|NUTRITION - ORIGINAL ARTICLE
|Year : 2021 | Volume
| Issue : 3 | Page : 199-205
Association Between Nutritional Status and Neutrophil Lymphocyte Ratio in Patients with Lung Cancer at Persahabatan Hospital, Indonesia
Lidya Anissa1, Yohannessa Wulandari1, Fariz Nurwidya2
1 Department of Nutrition, Faculty of Medicine, University of - Dr Cipto Mangunkusomo General Hospital, Jakarta, Indonesia
2 Department of Pulmonology and Respiratory Medicine, Faculty of Medicine Universitas −Persahabatan Hospital, Jakarta, Indonesia
|Date of Submission||13-Apr-2021|
|Date of Decision||22-Apr-2021|
|Date of Acceptance||27-May-2021|
|Date of Web Publication||28-Jul-2021|
Pulmonologist or Doctor Specialis of Pulmonology, PhD, Jl. Salemba Raya No. 6, Jakarta 10430
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Systemic inflammation in patients with lung cancer can be seen by the increase of neutrophil lymphocyte ratio (NLR) where these examinations are common in hospitals. Systemic inflammation can cause anorexia resulting in decreased nutrition intake of patients with lung cancer and affecting their nutritional status. One of the diagnostics of nutritional status for patients with lung cancer is using the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria that consist of decreased nutritional intake, weight loss, decreased muscle mass and subcutaneous fat mass, general or local fluid accumulation, and functional capacity. Malnutrition can be diagnosed if there are two of the six criteria. Aims: The study aims to determine the relationship between nutritional status and NLR in patients with lung cancer at Persahabatan Hospital in East Jakarta, Indonesia. Settings and Design: This cross-sectional study included 52 patients with lung cancer in oncology outpatient clinic of Persahabatan Hospital. Methods and Material: Data of characteristics subject were taken from interviews, physical examinations, laboratory analysis, and patients medical records in the oncology outpatient clinic of Persahabatan Hospital. Statistical analysis used chi-square or Fisher exact test to assess relationship between nutritional status and NLR (P < 0.05). Results: Based on nutrient intake, more than 50% of the subjects had low energy and protein intake. Based on patient generated subjective global assessment, 38.5% of subjects were at risk of malnutrition or moderate malnutrition, while 67.3% of them were malnutrition based on ASPEN. There was no statistically significant association between nutritional status and NLR (P = 0.35). Conclusions: There was no association between nutritional status and NLR, and so further research with larger samples is needed.
Keywords: Lung cancers, malnutrition, neutrophil lymphocyte ratio, nutritional status, systemic inflammation
|How to cite this article:|
Anissa L, Wulandari Y, Nurwidya F. Association Between Nutritional Status and Neutrophil Lymphocyte Ratio in Patients with Lung Cancer at Persahabatan Hospital, Indonesia. Int J Nutr Pharmacol Neurol Dis 2021;11:199-205
|How to cite this URL:|
Anissa L, Wulandari Y, Nurwidya F. Association Between Nutritional Status and Neutrophil Lymphocyte Ratio in Patients with Lung Cancer at Persahabatan Hospital, Indonesia. Int J Nutr Pharmacol Neurol Dis [serial online] 2021 [cited 2021 Oct 25];11:199-205. Available from: https://www.ijnpnd.com/text.asp?2021/11/3/199/322481
Key Messages: NLR is a laboratory assessment that is commonly used in hospitals and can be used to see nutritional status in patients with lung cancer so that with proper nutrition management the incidence of malnutrition in patients with lung cancer can be prevented.
| Introduction|| |
Lung cancer is the dominant cause of mortality worldwide for both males and females. Based on the data from Global Burden of Cancer (Globocan) in 2020, the mortality rate of lung cancer was in the first position (18%), followed by liver cancer (8.3%), gastric cancer (7.7%), breast cancer (6.9 %), and colon cancer (5.8%) throughout the world. In Indonesia, a total of 34,783 people were diagnosed with lung cancer and it was in the third position after breast and cervical cancer. The research conducted by Komalawati in 2016 stated that the number of patients with lung cancer at Persahabatan Hospital in 2013 was 616 and it increased to 880 people in 2014. A delayed diagnosed of lung cancer stages is the main cause of the increased of mortality rate for patients with lung cancer. Commonly, patients are diagnosed at the III-1V of its stage.
