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Neutrophil-to-Monocyte-Plus-Lymphocyte
Ratio as a Potential Marker for Discriminating
Pulmonary Tuberculosis from Nontuberculosis
Infectious Lung Diseases
You La Jeon, MD, PhD,1 Woo-In Lee, MD, PhD,1,2* So Young Kang, MD, PhD,1,2
Myeong Hee Kim, MD, PhD1,2
Laboratory Medicine 2019;XX:1–6
DOI: 10.1093/labmed/lmy083
ABSTRACT
Objective: To determine whether NMLR has more statistical strength
than NLR in discriminating TB from non-TB infectious lung diseases.
Methods: Among patients who underwent 3 or more TB culture tests
with molecular study between January 2016 and December 2017, 110
patients with TB, and 159 patients diagnosed with non-TB infectious
lung diseases were enrolled. The original complete blood count (CBC)
parameters and modified CBC indices, including NLR and NMLR, were
analyzed.
Results: The NLR and NMLR were significantly lower in TB patients
than in patients with other infectious lung diseases. However, the
area under the curve (AUC) for NMLR (0.90; 95% confidence interval
Complete blood count (CBC) parameters such as neutro-
phils, lymphocytes, and platelets, as well as modified CBC
indices representing ratios, have been suggested as diag-
nostic markers for many infectious or inflammatory diseases
and as prognostic markers for malignant diseases.1-4 In
Abbreviations
CBC, complete blood count; TB, tuberculosis; MLR, monocyte-to-
lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-
lymphocyte ratio; COPD, chronic obstructive pulmonary disease; NMLR,
neutrophil-to-monocyte-plus-lymphocyte ratio; PCR, polymerase chain
reaction; CRP, C-reactive protein; ROC, receiver operating characteristic;
WBC, white blood cell; PLT, platelet; AUC, area under the curve; CI,
confidence interval
1
Department of Laboratory Medicine, Kyung Hee University Hospital at
Gangdong, Seoul, South Korea, 2Department of Laboratory Medicine,
School of Medicine, Kyung Hee University, Seoul, South Korea
*To whom correspondence should be addressed.
wileemd@khu.ac.kr
© American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
[CI], 0.86–0.93) was significantly greater than that for NLR (0.88
[0.84–0.92]).
Conclusions: The neutrophil-to-monocyte-plus-lymphocyte ratio (NMLR)
can be used as a new index that is more powerful than neutrophil-to-
lymphocyte ratio (NLR) in discriminating tuberculosis (TB) from non-TB
infectious lung diseases.
NMLR had more statistical strength than NLR in discriminating TB from
non-TB infectious lung diseases.
Keywords: tuberculosis, complete blood cell count, neutrophil-to-
lymphocyte ratio, neutrophil-to-monocyte-plus-lymphocyte ratio,
infectious lung diseases, pneumonia
pulmonary tuberculosis (TB) infection, these CBC parame-
ters and modified indices have been assessed as diagnostic
markers. Patients with TB tend to have increased neutrophil
and monocyte counts and decreased lymphocyte counts,
compared with healthy subject individuals.5-7 Moreover, the
monocyte-to-lymphocyte ratio (MLR) was suggested as a
predictive marker of active TB in a report comparing healthy
subjects to patients with TB.8
Recently, the neutrophil-to-lymphocyte ratio (NLR) has
been reported as a useful marker for differential diagnosis
between TB and bacterial pneumonia or sarcoidosis.9,10
Also, the platelet-to-lymphocyte ratio (PLR) was also
introduced as a potential marker to identify TB infection
in patients with chronic obstructive pulmonary disease
(COPD).11 However, research on the role of CBC parameters
or modified indices in discriminating TB from non-TB infec-
tious lung diseases is lacking; further studies are needed.
1
Science
The aim of this study was to analyze the clinical efficacy
of the original CBC parameters and the modified CBC
indices, such as MLR, NLR, and PLR, with additional
CBC parameters in the differential diagnosis of TB from
non-TB infectious lung diseases. The neutrophil-to-mono-
cyte-plus-lymphocyte ratio (NMLR), defined as the neutro-
phil count/(monocyte count + lymphocyte count), was the
first marker we had developed for this study (considering
the CBC parameters of patients with TB), compared with
those in patients with non-TB infectious lung diseases. This
study evaluated the NMLR as a diagnostic marker to dif-
ferentiate TB from other infectious diseases in comparison
with other parameters, especially the NLR.
Material and Methods
