Protocols for aspirin challenge to detect respiratory reactions induced by NSAIDs

	Aspirin doses, mg
Time	Day 1*	Day 2	Day 3
Oral challenge protocol performed for patient management and based upon commercially available aspirin tablets
8 AM	40.5^¶	325 (done)
11 AM	81
2 PM	162
Alternate protocol performed for research purposes
8 AM	Placebo*	40.5^¶	325 (done)
11 AM	Placebo	81
2 PM	Placebo	162

For either protocol, begin only if baseline forced expiratory volume in one second (FEV₁) is 70% or greater than patient's best without bronchodilator. Alternatively, if the absolute FEV₁ value is greater than 1.5 L and represents the best prior FEV₁ value, proceed with oral challenge.
Patients are expected to develop some signs and symptoms in response to aspirin (acetylsalicylic acid [ASA]) during the challenge procedure. This confirms the diagnosis of a pseudoallergic NSAID reaction. When this protocol is used to desensitize a patient to aspirin, the provoking dose is repeated once symptoms have been treated and subsided, three hours after the previous dose. Most patients will have minimal or no symptoms to the repeated dose, but the dose should be repeated until the patient no longer reacts. The protocol then proceeds to completion. Most patients will not have additional symptoms.

NSAIDs: nonsteroidal anti-inflammatory drugs.
* Placebos are essential in research protocols but are usually not needed when the challenge is performed for the sole purpose of patient management. On the placebo day, FEV₁ values should vary by <10% from baseline, and starting FEV₁ value on day 2 should be within 10% of the starting value on day 1.
¶ Dose obtained by cutting an 81 mg tablet with a pill cutter. A lower starting dose of 20 mg is suggested for patients who are not taking a leukotriene-modifying drug, have a baseline FEV₁ of <80% of predicted, or who have a history of emergency department visits for acute asthma.

First protocol from: Macy E, Bernstein JA, Castells MC, et al. Aspirin challenge and desensitization for aspirin-exacerbated respiratory disease: A practice paper. Ann Allergy Asthma Immunol 2007; 98:172.
Alternate protocol modified with permission from: Stevenson DD, Simon RA, Zuraw BL. Sensitivity to aspirin and nonsteroidal antiinflammatory drugs. In: Middleton's Allergy: Principles and Practice, 6th Ed, Adkinson NF, Yunginger JW, Busse WW, et al (Eds), Mosby, St. Louis, MO 2003. p.1695.

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Protocols for aspirin challenge to detect respiratory reactions induced by NSAIDs