Chronic systemic inflammation often occurs in patients with lung cancer. Pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin 1 (IL-1), IL-6, play a central role in the inflammatory process. To detect the presence of inflammation, it can be done by calculating the neutrophil lymphocyte ratio (NLR). Neutrophils are active nonspecific mediator that trigger the body’s protective response, while lymphocytes are a protective component of inflammation. Neutrophil counts will increase and lymphocyte counts will decrease in responding to the body’s inflammation.
High NLR in patients with lung cancer can be the indicator of inflammation that will affect nutritional status. This occurs because systemic inflammation can cause anorexia, thereby reducing the food intake. Furthermore, if it is not being treated, it will affect malnutrition. Patients with lung cancer can be categorized as one of the groups with the highest prevalence of malnutrition. In a longitudinal prospective study about the prevalence of malnutrition of patients who come to Australian oncology clinics before chemotherapy or radiotherapy treatment, 69% of patients with lung cancer had malnutrition, higher than patients with colorectal cancer (57%) or head and neck cancer (45%). Hébuterne et al. found a 45% overall rate of malnutrition in inpatients with lung cancer.
The nutritional status is assessed based on clinical, physical, and anthropometric, as well as laboratory, examinations. Diagnosis of malnutrition may be made by the criteria of American Society for Parenteral and Enteral Nutrition (ASPEN), which consists of inadequate energy intake, weight loss, decreased subcutaneous fat mass, decreased muscle mass, local or general fluid accumulation, and functional status assessed by using hand grip strength. Malnutrition can be diagnosed if there are two of the six criteria.
The association between nutritional status and NLR has attracted the interest in recent years for its routine and readily available test. Tan et al. stated that there was a positive relationship between malnutrition in cancer patients based on the results of the patient generated subjective global assessment (PG-SGA) and NLR.
Prior research discussed more about the relationship between prognosis and NLR of patients with lung cancer. However, topic about the relationship between nutritional status and NLR is still limited. This study aims to identify nutritional status of patients with lung cancer that is linked to inflammatory status by using NLR.
| Subjects and Methods|| |
This cross-sectional study with consecutive sampling method was conducted from August 2020 to October 2020 at Persahabatan Hospital. This study had received approval from the Dr Cipto Mangunkusomo Hospital Faculty of Medicine Universitas Indonesia ethical committee (KET-174/UN2.F1/ETIK/PPM.00.02/2020) and Persahabatan Hospital ethical committee (78/KEPK-RSUPP/7/2020). The research consisted of 52 subjects. The patients were able to stand, primary lung cancer stage III-IV, males and females, 40 to 65 years old, and were willing to participate in the study by signing the informed consent. Subjects with the additional diseases such as diabetes mellitus, infection, steroids consumed, chronic heart disease, and immunodeficiency diseases were excluded.
Interview of subjects
Subjects were interviewed by using the subject characteristics, food intake, screening for malnutrition by using PG-SGA, and status therapy.
Dietary data were collected from each participant using validated semiquantitative food frequency questionnaire (SQ-FFQ) for the intake of energy and protein over the past 1 month. It is analyzed by using NutriSurvey 2007.
Nutrition status examination
Nutrition status examination consisted of history taking of weight loss and physical examination including weighing by using SECA 876 digital weighing scale to nearest 0.1 kg, examination of subcutaneous fat in the orbital area, upper arm circumference (triceps and biceps), chest and back area (ribs, lower back, midaxillary line), examination of muscle mass in temples (m.temporalis), clavicle bone area (m.pectoralis major, deltoid, m.trapezius), clavicle and acromion (m.deltoid), scapular area (m.trapezius, m.supraspinus, m.infraspinus), back of hands (m.interosseous), knees, upper thighs, calves, fluid accumulation (see the presence or absence of oedema), as well as examination of grip strength by using the Jamar dynamometer.
Complete peripheral blood test is carried out to determine NLR. The result is categorized into high NLR (NLR >3.0) and low NLR (NLR <3.0).
To assess association between subject characteristics with nutritional status and association between nutritional status with NLR using Chi-square or Fisher exact test with The Statistical Package for the Social Sciences (SPSS) version 20.1. The result states that there is a significant relationship if P < 0.05.
| Results|| |
Characteristics of the subjects in this study include age, gender, smoking status, smoking rate, energy and protein intake, PG-SGA screening, and therapy status. The data can be seen in [Table 1].
Patients with lung cancer who were willing to participate in this study consisted of 61.5% men and 38.5% women, and the most common age range was 50 to 60 years. As many as 55.8% of subjects are former smokers and 30.8% cancer patients were former heavy smokers.
In this study, 61.5% of subjects had low energy intake based on European Society for Clinical Nutrition and Metabolism (ESPEN) recommendation, which is less than 25 kcal/body weight per day. For protein intake, it showed 69.2% of subjects were less than 1 g/kg body weight per day. Based on screening by using PG-SGA, 38.5% subjects were found at risk of malnutrition or moderate malnutrition, while 28.8% had severe malnutrition.
As for this study, there were 10 new patients diagnosed with a therapy plan and 42 patients were being treated with oral chemotherapy or intravenous chemotherapy. The visits of lung cancer patients to the oncology clinic at the Persahabatan Hospital have been decreasing due to the coronavirus (COVID-19) pandemic. This study found that 67.5% of subjects had malnutrition [Table 2].
[Table 3] showed subject characteristics based on nutritional status. There was no significant association between age, gender, smoking status, smoking degree, and protein intake with nutritional status in this study (P = 0.647, P = 0.476, P = 0.797, P = P.072, P = 0.076, respectively). Otherwise there was significant association between energy intake, PG-SGA, and therapeutic status with nutritional status (P = 0.001, P < 0.001, P = 0.02, respectively).
We found that there was no significant association between nutritional status and NLR in patients with lung cancer (P = 0.35) [Table 4].
|Table 4 Association between nutritional status and neutrophil lymphocyte ratio|
Click here to view
| Discussion|| |
In this study, the biggest age range was between 50 and 60 years. These results almost similar to the data from Burhan et al. showed that 57% incidence of lung cancer at Persahabatan Hospital from 2015 to 2016 had the highest number of cases in the age range of 40 to 60 years old. Middle-aged people are susceptible to cancer due to the accumulation of cancer risk factors that cause genetic and epigenetic mutations.
In this study, patients with lung cancer were mostly males, which were 61.5%. This is in line with the research conducted by Sholih et al. and Pierzynski, which stated that the incidence rates of lung cancer based on gender were 76.7% and 53.46%, respectively, in males. It is assumed that men tend to have a previous smoking history in which smoking is one of the main factors of having lung cancer. 55.8% of patients with lung cancer were former smokers. In line with the study conducted by Pierzynski, 63.8% of patients with lung cancer had a history of smoking. The risk of lung cancer increases with the duration of smoking. Among the subjects in this study, 30.8% had a heavy Brinkman index in line with the research conducted by Burhan et al. at Persahabatan Hospital, which stated that as many as 33.7% of patients with lung cancer had a heavy Brinkman index.
Energy intake based on ESPEN recommendation is 25 kcal/kg body weight per day until 30 kcal/kg body weight per day. Low energy intake in lung cancer patient can be caused by systemic inflammation that can affect metabolism, suppressing the hunger center in the arcuate hypothalamus nucleus, which result in anorexia and decreased intake. Previous study at Dharmais Hospital with 49 patients with lung cancer showed that 53.1% of them had low energy intake. Protein intake based on ESPEN was 1 to 2 g/kg/day. For protein intake, this study showed that 69.2% of patients with lung cancer were less than 1 g/kg/day. The same thing is also found in research conducted by Amanda at Dharmais Hospital, 42.9% of their protein intake were less than 1 g/kg/day. The lack of protein intake in this study was because the subjects did not know how much protein should have been consumed according to their needs.
