RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

DR. DYANESHWAR NIRGUDE

Post graduate student
1

Name of the candidate and

address ( in block letters)

Department of medicine
Bangalore medical collage &
Research institution
Bangalore - 560001

Bangalore Medical Collage &

Name of the institution

Research Institution, Bangalore,

Fort Area K R Road, Bangalore 560002

Course of study and

subjects

M.D. (General Medicine)

Date of admission to the

course

01-07-2015

STUDY OF NEUTROPHIL LYMPHOCYTE COUNT RATIO

Title of Topic

IN COMMUNITY ACQUIRED PNEUMONIA PATIENTS AS

A PROGNOSTIC INDICATOR AT TERTIARY CARE
CENTRE.

Brief Resume of the intended work

6.1

Need for the study

Community-acquired pneumonia (CAP) is a common, potentially fatal disease despite

advances in both diagnosis and treatment 1.Although new techniques are being developed,
defining the microbial etiology and classifying the severity of Community Acquired
Pneumonia (CAP) both remain challenging issues. Biomarkers, preferably in combination
with clinical risk scores, are increasingly used to identify specific patients at risk, to judge
the severity of illness and prognosis of Community Acquired Pneumonia (CAP) and more
recently to guide antibiotic therapy2. As the allocation of resources is, however, important,
the high prices for the use of newly developed biomarkers make their use less attractive3.
Immuno-competent white blood cell populations play an important role in the systemic
inflammatory response to infection. Following endotoxemia the number of circulating
neutrophils increases while lymphocyte counts decrease 4. Recently, the latter showed its
potential in predicting bacteremia or the severity of several infectious diseases 5. Initially,
this so-called Neutrophil-Lymphocyte Count Ratio (NLCR) was studied as an infection
marker in ICU patients and found to correlate well with disease severity and outcome,
according to APACHE-II and SOFA scores6, In a retrospective study, the NeutrophilLymphocyte Count Ratio (NLCR) proved to be a simple and even better marker in
predicting bacteremia than routine parameters, like white blood cell (WBC) count and Creactive protein (CRP) level, in infectious emergency admissions 7.Other studies focused
on the use of the Neutrophil-Lymphocyte Count Ratio (NLCR)

in specific clinical

conditions, like appendicitis, or its use as an independent predictor of survival in patients

with various conditions ranging from oncological to cardiovascular diseases 8. As
Community Acquired Pneumonia (CAP) is an important reason for Emergency
Department (ED) admission and subsequent hospitalization, we prospectively study the
prognostic value of Neutrophil-Lymphocyte Count Ratio (NLCR) in Community Acquired
Pneumonia (CAP) patient.

6.2

Review of Literature
A study by de Jager CP1 et al 2007 showed that. Admission Neutrophil-Lymphocyte
Count Ratio (NLCR) at emergency department predicts severity and outcome of
Community Acquired Pneumonia (CAP) with a higher prognostic accuracy as compared
with traditional infection markers 9.
A study by Ate H1, 2013 et al study showed that. Because of similar clinical
manifestations and laboratory findings, differential diagnosis of pulmonary embolism and
community-acquired pneumonia (CAP) is generally difficult. Therefore, this study was
conducted to find good markers for the easy, cheap, and fast differential diagnosis of
pulmonary embolism and Community Acquired Pneumonia (CAP) . First day neutrophil
count (P=0.005),

NLR (P=0.002),

CRP (P<0.001),

erythrocyte sedimentation rate (P<

0.001), PCT (P<0.001),

NLR/D-dimer (P<0.001),

and PCT/D-dimer (P<0.001)

levels
were higher in patients with Community Acquired Pneumonia (CAP) compared with
patients with pulmonary embolism10.
A study by Yoon NB1, 2010et al showed that. Serum NLR levels were significantly
lowers in patients with pulmonary TB than in patients with bacterial Community Acquired
Pneumonia (CAP) . The NLR obtained at the initial diagnostic stage is a useful laboratory
marker to discriminate patients with pulmonary TB from patients with bacterial
Community Acquired Pneumonia (CAP) in an intermediate TB-burden country11.
A study by de Jager CP1, 2012et al showed that. In an emergency care setting, both
lymphocytopenia and Neutrophil-Lymphocyte Count Ratio (NLCR) are better predictors
of bacteremia than routine parameters like CRP level, WBC count and neutrophil count.
Attention to these markers is easy to integrate in daily practice and without extra costs12.
A study by Terradas R1, et al showed that. There is scarce evidence on the use of
eosinophil count as a marker of outcome in patients with infection. The aim of this study
was to evaluate whether changes in eosinophil count, as well as the neutrophil-lymphocyte
count ratio (NLCR), could be used as clinical markers of outcome in patients with
bacteremia. Conclusion: Both sustained eosinopenia and persistence of an NeutrophilLymphocyte Count Ratio (NLCR) >7 were independent markers of mortality in patients
with bacteremia13.
Objectives of the study

6.3

To find out the value of Neutrophil-Lymphocyte Count Ratio(NLCR)in Community

Acquired Pneumonia (CAP).
To study Neutrophil-Lymphocyte Count Ratio (NLCR) as prognostic indicator in
Community Acquired Pneumonia (CAP).

