A Diagnostic “Challenge”
Aspirin allergies affect about 10% of adults with asthma.
BRONX, NY - April 22, 2014 - Mr. Mendez*, a 27-year-old healthy professional baseball player experienced a sudden asthma attack during a game. He was intubated on the field and, after a week in the intensive care unit of a local hospital, was diagnosed with asthma and started on medication. A few weeks later, he took ibuprofen after a game to relieve pain and inflammation in his overworked muscles (a common practice among professional athletes). A few minutes later, he experienced another asthma attack and, following a 911 call, was again intubated. His doctors advised him to quit baseball. After a period of unemployment and a move to the New York City area where he had family, he found a job as a golf course superintendent. He soon noticed that he could no longer taste food or smell anything. Several allergists advised him to continue asthma medications and to use nasal sprays, none of which helped. He then saw an otolaryngologist and was diagnosed with nasal polyps, removed by sinus surgery. Two months after the sinus surgery, his polyps grew back. At the age of 32, he was referred to the Montefiore Drug Allergy Center, where he was diagnosed with aspirin-exacerbated respiratory disease (AERD).
Elina Jerschow, MD
AERD affects about 10 percent of all adults with asthma and 40 percent of patients with asthma and nasal polyps. These patients are sensitive to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs, including ibuprofen and naproxen). The diagnosis of these patients generally happens through an oral-graded aspirin challenge, currently considered the gold-standard diagnostic test for patients with aspirin-exacerbated respiratory disease (AERD). This method can induce asthma attacks in 40 to 85% of the people who undergo it. A new study by Dr. Elina Jerschow seeks to develop a safer, quicker, more cost-efficient method of identifying aspirin-sensitive asthma, and to elucidate the underlying cause of AERD.
The adult patient population of the Bronx has an extraordinarily high prevalence of asthma—more than twice the national average. “Many of my clinic patients were being referred for Samter’s triad—another name for AERD—and I was intrigued by this specific, usually more severe kind of asthma,” said Dr. Jerschow, Assistant Professor of Medicine (Allergy/Immunology) and Director of the Montefiore Drug Allergy Center.
Getting to the Bottom of Aspirin-Sensitive Asthma
The reason that some adult patients with asthma also develop extreme sensitivity to aspirin and NSAIDs is yet unknown, as are the changes in body chemistry that cause AERD. AERD appears most commonly in adults aged 20 to 40, most of whom have no childhood history of asthma, and generally involves the following symptoms:
- asthma (coughing, wheezing, shortness of breath, tightening in the chest)
- nasal polyps (noncancerous growths in the nose or sinuses)
- eosinophilia (elevated white blood cells) in peripheral blood, nasal polyps, and lungs
- hypersensitive reactions to aspirin and cyclooxygenase-1 (COX1) inhibitors, including acute bronchospasm (asthma attack), runny nose, and conjunctivitis (pink eye)
Nasal polyps are a particularly disruptive side effect of AERD. These teardrop-shaped growths interfere with mucus drainage, as well as the ability to smell and taste. Surgical removal provides only temporary reprieve, as polyp regrowth is common in AERD. Additionally, the surgical site’s proximity to the eyes and brain, and the buildup of scar tissue, present obstacles to the surgeons. Once polyps regrow, a patient’s asthma is usually harder to control and often worsens. Aspirin, however, prevents the regrowth of polyps.
“Some of my study participants have undergone as many as ten surgeries for nasal polyps,” said Dr. Jerschow. “Aspirin desensitization helps prevent polyp regrowth, which is essential.”
During an allergic reaction, offending substances such as pollen, mold, and animal dander incite an increase of eicosanoids (pro-inflammatory fatty acids) in the body, bringing on airway tightening and blockage, coughing, wheezing, and other symptoms. Aspirin and/or NSAIDs generate the same response in an AERD-affected individual. This imbalance of eicosanoids in affected individuals’ peripheral blood and tissue may be caused by specific changes in the genes possibly induced by infections and/ or environment.
Hope for Testing
The lack of understanding of AERD and its underlying cause has created a critical barrier in developing effective treatments for the condition. “Many practitioners are unaware of AERD and this is often why it takes so long to connect all the pieces of the puzzle before the correct treatment can be offered,” Dr. Jerschow said.
Additionally, the very act of diagnosing AERD is risky, since many patients will suffer an asthma attack in response to the standard oral-graded aspirin challenge. Dr. Jerschow's study will compare the pharmacological effects (biochemical changes in the body) of aspirin in AERD patients to those of aspirin-tolerant asthmatics. Her protocol, conducted on 25-30 participants aged 25-62 (some of whom are referred by the Department of Otorhinolaryngology - Head & Neck Surgery), will use a low-dose aspirin challenge to avoid allergic reactions. The low-dose aspirin challenge begins by giving the patient a small amount of aspirin. This approach usually does not lead to a dangerous allergic reaction, but may elicit changes in blood and urine chemistry that help to diagnose AERD. Appropriate diagnosis of AERD is a critical part of the process, as aspirin desensitization works for AERD patients but not for aspirin-tolerant asthmatics. Results of this study have the potential to advance understanding of the underlying mechanism of AERD and develop a safer diagnostic test.
This project is supported by a KL2 award granted by the Einstein/Montefiore Block Institute for Clinical and Translational Research. KL2 awards provide support for junior faculty members to conduct 2-to-3-year clinical or translation research studies. KL2 studies are supported by Einstein’s outstanding integrated research support system, including strong multidisciplinary mentorship (Dr. Jerschow’s work is mentored by Dr. Simon Spivack, Professor of Medicine and Chief of the Division of Pulmonary Medicine; Dr. David Rosenstreich, Professor of Medicine, Microbiology & Immunology, and Otorhinolaryngology, and Chief of the Division of Allergy/Immunology; and Dr. Victor Schuster, Professor of Medicine and Physiology & Biophysics, and Chair of the Department of Medicine), and access to the campus’s extensive network of core facilities.
Dr. Jerschow's study is potentially life changing for patients like Mr. Mendez, who, upon visiting the Montefiore Drug Allergy Clinic, was diagnosed with AERD and successfully desensitized to aspirin. His polyps shrunk, his sense of smell returned, and he was again able to enjoy food. Currently his asthma is well controlled and he again enjoys playing baseball with his son.
“The unusually high prevalence of asthma in the Bronx suggests that our area has many patients with AERD who have yet to be diagnosed,” said Dr. Jerschow. “Helping patients with allergies and asthma is the most important goal of my practice. Finding new and effective approaches to improving diagnosis and treatment of AERD is the key goal of my research.”
To refer a patient for evaluation, or to find out if you quality for participation, email Dr. Jerschow.
*Name changed to protect patient’s identity.