Using response to a standardized treatment to identify phenotypes for genetic studies of chronic rhinosinusitis

Objectives: Studies of the genetics of chronic rhinosinusitis offer potential insights into the pathophysiology of this poorly understood condition. However, genetic studies are both expensive and time consuming - hence the importance of establishing beforehand the proper population and target genes. We wished to identify patient factors associated with a proposed definition of severe chronic rhinosinusitis to minimize heterogeneity and maximize the impact of genetic contributions. We therefore wanted to determine if the response to a standardized therapy following endoscopic sinus surgery could be used as a viable phenotypic criterion for subsequent genetic studies. Design: Retrospective chart review. Setting: Tertiary sinus centre. Methods: Seventy-one cases of chronic rhinosinusitis refractory to medical and surgical treatment were studied. They formed two groups according to their response to a standardized treatment protocol. We collected information concerning patients' characteristics and bacteriology on endoscopic culture. Results: 60.5% patients were managed successfully with budesonide irrigations. Atopy was present in 33.8%, asthma in 69.0%, and aspirin sensitivity in 33.3%. The rate of asthma was higher in nonresponders. Bacterial colonization rates showed the presence of Staphylococcus aureus (36.4%), gram-negative rods (29.1%), and Pseudomonas aeruginosa (32.7%). Conclusions: Patients with refractory chronic rhinosinusitis represent a severely diseased, more homogeneous population in which the genetic contribution(s) to disease may be maximal. Strong associations with asthma, aspirin intolerance, and atopy suggest links between these disorders. Irrigation with budesonide solution appears to be effective in management. Studies of the genetics of chronic rhinosinusitis will include genes known to be involved with both asthma and innate immunity.