Molecular and Cellular Staging for the Severity of Chronic Rhinosinusitis

Abstract

To correlate objective and subjective clinical parameters with molecular, cellular, and histologic markers and to acknowledge the importance of these basic science parameters in a severity classification system for chronic rhinosinusitis (CRS). Retrospective analysis of prospectively collected data of consecutive patients undergoing endoscopic sinus surgery for CRS in an academic institution. The preoperative computed tomography (CT) scans of all patients with CRS scheduled for surgery were graded according to Lund and Mackay. The patients completed a Sino-Nasal Outcome Test (SNOT)-20 questionnaire and had a preoperative nasal endoscopy performed, which was graded by assigning an endoscopy score according to Lanza and Kennedy. Subjects had a medical questionnaire regarding presence of aspirin sensitivity, allergic rhinitis, asthma, and medication usage. Subjects also underwent pulmonary function testing and had skin tests for allergies. At the time of surgery, blood was drawn to determine the level of peripheral eosinophilia and the degree of polymorphisms of the leukotriene C4 synthase gene. Sinus mucosal and polyp tissue was examined pathologically for the number of eosinophils per high-powered filed (HPF) and was stained for EG2 to determine the portion of activated eosinophils. Leukotriene C4 levels (pg/g of tissue) were determined using a sensitive competitive enzyme immunoassay. Endoscopy and SNOT-20 scores were reevaluated 1 year after surgery. Data were analyzed for disease-severity correlation to recommend a severity classification system for CRS that incorporates the contribution of clinical, molecular, cellular, and histologic parameters. The presence of polyps resulted in higher preoperative CT scores and higher preoperative and postoperative symptom scores. Average preoperative CT scores were significantly higher in asthmatics and allergy patients and correlated with endoscopy scores. Patients with more than five eosinophils/HPF of sinus tissue had higher frequency of polyps and asthma and higher CT and endoscopy scores than patients without sinus tissue eosinophilia (less than or equal to 5 cells/HPF sinus tissue). The subgroup of patients with eosinophilic nasal polyps (eosinophilic hyperplastic rhinosinusitis) had more severe disease by CT and endoscopy than the subgroup of patients with nasal polyps (hyperplastic rhinosinusitis) but without eosinophilia. Similarly, patients without polyps but with tissue eosinophilia had more severe disease than patients without polyps and without eosinophilia. Leukotriene C4 levels were elevated in all patient groups. Symptom scores did not correlate with any of the parameters. We suggest the following severity classification system for CRS: 1) eosinophilic chronic hyperplastic rhinosinusitis (ECHRS): patients with polyps and sinus tissue eosinophilia; 2) noneosinophilic chronic hyperplastic rhinosinusitis (NECHRS): patients with polyps but without sinus tissue eosinophilia; 3) eosinophilic chronic rhinosinusitis (ECRS): patients without polyps but with sinus tissue eosinophilia; 4) noneosinophilic chronic rhinosinusitis (NECRS): patients without polyps and without sinus tissue eosinophilia.