biologic medicines, aspirin therapy has a significantly higher rate of adverse outcomes. biologics various novel biologic monoclonal antibody medications that have come to market in recent years have been used to treat aerd including dupilumab, mepolizumab, omalizumab, and benralizumab. among treatment options, biologics have the highest certainty and magnitude of improvement effect. however, due to the high cost and systemic nature of biologics, some patients whose symptoms are sufficiently controlled with other treatments may prefer to avoid them or not qualify under stricter prescription guidelines. among biologics and aspirin desensitization and therapy, dupilumab (dupixent) was show to be the most effective across six different patient-important outcomes. dupilumab and omalizumab have been shown to increase aspirin tolerance in aerd patients, however mepolizumab does not appear to have this effect. the mechanism through which dupilumab treats aerd and restores aspirin tolerance is not fully understood, but it is theorized that by blocking il-4, dupilumab increases ep2 expression back to normal levels, normalizing cox function and pge2 production. antileukotrienes leukotrienes are a family of inflammatory mediators derived from arachidonic acid that include cyslts implicated in aerd pathophysiology. drugs that prevent leukotriene production, such as zileuton, and that block leukotriene receptors, such as montelukast and zafirlukast, have proven to be useful in treatment of nasal polyposis. however, there may be limited additional benefit when used in conjunction with intra-nasal corticosteroids. in a large survey, aerd patients reported that zileuton was more effective at controlling their symptoms than montelukast. despite this, zileuton remains less prescribed than montelukast, likely due to concerns around risk of liver enzyme elevation. surgery often functional endoscopic sinus surgery is required to remove nasal polyps, although they typically recur, particularly if aspirin desensitization is not undertaken. approximately, 90% of patients have been shown to have recurrence of nasal polyps within five years after surgery, with 47% requiring revision surgery in the same time period. a complete endoscopic sinus surgery followed by aspirin desensitization has been shown to reduce the need for revision surgeries. exact cause of nasal polyp formation is unknown, however, differential gene expression analysis of aerd nasal polyp epithelial cells versus aerd non polyp nasal mucosa revealed dmrt3 could be potentially involved in nasal polyp development in aerd patients. furthermore, several genes are down-regulated, hinting at the de-differentiation phenomenon in aerd polyps. low omega-6/high omega-3 given that dysregulation of the arachidonic acid cascade has been implicated in aerd pathogenesis and that production of arachidonic acid and its downstream products is influenced by the interaction and metabolism of omega-3 and omega-6 essential fatty acids, dietary interventions targeting the two essential fatty acids are under study. a diet low in omega-6 fatty acids and high in omega-3 fatty acids—the opposite of an average modern western diet—has been shown to reduce arachidonic acid precursors and increase eicosapentaenoic acid (epa) and docosahexaenoic acid (dha). epa and dha are precursors for anti-inflammatory compounds that modulate leukotrienes, prostaglandins and thromboxanes that have been implicated in aerd pathogenesis. initial studies have shown that decreasing omega-6 intake and increasing omega-3 intake decrease urinary lte4 and prostaglandin d2 levels and significantly improved overall symptoms. aerd specialists routinely recommend this diet as a treatment option. alcohol the majority of those with aspirin exacerbated respiratory disease experience respiratory reactions to alcohol. one study found that 83% reported such reactions. of those who had reactions, 75% had a sinus reaction (runny nose, nasal congestion) and 51% had a lower respiratory reaction (wheezing, shortness of breath). the current theory on the cause of these reactions is that they may be related to polyphenols found in alcoholic beverages. a 2017 study found that alcohol sensitive patients reacted to catechins in red wine, but not to resveratrol. it has been suggested that steel fermented white wines and clear liquors may cause less of a reaction than other alcoholic beverages. desensitization to aspirin has been found to reduce reactions to alcohol. dietary salicylates given that aspirin is a salicylate, specifically acetyl salicylic acid, research has gone into low-salicylate diets such as the feingold diet to see if they benefit aerd patients. for example, a prospective randomized trial with 30 patients following a low-salicylate diet for six weeks demonstrated a clinically significant decrease in both subjective and objective scoring of severity of disease, but made note of the challenge for patients in following what is a fairly stringent diet. despite these findings, experts on the disease do not believe that dietary salicylates contribute to aerd symptoms. dietary salicylates do not significantly inhibit the cox-1 enzyme, which is the cause of aerd reactions. one confounding factor in the study that showed a benefit from avoidance of dietary salicylates is that a low salicylate diet involves eliminating wine and beer. the majority of aerd patients react to wine and beer for reasons that do not involve their salicylate content. there is also a strong placebo effect involved with any dietary intervention. in contrast to aspirin, dietary salicylates are not acetylated and therefore do not block cyclooxygenases and hence, there is no rationale why a low salicylate diet would be beneficial for aerd patients. alternate and related names aspirin-induced asthma aspirin-intolerant asthma nsaid-exacerbated respiratory disease (nerd) samter's triad (named for max samter) leukotriene associated hypersensitivity acetylsalicylic acid triad widal's triad (named for georges-fernand widal) francis' triad aspirin triad aspirin-induced asthma and rhinitis (aiar) history the first adverse reactions to aspirin were described in 1902 in germany, only four years after aspirin's commercial introduction. the first published report of an aspirin-induced asthma attack was in 1911. initial reports on the linkage between asthma, aspirin, and nasal polyposis were made by georges-fernand widal et al. in 1922. further studies were conducted by samter and beers in reports published in 1968, which brought full clinical characterization. the recognition samter brought to the disease through his studies led to it being called "samter's triad", although today "aspirin-exacerbated respiratory disease" is preferred to better reflect the progressive nature of the condition even when patients abstain from nsaids.