Rajiv Gandhi University of Health Sciences, Karnataka s25

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BANGALORE

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. NAME OF THE CANDIDATE AND ADDRESS

2. NAME OF THE INSTITUTION

3. COURSE OF THE STUDY AND SUBJECT

4. DATE OF ADMISSION TO THE COURSE

5. TITLE OF THE TOPIC

: DR. PRIYA SINGAL

415, LAL JYOTI APARTMENTS

SECTOR – 9, ROHINI, DELHI - 110085

: M. S. RAMAIAH MEDICAL COLLEGE, BANGALORE

: M. D. GENERAL MEDICINE

: 21 MAY 2008

: DIAGNOSTIC AND PROGNOSTIC VALUE OF SERUM PROCALCITONIN IN PNEUMONIA

6. BRIEF RESUME OF THE INTENDED WORK

6.1 NEED FOR THE STUDY

Nosocomial and community-acquired respiratory tract infections are a public health problem of major concern and a leading cause of mortality. Physical examination and chest radiography have modest ability to predict pneumonia. Definitive diagnosis requires microbiological documentation, although identification of a specific aetiology is frequently not possible, and no rapid test has been standardized for the diagnosis of “atypical” or viral pathogens. Furthermore, the differential diagnosis of pneumonia includes several non-infectious causes, including pulmonary embolism, malignancy and congestive heart failure, among others. A rapid diagnosis of pneumonia and an accurate differentiation from viral respiratory illnesses and non-infectious causes has important therapeutic and prognostic implications.

A novel approach to estimate the presence of an infection and its treatment response is the use of biomarkers. The utility of serum markers of systemic infection, such as C-reactive protein (CRP), lipopolysaccharide-binding protein, or procalcitonin (PCT), for the differential diagnosis of various infectious conditions, has become a matter of interest in the last few years.

Numerous clinical studies have proposed procalcitonin as a specific marker of bacterial infection or general inflammation status. Procalcitonin is released rapidly and has a long half-life, and the assay is highly reproducible.

In the current prospective observational study, we intend to study the utility of procalcitonin level in the diagnosis and prognosis of pneumonia.

6.2 REVIEW OF LITERATURE

Several studies have investigated the usefulness of procalcitonin in various clinical settings.

In a study of 545 patients in Switzerland by Müller B, et al, PCT, and to a lesser degree hsCRP, seemed to improve the accuracy of currently recommended approaches for the diagnosis of CAP, thereby complementing clinical signs and symptoms.1 Holm A, et al, in a study of 364 patients in Denmark, showed that in predicting radiographic pneumonia, bacterial infection, and hospitalisation, the sensitivity of procalcitonin values >0.06 ng/ml was 0.70, 0.51, and 0.67, and of CRP values > or =20 mg/l, 0.73, 0.56, and 0.74 respectively.2 Hirakata Y, et al, in a study of 88 patients in Japan, showed 93.3% of patients with mild CAP had negative PCT, and 48.3% of patients positive for PCT had moderate or severe CAP.3 Another study in Switzerland concluded that procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia.4 Nyamande K, Lalloo UG, used PCT to distinguish between pneumonia due to bacteria, Mycobacteria, Pneumocystis jirovecii in a HIV prevalence setting. The PCT levels were - PTB 4.16 ng/ml; PJP 1.138 ng/ml; and bacterial pneumonia 19.48 ng/ml.5 In a small study, Jereb M, Kotar T, showed that a significant difference between the typical and atypical pneumonia groups was found only for the procalcitonin serum concentration on admission. The standard laboratory markers of bacterial infections, such as C-reactive protein, total leukocyte count and immature polymorphonuclear cells, did not discriminate between typical and atypical etiology.6 Masiá M, Gutiérrez F, et al, in a one year study, stratified patients of CAP according to Pneumonia Severity Index (psi). Levels of PCT were shown to be higher in patients with high-severity risk classes (PSI classes III-V) and in those with complications or death. Among patients classified into PSI low-severity risk classes (classes I-II), levels tended to be higher in those with bacterial etiology.7 Boussekey N, et al, in a study in France, concluded that in ICU patients admitted for severe CAP, initial PCT values could be a predictor for complications and mortality.8 Hedlund J, Hansson LO, in an early study, showed that the severity of disease measured by APACHE II score was strongly associated with admission levels of PCT, but not with CRP.9 In 1996, Nylén ES, et al, saw that in patients with acute infectious pneumonia serum total CT (prohomone of calcitonin) progressively declined concomitantly with the clinical resolution of the pneumonia. On discharge, the patients who had persistent radiographic abnormalities had significantly higher levels than did those who had complete resolution.10

6.3 OBJECTIVES OF THE STUDY

1. To study the value of admission procalcitonin levels in the diagnosis of pneumonia and in distinguishing between bacterial and non-bacterial pneumonia.

