats/min, albumin < 3.3 mg/dL, creatinine < 1.5mg/dL and, PSI. The ICU

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admission rate and length of hospital stay did not differ significantly between BMI groups (Table 1). Of the variables that were found significant in univariable analysis, the following six variables were composition of the PSI: age, renal failure, heart failure, cerebrovascular disease, SBP, HR. Therefore, these variables were not included in the multivariate regression model [3]. We performed multivariable logistic regression analysis to investigate whether being underweight was an independent risk factor for mortality by adjusting for PSI and the other variable that significantly differed between BMI groups. In the multivariable regression model, the following three variables were associated with 30-day mortality in patients with CAP: severe thinness (BMI < 16 kg/m2), PSI IV/V, and hypoalbuminemia (albumin < 3.3 mg/dL) (Table 2). In terms of mortality prediction, the accuracy of PSI was 0.67 (95% CI,

ACCEPTED MANUSCRIPT 0.63–0.71), as measured by the AUC. When hypoalbuminemia was combined with PSI, the prediction accuracy significantly increased to 0.71 (95% CI, 0.66–0.75, P = 0.02). Finally, the

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accuracy further increased significantly to 0.74 (95% CI, 0.70–0.78) when severe thinness

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was assessed in combination with PSI and hypoalbuminemia (P = 0.005) (Fig. 3.). In KaplanMeier survival curves analysis, the probability of 30-day mortality as assessed with PSI was

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increased in patients with hypoalbuminemia and severe thinness (P < 0.001) (Fig. 4.).

4. DISCUSSION

Previous studies have shown that being underweight is associated with malnutrition and

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may increase the mortality and morbidity risk in patients with CAP [12-14]. We wanted to know what subgroup of the underweight population has a mortality risk in CAP and whether

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being underweight increased the predictability of mortality when assessed with PSI and

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albumin level. The cubic spline curve showed that the probability of 30-day mortality and the slope of the curve increased as BMI decreased. The increase in mortality rate was greater in

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patients with lower BMI (Fig. 2.), and the result corresponded with multivariable logistic regression analysis. Patients with lower BMI tended to have a higher 30-day mortality rate in test for trend analysis (P = 0.011). However, only severe thinness (BMI < 16kg/m 2) correlated significantly with prediction of 30-day mortality in multivariablete analysis (Table 2). Thus, we showed that severe thinness in the underweight population is a risk factor for mortality and can be used as a predictive factor for mortality when combined with PSI and the albumin level in patients with CAP. To the best of our knowledge, this is the first study to describe clinical outcomes in a subgroup of underweight patients with CAP. Corrales-Medina et al. previously showed that patients with lower BMI had a trend towards an increased mortality rate in pneumococcal, haemophilus CAP [12]. However the authors did not compare each

ACCEPTED MANUSCRIPT BMI group in terms of mortality rate. This study did not sufficiently consider the clinical information of underweight patients and the number of underweight patients was only 36.

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LaCroix AZ proved that underweight men who were diagnosed with pneumonia had a high

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mortality rate; however, the results were not adjusted for clinical factors that may influence mortality in pneumonia [13]. King et al. also investigated BMI and mortality in pneumonia,

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but did not consider clinical factors such as laboratory results that reflect the severity of

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pneumonia [27]. Therefore, based on previous studies, we could not conclusively determine whether being underweight increases the mortality-predictability of PSI in patients with CAP. In terms of obesity and pneumonia, several studies have showed that obesity is associated with a low mortality rate in patients with CAP. In these studies, the authors insisted that

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obesity was protective in patients with pneumonia [12,27-30]. Although patients in the higher BMI group had low mortality rate in our study, we did not observe a significant advantage for

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obese patients based on multivariate analysis. In our study, hypoalbuminemia was associated

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with mortality in patients with CAP, a finding that is supported by a previous study [10]. Hypoalbuminemia as well as BMI, reflects malnutrition and could be a predictive factor in

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patients with CAP.

This study had several limitations. First, this study was conducted in Asia, which might limit the applicability of these results to other populations. Asians have different body compositions and obesity complication rates from Europeans and other populations. Therefore, we used BMI modified cutoff values for an Asian population when defining overweight and obese participants based on WHO guidelines and several studies [11,21-24]. However cutoff values for defining underweight for Asians are the same as the international classification. Therefore, the results regarding underweight may be applicable to other populations. Second, this study was conducted in a single institute and included patients who

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exist despite our use of a prospectively collected database.

In conclusion, severe thinness (BMI < 16 kg/m2) is associated with an increased 30-day

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mortality risk in patients with CAP and improved the prognostic performance of PSI. We

mortality in patients with CAP.

Acknowledgments

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propose that physicians consider the patient’s nutritional state using BMI when predicting

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No authors declare a conflict of interest.

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Fig. 1. Study population

A total of 4169 patients were admitted to our ED and diagnosed with CAP during study

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period. Of these patients, 1421 were hospitalized. Patients with missing value were excluded from the analysis and the remaining 1403 patients were enrolled in this study. Enrolled

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patients were divided into 6 groups according to BMI

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Abbreviations: BMI, body mass index; CAP, community-acquired pneumonia; ED,

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emergency department.

Fig. 2. BMI and probability of 30-day mortality The probability of 30-day mortality was increased as the BMI decreased. Patients with lower BMI tended to have a higher 30-day mortality in test for trend analysis (P = 0.005). Abbreviation: BMI, body mass index.

Fig. 3. Mortality predictability of PSI, albumin and BMI

ACCEPTED MANUSCRIPT In terms of mortality prediction, PSI showed an accuracy of 0.67 (95% CI, 0.63–0.71), as measured by the AUC. When hypoalbuminemia (albumin < 3.3 mg/dL) was combined with

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PSI, the prediction accuracy was significantly increased to 0.71 (95% CI, 0.66–0.75, P =

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0.02). Finally, the AUC was increased significantly to 0.74 (95% CI, 0.70–0.78) when severe

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thinness (BMI