Aspirin-Exacerbated Respiratory Disease (AERD), although uncommon in the general population, is an important phenotype of severe asthma and nasal polyposis where it occurs in 15% of severe asthmatics, and up to 30% of those with nasal polyposis. An important therapy for AERD is aspirin therapy after desensitization (ADAT). This is an inexpensive and proven therapy to improve the burden of sinus disease in AERD. Aspirin desensitization is the mechanism by which tolerance is induced in AERD patients. This is a 1-2 day outpatient procedure whereby increasing doses of aspirin are administered and the patients invariably experience some degree of hypersensitivity reactions.

It is important to understand the effect of medications on the aspirin desensitization. It is known that the leukotriene modifier medications decrease the severity of the reactions in AERD. Other treatments such as antihistamines and the biologic agent omalizumab might have an effect on either blocking or blunting reactivity in AERD during desensitization.

Dupilumab is a new respiratory biologic approved for atopic dermatitis, eosinophilic asthma and nasal polyposis. As such, it is well situated to be used for many AERD patients whose disease cannot be well controlled. The effect of dupilumab on the aspirin desensitization process and reaction is unknown and is the topic of this investigation.

The primary objective is to determine the effect of dupilumab on reactions during aspirin challenge/desensitization.

Inclusion Criteria:

• Subjects >18 years old with Aspirin-Exacerbated Respiratory Disease

This is diagnosed via either a positive oral aspirin or intranasal ketorolac challenge OR a history of at least two stereotypical hypersensitivity reactions to aspirin leading to nasal-ocular symptom and/or asthmatic symptoms.

• Current treatment with dupilumab at standard asthma/nasal polyposis dosing of 300mg subcutaneously every 2 weeks for a minimum of 12 weeks.
• All subjects will be required to have a known history of nasal polyposis either via imaging, endoscopy, or nasal examination

Exclusion Criteria:

• History of gastrointestinal reactions (severe abdominal pain with or without vomiting) during NSAID triggered events
• Unstable asthma or history of severe reactions during previous desensitization attempts
• inability to take montelukast pretreatment
• history of gastrointestinal bleeding or bleeding disorder
• pregnancy
• previous use of any other respiratory biologic in the past 3 months (omalizumab, tezepelumab, mepolizumab, reslizumab, benralizumab)
• need for systemic corticosteroids to stabilize asthma prior to challenge
• time from sinus surgery <1 month.