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http://www.nytimes.com/2002/12/17/health/anatomy/17SINU.html?tntemail0

Doctors Rethinking Treatments for Sick Sinuses

By GABRIELLE GLASER

ver the last 10 years, many doctors have become convinced that the answer to chronic sinusitis, which afflicts millions and costs the United States an estimated $6 billion a year, could be successfully treated with surgery.

The introduction of fiber optic surgery, involving tiny scopes with cameras attached to a monitor, has become common, giving doctors access to the cramped, convoluted sinus passageways. Before the new technique was developed, doctors cut through the roof of the mouth or made incisions in the eyebrows to clear away scarred tissue or polyps.

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Many physicians said they thought the new tools could help cure the disease. But now, as many of those who have had the procedure return to their doctors' offices sick once again, the early hopes for surgery have been dashed. Researchers are shifting their focus to inflammation and the immune system.

"The medical community thought endoscopic surgery was the be-all and end-all," said Dr. Michael S. Benninger, chairman of the otolaryngology department at Henry Ford Hospital in Detroit. "Surgery still has a role for some problems. But it's certainly not the solution for everyone."

Dr. John H. Krouse, a professor and the director of rhinology and otolaryngic allergy at the Wayne State University School of Medicine in Detroit, agreed. For years, Dr. Krouse said, ear, nose, and throat surgeons were puzzled when patients returned to their offices just months or weeks after having surgery. Some patients had six operations, Dr. Krouse said.

Physicians, he added, began asking, "What are we doing?" and "What exactly are we treating?"

The disillusionment with surgery occurs as recognition is increasing that other common remedies for chronic sinus disease like antibiotics, steroids, antihistamines and decongestants also are falling short of expectations.

Researchers say they are beginning to suspect that they have to rethink the underlying causes. Instead of allergies and infections, long considered the primary culprits, doctors are asking why sinuses become sick in the first place. Increasingly, they are looking at inflammation or the responses of the immune system.

At this point, researchers are struggling even to define sinusitis, which affects an estimated 37 million Americans, or 13 percent of the population. The symptoms include repeated infections, persistent congestion, headaches, facial pain and malaise that can last for years.

According to the Centers for Disease Control and Prevention, chronic sinusitis is the most common long-term illness in the United States, affecting more Americans than asthma, arthritis and congestive heart disease. It strikes women more than men and is most common in the Southeast.

Sinusitis is also expensive and time consuming. It is responsible for nearly 14 million visits a year to doctors' offices, according to the National Institute for Allergy and Infectious Diseases.

The sinuses, hollow spaces surrounding the nose like grape clusters, are something of a mystery. Anthropologists theorize that they originated from evolution, allowing the head to be held upright. They also warm, cool and humidify air entering the lungs, equalize barometric pressure and provide resonance for the voice.

Each sinus has a duct no bigger than the lead of a pencil for the free exchange of air and mucus and is joined with the nasal passages by a continuous mucous membrane that, when healthy, resembles the lining of the inside of the mouth.

The membrane produces a pint to a quart of mucus a day, which is flushed out of the sinuses by tiny cilia, or hairlike filaments. They help pass pollen, bacteria and viruses from the nose to the back of the throat, where they are swallowed and then dissolved by stomach acids.

For reasons that are not entirely clear, the sinuses of people with chronic sinusitis are often mottled with inflammation. The ducts swell, trapping mucus, viruses and bacteria inside.

The dark moist hollows become ideal breeding grounds for infection. Frequently, the chronic swelling and infections cause polyps.

"No one is really sure what sets off the cascade of inflammation that makes some people sick," Dr. Krouse said. "We don't know why some respond to one treatment while others don't or why some symptoms bother some patients to distraction but are not noticeable to others. We are struggling to make sense of it. We're not even sure what this disease really is."

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For years, doctors expanded the sinus openings with surgery, stripped away membranes and removed bony structures, known as turbinates, which are responsible for humidifying inspired air. Sometimes, the procedures created more problems than they solved. Turbinates, it turns out, are essential to the health of the chambers and are primary defenders against disease.

