Diagnosis of Aspirin Hypersensitivity in Aspirin Exacerbated Respiratory Disease

This research study is being conducted within the established Airway Research Group at
Montefiore Medical Center and Albert Einstein College of Medicine in Bronx, NY. The patient
population in the Bronx has one of the highest asthma prevalences in the country. Thus, our
study participants are being recruited among the population most in need of a better
understanding of the disease process.

Visits 1 and 2: Low-dose challenge with 20 mg and 40 mg of ASA. ASA will be administered
orally to participants in both groups: 20 mg at Visit 1 and 40 mg at Visit 2. Visits will
take place at least 1 week apart. Blood and urine will be collected at several time points.

Visit 3: Oral graded ASA challenge will be performed to confirm or rule out the presence of
ASA-hypersensitivity. This visit will take place at least 1 week after Visit 2. Both groups
will undergo an oral graded ASA challenge as per earlier described protocol. Urine and plasma
will be collected from the patients at several time points. Hypersensitivity reactions will
be defined in four different ways: a) decline in forced expiratory volume in 1 second (FEV1)
of at least 15% combined and naso-ocular reaction; b) 20% decline in FEV1; c) isolated
naso-ocular reactions; d) isolated cutaneous reactions (hives and swelling). Patients with
reactions will be treated according to their symptoms.

Inclusion Criteria:

1. Participants of both sexes aged 18 years and older.

2. Patients with a history of ASA-induced asthma who had at least one asthma attack after
ingestion of aspirin or other NSAIDs.

3. Patients with a history of ASA-tolerant asthma who had been occasionally using aspirin
or other NSAIDs without any adverse reactions.

Exclusion Criteria:

1. Mental or legal incapacitation, or significant emotional problems, or a history of
psychiatric disorders at the time of the enrollment.

2. Pregnancy or breastfeeding at the time of enrollment.

3. History of a severe anaphylactic reaction precipitated by ASA and/or other NSAIDs
(such as ibuprofen, naproxen, indomethacin, Advil, Aleve, Motrin, diclofenac, etc.).

4. History of a severe bronchospasm precipitated by ASA and/or other NSAIDs requiring an
endotracheal intubation.

5. Chronic kidney disease (a calculated GFR based on the Modification of Diet in Renal
Disease (MDRD) equation is < 60 mL/min/1.73 sq.meter).

6. Chronic liver disease by history and/or abnormal liver function tests (SGOT and SGPT ≥
3 times above upper normal range).

7. Baseline FEV1 < 70% (or < 1.5 L) of predicted, or an exacerbation of asthma in the 6
weeks preceding the study.

8. An active infectious disease.

9. Anemia that requires work-up, black stools, active bleeding.

10. A history of gastrointestinal bleeding due to aspirin or other NSAIDS, gastritis, or
duodenal ulcer not proven to be due to Helicobacter pylori.

11. A history of hemophilia or any other bleeding disorder.

12. Unstable angina.

13. Participants taking aspirin and or other NSAIDs at the time of the study visits.

14. Participants taking leukotriene receptors inhibitors or 5-lypooxygenase (5-LO)
inhibitors at the time of the study visits.

15. In addition, participants taking one or more of the following drugs intake last 14
days prior to the enrollment will be excluded: lithium, warfarine, enoxaparin,
heparin, dalteparin, fluconazole, ketotifen. Short-acting antihistamines should be
stopped 5 days before the challenge; long-acting antihistamines should be stopped 1
week prior to the challenge.