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New target may promote development of novel therapies for chronic sinusitis

Published on November 23, 2009 at 1:12 AM · No Comments

A protein known to stimulate blood vessel growth has now been found to be responsible for the cell overgrowth in the development of polyps that characterize one of the most severe forms of sinusitis, a study by Johns Hopkins researchers suggests. The finding gives scientists a new target for developing novel therapies to treat this form of the disease, which typically resists all current treatments.

Chronic sinusitis, a constant irritation and swelling of the nasal passages, is a common condition thought to affect about one out of every six people. This problem has several forms with a range of severities. One of the most severe forms produces polyps, overgrowths of unhealthy sinus tissue that can block the nose and sinus passages and make breathing through the nose difficult or impossible. This often results in pain, swelling, and an increase in infections. Though researchers aren't sure how many people have this subtype, it's estimated to affect between 15 and 30 percent of sinusitis patients.

"This type of sinusitis isn't subtle-you can spot the patients with polyps from across the room. They're breathing through their mouths, they talk with nasal voices, they're constantly sniffling, and their faces are swollen," says Jean Kim, M.D., Ph.D., assistant professor in the Departments of Otolaryngology and Allergy and Clinical Immunology at the Johns Hopkins University School of Medicine, and a researcher at the Johns Hopkins Allergy and Asthma Center at the Johns Hopkins Bayview Medical Center.

Kim explains that surgery to remove the polyps is one of the most common treatments for this disease. However, nasal and sinus polyps in these patients almost always regrow. "Once the patient has entered the cycle of growing polyps, it's very hard to get out," she says. Another common treatment is oral steroids, but these drugs are fraught with many harmful side effects and also only temporarily treat the disease.

She and her Johns Hopkins colleagues have long studied sinusitis, often growing sinus cells isolated from patients in petri dishes. After noticing that cells from patients with polyps typically multiplied faster than cells from normal patients, the researchers speculated that cells from polyp patients might be producing extra amounts of some type of growth factor, a protein that encourages cell growth.

To identify which growth factor might be to blame, the researchers had sinusitis patients with and without polyps rinse their sinus passages with a wash solution, then tested the runoff for the presence of various growth factors. They found that solution from patients with polyps contained high amounts of a substance called vascular endothelial growth factor, or VEGF, a protein important for normal blood vessel growth that also seems to play a key role in a variety of diseases, including cancer. The more VEGF they found in a cell culture, the faster those cells grew.

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