New Test Promises Quicker, More Accurate Evaluation For Cystic Fibrosis Patients

New Test Promises Quicker, More Accurate Evaluation For Cystic Fibrosis Patients
ScienceDaily (Oct. 28, 2008) — Researchers at National Jewish Health have identified a simple gene-based blood test that more accurately and quickly measures cystic fibrosis patients’ response to therapy than current tests. The test, a measure of inflammatory gene expression, could improve patient care and help clear a backlog of promising medications now hung up in clinical trials.


The researchers are publishing the results of a small “proof-of-principal” trial in the November 1, 2008, issue of American Journal of Respiratory and Critical Care Medicine.

“The currently accepted test, a measure of a patients’ ability to exhale air, has several limitations that make it ineffective for some patients and not sensitive enough for clinical trials of many new medications,” said Dr. Milene Saavedra, lead author of the study and Assistant Professor of Medicine at National Jewish Health. “By measuring the activity of genes associated with the immune/inflammatory response, we can get a more accurate picture of the biological processes occurring inside the lungs.”

Cystic fibrosis is the most common lethal inherited disease in the western world, with about 30,000 patients in the US . Most patients die of respiratory failure generally in their 30s or 40s. Lung damage is caused primarily by chronic bacterial infections and the resulting severe airway inflammation. There is a critical need for new effective anti-microbial and anti-inflammatory medications to slow and/or prevent lung damage in young patients. Several promising therapies have gone through early stages of clinical testing but their progress is being hampered by the lack of a sensitive measure of therapeutic response to medications.

Currently, response to medication is measured by how much air a person can rapidly exhale: forced expiratory volume in one second or FEV1. FEV1 cannot be performed effectively for all patients, especially young and very sick patients. Generally patients’ FEV1 does improve when inflammation is reduced, but not all patients’ FEV1 improves significantly, and changes can take weeks to months to show up. It can be prohibitively expensive to conduct phase 2 or phase 3 trials of medications long enough to detect the changes in FEV1.

National Jewish researchers thought white blood cells circulating in the blood might be a good source of biomarkers for a more sensitive and accurate test. White blood cells are the predominant cell type at sites of tissue destruction in CF patients’ lungs. As they circulate through the lungs in the blood they encounter the inflammatory environment and alter their gene expression as a result. By measuring mRNA, scientists can identify which genes are being expressed and how strongly.

The researchers evaluated 18 CF patients who were suffering severe exacerbations of their disease. They withdrew blood before and after two weeks of intravenous antibiotic therapy. The severe exacerbation and antibiotic therapy served as a condensed model of illness and response to therapy; in these cases antibiotic therapy is usually successful, and patients’ clinical symptoms and FEV1 both improve rapidly.

Using microarray gene analysis of the blood samples, the researchers identified 10 genes that differed significantly in their expression before and after therapy. Using real-time polymerase chain reaction and additional statistical tools, the researchers identified three of those genes that most accurately correlated with a positive therapeutic response: CD36, CD64 and ADAM9. CD36 and CD64 are genes associated with cells’ absorption of foreign organisms and cellular debris. ADAM9 is associated with tissue destruction that allows inflammatory cells to move through tissue. This process is also believed to contribute to permanent tissue destruction.

“The expression of these genes correlated with FEV1, other inflammatory markers, and various clinical factors,” said co-author Dr. Jerry Nick , Associate Professor of Medicine at National Jewish. “When combined with FEV1, they offered a more accurate and sensitive measure of response to therapy than either alone. We believe they could be extremely useful in clinical care of patients and trials of new CF therapies.”

The researchers are now conducting a trial of 60 CF patients to provide stronger statistical evidence for the power of CD36, CD64 and ADAM9 to diagnose a positive response to therapy by CF patients.



Adapted from materials provided by National Jewish Medical and Research Center.

