RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
REGISTRATION OF SUBJECT FOR DISSERTATION
SYNOPSIS
1. NAME OF THE CANDIDATE AND ADDRESS/ DR.BHAGYALAKSHMI.S.
NO 5, SRINIVASA NILAYA ,
BTM 1ST STAGE, 8TH MAIN ROAD,
MHBCS, BANGLORE-29
2. NAME OF THE INSTITUTION / M.S.RAMAIAH MEDICALCOLLEGE,
M.S. RAMAIAH NAGAR,
MSRIT POST,
BANGLORE-560054
3. COURSE OF THE STUDY AND
SUBJECT / M.D. PHYSIOLOGY
4. DATE OF ADMISSION / 10/05/2010
5. TITLE OF THE TOPIC / STUDY OF PULMONARY FUNCTION
TESTS IN MULTITRANSFUSED CHILDREN WITH THALASSEMIA
6 BRIEF RESUME OF THE INTENDED WORK
6.1 INTRODUCTION AND NEED FOR THE STUDY:
Thalassemia is the most common hereditary haemoglobinopathy characterized by decreased or absent globin chain synthesis resulting in ineffective erythropoiesis and chronic haemolytic anemia. Regular blood transfusion along with iron chelation therapy is the mainstay of treatment in most of the developing countries. Repeated blood transfusion eventually leads to iron accumulation in various organs despite concomitant iron chelation therapy. Most commonly affected organs are heart, liver and pancreas. Dysfunction of these organs is responsible for morbidity and mortality in patients with thalassemia. Abnormalities in pulmonary functions in patients with thalassemia have been reported in various studies and most of them have demonstrated restrictive lung disease and impairment of diffusion capacity of the lungs1-5.
The precise cause for pulmonary dysfunction in thalassemia has not yet been established.
Most of the studies have tried to correlate serum ferritin levels with pulmonary function abnormalities but the results are conflicting1-6.
Most of the studies on pulmonary function tests in thalassemia are from the west and there is paucity of data from India. Hence we propose to take up this study of pulmonary function test in multitransfused children with thalassemia.
6.2 REVIEW OF LITERATURE:
Abu Ekteish FM et al1 reported pulmonary function abnormalities in 40 children with beta thalassemia major. All children were on regular blood transfusion at 4 weekly intervals to maintain hemoglobin above 10 gm% and also on regular chelation therapy with desferroxamine. Patients with history of asthma, cystic fibrosis, recent acute respiratory infection and other chronic diseases were excluded from the study.
Pulmonary function tests included Spirometry - Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), Ratio of Forced expiratory volume in 1 second to Forced vital capacity (FEV1/FVC), Peak expiratory flow rate (PEFR), Forced mid expiratory flow (FEF 25%-75%), Residual volume (RV), and Total lung capacity (TLC)), Single breath diffusion capacity of the lungs for carbon monoxide (DLCO) and Arterial blood gas (ABG). In patients with thalassemia mean values of FVC, RV, TLC, FEV1, PEFR and FEF25%-75% differed significantly from normal control subjects. Predominantly restrictive pattern was seen in 14 patients (35%), and these patients had significant reduction in RV, FVC, TLC and PEF with a FEV1/FVC ratio of more than 75%. Obstructive airway disease was found in 6 patients (15%) with a FEV1/FVC ratio less than 75%, increased RV and reduced FEF 25%-75%.Impairment of diffusion was found in 10 patients (22%) with DLCO reduced to less than 80% of predicted value. Serum ferritin level was measured in all children, to study its relationship to respiratory function impairment. No correlation was found between the severity of restrictive or obstructive disease and serum ferritin level.
It has been concluded that restrictive lung disease was the commonest pulmonary function abnormality found in the multitransfused children with thalassemia major.
Earlier studies also have reported restrictive pulmonary disease and impaired diffusion capacity of the lungs in multitransfused children with thalassemia2-5.
6.3 OBJECTIVES
- To study pulmonary function tests in multitransfused children with thalassemia.
- To compare pulmonary functions in multitransfused thalassemia children with normal children.
7 MATERIALS AND METHODS
7.1 SUBJECTS:
This study will be done on 10 children with thalassemia who are taking regular blood transfusion with or without iron chelation therapy at M S Ramaiah Medical College hospital, during the period January 2011 to December 2011.
CONTROLS:
Age and sex matched normal children.