We conducted a retrospective analysis of the demographic
characteristics, clinical information, and laboratory test
results of 110 patients with pulmonary TB and 159 patients
diagnosed with non-TB infectious lung diseases between
January 2016 and December 2017. All subjects underwent
3 or more Mycobacterium tuberculosis (MTB) culture tests
and/or molecular study (TB–polymerase chain reaction
[PCR] or X-pert MTB [Cepheid Inc.]) to confirm TB infection.
TB was diagnosed in patients with positive culture study
results or adenosine deaminase level of 70 IU per dL or
greater with lymphocyte-dominant exudative pleural effu-
sion and lung parenchymal lesion implying pulmonary TB.
Patients with clinical symptoms related to TB or radiologic
findings of suspected TB showing effective response
to anti-TB drug were included in the study, even if their
results from MTB culture were negative. Patients with
non-TB mycobacterial infection were excluded. The char-
acteristics of the patients with TB, according to diagnostic
criteria, are introduced in Table 1. Patients with non-TB
infectious lung diseases (non-TB group) included those
with bacterial or viral pneumonia, aspiration pneumonia, or
empyema.
The collected data included CBC results and levels of
C-reactive protein (CRP) as a common infectious disease
marker. These values were measured on patient admission.
The value of the original CBC parameters and modified CBC
indices were compared between patients with TB and those
without TB.
2  
Lab Medicine 2019;00;1–6
DOI: 10.1093/labmed/lmy083
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Also, we analyzed the distributions of the NMLR value
in 220 healthy subjects as a control group. These sub-
jects were randomly selected from among individuals
who underwent health check-ups at the same time as the
patient-recruitment period. The demographic characteristics
of the healthy subjects were as follows: mean (SD), 50.12
(10.87) years and sex ratio (male:female), 132:88. This study
was approved by Institutional Review Board of Kyung Hee
University Hospital at Gangdong, Seoul, South Korea.
For statistical analysis, we usd SPSS Statistics software for
Windows, version 20.0 (IBM Corporation) and Medcalc soft-
ware (Medcalc Software bvba). The data were presented as
numbers or mean (SD). Continuous variables were analyzed
using Mann-Whitney U tests for 2 groups. We used Pearson
χ2 testing for categorical variables. The comparisons of
receiver operating characteristic (ROC) curves between
variable parameters were performed using MedCalc soft-
ware for Windows, version 11.0. P values of .05 or less were
considered statistically significant.
Results
Study Population
The distribution and demographic characteristics of the
study population are presented in Table 1. Patients with
non-TB infectious lung diseases included those with
bacterial or viral pneumonia (n = 92), aspiration pneumo-
nia (n = 47), or empyema (n = 20). The mean (SD) ages
of patients with TB and non-TB infectious lung diseases
were 52.4 (19.7) and 68.3 (16.5) years, respectively. The
male-to-female sex ratios of both groups were similar.
Comparison of CBC Data between TB and
Non-TB Patient Groups
The original CBC parameters other than the monocyte count
and all the modified CBC indices showed statistical differ-
ences between the 2 groups. The white blood cell (WBC)
and neutrophil counts of patients in the TB group were
significantly lower than those in the non-TB group. However,
the lymphocyte and platelet (PLT) counts were significantly
higher in the TB group. The modified CBC indices, such as
the MLR, NLR, PLR, and NMLR with CRP, were statistically
significantly lower in the TB group (Table 2).
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Table 1. Demographic Characteristics of the Study Population
Variable Healthy TB Group Non-TB Group P Value
Subjects
No. 220 110 159
Age (y), mean (SD) 50.1 (10.9) 52.4 (19.7) 68.3 (16.5) <.001
Sex (male:female) 132:88 61:49 90:69 .85
Diagnostic criteria of TB or TB culture confirmed (94) Bacterial or viral
non-TB diseases (no.) TB pleurisy and lung lesion (8) pneumonia (92)
Symptomsa or radiologic findings with effective Aspiration pneumonia (47)
response to anti-TB drugs (8) Empyema (20)
Abbreviation: TB, tuberculosis.
a
Symptoms related to TB included cough, sputum, fever, weight loss, or night sweats.