Materials and methods

7.1

Source of data

The study would be conducted in patients with Community Acquired Pnuemonia admitted
in Victoria, Bowring and lady Curzon hospitals which are attached to Bangalore Medical
Collage & Research Institution during the study period ofNovember 2015-May 2017

7.2

Methods of collection of data ( including sampling procedure, if any)

A. Study design : Prospective study
B. Study period : November 2015-May 2017
C. Place of study: Victoria Hospital and Bowring and Lady Curzon Hospital, Bangalore
Medical Collage & Research Institution , Bangalore
D. Sample size: Sample size will be 100 with diagnosed cases of Community Acquired
Pnuemonia
E. Inclusion Criteria:
1. All patients who are 18 years and above
2. Patients who have Community Acquired Pnuemonia Clinically suspected
Community Acquired Pnuemoniawill be defined as the presence of sign and
symptoms of consolidation with or without opacity on plain chest radiography
(new cough, sputum production, dyspnoea, hypo- or hyperthermia, altered
breathe sounds upon physical examination).
F. Exclusion Criteria:
1. Age less than 18y.
2. Immunocompromise individuals.
3. Coexisting malignancy

G. Methodology:
All adult patients admitted in Victoria and Bowring and Lady Curzon Hospital
who are suspected to have Community Acquired Pnuemonia will be studied.
Clinically suspected Community Acquired Pnuemonia will be defined as the
presence of sign and symptoms of consolidation with or without opacity on plain
chest radiography (new cough, sputum production, dyspnoea, hypo- or
hyperthermia, altered breathe sounds upon physical examination).
The severity will be calculated in allCommunity Acquired Pnuemoniapatients as
per validated CURB-65 score.
The purpose of the CURB-65 score is to calculate the probability of mortality in
patients with Community Acquired Pnuemonia.

H. Assessment tools :
1. Proforma for written informed patient consent. (Attachment-I)
2. CRUB 65 score (Attachment-II)
3. Study proforma. (Attachment-III)
I. Statistical analysis :
Data will be analyses in SPSS 17 version for descriptive statistic Chi square test.
DATA COLLECTION
Age, gender, current smoking status,
Co-morbidity (Diabetes mellitus,Chronic Obstructive Pulmonary Disease,Heart
Disease, Gastrointestinal Disease, Cerebrovascular Disease, Renal Disease And
Chronic Liver Disease), additional therapy prior to presentation
Clinical symptoms (mental status, body temperature, blood pressure, heart and
respiratory rate, oxygen saturation),
5

 Laboratory data (CRP level, WBC count, absolute neutrophil count, absolute
lymphocyte count, Neutrophil-Lymphocyte Count Ratio (NLCR)

and urea

nitrogen levels) and

Radiological findings (infiltrate/with or without opacity). Biomarkers were
measured in all patients as part of routine clinical care.
7.3

Does the study require any investigation or intervention to be conducted on patients or

other humans or animals? If so please describe briefly.
Yes
The study requires the following investigations to be conducted on patients with
Community Acquired Pneumonia (CAP).
Investigation:

Complete hemogram

CRP level,

Absolute neutrophil count,

Absolute lymphocyte count,

Neutrophil-lymphocyte count ratio

Urea nitrogen levels

Sputum for culture and sensitivityand AFB

Radiological findings (infiltrate/with or without opacity).

7.4

Has ethical clearance been obtained from your institution in case of 7.3?
Yes. Ethical clearance has been obtained from Ethical clearance committee of the
institution.

