C-reactive protein as a prognostic marker and guidance for use of antibiotic therapy in patients presenting with lower respiratory tract manifestations in intensive care unit in tertiary care centre

Introduction: C-reactive Materials and Methods: It a prospective of Serum CRP level measured by latex agglutination method and other markers of infection like Complete blood count, Sputum microscopy culture and sensitivity and chest X-ray were done on presentation. CRP concentration of more than 20mg/l taken as positive. Number of CRP positive patients were correlated with patients of increased WBC count and positive sputum routine culture and sensitivity and results were compared using chi -square test. Result: Total 60 patients were taken for study out of which 38 were male and 22 were female. Out of which 24(40%) were diagnosed with pneumonia, 6(10%) with pulmonary Koch’s, 7(11.6%) with acute exacerbation of asthma, 11(18.3%) were COPD,4(6%) with congestive cardiac failure, 5(8.3%) with autoimmune disorder and 3(5%) with interstitial lung disease. Among them 29(48.3%) patients were found to have CRP value of more than 20mg/dl which is considered as positive, out of these 29 patients, 16(55.17%) were having pneumonia which was conﬁrmed on imaging and sputum culture and sensitivity. Out of these 29 patients with CRP positive 21(72.4%) were found to have sputum culture and sensitivity as positive for bacteria in which 4(19%) were diagnosed as autoimmune disorder,2(9%) with bronchial asthma, 10(47.6%) with pneumonia, 3(14.2%) with COPD, 2(9.5%) with pulmonary Koch’s. Among 29 patients with positive CRP, 18(62%) patients have the WBC count of >11,000cells/mm3. Patients with CRP positivity having positive culture sensitivity {21patients (72.4%)} were started on antibiotic therapy. Out of total 24 pneumonia cases, 10(41.6%) were sputum culture positive as well as CRP positive pneumonia. As according to the result of our study the patient of pneumonia had higher CRP in comparison with patients with COPD, bronchial asthma, Congestive cardiac failure, Autoimmune disorders, interstitial lung disease. Correlation of number of raised CRP positivity, sputum positivity and raised WBC count were statistically signiﬁcant with p value of <0.005 by using chi -square test. No signiﬁcant difference of CRP found in the age and sex distribution of the patients and no signiﬁcant mortality found. Patients with positive CRP, positive sputum culture and sensitivity were started on speciﬁc antibiotic therapy. Conclusion: Serum CRP levels is a useful marker for the diagnosis of Acquired in adult patients presenting with lower respiratory tract manifestations. Higher CRP values are suggestive of severity of the disease which may help in deciding the appropriateness of use of antibiotics in the line


Introduction
C-reactive protein is a acute phase plasma protein of the pentraxin family, is produced and released by hepatocytes and adipocytes, playing distinct roles in innate and adaptive immunity with inflammatory effects. 1,2 CRP has been reported to function by binding to the phosphocholine moieties that are located on some damaged cells and certain bacteria, and to have a crucial part in complement activation through strengthening phagocytosis, which may clear dead cells and bacteria. 3,4 Interleukin-6 (IL-6) and other cytokines such as Tumour necrosis factor(TNF), Interleukin-1(IL-1) and Transforming growth factor (TGF) are also involved in CRP production. 5,6 A number of conditions stimulate CRP synthesis including pulmonary infarction, vasculitis, liver disease, inflammation, neoplasia, bacterial infections are most potent stimuli leading to marked elevation of serum CRP with in few hours. Pneumonia elicits a powerful inflammatory response both locally and systematically with chemotactic cytokine release into peripheral circulation. CRP has also being used as an index of response to treatment in rheumatic fever and certain other conditions. 7 CRP is tested either by capillary precipitation of patient sera with anti-sera prepared in rabbits against purified CRP or by passive agglutination using latex particles coated with anti-CRP antibodies. 8 It is a simple blood test to distinguish between viral and bacterial pneumonia.
Raised CRP value in viral infection during first week may mislead the clinician in the decision to prescribe antibiotics and may also explain why the CRP has shown a higher specificity in predicting pneumonia after one week then in first week of respiratory tract infections. 9 2. Aim and Objectives of the Study

Materials and Methods
It is a prospective study of 60 patients admitting with the acute respiratory signs and symptoms in Intensive Care Unit of Mallareddy institute of medical sciences, Hyderabad, Telangana. Serum sample was preserved at the time of presentation and CRP was measured in undiluted sera and in dilution of 1/10, 1/20, 1/30, 1/40, 1/60, 1/80, 1/100 using a commercially available latex agglutination test (Humatex CRP). Value of CRP was calculated by multiplying the denominator of dilution by 6 to get value in mg/l. Mid-value of positive and negative titre was used in calculation. CRP concentration of > 20mg/l is taken as positive according to our lab. CRP level mean, median were calculated and CRP level positivity in patients is correlated with no of patients with raised WBC count and sputum culture positivity by using chi-square test and p value <0.005 is considered significant.

