Unanswered Questions
by Sarah Stone Wunder
March 2008
As the number of asthma cases climb globally, researchers focus on early intervention and effective treatments.
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In most countries, asthma in both adults and children isn’t a new disease, but the recent up-tick in the number of cases has researchers baffled. Incidence of asthma has increased at unprecedented rates during the past decade, and no one knows why.
According to the World Health Organization (WHO), asthma is the most common disease among children. More than 300 million people suffer from the disease, which claimed 255,000 lives in 2005. In the United States, asthma is the leading serious chronic illness of children, according to the U.S. Centers for Disease Control and Prevention. In 2005, an estimated 6.5 million children under age 18 (almost 1.4 million under age 5) had asthma, 3.8 million of whom had an asthma attack, and many others have “hidden” or undiagnosed asthma.
Globally, incidences of asthma have been on the rise for reasons researchers still haven’t been able to identify. Dr. Stanley J. Szefler, head of Pediatric Clinical Pharmacology in the Department of Pediatrics at the National Jewish Medical and Research Center in Denver, Colo., USA, and principal investigator for the Denver site of the Childhood Asthma Research and Education (CARE) Network, says cases of both allergies and asthma have increased in prevalence over the past several decades for unknown reasons. “There are several theories related to diet, obesity, as well as the hygiene hypothesis,” Szefler says.
Under this hypothesis, because people have increased their use of antibiotics and anti-bacterial cleansers, children are exposed to fewer microbial organisms. As a result, they shift their attention to building up immunity to allergens and eventually develop reactions to the allergens in the environment, Szefler says.
“The cleaner the environment, and the more use of antibiotics, the more likely children will respond to allergens, which contribute to asthma,” he says. However, this hypothesis is just one of many researchers have about asthma’s growing prevalence. “Nobody has identified the one single item that’s causing it.”
Regional Risk Factors
One of the theories on asthma’s rise centers on environmental factors that contribute to allergic reactions. Because both indoor and outdoor allergens can contribute to asthma and asthma attacks, where someone lives might have as much of an effect on asthma prevalence as genetics, ethnicity and other risk factors.
In fact, the Journal of Allergy and Clinical Immunology recently published a study of 49,000 public school students in Chicago, Ill., USA. The survey broke down asthma rates by zip code within the city, and showed that rates of asthma can differ dramatically by zip code, even if the areas have a similar ethnic makeup.
Also, according to WHO, although urbanization is often associated with asthma, the direct correlation is still unclear. It occurs in all countries regardless of the level of development, and more than 80 percent of asthma deaths occur in low- and lower-middle income countries.
A Caring Network
Among many organizations concentrating on asthma, one that has focused solely on childhood asthma is the CARE Network, established in 1999 by the U.S. National Heart, Lung and Blood Institute (NHLBI). Five clinical centers and a data-coordinating center participate in this research network. Since its founding, the CARE Network has conducted several studies for children with asthma, the results of which it shares with the healthcare community. Currently, the network is conducting two trials: BADGER and TREXA.
BADGER, which stands for “Best ADd-on Therapy Giving Effective Response,” is a 56-week randomized, double-blind, three-treatment, three-period cross-over trial that will evaluate the differential improvement in control that is achieved following three separate treatment interventions in children whose asthma is not acceptably controlled on a low dose of inhaled corticosteroid (ICS). The purpose of the trial is to determine the different treatment effects of the following three step-up therapies: (1) doubling the dose of the current ICS regimen; (2) adding a long-acting beta-agonist and not increasing the ICS dose; (3) adding a leukotriene receptor antagonist and not increasing the ICS dose.
TREXA, which stands for “TReating Children to Prevent EXacerbations of Asthma,” is a 44-week randomized, double-blind, double-masked, four-treatment, parallel trial that will evaluate various strategies for weaning children from ICS therapy. The goal is to determine a strategy that provides the best protection against the development of exacerbations in children whose asthma is acceptably controlled on a low dose of ICS.
Szefler, who is a participating member of the CARE Network along with National Jewish Medical and Research Center, says that the goal with both trials is to determine which treatments work best with different individuals and their specific symptoms and characteristics.
Szefler says new treatments for childhood asthma are on the horizon. Typically, treatments are approved for adults first, and then they move down to older children, and eventually to children under five. Treatments currently on that path are anti-immunoglobulin E (IgE) medications, such as Xolair (omalizumab). This injectable monoclonal antibody is approved in the United States and in Europe for children over 12.
“It’s targeted toward the more moderate to severe asthmatic having frequent exacerbations,” he says. “Children would take it once a month, or sometimes twice a month, depending on their weight and IgE level.”
In addition to new therapies, researchers also are focusing on early intervention, Szefler says. “If you catch it early and treat it effectively, you get better outcomes,” he says. Although asthma can probably never be totally preventable, researchers are getting closer to greatly reducing its effects, Szefler says.
“Patients can vary in their response to medications,” he says. “The information is falling into place to help us select the most effective and safe medication for individual patients. Szefler says that the key will be whether scientists can develop an effective strategy to do that. “Genetics and biomarkers and patient characteristics will help us pinpoint the patient population that needs the greatest attention. How quickly it will happen, I don’t know, but it seems to be moving pretty quick.”
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