Navigation Links
Researchers find common childhood asthma unconnected to allergens or inflammation
Date:5/23/2013

NEW YORK (May 23, 2013) -- Little is known about why asthma develops, how it constricts the airway or why response to treatments varies between patients. Now, a team of researchers at Weill Cornell Medical College, Columbia University Medical Center and SUNY Downstate Medical Center has revealed the roots of a common type of childhood asthma, showing that it is very different from other asthma cases.

Their report, in Science Translational Medicine, reveals that an over-active gene linked in 20 to 30 percent of patients with childhood asthma interrupts the synthesis of lipid molecules (known as sphingolipids) that are part of cell membranes found all over the body.

Although the researchers do not yet understand why asthma results from reduced production of sphingolipids, their experiments clearly show a link between loss of these lipids and bronchial hyperreactivity, a key feature of asthma.

What makes this pathway unique, investigators say, is that it is not related to allergens and, the investigators discovered, has nothing to do with inflammation.

"Usually asthma is thought to be an inflammatory disease or a reaction to an allergen. Our model shows that asthma can result from having too little of a type of sphingolipids. This is a completely new pathway for asthma pathogenesis," says the study's senior author, Dr. Stefan Worgall, chief of the Pediatric Pulmonology, Allergy and Immunology Division at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

This is very good news, he adds. "Our findings are not only valuable in understanding the pathogenesis of this complex disease, but provide a basis to develop novel therapies, especially asthma agents based on a patient's genotype," says Dr. Worgall, who is also a distinguished professor of pediatric pulmonology, professor of pediatrics and associate professor of genetic medicine at Weill Cornell Medical College.

Precision Medicine for Asthma

Asthma is a significant health problem affecting about 7 million children in the United States. Nearly 10 percent of American children 017 years of age have asthma, making it the most common serious respiratory childhood disease. Its prevalence is even higher among inner-city children, says Dr. Worgall. Besides causing suffering, disability and alarm, the economic toll is significant, he says: In 2009, asthma caused 640,000 emergency room visits and 157,000 hospitalizations, plus 10.5 million missed school days.

"Yet while it has become increasingly evident that asthma takes several forms, treatment of the disorder is uniform," he says. "Most therapies are designed to reduce inflammation, but they do not help all sufferers."

The notion that asthma has different forms gained ground after several genome-wide association studies (GWAS) found variation in a gene, later identified as ORMDL3, in to up to 30 percent of asthma cases. In 2007, over-production of the gene's protein was connected to childhood asthma, and this gene has been the most consistent genetic factor identified so far for asthma.

In 2010, a study in yeast found that ORMDL3 protein inhibits sphingolipid de-novo synthesis.

This finding prompted the researchers to investigate whether sphingolipid production is connected to asthma. Their study shows that this is indeed true in mouse models of the disease. Using mouse models, the researchers found that inhibition of an enzyme, serine palmitoyl-CoA transferase (SPT), which is critical to sphingolipid synthesis, produced asthma in mice and in human airways, as it did in mice that had a genetic defect in SPT.

The airway hyperactivity seen in the mice was not linked to increased inflammation, and the scientists saw a decreased response of the lung and airways to magnesium -- which is often used in emergency rooms to relieve chest tightness of patients with asthma attacks.

"In our mouse models, we found that magnesium was not effective at inducing airway relaxation, suggesting the same would be true for humans whose asthma is linked to ORMDL3," says the study's first author, Dr. Tilla S. Worgall, assistant professor in the Department of Pathology and Cell Biology and a member of the Institute of Human Nutrition at Columbia University Medical Center. "The association of decreased de novo sphingolipid synthesis with alterations in cellular magnesium homeostasis provides a clue into the mechanism of asthma. Therefore, therapies that circumvent the effect of the ORMDL3 genotype may be effective treatments for asthma sufferers. We are now working towards developing these new therapies."


'/>"/>

Contact: John Rodgers
jdr2001@med.cornell.edu
646-317-7401
Weill Cornell Medical College
Source:Eurekalert

Related medicine news :

1. NIH awards $20 million over 5 years to train next generation of global health researchers
2. Researchers develop a new cell and animal model of inflammatory breast cancer
3. Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance
4. Researchers Find Gene Mutations That May Be a Key to Autism
5. Researchers find evidence of banned antibiotics in poultry products
6. NJ stroke researchers report advances in spatial neglect research at AAN Conference
7. Autism by the numbers: Yale researchers examine impact of new diagnostic criteria
8. Researchers Map Brain Regions Linked to Intelligence
9. Researchers ID Genes That May Determine Mental Illness
10. Researchers Develop Blood Test for Depression
11. University of Cincinnati researchers win $3.7M grant from US Department of Defense
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... , ... June 25, 2016 , ... ... policy issues and applications at AcademyHealth’s Annual Research Meeting June 26-28, 2016, at ... on several important health care topics including advance care planning, healthcare costs and ...
(Date:6/25/2016)... ... 2016 , ... "With 30 hand-drawn hand gesture animations, FCPX users can easily ... of Pixel Film Studios. , ProHand Cartoon’s package transforms over 1,300 hand-drawn pictures ... . Simply select a ProHand generator and drag it above media or text in ...
(Date:6/25/2016)... ... June 25, 2016 , ... Dr. Calvin Johnson has ... he has implemented orthobiologic procedures as a method for treating his patients. The ... first doctors to perform the treatment. Orthobiologics are substances that orthopaedic surgeons use ...
(Date:6/24/2016)... ... ... A recent article published June 14 on E Online details ... to state that individuals are now more comfortable seeking to undergo not only the ... and cheek reduction. The Los Angeles area medical group, Beverly Hills Physicians (BHP) notes ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Marcy was in a crisis. Her son James, ... out at his family verbally and physically. , “When something upset him, he couldn’t control ... use it. He would throw rocks at my other children and say he was going ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Mass. and SAN CLEMENTE, Calif. , ... California -based mobile pulmonary function testing company, is now able ... PFT devices developed by ndd Medical Technologies , Inc. ... testing done in hospital-based labs.  Thanks to ndd,s EasyOne PRO ® ... , can get any needed testing done in the comfort ...
(Date:6/24/2016)... Belgium , June 24, 2016 /PRNewswire/ ... announced the appointment of Dr. Edward Futcher ... a Non-Executive Director, effective June 23, 2016.Dr. Futcher ... and Nominations and Governance Committees.  As a non-executive ... provide independent expertise and strategic counsel to VolitionRx ...
(Date:6/23/2016)... 23, 2016 Any dentist who has made an ... current process. Many of them do not even offer this ... and high laboratory costs involved. And those who ARE able ... such a high cost that the majority of today,s patients ... Parsa Zadeh , founder of Dental Evolutions Inc. and ...
Breaking Medicine Technology: