Role of CRP in Lower Respiratory Tract Infections

Address for correspondence Dr. Gursharan Singh Narang Prof. and Head of Department, Department of Paediatrics, Sri Guru Ramdas Institute of Medical Science and Research, Amritsar, Punjab, India. E-mail: gsnarang@gmail.com How to cite this article ? Kaur J, Narang GS, Arora S. Role of CRP in Lower Respiratory Tract Infections. J Nepal Paediatr Soc 2013;33(2):117-120. Role of CRP in Lower Respiratory Tract Infections


Introduction
C -reactive protein (CRP) is an acute phase protein that increases on infl ammatory triggers and decreases rapidly with resolution of infl ammation.It is synthesized and secreted by the liver in response to infl ammatory cytokines, particularly IL-6 and others such as tumour necrosis factor (TNF), IL-I and transforming growth factor 1,2 .CRP synthesis increases within 4-6 hours of an infl ammatory trigger and doubles every 8 hours.It peaks at 36 to 50 hours 3 .The ability to measure CRP quickly and quantitatively has made it increasingly useful in clinical practice.The defi nition of the presence, the aetiology and the severity of lower respiratory tract infection (LRTI) as well as the treatment choice and duration are frequently a real problem for the treating physician.Clinical features are sometimes misleading and not specifi c varying according to the aetiology (bacterial or viral), virulence, and adequacy of host response and presence of concomitant diseases.The aetiology is also poorly established due to inadequate patient defi nition and limited pathogen detection (16-55%) resulting from a combination of inadequate clinical sampling and pathogen detection methodology, particularly for respiratory viruses 4,5 .Excessive use of antibiotics is the main cause of the spread of antibiotic-resistant bacteria 6,7 .Thus, avoidance of irrational antibiotics is essential to combat emergence of antibiotic-resistant micro-organisms 8,9 .In view of this diagnostic and therapeutic dilemma, a more reliable test for the differential diagnosis of bacterial respiratory tract infections in need of antibiotics from other respiratory disease would be extremely helpful 10 .There is a clear need for diagnostic and prognostic biomarkers in LRTIs.The aim of this study was to fi nd out about the role of CRP in distinguishing between bacterial and viral etiology of LRTI

Materials and Methods
This was a prospective study.The subjects included 50 patients in the age group of two months to fi ve years of either sex with complaints of fever, cough and fast breathing attending the indoor and OPD of the department of Paediatrics of Sri Guru Ramdas Institute of Medical Sciences and Research, Amritsar.Diagnosis of lower respiratory tract infections was made according to WHO criteria.

d) HIV positive patients
A detailed history and complete clinical examination was done.The subjects were screened for Hb, TLC, DLC, PBF, ESR and Quantitative CRP.Chest X-ray (PA view) was done in all cases and USG or CT chest was done whenever indicated.
CRP was done by Nycocard CRP single test, an in vitro test that is used for the rapid determination of CRP.Nycocard CRP single test is a solid phase, sandwich format, immunometric assay.In this test there is a membrane coated with immobilised CRP-specifi c monoclonal antibodies.A diluted sample is applied to the test device.When the sample fl ows through the membrane, the C reactive proteins are captured by the antibodies.CRP trapped on the membrane will then bind the gold-antibody conjugated added, in a sandwich type reaction.A paper layer underneath the membrane absorbs excess liquid.In the presence of pathological level of CRP in the sample, the membrane appears red-brown with colour intensity proportional to the CRP concentration of the sample.The colour intensity is measured quantitatively with the NYCO card Reader.The data was analysed by chi-square test using SPSS 15.0 version software

Results
CRP was found to be 61.72 ± 36.665 mg/l in patients with bacterial aetiology.And those with probable viral aetiology (e.g.bronchiolitis) had mean CRP of 5.24 ±1.411 mg/l.The mean difference was found to be 56.486 and p-value is less than 0.001 that is highly signifi cant.
The receiver-operating characteristic curve area under the curve for relative CRP variation was 0.973 (95% confi dence interval = 0.61-0.86).The larger the area, the better is the diagnostic test.The cut-off CRP level for differentiating bacterial and viral aetiology on 7.5 mg/l the sensitivity is 90.5% with the specifi city of 96%.But if we take 11 mg/l as a cut-off the sensitivity is100% but specifi city decreases to 89.7%.So we take 9 mg/l as cut of level of CRP with sensitivity of 100% and specifi city of 96 %.

Discussion
Irrational prescription of antibiotics for respiratory tract infections is partly caused by diagnostic uncertainty about aetiology.Tests for C reactive protein are increasingly used to guide antibiotic prescribing for infections of the lower respiratory tract.
In this study, in LRTI of bacterial aetiology mean CRP was found to be 61.72 ± 36.665 mg/l and those with probable viral aetiology had mean CRP of 5.24 ±1.411.Similar observations were made by Smith et al 11 who observed mean CRP in pneumonia is 217 ± 16 mg/l and in bronchiolitis mean CRP is 18 ± 3 mg/l.Though the levels of CRP in our study are lesser than in the study by Smith et al, it could be because of prior antibiotic use, single measurement of CRP in our study, varied time interval of presentation and inclusion only of uncomplicated cases of pneumonia.Flanders et al 12 also evaluated median CRP levels which were signifi cantly higher for patients with pneumonia than viral LRTI (60 mg/l versus 9 mg/l; P < 0.001).Dagga et al 13 observed that the mean CRP was 75.87±17.1 mg/l in patients with pneumonia and 16.71±20.76mg/lin patients with COPD in acute exacerbation.Mean CRP levels were 121.3+/-122 and 27.2+/-26 mg/l, respectively in bacterial and viral LRTI in study conducted by Marcus et al 14 .The study aimed at differentiating bacterial and viral LRTI and CRP levels were higher in former than later.
In present study the receiver-operating characteristic curve area under the curve for relative CRP variation was 0.973 (95% confi dence interval = 0.61-0.86).Lala SG et al 15 also assessed the discriminative ability of CRP values by ROC plots in pneumonia and found it to be 0.80.This was similar to observation made by Flanders et al 12 who got 0.83 area.
The cut-off of 9 is taken as the best chosen CRP value in this study with 100% sensitivity and specifi city of 96.6%.In a similar study by Pullium et al 16 a CRP cutoff point of 7 was determined with sensitivity of 79% and specifi city of 91%.Lala SG et al 15 concluded that CRP ≥10 mg/l identifi ed 90% of all bacteraemic pneumonias.The optimal cut off point for CRP 4.4 mg/l achieved a sensitivity of 63% and specifi city of 81% for detection of occult bacterial infection in Daniel J et al study 17 .The difference in the cut off values can be explained by different techniques of CRP measurements used in different studies.Inspite of difference in cut-off values, the sensitivity and specifi city is signifi cant to help differentiate bacterial and viral LRTI.

Conclusion
CRP is a reliable biomarker to differentiate bacterial and viral LRTI, thus it can empower physicians to safely prescribe lesser and appropriate antibiotics reducing the over usage, toxicity and resistance of antibiotics.
a) Immuno-compromised patients.b) Patients with congenital heart disease.c) Patients with congestive heart failure.

Fig 1 :
Fig 1: ROC Curve showing sensitivity and specifi city of CRP.

Table 2 :
Depicting the cut off value of CRP

Table 1 :
Showing the correlation of CRP with bacterial and viral LRTI *p < 0.001; Highly signifi cant