Inclusion criteria
1. Age >18 years old admitted to our hospital, 2. Respiratory symptoms like cough, sputum production, dyspnoea, tachypnoea, pleuritic pain as main complaint with or without fever.

Measurements
Patients with known response to initial adequate treatment in emergency department.
At the initial visit to emergency department patients demographic data and basic clinical information was collected and in addition to it markers of infection like Complete blood count, Serum CRP level measured by latex agglutination method, sputum for gram staining, AFB, culture sensitivity, blood culture and sensitivity, chest Xray, HRCT and 2 Decho were done. To stratify the severity CURB 65 score (confusion, serum urea, respiratory rate and systolic blood pressure of patient) were used to decide the severity of pneumonia patients. LRTI was defined by the presence of atleast one respiratory symptom (cough, sputum production, dyspnoea, tachypnoea, i.e. crepitations or wheeze or one sign of infection like temp>38 • C, shivering, leucocyte count <4000 or For pneumonia a new infiltrate, haziness, consolidation, effusion on chest X-ray.initiative for chronic obstructive lung disease(gold guidelines) as FEV1/FEC ratio <70%. Acute bronchitis defined as LRTI in the absence of underlying lung disease or COPD or infiltrates on chest X-ray.grounds(history, physical examination, chest high resolution computerised tomography, electrocardiogram, echocardiogram).

Results
Total 60 patients admitting into Mallareddy institute of medical sciences, Hyderabad, Telangana has been included in these prospective study. CRP was measured in undiluted sera and in various dilution at the time of presentation as already described and value calculated. The parenchymal involvement of lung in various diseases was confirmed on chest X ray and high resolution CT scan of chest and cardiac involvement was proved on echocardiography. Total 60 patients were taken for study out of which 38 were male and 22 were female( Table 1). Out of which 24(40%) were diagnosed with pneumonia,6(10%) with pulmonary koch's, 7(11.6%) with acute exacerbation of asthma, 11(18.3%) were COPD, 4(6%) with congestive cardiac failure, 5(8.3%) with autoimmune disorder and 3(5%) with Interstitial lung disease ( Table 2). Among them 29(48.3%) patients were found to have CRP value of more than 20mg/l which is considered as positive as shown in Table 3 out of these 29 patients, 15(51.7%) were having pneumonia which was confirmed on imaging and sputum culture and sensitivity (Table 7 ). for bacteria in which 4(19%) were diagnosed as autoimmune disorder,2(9%) with bronchial asthma, 10(47.6%) with pneumonia, 3(14.2%) with COPD, 2(9.5%) with pulmonary Koch's (Table 7). T8 suggest positive pneumonia patients.
Among 29 patients with positive CRP, 18(62%) patients have the WBC count of >11,000cells/mm 3 . Out of 24 Patients with pneumonia have increase WBC count in 10 patients, 2 patients in COPD, 3 patient in autoimmune disorders, in 2 patients of bronchial asthma no patient with Congestive cardiac failure no patient with tuberculosis and interstitial disease as shown in (Table 9 ). Patients with CRP positivity who were having positive culture sensitivity {21 patients(72.4%)} were started on antibiotic therapy. Out of total 24 pneumonia cases,10(41.6%) were sputum culture positive as well as CRP positive pneumonia. Out of 15 patients with CRP positive in pneumonia 10 cases(66.6%), were found to have raised WBC count. All these 10 cases have sputum positive on culture sensitivity (Table 9 ) patient with pneumonia (24) 10 patient have sputum culture as positive and were started on antibiotics, 5 patients with autoimmune disorders 4 were sputum positive, in 11 COPD patients 3 patients were sputum positive and started on antibiotics, out of 6 patients with Tuberculosis 2 were sputum positive were started on antibiotics and out of 7 patients in bronchial asthma 2 were sputum positive and started on antibiotics, whereas in congestive cardiac failure (4) and interstitial lung disease (3) were not having any sputum positivity so no antibiotic therapy was given (Table 9).
In our study the correlation of raised WBC count in no of patients is done with no of CRP positive individuals is done using chi -square test as shown in Table 10. 18 patients with CRP positive were having raised WBC count which is 62.1% which is found statistically significant.
In our study the correlation of CRP level positivity is done with antibiotic use in patient as shown in Table 11 that antibiotic given in 21 CRP positive patients out of 29 which is 72.4% patients which is statistically significant as p value <0.005 using chi-square test. The correlation of antibiotic usage with raised WBC count is also found out as shown in Table 12 that 14 patients with raised WBC count were given antibiotics which is 77.8% which is statistically significant by chi-square test with p value of <0.005.
As according to the result of our study the patients of pneumonia and autoimmune disorders had higher CRP in comparison with patients with COPD, bronchial asthma, Congestive cardiac failure and Interstitial lung disease. Patient with high CRP have raised WBC count. No significant difference of CRP found in the sex distribution of the patients. Patients with positive CRP, Positive sputum culture and sensitivity with increased WBC counts were started on specific antibiotic therapy. A CRP value of more than 20mg/l is considered positive.

Discussion
In healthy adults, the normal concentrations of CRP varies between 0.8 mg/L to 3.0 mg/L. However, some healthy adults show elevated CRP at 10 mg/L. CRP concentrations also increase with age, possibly due to subclinical conditions. There is also no seasonal variations of CRP concentrations. Gene polymorphism of interleukin 1 family, interleukin 6, and polymorphic GT repeat of the CRP gene do affect the usual CRP concentrations when a person does not have any medical illnesses. 10 CRP is used mainly as an inflammation marker. Apart from liver failure, there are few known factors that interfere with CRP production. 10 Interferon alpha inhibits CRP production from liver cells which may explain the relatively low levels of CRP found during viral infections compared to bacterial infections. 11 The plasma half-life of CRP is 19 hours, and is constant in all medical conditions. When there is a stimulus, the CRP level can increase 10,000fold from less than 50 µg/l to more than 500 mg/L. Its concentration can increase to 5 mg/L by 6 hours and peak at 48 hours. Therefore, the only factor that affects the blood CRP concentration is its production rate, which increases          1  Pneumonia  24  15  10  10  10  2  COPD  11  3  3  2  3  3  Tuberculosis  6  2  2  0  2  4  Autoimmune disorder  5  4  4  3  4  5 Congestive cardiac failure      In acute inflammation, CRP can increase as much as 50 to 100 mg/L within 4 to 6 hours in mild to moderate inflammation or an insult such as skin infection, cystitis, or bronchitis. It can double every 8 hours and reaches its peak at 36 to 50 hours following injury or inflammation.CRP between 100 and 500 mg/L is considered highly predictive of inflammation due to bacterial infection. Once inflammation subsides, CRP level falls quickly because of its relatively short halflife. 12 CRP concentrations between 2 and 10 mg/L are considered as metabolic inflammation: metabolic pathways that cause arteriosclerosis and type II diabetes mellitus. Normal levels increase with aging. 13 Higher levels are found in late pregnant women, mild inflammation and viral infections (10-40 mg/L), active inflammation, bacterial infection (40-200 mg/L), severe bacterial infections and burns (>200 mg/L). 14 In our study we took CRP > 20 mg/l as positive according to our laboratory values. And our study shows that CRP value in case of pneumonia patients with sputum positivity has higher value than in sputum negative pneumonia. According to the table no-the153.25,86.20Interstitial lung disease is 42.3, Tuberculosis is 27.50, Bronchial asthma is 22.86.
According to table no-14 the median values of Pneumonia is 95, Autoimmune is 42, ILD is 40, Bronchial asthma is 14, COPD is 17, CCF is 12.5 and TB is 18.5. The British Thoracic Society stated that the measurement of serum CRP on admission may be helpful in distinguishing pneumonia from other lower respiratory tract infestations with moderate weight being placed on this recommendation. 15

Conclusion
Serum CRP levels is a useful marker for establishing the diagnosis of Higher CRP values are suggestive of severity of the disease which may help in deciding the appropriateness of use of antibiotic in the line of management with lower infections.

Limitations
No relationship found in our study between CRP level and parenchymal and endobronchial involvement in lung and parenchymal involvement and causative organism.

Source of Funding
None.

Conflict of Interest
None declared.

Acknowledgements
There was no grant from any source, here was no connection with companies producing any substance or apparatus for my article and there was no writing assistance for my article.