William Busse Targets a Key Factor in Asthma Among Inner-City Youth

The typical cockroach is about the size of a human thumbnail. It likes to burrow in dark, cold spaces and can multiply faster than raindrops in a thunderstorm.

 

The cockroach also turns out to be the greatest cause of allergies and a key player in determining how severe asthma will be in the millions of inner-city children in the United States who have the disease.

 

In 2002, with the leadership of William Busse, MD '66, the University of Wisconsin School of Medicine and Public Health in Madison received its largest research grant ever, a six-year, $55.8 million award from the National Institutes of Health (NIH) to study the causes of the urban asthma epidemic that affects people under 20 years of age.

 

A major goal of the research is to develop treatments to improve control of asthma in this young population.

 

Last fall, the grant was renewed for another five years, bringing in an additional $56.3 million to continue the work on inner-city asthma. Joining Busse on the School of Medicine and Public Health research team, part of the Inner City Asthma Consortium (ICAC), are Christine Sorkness, PharmD, and James Gern, MD, of the Department of Medicine.

 

They lead a national research group from eight inner-city sites and two basic science investigators who will comprehensively explore new treatments and causes of asthma in the high-risk youngsters.

 

Cockroaches a Key Culprit in Inner-City Asthma

 

Asthma is very common, especially in children. Mortality related to it is beginning to decrease worldwide and in the U.S. - except in the inner city. In children living there, asthma is more frequent, more severe and more difficult to treat than asthma in other children, says Busse.

 

"These characteristics and the fact that these children are at high risk for asthma continue to make this disease a major public health issue and the focus of research at the NIH," he says. "Our focus in this project is on inner-city children, but the results of our efforts should be applicable to all patients with asthma."

 

In the inner city, cockroaches are a principal culprit in the asthma puzzle.

 

"Children living in the inner city are allergic to the usual suspects - house dust mites, animal dander and pollen - but cockroach sensitivity is a major problem for this group of patients, particularly for those with asthma," Busse says.

 

Other factors are involved, he notes, but an allergy to cockroach appears to be a central factor in driving asthma severity in the inner city. For that reason, cockroach allergy needs to be a principal target of treatment and research.

 

The research proposed in the renewed ICAC grant will build on findings from the initial grant.

 

One of the studies recently completed, the Inner City Anti-IgE Therapy for Asthma, or ICATA, evaluated the effectiveness of treatment with a monoclonal antibody against IgE, the antibody causing allergic disease. The anti-IgE treatment, omalizumab, is given as an injection and reduces IgE levels. This drop in IgE can reduce the severity of allergic disease and asthma in some patients.

 

The children who received anti-IgE treatment had reduced symptoms and less need for inhaled corticosteroids and long-acting beta agonists. The treatment also decreased asthma exacerbations - especially those attacks that are severe enough to require systemic corticosteroids such as prednisone, emergency room treatments or hospitalizations.

 

"Since exacerbations are the major cause of morbidity and health care costs, reducing them is especially relevant both for the patient's wellbeing and the health care system," Busse notes.

 

But the most exciting thing about anti-IgE treament, the researchers found, is its effect on the "September epidemics of asthma." These are the spike in emergency visits or hospitalizations for asthma attacks that occur when children return to school after summer vacation, and catch a cold.

 

"We've known that the common cold virus is the major infectious trigger of asthma at this time of the year. The return to school acts as an incubator to spread the cold to the children and eventually other family members," explains Busse. "We've also known that having allergies is a risk factor for an asthma attack when children, and adults, get a cold."

 

What the researchers didn't realize was how important allergies and IgE antibodies were to this relationship. Anti-IgE treatment virtually "wiped out" the asthma attacks that occurred during the September epidemic in the inner-city children.

 

"What was most impressive was that the anti-IgE treatment even worked in children who were receiving guideline treatment and had been on all the right medications and at the right doses when they got a cold," says Busse.

 

The usual treatment was not sufficient to prevent asthma attacks in most of these children.

 

"These findings are new evidence that in addition to the well-recognized contribution of a respiratory viral infection to a flare-up of asthma in September, IgE and allergies are equally important," says Busse. "That makes allergies and IgE highly viable targets for treatment."

 

Steps Toward Personalized Care for Asthma

 

The new grant will support the School of Medicine and Public Health's team's efforts to more fully understand and effectively treat children who are most likely to suffer severe September attacks. For starters, the researchers hope to treat children with anti-IgE right before they return to school, and to treat them for a shorter period of time. This simplified treatment should increase patient convenience, decrease disease morbidity and lower the cost of asthma care.

 

But work in the ICAC involves more than understanding September epidemics and cockroach allergy.

 

The researchers will continue to follow their recruited birth cohort of inner-city children at high risk for asthma, who are now four years old and beginning to develop asthma. Because the immunology and environment of these children is well defined and characterized, the ICAC group expects to learn what causes asthma in them and how it may differ from that which occurs in children raised in the suburbs.

 

"With this expanded information and insight, we hope to determine which risk factors make this disease in these children so difficult to treat," says Busse. "We'll have taken an important step toward creating a personalized care approach to improve the treatment of these children."

 

In the end, the researchers hypothesize that the cockroach, with its unique and potent allergen characteristics, will be a critical factor in solving this puzzle.

 

"The cockroach has survived for millions of years, and will likely continue to thrive in our environment," says Busse. "So it's unlikely we will be able to rid homes of these critters."

 

But the NIH funding gives the researchers the resources and manpower needed to thoroughly address the issue and overcome a major health care problem.

 

"If we can unravel more fully how cockroaches contribute to asthma," Busse says, "we can outsmart them by developing more effective and specific treatments."

 

By Aaron Conklin

This story appears in the summer 2010 issue of Quarterly.

Date Published: 08/19/2010