Relief for Aspirin-Sensitive Asthma Patients a Diagnostic

Most of us are familiar with asthma, either from personal experience or through someone we know who suffers from the potentially debilitating chronic lung disease. According to the National Heart, Lung, and Blood Institute, approximately 25 million Americans, 7 million of them children, are affected by the blocked airways and difficulty with breathing caused by asthma.

Dr. Elina JerschowA small percentage of these patients—10 percent of all adults with asthma and 40 percent of patients with asthma and nasal polyps—experience a form of asthma known as Aspirin Exacerbated Respiratory Disease (AERD), in which intolerance to aspirin and other non-steroidal, anti-inflammatory drugs, or NSAIDs, such as ibuprofen and naproxen, can lead to severe asthma attacks.

As an example, take Juan Mendez*, a former professional baseball player. During a game, Mr. Mendez had a sudden asthma attack, severe enough that he was intubated on the field. He spent a week in an intensive care unit, where he was diagnosed with asthma and started on medication.

A few weeks later, Mr. Mendez took ibuprofen after a game to relieve pain and inflammation in his overworked muscles (a common practice among professional athletes). Minutes later, he had another asthma attack that required a call to 911. He was again intubated. His doctors advised him to quit baseball. He was 27.

Mr. Mendez eventually moved to the New York City area, where he had family. While working as a golf course superintendent, he noticed that he could no longer taste food or smell anything. He saw several allergists, each of whom advised him to continue taking asthma medications and to use nasal sprays, none of which helped. He then saw an otolaryngologist and was diagnosed with nasal polyps. He underwent sinus surgery to have them removed.

Learning about AERD

Two months after the surgery, his polyps returned and Mr. Mendez continued to suffer. At the age of 32, he was referred to the Montefiore Drug Allergy Center. It was there he learned that his symptoms were related to AERD.

According to Dr. Elina Jerschow, assistant professor of medicine at Einstein and director of the Montefiore Drug Allergy Center, the diagnosis of patients with AERD generally happens through an oral-graded aspirin challenge, currently considered the gold-standard diagnostic test for patients with disease. This method can induce asthma attacks in 40 to 85 percent of people who undergo it.

A new study led by Dr. Jerschow seeks to develop a safer, quicker, more cost-efficient method of identifying aspirin-sensitive asthma, and to shed light on 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.

Getting to the Bottom of Aspirin-Sensitive Asthma

The reason that some adult patients with asthma also develop extreme sensitivity to aspirin and NSAIDs remains unknown, as are the changes in body chemistry that cause AERD. The disease appears most commonly in adults aged 20 to 40, most of whom have no childhood history of asthma. It 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; and
• 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 relief, since polyp regrowth is common in AERD. Proximity of the surgical site to the eyes and brain, as well as the buildup of scar tissue, present obstacles for surgeons. Once polyps regrow, a patient's asthma is usually harder to control and often worsens. Aspirin, however, can prevent the regrowth of polyps.

"Some of my study participants have undergone as many as 10 surgeries for nasal polyps," said Dr. Jerschow. "Reducing negative reaction to aspirin, or aspirin desensitization, helps prevent polyp regrowth, which is essential."

She explained that 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, causing airway tightening and blockage, coughing, wheezing, and other symptoms in patients with asthma. "For individuals with AERD, aspirin and/or NSAIDs generate the same response," she noted.

Dr. Jerschow believes that 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 one's 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. "It often takes very long to connect all the pieces of the puzzle before the correct treatment can be offered," Dr. Jerschow explained.

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 used to make the diagnosis. Dr. Jerschow's study is aimed at devising a safer diagnosis of AERD. Appropriate diagnosis of AERD is a critical part of the process, since aspirin desensitization is effective 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 could lead to development of a safer diagnostic test.

The Einstein/Montefiore Block Institute for Clinical and Translational Research is funding Dr. Jerschow's project through a KL2 award, which provides support for junior faculty members to conduct two- to three-year clinical or translational research studies. KL2 studies also benefit from Einstein's outstanding integrated research support system, which includes strong multidisciplinary mentorship. In addition to having access to the campus's extensive network of core facilities, Dr. Jerschow receives insights and guidance from several mentors: Dr. Simon Spivack, professor of medicine and chief of pulmonary medicine; Dr. David Rosenstreich, professor of medicine, of microbiology & immunology, and of otorhinolaryngology, and chief of allergy/immunology; and Dr. Victor Schuster, senior vice dean and professor of medicine and of physiology & biophysics.

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 have shrunk, his sense of smell has returned, and he is again able to enjoy food. Currently, his asthma is well controlled and he 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. And finding new and effective approaches to improving diagnosis and treatment of AERD is the key goal of my research."

*Name changed to protect patient's identity.