2. To study if procalcitonin levels have a bearing on the prognosis of pneumonia.

7. MATERIALS AND METHODS

7.1 SOURCE OF DATA

A minimum of 80 patients, aged more than 18 years, admitted to M. S. Ramaiah Hospitals with the diagnosis of pneumonia from Nov’08 – May’10, will be included in the study.

7.2 METHOD OF COLLECTION OF DATA

Patients satisfying the inclusion criteria and admitted in the Department of Medicine and Department of Pulmonology of M. S. Ramaiah Hospitals will be included in the study.

The study will enrol 40 patients of community-acquired pneumonia and 40 patients of ventilator-associated pneumonia, above 18 years of age.

A detailed history will be elicited from the patients, and general physical examination and systemic examination of the patients will be carried out. Data will be collected in a pre-requisite proforma.

Routine hemogram with hematocrit, routine urine analysis, renal function tests, random blood sugar, liver function tests, serum electrolytes, C-reactive protein, chest X-ray, sputum Gram’s stain, sputum culture, sputum acid-fast bacilli, blood culture, and serum procalcitonin, will be done for all patients.

The proposed study is a prospective observational study and appropriate statistical analysis will be done.

INCLUSION CRITERIA

Eighty adult patients admitted to M. S. Ramaiah Hospitals with the diagnosis of pneumonia.

EXCLUSION CRITERIA

1. Patients with malignancy

2. Patients with history of recent trauma

7.3 DOES THE STUDY REQUIRE ANY INVESTIGATIONS OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS?

YES

CBC with hematocrit
Urine routine
Renal function tests
Random blood sugar
Liver function tests
Serum electrolytes
C-reactive protein
Chest X-ray PA view
Sputum - Gram’s stain

- Culture

- Acid-fast Bacilli (x 3)

Blood culture

11. Serum procalcitonin

7.4 HAS ETHICAL CLEARANCE BEEN TAKEN FROM YOUR INSTITUTION?

YES

8. LIST OF REFERENCES

1. Müller B, Harbarth S, Stolz D, Bingisser R, Mueller C, Leuppi J, et al. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis 2007; 7: 10.

2. Holm A, Pedersen SS, Nexoe J, Obel N, Nielsen LP, Koldkjaer O, et al. Procalcitonin versus C-reactive protein for predicting pneumonia in adults with lower respiratory tract infection in primary care. Br J Gen Pract 2007; 57(540): 555-60.

3. Hirakata Y, Yanagihara K, Kurihara S, Izumikawa K, Seki M, Miyazaki Y, et al. Comparison of usefulness of plasma procalcitonin and C-reactive protein measurements for estimation of severity in adults with community-acquired pneumonia. Diagn Microbiol Infect Dis 2008; 61(2): 170-4.

4. Christ-Crain M, Stolz D, Bingisser R, Müller C, Miedinger D, Huber PR, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 2006; 174(1): 84-93.

5. Nyamande K, Lalloo UG. Serum procalcitonin distinguishes CAP due to bacteria, Mycobacterium tuberculosis and PJP. Int J Tuberc Lung Dis 2006; 10(5): 510-5.

6. Jereb M, Kotar T. Usefulness of procalcitonin to differentiate typical from atypical community-acquired pneumonia. Wien Klin Wochenschr 2006; 118(5-6): 170-4.

7. Masiá M, Gutiérrez F, Shum C, Padilla S, Navarro JC, Flores E, et al. Usefulness of procalcitonin levels in community-acquired pneumonia according to the patients outcome research team pneumonia severity index. Chest 2005; 128(4): 2223-9.

8. Boussekey N, Leroy O, Georges H, Devos P, d'Escrivan T, Guery B. Diagnostic and prognostic values of admission procalcitonin levels in community-acquired pneumonia in an intensive care unit. Infection 2005; 33(4): 257-63.

9. Hedlund J, Hansson LO. Procalcitonin and C-reactive protein levels in community-acquired pneumonia: correlation with etiology and prognosis. Infection 2000; 28(2): 68-73.

10. Nylén ES, Snider RH Jr, Thompson KA, Rohatgi P, Becker KL. Pneumonitis-associated hyperprocalcitoninemia. Am J Med Sci 1996; 312(1): 12-8.

9. SIGNATURE OF THE CANDIDATE

10. REMARKS OF THE GUIDE

Study will generate data in our set-up and will be a useful tool in the diagnosis and prognostication of pneumonia, which is a common clinical problem.

11. NAME AND DESIGNATION OF THE GUIDE

11. 1 SIGNATURE OF THE GUIDE

11. 2 HEAD OF THE DEPARTMENT

11.3 SIGNATURE OF HOD

12. REMARKS OF THE CHAIRMAN AND PRINCIPAL

12.1 SIGNATURE

: DR. U. SUDHIR, M. D.

PROFESSOR

DEPT. OF MEDICINE

M. S. RAMAIAH MEDICAL COLLEGE, BANGALORE

: DR. MEDHA Y. RAO, M. D.