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Chronic sinusitis caused by fungus
By LOIS BAKER
Contributing Editor
Researchers at UB and the Mayo Clinic have shown that chronic sinusitis is an immune disorder caused by fungus, opening up a promising new avenue for treating this ubiquitous and debilitating condition, for which there is no FDA-approved therapy.
Coronal CT scan of a patient with chronic rhinosinusitis (CRS) before and after topical nasal therapy with amphotericin-B. The gray density within the sinuses seen in the before picture, on the left, representing inflamed memebranes, are seen to significantly diminish after treatment with topical fungicide in the after therapy image seen on the right. This change represents the objective improvement, which was the primary outcome measure for the study. There was statistically significant improvement in the treatment group, and worsening in the placebo group.
Results of their research suggest that common airborne fungi lodge in the mucus lining of the sinuses in most people, but initiate an immune response only in individuals prone to chronic sinusitis. The immune response causes the fungi to be attacked, which leads to damage of the sinus membranes, resulting in full-blown symptoms.
"We hope this study will lead to the first treatment aimed at the root cause of chronic sinusitis, rather than a treatment just to mask the symptoms," said David A. Sherris, interim chair of the UB Department of Otolaryngology in the School of Medicine and Biomedical Sciences.
Sherris presented the study findings on Tuesday at the annual meeting of the American Academy of Allergy, Asthma and Immunology in San Francisco. The research was conducted while Sherris was at the Mayo Clinic.
Through a randomized, placebo-controlled, double-blind pilot trial using the fungicide Amphotericin-B applied intranasally, the researchers found that the treatment group showed a significant decrease in the inflammatory thickening of the sinus membranes compared to the control group.
Inflammation in the mucus also decreased significantly in those receiving the drug, compared to placebo, and 70 percent of patients on the medication had a decrease in the amount of nasal swelling, results showed.
"We showed in 1999 that fungal organisms were present in the mucus of 96 percent of patients who had surgery for chronic sinusitis, and that inflammatory cells were clumped around the fungi, which indicated to us that the condition was an immune disorder caused by fungus, " said Sherris. "But many doctors didn't believe us."
"Next, we conducted various immunologic studies and an open trial using the fungicide treatment and found that 75 percent of patients improved on the new therapy. Now we have similar results from a randomized, blinded trial with a control group, which is the 'gold standard' in drug testing. Our next step is to conduct a multi-center trial using antifungals, which we hope will lead to FDA approval of antifungal treatment for this chronic disease."
Chronic sinusitis, a disease of the nasal passages and the surrounding sinus cavities, is thought to affect 16.8 percent of the adult population of the U.S. It causes long-term nasal congestion, production of thick mucus, loss of sense of smell and creates an environment for opportunistic bacterial infections that exacerbate those symptoms. Sherris said studies have shown that chronic sinusitis exceeds even congestive heart failure in its adverse effects on quality of life.
Little is known about the causes of this disease. Without a specific target for intervention, physicians often simply treated the secondary bacterial infections in hopes of providing a modicum of relief.
The current trial involved 24 patients with chronic sinusitis who were randomly assigned to receive the treatment or a placebo. Neither the patients nor the investigators knew who received the drug or the inactive agent. The final analysis involved data from 10 treatment patients and 14 controls, all of whom were in the trial for six months.
Researchers took CT scans (special x-rays of the sinuses) at baseline and at six months. They also graded patients' inflammation by direct exam with an endoscope in the nose at the start of the study, and at three and six months.
The CT scans showed that the treatment group had a mean 8.8 percent decrease in inflammatory mucus thickening, while the placebo group had an increase of 2.5 percent. Sherris said 70 percent of patients in the treatment group also showed significant improvement when their nasal passages were viewed through an endoscope, while the placebo group showed no change. Markers of inflammation in the mucus also decreased significantly in the treatment group, compared to the placebo group.
Additional researchers on the study, all from the Mayo Clinic, were Jens U. Ponikau, Amy Weaver, Evangelo Frigas and Hirohito Kita.
The research was supported by grants from the National Institutes of Health and the Mayo Foundation for Education and Research.