Some of the 37 million Americans who suffer from chronic sinus infections were elated earlier this fall when researchers at the Mayo Clinic announced a startling discovery: The cause of their misery was not allergies to pollen, mold or other substances or an overgrowth of bacteria, but a reaction to fungus. Surely, sinus sufferers thought, this discovery might herald new treatments that would effectively target the cause of these infections, and not just the symptoms.
But in the weeks since the study appeared in a small journal published by the clinic, which is based in Rochester, Minn., some sinus specialists have expressed serious doubts about the study and its conclusions.
Chronic sinusitis is characterized by a runny nose, persistent congestion, headaches and dental or facial pain lasting three or more months. Doctors believe the condition is caused by allergies to dogs, pollen, mold or a myriad of substances or by a smoldering bacterial infection deep in the labyrinthine cavities of the sinuses.
In addition, chronic sinusitis often leads to the formation of nasal polyps, small benign growths that further impair breathing and can only be removed surgically.
Surgery is considered a last resort for sinus sufferers and is often not a permanent cure. Most chronic sinus infections are treated with a combination of antibiotics, steroid nasal sprays or pills and decongestants.
By contrast acute sinusitis, an infection that lasts less than four weeks, is often caused by bacteria; it is typically preceded by a cold. Acute sinus infections may clear up on their own without drugs.
There is a third type of sinus infection known as allergic fungal sinusitis--an allergy to fungi. Only about 6 or 7 percent of patients are believed to suffer from this form of the disease.
But the Mayo researchers, led by otolaryngologist Jens Ponikau, said that their studies of more than 200 patients have led them to conclude that allergic fungal sinusitis is not rare at all, but is in fact the primary cause of chronic sinusitis.
The Mayo team said they found 40 different kinds of fungi in the mucus of 96 percent of 210 chronic sinusitis patients, and in all of 14 healthy patients who had no allergies or history of sinus infections.
To fight these fungi, white blood cells called eosinophils are dispatched by the body's immune system. These white blood cells irritate the nasal membranes, causing infection.
Ponikau and his colleagues David Sherris and Eugene Kern hypothesize that in patients with persistent sinusitis, eosinophils are attacking the fungi, and as long as the fungi remain in the nose, so do the eosinophils.
Current treatments for chronic sinusitis are largely useless against fungi, Ponikau said, because they attack the symptoms but not the underlying cause.
But some of Ponikau's peers at other institutions are skeptical that fungi are a common cause of sinusitis.
"If 100 percent of controls have [fungi], why does it mean anything?" asked Ralph B. Metson, an otolaryngologist at the Massachusetts Eye and Ear Infirmary in Boston and a clinical associate professor at Harvard Medical School. "I think they're drawing the wrong conclusions."
So does B. J. Ferguson, chief of the division of sino-nasal and allergic disorders at the University of Pittsburgh School of Medicine. "I think it's fundamentally flawed," said Ferguson, who has previously reviewed some of Ponikau's data. "Chronic sinusitis is a lot of different things. My concern is that by grouping all these patients together, [the Mayo researchers] are confusing things that have different causes."
In an interview, Ponikau said that while the presence of fungi was nearly universal, only people who were sensitive to them developed sinus infections. He compared the process to hay fever: Everyone breathes pollen, but only people who are sensitive to it become allergic and develop symptoms.
Ponikau said that he initially encountered similar skepticism about his hypothesis among the otolaryngology staff at Mayo. He added that his team's findings have been confirmed by a university medical center in Europe, which he declined to name, citing a secrecy agreement.
"I know people are very skeptical about it," he said of the study, "because it's a very dramatic step out of the box."
Ponikau compared it to the theory that certain kinds of stomach ulcers are caused by a bacterial infection and can be cured by antibiotics, a theory propounded by an Australian researcher that was widely ridiculed but later proved true.
"This is natural," he said. "Every kind of scientific revolution has resistance to begin with."
One of the factors fueling the interest in the Mayo study is the paucity of effective treatments for chronic sinus infections, the most common chronic condition in the United States, according to federal health statistics. For reasons that are unclear, the incidence of sinusitis has increased dramatically in the past two decades.
Mayo researchers, in partnership with pharmaceutical companies, are testing various topical compounds to see if they might prove effective in controlling or eradicating fungi as a treatment for sinusitis. Current antifungal drugs are either not meant to be taken orally or must be taken in such high doses that they would be toxic.
"Patients are desperate and physicians are desperate," said Ponikau, because so few treatments have proved effective in the long run and because sinus surgery is not a permanent cure for many patients.
Ferguson, the Pittsburgh otolaryngologist, agreed. The publicity about the Mayo study has "been a headache," she said. "In the real world, patients come in and say, 'I just heard about this and I'm sure I have a fungal infection,' " when they probably don't.
Both Ferguson and Harvard's Metson said that while they remain unconvinced of the validity of the Mayo researchers' theory, they believe it deserves further study.
"I congratulate the authors on pursuing an intriguing hypothesis which will require additional investigation," Metson said.