There are few moments in history that become memorable and these moments are influential in shaping the future of mankind. Scientific research has become the powerful force it is today due to the efforts of dedicated researchers, funding agencies that believe in the research project, and individuals who participate in clinical research. The participation of individuals in clinical trials is a very important part of the research process, and without these volunteers, the medications in the market today would not be available.
EXPLORING THE HUMAN GENOME: FINDING THE GENETIC LINKS TO COPD
Research is demonstrating that susceptibility to developing COPD may be caused by genes. Alpha-1 Antitrypsin Deficiency is the most common known genetic risk factor for COPD, and the information retrieved from investigating Alpha-1 Antitrypsin Deficiency has led researchers to learn about the biological processes that lead to COPD. As many as 3% of individuals with COPD have undetected Alpha-1 Antitrypsin Deficiency. It is also well known that not all smokers develop COPD, suggesting that susceptibility to developing COPD has a genetic basis. But the information researchers have learned from Alpha-1 Antitrypsin Deficiency has brought up questions as to what are the other genetic risk factors for COPD.
Scientific researchers are about to begin an investigation to find the genes that cause a susceptibility to developingCOPD. This groundbreaking study—recently awarded $37 million by the National Heart, Lung, and Blood Institute (NHLBI)—has the potential of changing how we know COPD and COPD treatment. In essence, this study can change the future of COPD.
THE FUTURE IS HERE
Earlier this year, two scientific investigators, along with collaborators from many of the leading medical centers in the U.S., proposed a study to the NHBLI that would open the doors to understanding more about the mechanisms of lung disease. Dr. James Crapo of the National Jewish Medical and Research Center in Denver, Colorado, along with Dr. Edwin Silverman of the Brigham and Women’s Hospital in Boston, Massachusetts, proposed a genetic epidemiology study of COPD—a study to characterize COPD in the U.S. population and to find the genes that create a risk for developing this disease. The study will bring together a large cohort of individuals who have COPD or are at risk for developing COPD. The study will analyze genetic variations across the entire human genome to identify the primary genes that determine why some individuals are more susceptible to developing COPD than other individuals.
After months of review, this genetic epidemiology study was approved by the NHLBI and is beginning its investigation. “The National Heart, Lung, and Blood Institute is excited to fund what will be the largest study ever of the genetics ofCOPD. Identifying genetic factors that contribute to this devastating disease will help us understand the biological mechanisms involved, and will ultimately lead to better treatments and improved outcomes for patients,” said Elizabeth G. Nabel, M.D., Director of the NHLBI.
The importance of this study is paramount, and the information that scientists will retrieve from it will eventually affect the treatment of COPD greatly. “This new program on the genetic epidemiology of COPD offers a unique opportunity to find the set of genes that controls susceptibility to COPD,” said Dr. Crapo. “Finding these genes will not only help us understand how and why this disease occurs. We expect it to point to new therapies that can change the outcome and improve the quality of life for everyone with this disease.”
HOW IT WORKS
The study will take an estimated five years to complete. In order to identify the genetic basis of COPD, a study group of 10,500 individuals will be formed. Thirteen medical centers across the U.S. will host the clinical evaluations of eligible individuals that want to participate in the study. The clinical evaluations will be conducted physiologically and radiographically, meaning that the individual will be taking a spirometry test, tested on a 6-minute walk, and scored on a BODE scale (body mass index, degree of airflow obstruction, degree of dyspnea, and exercise capacity). The individual will also be given a chest CT scan, complete a set of questionnaires, and donate about 30cc (6 teaspoons) of blood for genetic analysis.
The genetic analysis will search for the primary genes that make certain individuals more susceptible to developingCOPD than others. It is well known that not all smokers develop COPD. “COPD is clearly a genetically-influenced disease. Only 10-20% of smokers develop severe lung impairment,” said Dr. Crapo. Therefore researchers are looking for associations between genes across the entire human genome that affect the development of COPD. The cohort of 10,500 individuals will include both male and female non-Hispanic white and African American individuals with or at risk of developing COPD.
The study will be conducted in phases in order to narrow down and, in the end, identify the genes that affect the development of COPD. Approximately 3,000 individuals (1,000 non-Hispanic white males, 1,000 non-Hispanic white females, 500 African American males, and 500 African American females) will be used in each of the first three phases. In the first phase, the first cohort of individuals will be stratified by their racial group. Their genome will be analyzed using an SNP screen (single nucleotide polymorphism), which means that they will identify the differences in nucleotides at over 500,000 carefully selected positions across the entire human genome.
Once the SNP screen identifies portions of the genome that are possibly associated with the development of COPD, the genome of the second group of individuals will be analyzed to confirm which of the genetic associations found in the first group of individuals carry through in the second group. This will allow the investigators to narrow down the regions where the primary genes that affect the development of COPD are likely located. At this stage, the study is expected to be able to identify about 50 genetic regions that may be important in both non-Hispanic white and African American study participants. To find the actual genes, the detailed genetic code of these 50 genetic regions will be mapped in the third group of study participants. The goal is to find the three to five specific genes that likely play a primary role in determining the risk of developing COPD in both non-Hispanic white and African American individuals.
In the fourth phase, each of the identified genes will be further analyzed in four different cohorts to confirm their association with, and importance in, COPD.
BE PART OF HISTORY: SIGN UP!
The purpose of this genetic epidemiology study of COPD is to pinpoint the genetic cause of COPD. It is hoped that this study will spark the development of new drugs and therapies that will improve the quality of life for individuals withCOPD, and one day, find a cure. This approach to studying COPD will place COPD and lung disease on the cutting edge of genetic research. It will be the first research study that will bring together such a large group of subjects with lung disease for a “whole-genome” association study. The information that the COPD community will receive from this study will be outstanding.
To help this and other studies find better treatments for individuals with COPD, the COPD Foundation has partnered with the National Jewish Medical and Research Center in order to create the COPD Research Registry. Launched in the spring of 2007, the COPD Foundation Research Registry is a confidential database of individuals interested and eligible to participate in clinical research, including this groundbreaking genetic epidemiology study of COPD. The Registry is hosted at the National Jewish Medical and Research facility in Denver, Colorado, in order to ensure the strictest confidentiality of personal information.
The Registry needs to collect 20,000 names of individuals willing and able to participate in the genetic epidemiology study and/or other clinical studies of COPD. A large number of participants is necessary for the genetic study in order to give the research statistical power to correctly identify the genetic risk factors in both racial groups. The study needs three types of individuals:
- Smokers without COPD,
- Smokers with possible COPD, or
- Smokers with definite COPD.
If you fall into one of these categories, call the C.O.P.D. Information Line (1-866-316-COPD) for more information about signing up for the COPD Foundation Research Registry.
Your privacy is a primary concern of the research team. Rest assured, your information will be kept confidential.
The next revolutionary scientific research study will soon begin its investigation, and the opportunity to be part of it is now in the hands of the U.S. COPD community. Take action to help one another, to find new therapies, and to change the course for COPD in the future. Help find a cure!