INCLUSION CRITERIA:
· Children with diagnosis of thalassemia
· Age group 3 years and above
· Thalassemia children who are on regular blood transfusion with or without iron chelation therapy
EXCLUSION CRITERIA:
Children with
· Respiratory diseases
· Cardiac diseases
7.2 METHODS:
Children who fulfill the inclusion criteria for the study will be selected. Informed consent will be obtained from parents of all cases and controls. Details such as age, sex, age at diagnosis, age at first blood transfusion, cumulative amount of blood transfusions, duration of iron chelation therapy, pre transfusion haemoglobin level, mean ferritin level over preceding one year and physical examination findings will be recorded on a proforma. Pulmonary function tests will be done using MIR Spirobank G spirometer, within 3 days of blood transfusion. Following parameters will be recorded in the spirometry - Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), Ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), Peak expiratory flow rate (PEFR), and Mid peak expiratory flow (PEF25%-75%). Pulmonary function tests will be done three times, and the best values will be taken for the study. Serum ferritin level will be estimated by chemiluminescent immunometric assay7. Haemoglobin estimation will be done by Beckmen Coulter machine using cyanmethaemoglobin automated method.
DESIGN OF THE STUDY:
Case control study (cases - thalassemia children and controls - age and sex matched normal children)
SAMPLE SIZE
The literature review indicates mean FVC level to be around 79.6 (SD±15.4) among thalassemia patients as compared to 91.7 (SD±9.5) among normal subjects. In order to estimate the above differences with the power of 80% and alpha error of 5% it is estimated that nearly 10 subjects should be studied in each group.
STATISTICAL METHODS:
Descriptive statistics- Mean, median and standard deviation will be used to compare the various quantitative parameters such as FVC, FEV1, FEV1/FVC, PEF25%-75%, PEFR and serum ferritin. Student‘t’ test will be used to compare the pulmonary function test parameters between the cases and controls. Correlation analysis will be used to correlate various pulmonary function test parameters with serum ferritin levels and amount of blood transfusion. Probability value of less than or equal to 0.05 will be considered as statistically significant.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATIONS AND INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS?
Yes. Pre transfusion hemoglobin and serum ferritin level are done as a part of standard care for thalassemia patients.
7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
Yes. Certificate enclosed
8 REFERENCES:
1. Abu-Ekteish FM, Al Rimawi HS, Al Ali MK and Shehabi IM. Pulmonary function tests in children with beta-thalassemia major. Chronic respiratory disease 2007; 4(1):19-22.
2. Parakh A, Dubey AP, Chowdhry V, Sethi GR, Jain S, Hira HS. Study of Pulmonary function tests in thalassemic children. J Pediatr Hematoloncol 2007;29(3):151-155
3. Jamal R, Baizura J, Hamidah A, Idris N, Jeffrey AH and Roslan H. Abnormalities in lung function among multiply transfused thalassemia patients: Results from a thalassemia center in Malaysia. Southeast Asian J Trop Med Public Health 2005;36(1):265-269
4. Carnelli V, D’Angelo E, Pecchiari M, Ligorio M, and D’Angelo E. Pulmonary Dysfunction in transfusion- dependent Patients with thalassemia major. Am J respire crit car med 2003; 168:180-184.
5. Arora M, Chandra J, Suri JC, Narayana S and DuttaAK. Pulmonary functions in transfusion dependent beta thalassemia. Indian Journal of pediatrics, 2001; 68(3):239-243
6. Li AM, Chan D, Li CK, Wong E, Chan YL, Folk TF. Respiratory function in patients with thalassemia major: Relation with iron overload. Arch Dis child 2002; 87:328-330
7. Alfrey CP. Serum ferritin assay. CRC Crit Rev Clin Lab Sci 1978; 9:179-208.
9 SIGNATURE OF THE CANDIDATE:
10 REMARKS OF THE GUIDE:
Thalassemia results in ineffective erythropoiesis and hemolytic anemia. Children
with thalassemia, quite commonly suffer from respiratory abnormalities also.
Etiology of the respiratory problems is still not clear. Incidence of respiratory
abnormalities and their etiology is worth investigating in Indian scenario as
thalassemia is quite common and the longevity of patients has increased with
modern treatment.
11.1 NAME AND DESIGNATION OF GUIDE:
Dr Jaisri G, MBBS, MD
Professor and Head
Department of Physiology
MS Ramaiah Medical College
Bangalore
SIGNATURE:
11.2 CO-GUIDE:
Dr (Lt Col) ATK Rau, MD
Professor and Head
Department of Pediatrics
MS Ramaiah Medical College
Bangalore
SIGNATURE:
11.3 CO-GUIDE:
Dr Vasanthi Ananthakrishnan, MBBS, MD
Associate Professor
Department of Physiology
MS Ramaiah Medical College
Bangalore
SIGNATURE:
11.4 HEAD OF THE DEPARTMENT: Dr Jaisri G, MBBS, MD
SIGNATURE:
12 REMARKS OF THE CHAIRMAN AND PRINCIPAL:
SIGNATURE: