BALTIMORE-- Some people who suffer from repeated sinus infections may be predisposed to them because they carry the same genetic mutation responsible for cystic fibrosis (CF), new findings suggest.[1]

"For years we've known that children and adults with CF have severe sinus infections--it's almost a given with the disease," said Garry R. Cutting, MD, a geneticist at the McKusick-Nathans Institute of Genetic Medicine, at the Johns Hopkins University School of Medicine, in Baltimore. "We've long wondered if having just one mutant CFTR gene has any health effects. Now we can confirm what we've suspected: Genes may play a role in chronic sinus disease," Dr. Cutting said in an interview with RESPIRATORY REVIEWS.

Dr. Cutting and colleagues conducted a case-control study to determine whether mutations in the cystic fibrosis transmembrane regulator (CFTR ) gene predispose patients to chronic rhinosinusitis. They analyzed blood samples from 147 patients who had presented to the Johns Hopkins Otolaryngology--Head and Neck Surgery Clinic because of repeated bouts of chronic rhinosinusitis and from 123 controls who were matched for age and other demographic factors. All blood samples were tested for 16 of the most common mutations of the CF gene. The researchers also analyzed differences in the patients' nasal tissues.

Eleven of the sinusitis patients were found to be carriers of a mutated CF gene; most had the common form of the mutation (Delta F508). In contrast, only two people in the control group were carriers. The researchers also found a significantly increased prevalence of homozygosity for the M470V allele in the patients with chronic rhinosinusitis (61%, vs 53% in the controls). Although both the sinusitis and control patients scored within normal range in the nasal conductance tests, the sinusitis patients had subtle abnormalities, probably due to the mutant CF gene, according to Dr. Cutting.

LONG-TERM TREATMENT IMPLICATIONS

"We want to be clear that these patients don't have cystic fibrosis," he noted. But, he added, "this knowledge may prove useful therapeutically. Some sinusitis patients might be helped by treatments developed for CF. Further, genetic testing may [eventually] allow us to single out patients with the most severe form of chronic sinusitis, those who may benefit from therapy aimed precisely at their underlying problem," said Dr. Cutting.

He and his colleagues hope that by better understanding the genes and underlying biology involved in sinusitis, they will be able to develop more effective ways of treating the disease. "For example, patients with a sinus infection typically take agents like pseudoephedrine, which have a drying effect. But in a respiratory infection, cells lining the sinuses are forced to produce more fluid. In patients carrying a mutant CFTR gene, this may severely tax cells [in which] water output is already below par, perhaps increasing susceptibility to infection," suggested Dr. Cutting.

However, he does not recommend that patients with chronic sinus infections get tested for the CF mutation. "The research is still at an early stage. Additional studies are needed to confirm our findings," Dr. Cutting emphasized.

The next step, according to Dr. Cutting, is to determine whether the sinuses of carrier patients respond differently than do those of other subjects to stresses such as cold viruses or cold air. "This could point the way to drug trials and, potentially, to new, targeted ways to treat sinus infections," he said.

--Deborah L. O'Connor

Reference
1. Wang XJ, Moylan B, Leopold DA, et al. Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA. 2000;284:1814-1819.