ICMR STS PROJECT FORMAT

 

1. REFERENCE ID: 2018-01743

2. TITLE:

A CORRELATION BETWEEN
PLASMA BRAIN NATRIURETIC PEPTIDE LEVELS AND CARDIOVASCULAR MORBIDITY IN
PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

 

3. INTRODUCTION:

 

Chronic Obstructive
Pulmonary Disease (COPD) is among the top five leading causes of death worldwide
1. COPD makes up 42% of the annual mortalities due to non-communicable
diseases, only behind cardiovascular conditions in that regard. COPD is a broad
term used to describe progressive lung diseases such as emphysema, chronic
bronchitis and non-reversible asthma.

COPD is characterized by
persistent airflow limitation that is typically progressive and associated with
an enhanced chronic inflammatory reaction in the airways and lung tissue in
response to harmful particles or gases 2. The chronic airflow limitation in
COPD is caused by the combination of parenchymal destruction (emphysema) and
small airways disease (obstructive bronchiolitis), of which the relative
presence varies from person to person 2.

Due to the size and varied
nature of the Indian population, the frequency of COPD in India has not been
well studied. A few studies carried out by Murthy & Sastry3 and Jindal4
approximate that the prevalence may average around 5% in adults, with higher
frequencies in males, smokers, varying with living conditions (rural/urban) and
type of fuel used domestically.

Plasma BNP is a non-invasive
biomarker to diagnose and monitor cardiac diseases as well as heart failure 5,
6. It is known that plasma BNP levels are elevated in cor pulmonale patients,
due to right atrial stretch in reply to increased right ventricular afterload
5. Although increased BNP level was reported as a risk factor for death
independent of chronic lung disease 7, few studies have assessed the
prognostic value of BNP for identifying the possibility of progression to
secondary pulmonary hypertension and for determining COPD severity.

After collection of the
required data (plasma BNP values of patients, Spirometry readings, pulmonary
artery systolic pressure PASP from 2D echocardiogram), the research will
compare the measured plasma BNP levels with the PASP values obtained from the
2D-Echocardiogram, as well as with the COPD severity of the patient- according
to the FEV1% values obtained from Spirometry (as per the GOLD
staging system).

Therefore, the aim of the
present study is to investigate the use of plasma BNP levels as a prognostic
marker for COPD progression to cardiovascular conditions, and use it to stage
COPD severity in COPD patients.

 

4. OBJECTIVES OF THE STUDY:

1.     To measure the plasma BNP levels in COPD patients

2.     To
find a correlation between determining
COPD severity and identifying the possibility of progression to secondary
pulmonary hypertension.

3.     To examine the value of plasma BNP levels in COPD patients
to predict severity and staging of COPD (according to the Global Initiative for Chronic
Obstructive Lung Disease classification)

 

5. METHODOLOGY:

v Study
design:  Case control study

v Study
period: 

1.     Period needed for collecting data: 2 months

2.     Period required for analyzing data: 1 month

v Inclusion criteria:

1.    
Patients with stable COPD were
enrolled with a history of smoking, and an FEV1 <80% of predicted values, aged between 18-60 years. 2.     Controls:  Age and Sex-matched with a history of smoking.   v Exclusion criteria:   1.     Patients with respiratory disorders other than COPD 2.     Patients with pulmonary embolisms 3.      Patients with infectious diseases, 4.      Patients with malignancy, 5.      Patients with history of recent surgery, 6.     Patients with endocrine, hepatic, or renal dysfunction.     v Sample size with proper justification:   §  Sample size: 40 in each group (20 controls and 20 cases).   §  In a previous study conducted by Mansour et al (2012), it was found that there was a significant difference in the mean plasma pro-BNP levels between controls and COPD cases. The mean plasma pro-BNP values in the controls were 17.4 ± 4.7 and among the COPD cases were 58.08± 5.84.   §  In the present study expecting similar findings, considering the mean difference of 5pg/mL, ?-error of  5%, power of  80% and effect size of 0.9, sample size was estimated to be a minimum of 18 in each group. Hence, it was decided to include 20 controls and 20 COPD cases.     v Detailed Description of Procedure:- §  Selection of Subjects :- 20 patients will be selected based on the inclusion criteria admitted to Ramaiah Teaching Hospital. The cases are restricted to those between the ages of 18- 60. 20 age-matched controls will be selected. Informed consent will be obtained from both cases and controls after explaining the nature and purpose of the study after obtaining the ethical clearance from the institute.   Systemic examination will be done in the patients, and hospital records will be accessed for the following investigations: chest X-ray, Pulmonary Function Tests (PFTs, including Spirometry), electrocardiograph (ECG), 2D-echocardiography (ECHO).   Blood samples will be collected for the estimation of proBNP levels (The half-life of BNP is 20 min and NT-proBNP has a half-life of 120 min) by using ELISA kit method.   §  Biochemical estimate Required :- v Total plasma Brain Natriuretic Peptide (BNP) level.   v BNP is synthesized as a prehormone (proBNP). Upon release into circulation it is cleaved into equal amounts of biologically active C-terminal fragment (BNP), and the biologically inactive N-terminal fragment (NT-proBNP). The half-life of BNP is 20 min, whereas NT-proBNP has a half-life of 120 min. This explains why NT-proBNP plasma values are approximately six times higher than BNP values, even though both molecules are released in equimolar proportions.     v Place of Study: -Ramaiah Memorial Hospital   v Investigations: - Plasma BNP levels     v Potential Risks and Benefits: - 1.     The blood sample collected as a part of the routine biochemical investigations would also be used in this study. Therefore there is no introduction of any additional risks.   2.     By conducting this study, we look to utilize plasma BNP to help us identify cardiovascular complications arising from COPD early so as to prolong the life of the individual through appropriate intervention and management.   v Statistical Methods:- 1.     All the quantitative variables (age, BMI, plasma BNP levels, etc.) will be summarized using descriptive statistics such as mean and standard deviation OR median and range. 2.     All qualitative variables (sex, stage of COPD, etc) will be presented using frequency and percentage (%). 3.     Mean/Median plasma BNP levels between the controls and cases will be compared and tested for statistical significance using independent t-test (student's t-test) OR MannWhitneyU test.   v Ethical Considerations and Methods to Address Issues:-   A written informed consent form would be provided to the participants. The participants will be informed about the procedure before collection of the blood sample.     6. IMPLICATIONS OF THE STUDY: 1.     The research aims to use plasma BNP as a prognostic marker to identify cardiovascular morbidity in COPD patients.   2.     The research aims order to prolong the lifespan of individuals with COPD through early intervention and management.     3.     The research will focus on finding a result that enables us to establish the severity of COPD via a biochemical means.