Eosinophils isolated from the blood of aspirin-induced asthma subjects (as well as severe asthmatic patients) greatly overproduce 15-hydroxyicosatetraenoic acid and eoxin C4 when challenged with arachidonic acid or calcium ionophore A23187, compared to the eosinophils taken from normal or mildly asthmatic subjects; aspirin treatment of eosinophils from aspirin intolerant subjects causes the cells to mount a further increase in eoxin production. These results suggest that 15-lipoxygenase and certain of its metabolites, perhaps eoxin C4, is contributing to aspirin-induced asthma in a fashion similar to 5-lipoxygenase and its leukotriene metabolites. Treatment
Medication
Avoidance of NSAID medications will not stop the progression of the disease. The preferred treatment for many patients is desensitization to aspirin, undertaken at a clinic or hospital specializing in such treatment. Patients who are desensitized then take a maintenance dose of aspirin daily to maintain their desensitization. The recommended maintenance dose for symptom control is 650 mg to 1300 mg aspirin daily. While on daily aspirin, most patients have reduced need for supporting medications, fewer asthma and sinusitis symptoms than previously, and an improved sense of smell. Desensitization to aspirin reduces the chance of nasal polyp recurrence and may slow the regrowth of nasal polyps. Once desensitized to aspirin, most patients can safely take other NSAID medications again.Even patients desensitized to aspirin may continue to need other medications including nasal steroids, inhaled steroids, and leukotriene antagonists. Leukotriene antagonists and inhibitors (montelukast, zafirlukast, and zileuton) often are helpful in treating the symptoms of AERD.
Anosmia (lack of smell) also is common, as inflammation within the nose and sinuses likely reaches the olfactory receptors.The respiratory reactions to NSAIDs vary in severity, ranging from mild nasal congestion and eye watering to lower respiratory symptoms including wheezing, coughing, an asthma attack, and in rare cases, anaphylaxis. In addition to the typical respiratory reactions, about 10% of patients with AERD manifest skin symptoms such as urticaria and/or gastrointestinal symptoms such as abdominal pain or vomiting during their reactions to aspirin.In addition to aspirin, patients also react to other NSAIDs such as ibuprofen, and to any medication that inhibits the cyclooxygenase-1 (COX-1) enzyme, although paracetamol (acetaminophen) in low doses is generally considered safe. NSAIDs that are highly selective in blocking COX-2 and do not block its closely related paralog, COX-1, such as the COX-2 inhibitors celecoxib and rofecoxib, also are regarded as safe. Nonetheless, recent studies do find that these types of drugs, e.g. acetaminophen and celecoxib, may trigger adverse reactions in these patients; caution is recommended in using any COX inhibitors. In addition to aspirin and NSAIDs, consumption of even small amounts of alcohol also produces uncomfortable respiratory reactions in many patients. Cause
The disorder is thought to be caused by an anomaly in the arachidonic acid metabolizing cascade that leads to increased production of pro-inflammatory cysteinyl leukotrienes, a series of chemicals involved in the bodys inflammatory response.