Chronic Obstructive Pulmonary Disease (COPD) isamong the top five leading causes of death worldwide 1.
COPD makes up 42% ofthe annual mortalities due to non-communicable diseases, only behindcardiovascular conditions in that regard. COPD is a broad term used to describeprogressive lung diseases such as emphysema, chronic bronchitis and non-reversibleasthma.COPD is characterized by persistent airflowlimitation that is typically progressive and associated with an enhancedchronic inflammatory reaction in the airways and lung tissue in response toharmful particles or gases 2. The chronic airflow limitation in COPD iscaused by the combination of parenchymal destruction (emphysema) and smallairways disease (obstructive bronchiolitis), of which the relative presencevaries from person to person 2.
Due to the size and varied nature of the Indianpopulation, the frequency of COPD in India has not been well studied. A fewstudies carried out by Murthy & Sastry3 and Jindal4 approximate thatthe prevalence may average around 5% in adults, with higher frequencies inmales, smokers, varying with living conditions (rural/urban) and type of fuelused domestically.Plasma BNP is a non-invasive biomarker to diagnoseand monitor cardiac diseases as well as heart failure 5, 6. It is known thatplasma BNP levels are elevated in cor pulmonale patients, due to right atrialstretch in reply to increased right ventricular afterload 5. Althoughincreased BNP level was reported as a risk factor for death independent ofchronic lung disease 7, few studies have assessed the prognostic value of BNPfor identifying the possibility of progression to secondary pulmonary hypertensionand for determining COPD severity.
After collection of the required data (plasma BNPvalues of patients, Spirometry readings, pulmonary artery systolic pressurePASP from 2D echocardiogram), the research will compare the measured plasmaBNP levels with the PASP values obtained from the 2D-Echocardiogram, as well aswith the COPD severity of the patient- according to the FEV1% valuesobtained from Spirometry (as per the GOLD staging system).Therefore, the aim of the present study is toinvestigate the use of plasma BNP levels as a prognostic marker for COPD progressionto cardiovascular conditions, and use it to stage COPD severity in COPDpatients. 4.OBJECTIVES OF THE STUDY:1. Tomeasure the plasma BNP levels in COPD patients2. Tofind a correlation between determiningCOPD severity and identifying the possibility of progression to secondarypulmonary hypertension.3.
Toexamine the value of plasma BNP levels in COPD patients to predict severity andstaging of COPD (accordingto the Global Initiative for Chronic Obstructive Lung Disease classification) 5.METHODOLOGY:· Studydesign: Case controlstudy· Studyperiod: 1. Periodneeded for collecting data: 2 months2. Periodrequired for analyzing data: 1 month· Inclusioncriteria:1. Patients with stable COPD were enrolled with a historyof smoking, and an FEV1 <80% of predicted values, aged between 18-60 years. 2. Controls: Ageand Sex-matched with a history of smoking.
· Exclusioncriteria: 1. Patients withrespiratory disorders other than COPD 2. Patients with pulmonaryembolisms3. Patients with infectious diseases,4. Patients with malignancy,5.
Patients with history of recent surgery,6. Patients withendocrine, hepatic, or renal dysfunction. · Sample size withproper justification: § Samplesize: 40 in each group (20 controls and 20 cases). § Ina previous study conducted by Mansour et al (2012), it was found that there wasa significant difference in the mean plasma pro-BNP levels between controls andCOPD cases. The mean plasma pro-BNP values in the controls were 17.4 ± 4.7 andamong the COPD cases were 58.
08± 5.84. § Inthe present study expecting similar findings, considering the mean differenceof 5pg/mL, ?-error of 5%, power of 80% and effect size of 0.9, sample size wasestimated to be a minimum of 18 in each group. Hence, it was decided to include20 controls and 20 COPD cases.
· Detailed Description ofProcedure:-v Selection of Subjects:-20 patients will be selected basedon the inclusion criteria admitted to Ramaiah Teaching Hospital. The cases arerestricted to those between the ages of 18- 60. 20 age-matched controls will beselected. Informed consent will be obtained from both cases and controlsafter explaining the nature and purpose of the study after obtaining theethical clearance from the institute.
Systemic examination will be done inthe patients, and hospital records will be accessed for the followinginvestigations: chest X-ray, Pulmonary Function Tests (PFTs, includingSpirometry), electrocardiograph (ECG), 2D-echocardiography (ECHO). Blood samples will be collected forthe estimation of proBNP levels (The half-life of BNP is 20 min and NT-proBNPhas a half-life of 120 min) by using ELISA kit method. v Biochemical estimateRequired :- § Totalplasma Brain Natriuretic Peptide (BNP) level. § BNPis synthesized as a prehormone (proBNP). Upon release into circulation it iscleaved into equal amounts of biologically active C-terminal fragment (BNP),and the biologically inactive N-terminal fragment (NT-proBNP). The half-life ofBNP is 20 min, whereas NT-proBNP has a half-life of 120 min.
This explains whyNT-proBNP plasma values are approximately six times higher than BNP values,even though both molecules are released in equimolar proportions. · Place of Study: -Ramaiah Memorial Hospital · Investigations: -Plasma BNP levels · Potential Risks andBenefits: -1. Theblood sample collected as a part of the routine biochemical investigationswould also be used in this study.
Therefore there is no introduction of anyadditional risks. 2. Byconducting this study, we look to utilize plasma BNP to help us identifycardiovascular complications arising from COPD early so as to prolong the lifeof the individual through appropriate intervention and management. · StatisticalMethods:- 1.
Allthe quantitative variables (age, BMI, plasma BNP levels, etc.) will be summarizedusing descriptive statistics such as mean and standard deviation OR median andrange.2. Allqualitative variables (sex, stage of COPD, etc) will be presented usingfrequency and percentage (%).3. Mean/Medianplasma BNP levels between the controls and cases will be compared and testedfor statistical significance using independent t-test (student’s t-test) ORMannWhitneyU test. · Ethical Considerations and Methods to Address Issues:- Awritten informed consent form would be provided to the participants.
Theparticipants will be informed about the procedure before collection of theblood sample. 6.IMPLICATIONS OF THE STUDY: 1. Theresearch aims to use plasma BNP as a prognostic marker to identifycardiovascular morbidity in COPD patients. 2. Theresearch aims order to prolong the lifespan of individuals with COPD throughearly intervention and management. 3.
Theresearch will focus on finding a result that enables us to establish theseverity of COPD via a biochemical means.