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asthma and usually do not have a history of pediatric asthma. Aspirin triad or AERD patients also have less atopy than aspirin-tolerant asthmatics. 17 Even when AERD patients do have a positive allergy test, the reac- tion to the allergy test is often mild and does not correlate to the severity of their nasal polyposis or asthma. In other words, the total serum IgE in AERD patients is lower than AScA (unified airway) CRS. 18 On nasal endscopy, AERD patients had an abun- dant amount of polyps and the highest NE score (Table III). The nasal polyps biopsy demonstrates an extensive amount of eosinophils, mast cells, and hypercellularity. Even though AERD and AScA have similar phenotype, and both have intrinsic inflammation, they are different in terms of their immunologic inflammatory pathway. Aspirin-exacerbated respiratory disease inflamma- tion has been classically described by elevated levels of cysteinyl leukotrienes and not described as an adaptive immunity process. 19 However, in our study, the CD4 cells were elevated in AERD compared to the control group. If there is an adaptive immunity involved with AERD, it likely involves IL4, because IL4-producing cells were elevated in AERD. An interesting discovery was that the elevated IL4-producing cells in AERD were CD45 1 CD4 2 cells. That means that IL4 is not being produced by Th2 cells, but rather by another CD45 1 cell. The most likely CD45 1 CD4 2 cell producing the IL4 is the mast cell, which was elevated in AERD and ASsA patients. The interplay between IL4 and cysteinyl leukotrienes is that IL4 stimulates expression of LTC 4 synthase and upregulates cysLT1 receptor expression. Also, IL4 can prolong eosinophil survival and is a cofac- tor for mast cell growth. Similar to AScA, the amount of inflammation in AERD is so high that it is difficult to manage with medi- cal treatment alone. In a study evaluating urine LTE4 in AERD patients, urine LTE4 was measured before and after ESS. 18 Urine LTE4 dropped from 227 pg/mg preop- eratively to 72 pg/mg postoperatively ( P < .05). Because urine LTE4 is a metabolite of cysteinyl leukotriene, this study demonstrated that debulking the nasal polyp dur- ing ESS decreases the primary inflammatory mediator in AERD patients. Detailed management of aspirin triad has been described. 20 To summarize, initial medical management of oral steroid and oral zileuton should be considered. Zileuton is an inhibitor of 5-lipoxygenase and thus inhib- its the production of cysteinyl leukotrienes. However, a baseline liver function test should be performed prior to the use of zileuton, because there is a 4% chance of liver toxicity. If the medical management does not control the patient’s symptoms, ESS should be performed to debulk the inflammatory polyp to decrease the inflammatory load in the nasal polyps and to allow for topical medica- tions into the sinuses. Postoperatively, zileuton should be continued with careful monitoring of the liver enzymes, specifically alanine aminotransferase. Topical steroid spray, irrigation, or drops should be considered in conjunction with the zileuton. Aspirin desensitization is another possibility, especially if pharmacotherapy is not effective. The exact mechanism for aspirin

rhinitis and asthma. Interestingly AERD or aspirin triad patients commonly do not have a history of pediatric allergy or asthma. In fact, AERD patients have less atopy than aspirin-tolerant asthmatics or AScA (unified airway) patients. 17 Asthma in ASsA usually develops during the adult years. This is similar to AERD and unlike AScA. The natural progression of AERD patients demonstrates that rhinitis develops first. Asthma appears an average of 2 years after initial symptoms of rhinitis. 18 Nasal polypo- sis then ensues, followed finally by aspirin sensitivity. In other words, AERD patients can develop asthma and nasal polyposis while still being aspirin tolerant for a few years prior to eventually becoming aspirin intolerant. This is consistent with our study, because ASsA is younger than the AERD (Table II). The ASsA patient can represent a precursor of AERD prior to aspirin intoler- ance. In fact, a few patients under the author’s care with adult onset asthma and severe nasal polyposis who were initially aspirin tolerant, eventually became aspirin intol- erant during the course of their management. However, to confirm that ASsA might be a precursor to AERD, ele- vated levels of cysteinyl leukotrienes or urine LTE4 should be measured and confirmed. For now, these ASsA patients are counseled to avoid the use of NSAIDS. It was interesting to note that CD4 cells were higher in ASsA than the control group. This finding implies that T helper cells may play a role for these patients. In fact, IL4 was higher in ASsA than CF. Another CRS subclass that had higher IL4 than CF but did not reach significance was AERD, which lends cre- dence that ASsA may be a precursor to AERD. Fig. 11. Axial computed tomography of the frontal sinus demon- strating an expansile heterogenous mass in the right frontal sinus extending into the right frontal lobe. The inflammatory process has extended from the right frontal sinus to involve the left frontal sinus.

Aspirin Triad or Aspirin Exacerbated Respiratory Disease

Aspirin triad or AERD patients have the worst sinus symptoms among CRS patients. 19 In our study they had the highest statistically significant CSS score. Aspirin triad patients have a history of adult onset

Laryngoscope 123: March 2013

Han: Subclassification of Chronic Sinusitis

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