Asthma, Aspirin-induced
Conditions
Keywords
aspirin, asthma, diagnosis, prostaglandins, leukotrienes
Brief summary
To diagnose aspirin hypersensitivity in asthmatics by using and safe, low-dose aspirin oral challenge. Hypothesis 1: A low dose of oral ASA (20 or 40 mg) will induce significantly different concentrations of arachidonic acid metabolites in ASA-sensitive asthmatics as compared to ASA-tolerant asthmatics. Hypothesis 2: The low dose (20 or 40 mg) ASA challenge will be well tolerated by ASA-sensitive asthmatics.
Detailed description
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.
Interventions
None listed
Sponsors
Montefiore Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Eicosanoid Metabolites Concentration | 2 hours | eicosanoid metabolites concentration in plasma and urine 2 h post ASA challenge |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Related Adverse Events | 24 hours after the challenge | Adverse reactions defined as bronchospasm requiring endotracheal intubation. The adverse reactions will be assessed through a post challenge follow-up with the patient at baseline and 24 hours after the challenge |
| Change in Forced Expiratory Volume in One Second (FEV1) in Aspirin Exacerbated Respiratory Disease (AERD) Patients | 12 months | We will assess FEV1% change from baseline at 12 months in AERD patients who have been on aspirin treatment for 12 months (current standard of care) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aspirin-sensitive Asthmatics patients with aspirin exacerbated respiratory disease | 16 |
| Aspirin-tolerant Asthmatics aspirin-tolerant patients with asthma | 13 |
| Total | 29 |
Baseline characteristics
| Characteristic | Aspirin-tolerant Asthmatics | Total | Aspirin-sensitive Asthmatics |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 29 Participants | 16 Participants |
| Age, Continuous | 42.6 years STANDARD_DEVIATION 2.4 | 40.3 years STANDARD_DEVIATION 2.9 | 37.8 years STANDARD_DEVIATION 3.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 17 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 11 Participants | 7 Participants |
| Region of Enrollment United States | 13 participants | 29 participants | 16 participants |
| Sex: Female, Male Female | 7 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 13 |
| serious Total, serious adverse events | 0 / 16 | 0 / 13 |
Outcome results
Primary
Eicosanoid Metabolites Concentration
eicosanoid metabolites concentration in plasma and urine 2 h post ASA challenge
Time frame: 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin-sensitive Asthmatics | Eicosanoid Metabolites Concentration | 6.91 log-pg/mg creatinine | Standard Error 0.15 |
| Aspirin-tolerant Asthmatics | Eicosanoid Metabolites Concentration | 5.8 log-pg/mg creatinine | Standard Error 0.12 |
Secondary
Change in Forced Expiratory Volume in One Second (FEV1) in Aspirin Exacerbated Respiratory Disease (AERD) Patients
We will assess FEV1% change from baseline at 12 months in AERD patients who have been on aspirin treatment for 12 months (current standard of care)
Time frame: 12 months
Population: AERD patients will continue aspirin treatment for 12 months and the change from baseline in their FEV1% predicted will be monitored during this time
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin-sensitive Asthmatics | Change in Forced Expiratory Volume in One Second (FEV1) in Aspirin Exacerbated Respiratory Disease (AERD) Patients | 12 change in percent predicted FEV1 | Standard Error 1.1 |
Secondary
Treatment-Related Adverse Events
Adverse reactions defined as bronchospasm requiring endotracheal intubation. The adverse reactions will be assessed through a post challenge follow-up with the patient at baseline and 24 hours after the challenge
Time frame: 24 hours after the challenge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin-sensitive Asthmatics | Treatment-Related Adverse Events | 0 participants |
| Aspirin-tolerant Asthmatics | Treatment-Related Adverse Events | 0 participants |