Carrier Screening For CF In US Genetic Testing Laboratories:

Carrier Screening For CF In US Genetic Testing Laboratories: A Survey Of Laboratory Directors
Main Category: Cystic Fibrosis
Also Included In: Genetics
Article Date: 28 Oct 2008 - 3:00 PDT

Market pressures may have more influence on clinical practice than laboratory guidelines: That's one conclusion of a Center survey, which found that guidelines for cystic fibrosis (CF) carrier screening have only been partially adopted. David Kaufman, Sara Katsanis, Gail Javitt, Juli Murphy, and Kathy Hudson report in the October issue of Clinical Genetics that seven percent of responding genetic testing laboratories adopted two major screening guidelines issued by the American College of Medical Genetics and the American College of Obstetricians and Gynecologists, and that 13 percent have adopted neither recommendation. These findings indicate that factors other than clinical guidelines may influence laboratories' CF screening practices.

CF is an incurable, progressively disabling, and fatal disease of the sweat and mucus glands, which develops in people who have inherited two mutated copies of the CFTR gene. One in 31 Americans is a carrier of a mutated CFTR gene, making CF one of the most common major genetic disorders. In 1997, a panel convened by the National Institutes of Health concluded that genetic testing for CF should be offered to couples currently planning a pregnancy as well as couples seeking prenatal testing. Because more than 1,300 disease-causing mutations have been identified in CFTR, and different laboratories can test for different mutations, in 2001, the American College of Medical Genetics and the American College of Obstetricians and Gynocologists issued sets of CF testing guidelines (revised in 2004) to improve and standardize population-based CF carrier screening. The study conducted by GPPC focused on two primary components of these guidelines. First was the recommendation that prospective parents be tested for the a CF mutation known as the 5T allele only as a "reflex" after another CF mutation, called R117H, has been identified first. This is because although the 5T allele is relatively common, it can cause CF only when found in combination with R117H. Because the 5T allele is found in between five and nine percent of the general population, screening all pregnant couples for the 5T allele instead of testing only those with an R117H mutation can identify and alarm a large number of individuals who are not at risk of having a child with CF, and provoke unnecessary invasive prenatal testing. The second major recommendation made to laboratories was that they should only screen a panel of 23 of the most relevant, well-studied mutations, which reliably identifies the majority of couples at risk of having a child with CF but remains cost-effective.

The Center survey sought to examine how guidelines for genetic testing for CF have influenced the practice of laboratories that perform the tests - a "necessary first step," write the authors, "in understanding the effectiveness of developing such guidelines, the realities and barriers that may limit uptake, and whether adoption of guidelines (or the lack thereof) has any serious consequences for genetic screening programs." If research shows that the adoption of genetic testing guidelines improves the health outcomes of people getting the test, then finding ways to overcome barriers to their adoption will be critical.

Of 190 responding genetic testing laboratories (a 55 percent response rate), 45% offered CF screening to potential parents for the presence of a mutated CFTR gene. The survey assessed these laboratories' adoption of two primary components of the CF carrier screening guidelines: the reflexive reporting of 5T test results, and the recommended 23-mutation screening panel. While four of five CF screening laboratories followed the 5T guidelines, 90% of laboratories tested more than 23 mutations (some tested up to 150 mutations). Just seven percent of laboratories adopted both guidelines, and 13 percent of respondents adopted neither the 5T guidelines nor the 23-mutation panel.

These results suggest that laboratories' screening practices are affected by factors other than clinical guidelines - possibly including market pressures to purchase CF testing kits that test for more than 23 mutations, despite the lack of clarity about the utility of such testing in the general population. Laboratories' choice of which CF testing kits to use also may be limited by the testing platforms used in a particular lab. The authors note that their findings carry implications beyond CF, and may impact the development of recommendations for other types of genetic testing: "As new guidelines for other population-based genetic tests emerge, it will be useful and important to understand the extent of their influence on practice."

Written by Sara Brinda

Kaufman, D.J., S.H. Katsanis, G.H. Javitt, J.A. Murphy, J.A. Scott, and K.L. Hudson. Carrier screening for cystic fibrosis in US genetic testing laboratories: a survey of laboratory directors. Clinical Genetics 74: 367-373.

The Genetics and Public Policy Center at Johns Hopkins University

The tremendous success of the Human Genome Project has laid the foundation for a true revolution in public health, promising improved diagnosis, more effective medicines, and individually tailored health care. The Genetics and Public Policy Center was created in 2002 at Johns Hopkins University by Pew Charitable Trusts to help policymakers, the press, and the public understand and respond to the challenges and opportunities of genetic medicine and its potential to transform global public health.

http://www.dnapolicy.org

Zanyce

Zanyce is my 11 month old daughter who has Cystic Fibrosis. I would to THANK YOU for helping my family in a time of need. Just when I gave up all hope Cystic Fibrosis Reaching Out Foundation was there and answered my prayers.Your help is very well appreciated.

ATTENTION Physically Active Adults with CF:

We need YOU for an exercise study!

We are researching salt loss in sweat during exercise in the heat and the impact that this has on fluid and electrolyte balance.


Why participate?

You will gain valuable information about your hydration and electrolyte needs during exercise in the heat. You will also find out your aerobic fitness, your percent body fat, and your bone mineral density. By participating, you will help to uncover important research findings that may impact quality of life issues for CF patients. You will also be compensated $100 for your time.

In order to participate you must meet the following criteria:

Age 18-40 years
In stable clinical status with sound pulmonary function, and approved by a CF physician for participation in this study
Regularly physically active in aerobic exercise at least 90 minutes/week for at least the past six months
Willing to perform a maximal exercise test on the bike and have your body composition measured with a DEXA (low-dose X-ray) scan (first session)
Willing to perform a stationary bike ride (low to moderate intensity) in the heat up to ~ 2hrs in duration (second session)
Willing to have a flexible blood catheter inserted into arm vein for periodic blood collection during riding
Willing to swallow a pill-size sensor for body temperature monitoring
Willing to have two small (4 mm diameter) skin biopsies removed from the shoulder blade area under local anesthesia by a dermatologist


For more information please contact:

Mary Beth Brown, Exercise Physiology Laboratory
Georgia Tech School of Applied Physiology
(404) 713-1697 email: bethbrown@gatech.edu
Or Jeannie Peabody, Clinical Research Coordinator; Emory Cystic Fibrosis Center, 404-712-3930

Who is Dr. Larry McKean?

He can be described by the profound human emotion:COMPASSIONATE

This is being reprinted in part from the Summer of 2002 “Reaching Out” newsletter written by Monique Colie and updated by Susan Burroughs.

Dr. Lawrence McKean (Dr. Larry) grew up in New Berlin, Wisconsin in a large family with 5 sisters and 2 brothers. He is the only M.D. in the family and the only sibling to look for warmer winters and leave Wisconsin. He and his wife, Martha, have a son Jonathan and another son, Peter, who died in 1999 at the age of 23.

Dr. Larry has an interest music, including classical, rock-n-roll and country-western. He enjoys listening to bands play in some of the college clubs around Athens. Dr. Larry’s other interest is his hardwood tree farm, which he started as a “legacy” to his son Peter. He shares with us that Peter was very creative and artistic, particularly working with hardwoods. In fact, he made wooden bowls and even constructed his own guitar.

He graduated from the Medical College of Wisconsin and completed his residency training in Pediatrics and his fellowship training in Allergy and Immunology at Emory University in Atlanta. He then joined the faculty at Emory University as an Assistant Professor of Pediatrics and started working with Dr. Daniel Caplan at the Cystic Fibrosis Center. He gives credit to Dr. Caplan for teaching him not just about CF, but about practicing medicine and caring for patients, not just prescribing medications. He has done research and published papers and book chapters on cystic fibrosis (CF), CF-related diabetes, and mechanisms of allergic reactions. In 1993, he left the faculty at Emory University to establish the Asthma & Allergy Clinic for Children, PC in Athens, GA. In 2002, he was asked to return to the Fibrosis Center after Dr. Caplan had a stroke. He helped to keep the CF Center running until Dr. Caplan could return. He treated both children and adults with CF and participated in studies involving treatment of infections that occur in CF patients. He is particularly proud of developing a protocol that has cleared cepacia in 5 patients. In addition to specializing in the treatment of patients with Cystic Fibrosis, Dr. McKean specializes in the evaluation and treatment of recurrent infections
in young children and the evaluation and treatment of asthma and allergic diseases.

Dr. Larry has worked with cystic fibrosis patients with his mentor Dr. Dan Caplan for many years. He had a role in helping design the CF Center that stood on the corner of Clifton and Houston Mill Road until June of this year. Even though he has not always been at the CF Center he has continued practicing medicine and treating cystic fibrosis patients throughout the years. Many of us have continued to rely on his expertise in the field of cystic fibrosis and we are thankful that he remains in the Atlanta area. He has a private practice in Atlanta with Atlanta ENT, Sinus & Allergy Associates, PC.

There have been a lot of change at the Emory Cystic Fibrosis center for the adult patients. Many of us have already felt how complicated the Emory system is to work with. In addition, we have been denied access to the physicians, social workers and healthcare team we have grown to love and trust. I am now 48 years old with cystic fibrosis. These people are the ones that I attribute to making it to this “ripe old age”. I personally need to have Dr. Dan Caplan and Dr. Larry McKean in my life: monitoring my care and coordinating my care with my lung transplant team.

When I received my “letter” telling me who I would have to see for my cystic fibrosis care, I was most upset. Then I realized I do have a choice. THANK YOU DR. MCKEAN for being there for me and all my cystic fibrosis friends.

Dr. Larry McKean
17 Executive Park Drive, Suite 250
Atlanta, GA 3032
(678) 904-4390 Office
http://www.atlantaent.com/
ehandsome@atlantaent.com Office Manager

Ms. Jessica Enders, CF Registered Dietician

Ms. Jessica Enders, in her own words.... I received my Bachelor of Science in Human Ecology: Food, Nutrition and Dietetics from the University of Tennessee at Chattanooga, graduating in 2002. I then moved to Nashville to complete my Dietetic internship at Vanderbilt Medical Center completing the program in June 2003. I then moved to Atlanta where I began working at Emory University Hospital in September 2003 at which time I passed the Registered Dietitians Exam to become a RD. Outside of work I enjoy running in various races around Atlanta, scrapbooking and I am a black belt in USA GoJu Federation karate where I have been working out for the past 6 years. I have been married to my husband Jamie for 3 years this past May. We have two "children", Gracie a gray feisty feline, and Shadow a 70 pound sensitive black lab that allows the cat to run the house! Contact e-mail address: Jessica.Enders@emoryhealthcare.org

Ms. Welela Berhanu, CF Registered Nurse

Ms. Welela Berhanu is Emory University's CF Registered nurse. In her own words... I am originally from Ethiopia. I have been working as a nurse since 1989. I received an Associate Degree in Nursing from Massachusetts Bay Community College in Wellesley, MA. In 2005, I received a Bachelors of Science in Nursing from Georgia State University. I joined Emory ten years ago. the last eight years I have been working in 6G in the General Medicine Unit as a bedside RN, where I had the opportunity to care for patients with many acute and chronic illnesses, including CF. Emory University Hospital's General Medicine Unit is the only specialized inpatient care unit that cares for the adult cystic fibrosis population in the Emory Healthcare system. I have gained a great deal of experience and understanding of this disease and its treatment by working closely with patients and an interdisciplinary team. Outside work, I am a full time mom taking care of my two wonderful children. Tihute is almost four and full of energy, with a great imagination. He is in a "rescue mission" each day as a fire fighter or on a helicopter rescue team. Luam is 20 months. She is quiet, ladylike and loves her shoes. I am excited about this new opportunity and loof forward to working with adults in the Cystic Fibrosis adult program. You may contact Welela at welela.berhanu@emoryhealthcare.org