Still, some problems like polyps or anatomical blockages may call for surgery. Surgeons are finding that when procedures are necessary, a less aggressive approach often yields better results than the radical designing of the sinuses that was done in years past.

Nonsurgical treatments have included oral and intravenous antibiotics, antihistamines and decongestants, as well as oral and topical steroids.

Steroids work to calm inflammation, and some doctors find them effective. Often the only relief many patients receive is from prednisone, a powerful steroid.

"We began to see that we were not going to solve this puzzle with a better antibiotic, or a better procedure," Dr. Krouse said. "That points to inflammatory and immunologic processes, not surgical or infectious ones."

Researchers at the Mayo Clinic achieved a breakthrough in 1999, when they found that some inflammation was caused by an immune response to fungi in the nose. Patients and control subjects had many different species of fungi in the nose. But just those with chronic sinusitis have white blood cells, known as eosinophils, that are activated by the immune system, the researchers found.

Led by Dr. Jens Ponikau, they discovered that the immune system sends eosinophils to attack fungi. The eosinophils release a protein that irritates the membranes in the nose. The irritation remains as long as the fungi are present.

A paper on their findings will be published in a peer-reviewed journal next month.

The Mayo team is treating patients with antifungal solutions. Clinical trials are continuing, and patients who have been treated have given encouraging reports. "But we have to settle in for the long haul," Dr. Ponikau said. "It's a paradigm shift, a different way of looking at the disease."

Some doctors have succeeded with a class of asthma drug called leukotriene receptor antagonists. They works by blocking leukotrienes, substances that the immune system secretes in asthma and allergy attacks and that inflame the respiratory tract. Patients with sinus disease often have asthma, as well.

"Asthma patients who used these drugs found that their sinus symptoms were eased,," said Dr. Michael Setzen, who has a practice in Manhasset, N.Y., and is an assistant clinical professor of otolaryngology at the New York University School of Medicine. "If it works, patients know it right away."

An asthma medication, Singulair, the trade name for montelukast, is awaiting approval from the Food and Drug Administration for allergy symptoms. Many doctors, however, prescribe it for sinus problems.

Dr. Alexander C. Chester, an internist in Washington, treats hundreds of patients with sinusitis. He recommends cutting dairy products from the diet. Eliminating milk was popular advice some years ago, but lost currency because the benefits could not be verified, Dr. Chester said.

In 10 percent of his patients, he said, eliminating milk products substantially improves sinusitis and all its symptoms. It is possible that less milk means less mucus, but researchers are unsure exactly why reducing milk in the diet is effective.

Dr. Chester and other experts also urge common sense. Patients with sinusitis should be evaluated for anatomical obstructions (in those cases, surgery can help), allergies and strength of the immune system, Dr. Krouse said, adding, "We need as much information on a patient-by-patient basis as we can get."

Dr. Benninger of Detroit asks patients to complete a questionnaire about physical, emotional and social difficulties. Routinely, patients report high levels of fatigue, depression and sexual dysfunction. "This disease is so much more than just its symptoms," he said.

Many doctors encourage patients to avoid wine and beer, which can cause passageways to swell. Smoking and tobacco smoke should also be avoided.

The doctors agree that patients should exercise, drink enough water and irrigate their noses with a homemade saline solution. Many over-the-counter solutions have a preservative, benzalkonium chloride, that can be irritating and may paralyze cilia.

Some doctors also find promise in an over-the-counter nasal saline spray made with xylitol, a natural sweetener used in chewing gum and mints since the 1960's. Xylitol is also produced in small amounts in the human body in normal metabolism.

A recent study in Finland found that xylitol, a natural antimicrobial, was effective in reducing the ability of common respiratory bacteria, including Streptococcus pneumoniae and Hemophilus influenzae, to adhere to the mucous membrane.

The doctors who treat patients with chronic sinusitis are frustrated, too. "We're not even close to having all the answers," Dr. Setzen said. "Our big hope is that we can help these people who are nasal cripples. A functioning nose is essential to the quality of one's life."

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