List of References

1. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, et al. (2007) Infectious Diseases
Society of America/American Thoracic Society consensus guidelines on the management of communityacquired pneumonia in adults. Clin Infect Dis 44 Suppl 2S2772.
2.Christ-Crain M, Muller B (2007) Biomarkers in respiratory tract infections: diagnostic guides to
antibiotic prescription, prognostic markers and mediators. EurRespir J 30: 556573.
3.Heyland DK, Johnson AP, Reynolds SC, Muscedere J (2011) Procalcitonin for reduced antibiotic
exposure in the critical care setting: A systematic review and an economic evaluation. Crit Care Med 39:
17921799.
4.Jilma B, Blann A, Pernerstorfer T, Stohlawetz P, Eichler HG, et al. (1999) Regulation of adhesion
molecules during human endotoxemia. No acute effects of aspirin. Am J RespirCrit Care Med 159: 857863Jilma B, Blann A, Pernerstorfer T, Stohlawetz P, Eichler HG, et al. (1999) Regulation of adhesion
molecules during human endotoxemia. No acute effects of aspirin. Am J RespirCrit Care Med 159: 857863.
5. Wyllie DH, Bowler IC, Peto TE (2005) Bacteraemia prediction in emergency medical admissions: role
of C reactive protein. J ClinPathol 58: 352356
6.Zahorec (2001) Ratio of neutrophil to lymphocyte counts-rapid and simple parameter of systemic
inflammatiion and stress in critically ill. BratislLekListy 102: 514.
7. de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, et al. (2010)
Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional
infection markers in an emergency care unit. Crit Care 14: R192.
8. Ommen SR, Hodge DO, Rodeheffer RJ, McGregor CG, Thomson SP, et al. (1998) Predictive power of
the relative lymphocyte concentration in patients with advanced heart failure. Circulation 97: 1922.

9. de Jager CP1, Wever PC, Gemen EF, Kusters R, van Gageldonk-Lafeber AB, van der Poll T, Laheij RJ.
10Ate H1, Ate , Bozkurt B, elik HT, zol D, Yldrm Z. Ann Lab Med. 2013 Mar;33(2):105-10.
11. Yoon NB1, Son C, Um SJ. Crit Care. 2010;14(5):R192.
12. de Jager CP1, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. PLoS
One. 2012;7(8):e42860.
13..Terradas R1, Grau S, Blanch J, Riu M, Saballs P, Castells X, Horcajada JP, Knobel H.
14. Joshi VD, Kalvakolanu DV, Cross AS (2003) Simultaneous activation of apoptosis and inflammation
in pathogenesis of septic shock: a hypothesis. FEBS Lett 555: 180184
15.Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, et al. (2006) Duration of hypotension before
initiation of effective antimicrobial therapy is the critical determinant of survival in human septic
shock.Crit Care Med 34: 15891596.

Signature of Candidate

10

Remarks of guide

11

11.1 Name and designation of

the Guide

Community acquired pneumonia is a major cause of

morbidity and mortality in hospitalized patients in our
country. Neutrophil-lymphocyte count ratio was studied as
an infection marker in ICU patients and found to correlate
with disease severity and outcome. Neutrophil-lymphocyte
count ratio is simple and better marker in predicting
bacteremia in community acquired pneumonia patients and
their outcome. Hence this studied is recommended.

ASSOC. PROF DR. M. NARAYANSWAMY

11.2 Signature

11.3 Head of the Department

Dr. VEERANNA GOWDA

PROFESSOR AND HOD
DEPARTMENT OF MEDICINE
Bangalore Medical Collage & Research Institution

11.4 Signature

12

12.1 Remarks of the Chairman

and Principal
12.2 Signature

PATIENT INFORMATION AND CONSENT FORM

ATTACHMENT1
SIGNATURE PAGE

To become part of this study and to authorize use and disclosure of your personal health
Information, you or your legal representative must sign and date this page.
By signing this page, you are conforming the following:
1
2
3
4
5
6

You have read all of the information in this patient Information and Consent form,
and you have had time to think of it.
All of your questions have been answered to your satisfaction.
You voluntarily agree to be a part of this study.
You refuse to participate or freely choose to stop being a part of this study at any
time.
You allow the study doctor to use and disclose your personal health information as
described in this document.
You agree that your sample can be used for any other studies.
-----------------------------------Signature of the patient

---------------------------------------(dd/mm/my)

------------------------------------Patient name

----------------------------------------patient initials and number

----------------------------------------Signature of Principal investigator

---------------------------------------(dd/mm/my)

Name of Principal investigator

I hereby state the study procedures were explained in detail and all
questions were fully and clearly answered to the above maentioned participant.
------------------------------------------------------------------Name of Individual Condunting Informed Consent
----------------------------------------------------------------Signature of Individual Conducting Informed Consent
10

-------------------------(dd/mm/yy)

ATTACHMENT I

PROFORMA FOR WRITTEN INFORMED CONSENT

Date:
Place:

I Mr. /Mrs.Son/daughter/wife of Mr.aged about years, have been explained in a language

understood by me about the study entitled study of neutrophil lymphocyte count ratio values in
community acquired pneumonia patients as a prognostic indicator.at the department of General

medicine of Victoria hospital and Bowring and Lady Curzon hospital Bangalore.
I have been explained about the procedures and investigations that will be done during this study.
I have no objections in sharing my patients medical information and details in case records with
the investigators of this study.I have been informed that I will not be sharing any
incentives.Personal

identity

will

not

be

revealed

and

data

may

be

used

for

publication/dissertation purpose.
I understand that my patients participation in this study is entirely voluntary and I willfully give
consent regarding participation of my patientin this study for the specified duration.

Signature of the caregiver

Relation with the patient

Signature of the doctor

11

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ATTACHMENT II

CURB-65:
CURB-65, also known as the CURB criteria, is a clinical prediction rule that has been
validated for predicting mortality in community-acquired pneumonia and infection of any
site. The CURB-65 is based on the earlier CURB score and is recommended by the British
Thoracic Society for the assessment of severity of pneumonia.
The score is an acronym for each of the risk factors measured. Each risk factor scores one
point, for a maximum score of 5:

Confusion of new onset (defined as an AMTS of 8 or less)

Blood Urea nitrogen greater than 7 mmol/l (19 mg/dL)

Respiratory rate of 30 breaths per minute or greater

Blood pressure less than 90 mmHg systolic or diastolic blood pressure 60 mmHg or less

age 65 or older

Symptom
Confusion
BUN>7 mmol/l
Respiratory rate>=30
SBP<90mmHg, DBP=<60mmHg
Age>=65

CURB-65
Points
1
1
1
1
1
14

Predicting death:

Pneumonia
The risk of death at 30 days increases as the score increases:

00.6%

12.7%

26.8%

314.0%

427.8%

527.8%

The CURB-65 has been compared to the pneumonia severity index in predicting
mortality from pneumonia. It was shown that the PSI has a higher discriminatory power
for short-term mortality, and thus is more accurate for low risk patients than the CURB65 or its predecessor, the CURB score. However, the PSI is more complicated and
requires arterial blood gas sampling amongst other tests; given this, the CURB-65 score
is more easily used in primary care settings. A variant of the CURB-65 that omits the urea
measurement (CRB-65) is even simpler, as it relies only on history and examination
findings rather than blood tests.
The CURB-65 is used as a means of deciding the action that is needed to be taken for that
patient.

0-1: Treat as an outpatient

2: Consider a short stay in hospital or watch very closely as an outpatient

3-5: Requires hospitalization with consideration as to whether they need to be in

the intensive care unit

Any infection
Patients with any type of infection (half of the patients had pneumonia), the risk of death
increases as the score increases:

0 to 1 <5% mortality

2 to 3 < 10% mortality

15

4 to 5 15-30% mortality

SOFA score
Respiratory System:
The Sequential Organ Failure Assessment score, or just SOFA score, is used to track a
patient's status during the stay in an intensive care unit (ICU). It is one of several ICU
scoring systems.
PaO2/FiO2 (mmHg)

SOFA score

< 400
< 300
< 200 and mechanically ventilated
< 100 and mechanically ventilated

1
2
3
4

16

ATTACHMENT III

STUDY PROFORMA
DATE:
I.P. NO./O.P. NO. 1. PATIENT INFORMATION:
NAME
AGE
SEX
I.P. NO./ O.P. NO. -

ADDRESS

OCCUPATION

2. HISTORY OF PRESENT ILLNESS:

17

3.PAST HISTORY:
DIABETES MELLITUS
HYPERTENSION
RENAL FAILURE
LIVER FAILURE
BRONCHIAL ASTHMA/COPD
TUBERCULOSIS
OTHERS

4. FAMILYHISTORY:

5. PERSONAL HISTORY:
DIET/SLEEP
BLADDER AND BOWEL HABITS
SMOKING
ALCOHOLISM

18

OTHER SUBSTANCE ABUSE

6.TREATMENT HISTORY:

7.GENERAL PHYSICAL EXAMINATION:

VITALS SIGNS
Weight(kg)
Height(ft)
Temperature(degree Celsius)
Respiratory rate(per min)
Pulse rate(per min)
Blood pressure(mm Hg)

BASELINE

8.SYSTEMIC EXAMINATION:
CVS
RS
ABDOMEN
CNS
VII.INVESTIGATIONS:
COMPLETE HEMOGRAM
CRP LEVELs
ABSULUTE NEUTROPHIL COUNT,
ABSULUTE LYMPHOCYTE
COUNT
NEUTROPHIL-LYMPHOCYTE
COUNT RATIO
UREA NITROGEN LEVELS
SPUTUM FOR C/S AND AFB

19

RADIOLOGICAL FINDINGS
(INFILTRATE/WITH OR WITHOUT
OPACITY)

20