In this study, 38.5% of our respondents were in the moderate malnutrition category or at risk of malnutrition. Supported by Silva et al. which had a cross-sectional study in Brazil on all types of cancer, figuring out of 32 patients with lung cancer, 17.3% had been screened by using PG-SGA were in the moderate malnutrition category or at risk of malnutrition and 10.1% of the patients were in the category of severe malnutrition. A study conducted in China by Ge et al. found that of 495 patients with advanced lung cancer, 264 (53.3%) needed nutritional support.
Nutritional status in this study is assessed based on ASPEN criteria, consisting of weight loss, energy intake, subcutaneous fat, muscle mass, local/general fluid accumulation, and functional status (grip strength). Malnutrition can be seen if there are two of the six criteria. It is found that 67.5% of patients with lung cancer who were the subjects of this study had malnutrition. Based on another study, the prevalence of malnutrition in lung cancer was 45% to 69%. Malnutrition of patients with lung cancer affects the clinical condition, decreases quality of life, decreases functional status, and effects the prognosis. Appropriate and fast nutritional therapies are expected to improve the quality of life of patients with lung cancer.
There was no significant result between age and nutritional status (P = 0.866). This result is different from the research conducted by Silva et al., which found that there was a significant relationship between age and nutritional status of patients with lung cancer. The difference in results can be attributed to different criteria for malnutrition. In a study conducted by Silva et al., the criteria for malnutrition are based on WHO criteria [using body mass index (BMI)]. Diagnosis of malnutrition using body mass index does not assess weight loss, only uses actual weight. For gender, no significant relationship with nutritional status (P = 0.476) toward patients was found. This is in line with a study conducted at the University of Pennsylvania Hospital by Hudson et al.. There was no significant connection between gender and nutritional status (P = 0.1355) of all inpatients from 2013 to 2015. This occurred because both males and females had the same risk of malnutrition. Another study conducted by Silva et al. found a significant relationship (P < 0.05) between smoking status and malnutrition. In contrast to this study, there was no significant relationship between smoking status and nutritional status. This is because of the homogeneous data on the distribution of smoking status of patients.
Malnutrition in cancer patients can occur due to anorexia as well as metabolic and endocrine changes due to tumor factors and inflammatory cytokines produced by cancer cells or host or due to chemotherapy effects such as nausea, vomiting, dry mouth, greening disorders, and it can also be due to the effects of cancer itself. Cancer cells stimulate the release of inflammatory cytokines so as to stimulate the effects of satiety in the central nervous system, result in reduced feeding intake, and can lead to malnutrition.,, Research conducted by Darmawan and Adriani on cancer patients at Dr. Ramelan Hospital Surabaya revealed that there is a significant association between energy intake and nutritional status (P = 0.024). In this study, 75% of subjects were malnourished with protein intake less than 1 g/kg/day, but there was no significant relationship with nutritional status (P = 0.076). This occurred because in case of the subjects who were well nourished, their protein intake were assessed by the SQ-FFQ below 1 g/kg/day.
In this study, there is a significant relationship between patient-generated subjective global assessment (PGSGA) and nutritional status (P < 0.001). This is in line with the study conducted by Ge et al. in China in which there was a significant relationship between PGSGA and nutritional status (P < 0.001) in 495 patients with lung cancer. This indicates the importance of screening so that patients who are at risk of malnutrition would be immediately given the nutritional therapy, both counselling and other nutritional therapies. Nutritional therapy, which is done earlier, can affect overall survival.
In this study, there was a significant relationship between therapeutic status and nutritional status (P = 0.02). Kiss et al. found that out of 207 patients with lung cancer, 33% were malnourished prior to therapy, which increased to 50% after treatment. Malnutrition that occurs in patients who are being treated is from the side effect of the therapy itself. The side effects of chemotherapy that often occur and affect the nutritional status are nausea and vomiting. Chemotherapy causes the release of neurotransmitters such as dopamine, serotonin, and substance P that send signals through the chemoreceptor trigger zone in the postrema area to the vomiting center.
