Protein discovered to be sign of severe asthma in med school study

Asthma may literally be “in our blood.”

A recent study by Yale School of Medicine researchers found elevated levels of the protein YKL-40 in the blood of patients with severe asthma — the most advanced state — which affects some 2.5 million Americans.

The discovery that the protein is a biomarker for asthma may help researchers develop a novel therapeutic drug for the treatment of the disease that targets the protein, researchers said.

In the short term, the finding provides the first known method for assessing the severity of a patient’s asthma with a simple blood test, said Jack Elias, the School of Medicine’s chair of medicine and lead author on the study.

“YKL-40 levels are significantly higher in the blood of patients with severe asthma,” he said. “This [finding] may be useful clinically and give us a clue as to why they have this severe disease. Down the road, there could be new treatments and new ways to characterize asthma.”

The YKL-40 protein belongs to a family of molecules that may have originally evolved to protect the lungs and airways.

In the study, researchers correlated levels of YKL-40 in 253 adult patients with and without asthma. Results found a positive correlation between the level of the protein and asthmatic severity, which was measured by a patient’s quality of lung function and thickness of bronchial wall.

This correlation may give physicians a way to detect asthma earlier and more accurately predict their prognosis, said Geoffrey Chupp, Yale professor of medicine and co-author of the study.

Early tests also indicate that the biomarker may be a useful target for therapeutic drugs, but more research needs to be done to confirm this finding, Elias said.

He said researchers inferred this result from studies demonstrating that “knocking out” YKL-40 decreases specific types of tissue inflammation, a common symptom of asthma.

Chupp said the study may also shed new light on the environmental influences at play in the formation and development of the disease. According to the study, YKL-40 binds to a specific molecule in the body called chitin — an abundant protein commonly found in dust mites, crustaceans and fungi and an allergen that can trigger asthma, Chupp said.

“How YKL-40 interacts with the environment may be an interesting line of further investigation,” he said. “This family of molecules may provide a new avenue to better understand how environmental exposure could potentially be driving disease.”

Chupp said the study’s observed correlation does not prove that elevated levels of YKL-40 cause asthma, only that the increased amount of the protein appears to signal the severity of the disease in a patient.

In October 2004, medical school researchers found that severe asthma is controlled by a gene — called the MIF gene — that controls how asthma will develop in a patient once someone has the disease, said Richard Bucala, Yale professor of medicine and co-author of the study.

Once someone has asthma, there are genes that will control how severe the disease will be, Bucala said.

“The results supported an important role for MIF in the pathogenesis of human asthma,” Bucala said.

He said this new finding shows that YKL-40 may also be similarly useful to researchers and physicians.

School of Medicine researchers are currently testing whether YKL-40 may be used as a drug target for forms of specific therapy for asthma, Elias said.

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