Table 2. Laboratory Data of the Study Population

Variable Mean (SD) P Value

Healthy Subjects TB Group Non-TB Group

9
WBC (10 /L) 5.60 (1.64) 8.42 (2.93) 12.66 (5.53) <.001
Hemoglobin (g/dL) 14.66 (1.51) 12.76 (1.75) 11.60 (1.89) <.001
Hematocrit (%) 43.60 (3.84) 38.43 (4.75) 34.92 (5.32) <.001
Platelet (109/L) 244.45 (48.92) 320.05 (110.26) 275.08 (123.10) .001
Neutrophil (109/L) 3.17 (1.29) 5.91 (2.63) 10.69 (5.11) <.001
Lymphocyte (109/L) 1.84 (0.56) 1.58 (0.64) 1.08 (0.54) <.001
Monocyte (109/L) 0.38 (0.13) 0.74 (0.34) 0.77 (0.51) .67
MLR 0.22 (0.10) 0.55 (0.34) 0.81 (0.66) <.001
NLR 1.88 (1.19) 4.37 (2.68) 12.42 (9.26) <.001
PLR 1.44 (0.51) 2.37 (1.34) 3.02 (1.68) .001
NMLR 1.51 (0.82) 2.71 (1.28) 6.80 (4.19) <.001
CRP (mg/dL) 4.97 (6.12) 4.97 (6.12) 15.32 (9.25) <.001
Abbreviations: TB, tuberculosis; WBC, white blood cells; MLR, monocyte-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; NMLR, neutrophil-to-
monocyte-plus-lymphocyte ratio; CRP, C-reactive protein

interval (CI), 0.86–0.93]) (Table 3). The NMLR also had a

Table 3. Comparison of AUC Values of Various
CBC Markers for Discriminating TB from Non-TB significantly higher AUC than those of the MLR (P <.001),
Infectious Lung Diseases NLR (P = .009), and PLR (P <.001) (Figure 1). An NMLR
cut-off value of 3.95 had sensitivity and specificity of
CBC Markers AUC 95% CI
90.0% and 78.6%, respectively, for differentiating TB
Neutrophil count 0.80 .75–.85
and non-TB groups. The sensitivity and specificity
Lymphocyte count 0.73 .67–.78
Monocyte count 0.49 .43–.55 of NLR was 83.6% and 78.6%, respectively (cut-off
MLR 0.66 .60–.72 value, 6.4).
NLR 0.88 .84–.92
PLR 0.62 .56–.68 The NMLR of healthy subjects was lower than that of
NMLR 0.90 .86–.93
patients with TB (mean [SD], 1.51 [0.82] and 2.71 [1.28],
Abbreviations: AUC; area under the curve; CBC, complete blood count; TB,
tuberculosis; CI, confidence interval; MLR, monocyte-to-lymphocyte ratio; NLR,
respectively; P <.001) (Figure 2). The AUC of the NMLR for
neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; NMLR, neutrophil-to- differentiating patients with TB from healthy subjects was
monocyte-plus-lymphocyte ratio.
0.85 (95% CI, 0.80–0.88). At a cut-off value of 1.77, the sen-
sitivity and specificity were 79.1% and 82.7%, respectively.
Among the original CBC parameters and the modified The CRP showed a higher AUC (0.83 [95% CI, 0.78–0.87])
CBC indices, the area under the curve (AUC) value than those of the original CBC parameters and modified
was highest for the NMLR (AUC, 0.90 [95% confidence CBC indices other than the NLR and NMLR.

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DOI: 10.1093/labmed/lmy083
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100

Discussion
80 Because South Korea is a country with an intermediate-level
TB burden, it is necessary to consider TB as an exclusive
diagnosis for suspected infectious lung diseases.12 It is
60
important to discriminate TB at an early stage of disease
Sensitivity

evaluation because prompt isolation and treatment of TB

can reduce its transmission. The findings of this study
40
demonstrated that CBC data can provide a clinically impor-
tant clue because primary laboratory results can provide an
impression for discriminating TB from non-TB infectious lung
20
diseases.
NLR
NMLR
In this study, we analyzed the differences in CBC charac-
0
teristics between patients with TB and non-TB infectious
0 20 40 60 80 100
100-Specificity lung diseases, as well as the newly designed NMLR index
based on CBC results. The NMLR showed strong power,
Figure 1 compared with that of the original CBC parameters or other
The areas under the curves (AUC) for NLR and NMLR in modified CBC indices, in distinguishing TB from non-TB
discriminating TB from non-TB infectious lung diseases were 0.88 infectious lung diseases.
(95% confidence interval: 0.84–0.92) and 0.90 (0.86–0.93). NLR
indicates neutrophil-to-lymphocyte ratio; NMLR, neutrophil-to- The physiological immune response of peripheral leuko-
monocyte-plus-lymphocyte ratio. cytes to general infectious diseases showed that patients
had increased neutrophil counts and decreased lymphocyte

25
P <0.001

20

15

10 P <0.001

NMLR NMLR NMLR

Non-TB patients TB patients Healthy subjects

Figure 2
The distribution of NMLR of TB patients was slightly higher than that of healthy subjects and lower than that of non-TB patients. The bars
indicate the mean value for each group. NMLR indicates neutrophil-to-monocyte-plus-lymphocyte ratio, TB, tuberculosis.

4  
Lab Medicine 2019;00;1–6 www.labmedicine.com
DOI: 10.1093/labmed/lmy083

counts, compared with those values in healthy subjects.13-16
The NLR has been shown to be a predictive marker for
various infectious diseases by maximizing these CBC
characteristics. However, patients with TB are character-
ized by having an increased monocyte count, in addition to
neutrophil increase and lymphocyte decrease.5,6,8,9
Two studies8,17 have suggested the MLR as a predictive
marker of TB, to differentiate patients with TB from healthy
populations based on these findings. However, few reports
suggest that the original CBC parameters or modified CBC
indices may be helpful in the differential diagnosis of infec-
tious lung diseases, including TB.
In the present study, we observed relatively increased
neutrophil counts and decreased lymphocyte counts in
the TB group, compared with those counts in the non-TB
group. These results were consistent with those from
a previous study comparing patients having TB with
patients having bacterial pneumonia.9 Also, there was no
significant difference in the monocyte counts between the
TB and non-TB groups; however, the monocyte percent-
age was significantly higher in the TB group (mean [SD],
8.91 [2.87] vs 6.19 [3.06]; P <.001; data not shown). The
percentages of patients in the TB and non-TB groups with
monocyte levels greater than 10% were 8.2% and 26.4%
(P <.001), respectively. These results are associated
with the role of monocytes in the pathophysiology of TB
infection.
The host immune response to TB depends predominantly
on monocytes/macrophages and lymphocytes, unlike
in other infectious diseases.18,19 TB is associated with
increased production and release of monocytes in the bone
marrow.20 However, the role of neutrophils in the patho-
physiology of TB remains unknown but is known to be
limited.21,22
In the present study, the pathophysiologic characteris-
tics of TB were reflected in the CBC data. The NMLR is a
modified CBC index designed for this study, considering
such differences in CBC parameters between patients
in the TB and non-TB groups. The results of this study
showed the NMLR to have a stronger discriminating
power than those other previously reported indices, espe-
cially the NLR (AUC of NMLR and NLR, 0.90 and 0.88,
respectively; P = .009). For cases of suspected pulmonary
infectious disease, TB should be considered for NMLR
values less than 3.95.
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However, the value of AUC for differentiating patients with
TB from healthy subjects was not high, although the NMLR
of the patients with TB was significantly higher than that
of the healthy subjects (Figure 2). Therefore, the NMLR is
more suitable for discriminating TB among infectious lung
diseases in patients than among healthy subjects.
The MLR and PLR were also analyzed in this study. They
had lower AUC than those of the original CBC parameters,
such as neutrophil or lymphocyte counts (AUC of MLR,
PLR, neutrophil count, and lymphocyte count: 0.66, 0.62,
0.80, and 0.73, respectively). Therefore, MLR and PLR have
low clinical usefulness for differentiating TB from non-TB
infectious lung diseases.
CRP yielded a greater AUC than the original CBC parameters
or MLR and PLR. However, CRP had a lower discriminating
power (AUC, 0.83 [95% CI, 0.78–0.87]), compared with those
of NLR or NMLR, for differentiating TB from non-TB infec-
tious lung diseases, as confirmed in previous studies.9,13
In the present study, the NMLR showed better performance
than the NLR for discriminating TB from non-TB infectious
lung diseases, although the difference in their values was
not itself great (Figure 1). The NMLR can be obtained by
simple calculation of CBC parameters, so it can be easily
applied in clinical practice.
The limitations of this study include the irregular age distri-
butions between patients in the TB and non-TB groups and
the fact that the study was conducted retrospectively and in
a single center. Because the patients with non-TB myco-
bacterial infection were excluded in this study, the findings
of the study cannot be applied in this population.
Conclusions
The results of the present study suggested that the newly
designed NMLR is a more useful tool than the NLR for the
differential diagnosis of TB from non-TB infectious lung
diseases. The NMLR can provide a clinical impression at an
initial stage of evaluation, in which infectious lung diseases,
including TB, are suspected. An NMLR value less than 3.95
in these subjects suggests the possibility of TB, so appro-
priate evaluation and management should be implemented
immediately. LM
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