This study showed that there was no association between nutritional status and NLR in patients with lung cancer. This result is different from the study conducted by Pessanha et al. in 87 patients with gastrointestinal cancer in which it was found that there was a relationship between nutritional status assessed based on weight loss, NRI, and SGA with NLR (P=0.002, P=0.001, and P=0.009). Weight loss categorized as weight loss in >10% for 6 months and ≤10% for 6 months, nutrition risk index (NRI) and screening by using SGA with NLR of patients (P = 0.002, P = 0.001, and P = 0.009). Weight loss is one of the diagnostic criteria for malnutrition based on ASPEN. In this study, there was no significant relationship between weight loss and the value of NLR. This is stated, probably, because the total patients in this study had weight loss of >10% or ≤10% for 6 months, not as many as in the study conducted by Pessanha et al. NRI is a nutritional status screening that is assessed based on serum albumin and body mass index, but does not assess food intake, weight loss, or physical and functional status examinations that allows a different diagnosis of nutritional status. In the screening with the SGA method, the components of the examination are not as complete as the examination of nutritional status by using ASPEN criteria. In ASPEN, there is an examination of functional capacity by assessing grip strength and there is an assessment of intake as well, and so those patients screened using SGA are not malnourished. However, based on the ASPEN criteria, there is an examination of grip strength and intake assessment can be diagnosed with malnutrition.
In previous studies, there was linking of nutritional status to the NLR conducted in cancer patients who had not received therapy. In this study, the patients being treated have a NLR value below three. However, malnutrition occurred due to the side effect of the therapy itself. Neutrophils release cytokines and chemokines that play a role in the growth and proliferation of tumor cells and the spread of tumor cells (metastasis), while the lymphocytes have a role to press cancer cells and prevent the spread of cancer cells. In a study conducted by Lee et al., there were 199 patients with lung cancer who received chemotherapy, the decrease in the NLR after having a therapy, where there was a decrease also in the number of neutrophils, and an increase in the number of lymphocytes was attributed to a good tumor response and an effect on the survival of patients with lung cancer. The decrease in inflammatory response, as seen from the decrease in the NLR, shows the shrinkage of cancer cells as well as the success of therapy and the sensitivity of it.
Anticancer therapy aims to press neutrophil activity by suppressing chemokine receptors (CXCR2), which plays a role in the spread of cancer. The suppression of CXCR2 and CXCR1 activity is able to influence the clinical state of cancer. In addition, cancer therapy aims to inhibit IL-23 and IL-17, which stimulate the increase in neutrophils mediated by granulocyte-colony stimulating factor (G-CSF). G-CSF plays a role in the maturation of neutrophils. Taken together, neutrophil is an important indicator for anticancer therapy.
There are strengths of this study. This study assessed food intake using SQ-FFQ method so that it can examine the usual intake of the subject and diagnostic malnutrition using ASPEN criteria is more detail than using WHO criteria based on body mass index, which has more often been used in other studies. However, this study had a limitation, which was the length of therapy for patients with lung cancer. In this study, it varied considerably and it could affect the result of the study.
| Conclusion|| |
There was no significant association between nutritional status and NLR in patients with lung cancer at Persahabatan Hospital. Therefore, it is necessary to conduct a similar study with the criteria for diagnosis of malnutrition by using ASPEN with a larger number of samples of pre-treatment cancer patients, which can affect the NLR.
The authors would like to thank Universitas Indonesia for funding this research through PUTI Grant with contract number NKB-4691/UN2.RST/HKP.05.00/2020.
Financial support and sponsorship
This study was supported by PUTI grant Universitas Indonesia.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Komalawati D. Pengaruh Progressive Muscle Relaxation (PMR) Terhadap Myalgia Pada Pasien Kanker Paru Yang Menjalani Kemoterapi. J Kesehat Holist 2018;2:37-46.
Tatun R, Icksan AG, Syahruddin E, Kekalih A. Gambaran CT Scan Toraks Sesuai dengan Jenis Sitologi / Histologi pada Pasien Kanker Paru yang Merokok. 2015;3:177-85.
Imtiaz F, Shafique K, Mirza S, Ayoob Z, Vart P, Rao S. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med 2012;5:2-6.
Pessanha LL, Schmidt Mo M, Ribeiro Ca L et al.
Neutrophil-to-lymphocyte ratio and nutritional status in patients with cancer in hospital admission. Int J Cancer Res 2019;15:9-16.
Kiss N. Nutrition support and dietary interventions for patients with lung cancer: current insights. Lung Cancer Targets Ther 2016;7:1-9.
Hébuterne X, Lemarié E, Michallet M, De Montreuil CB, Schneider SM, Goldwasser F. Prevalence of malnutrition and current use of nutrition support in patients with cancer. J Parenter Enter Nutr 2014;38:196-204.
White JV, Guenter P, Jensen G, Malone A, Schofield M. Consensus statement: Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Parenter Enter Nutr 2012;36:275-83.
Tan CSY, Read JA, Phan VH, Beale PJ, Peat JK, Clarke SJ. The relationship between nutritional status, inflammatory markers and survival in patients with advanced cancer: a prospective cohort study. Support Care Cancer 2015;23:385-91.
Burhan E, Ramdhani RR, Zaini J. Proporsi Tuberkulosis Laten Pada Pasien Kanker Paru di Rumah Sakit Umum Pusat Persahabatan Jakarta. J Respir Indo 2019;39:256-65.
Sholih MG, Perwitasari DA, Hendriani R et al.
Risk factors of lung cancer in Indonesia: a qualitative study. J Adv Pharm Educ Res 2019;9:41-5.
Pierzynski JA, Ye Y, Lippman SM, Rodriguez MA, Wu X, Hildebrandt MAT. Socio-demographic, clinical, and genetic determinants of quality of life in patients with lung cancer. Sci Rep 2018;8:1-8.
Hecht SS. Cigarette smoking and lung cancer: Chemical mechanisms and approaches to prevention. Lancet Oncol 2002;3:461-9.
Arends J, Bachmann P, Baracos V et al.
ESPEN guidelines on nutrition in cancer patients. Clin Nutr 2017;36:11-48.
Amanda P, Sunardi D, Sutandyo N. Correlation between carbohydrate, protein and fat intake with serum C-reactive protein level in patients with lung cancer stage IIIB-IV. World Nutr J 2018;1:31-7.
De Melo Silva FR, De Oliveira MGOA, Souza ASR, Figueroa JN, Santos CS. Factors associated with malnutrition in hospitalized cancer patients: A croos-sectional study. Nutr J 2015;14:1-8.
Ge T, Lin T, Yang J, Wang M. Nutritional status and related factors of patients with advanced lung cancer in northern China: a retrospective study. Cancer Manag Res 2019;11:2225-31.
Hudson L, Chittams J, Griffith C, Compher C. Malnutrition identified by Academy of Nutrition and Dietetics/American Society for parenteral and enteral nutrition is associated with more 30-day readmissions, greater hospital mortality, and longer hospital stays: a retrospective analysis of nutrition assessment data in a major medical center. J Parenter Enter Nutr 2018;42:892-7.
Mondello P, Mian M, Aloisi C, Famà F, Mondello S, Pitini V. Cancer cachexia syndrome: pathogenesis, diagnosis, and new therapeutic options. Nutr Cancer 2015;67:12-6.
Ridge C, McErlean A, Ginsberg M. Epidemiology of lung cancer. Semin Intervent Radiol 2013;30:93-8.
Aapro M. CINV: still troubling patients after all these years. Support Care Cancer 2018;26:S5-9.
Darmawan A, Adriani M. Status Gizi, Asupan Energi dan Zat Gizi Makro Pasien Kanker yang Menjalani Kemoterapi di RUMKITAL Dr. Ramelan Surabaya. Amerta Nutr 2019;3:149-57.
Kiss NK, Krishnasamy M, Isenring EA. The effect of nutrition intervention in patients with lung cancer undergoing chemotherapy and/or radiotherapy: a systematic review. Nutr Cancer 2014;66:47-56.
Lee Y, Kim SH, Han JY, Kim HT, Yun T, Lee JS. Early neutrophil-to-lymphocyte ratio reduction as a surrogate marker of prognosis in never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy. J Cancer Res Clin Oncol 2012;138:2009-16.
Ocana A, Nieto-Jiménez C, Pandiella A, Templeton AJ. Neutrophils in cancer: prognostic role and therapeutic strategies. Mol Cancer 2017;16:1-7.
[Table 1], [Table 2], [Table 3], [Table 4]