Vol. 14 •Issue 2 • Page 23
Drug Data
Emerging Asthma Therapies Target Each Patient’s Inflammatory Profile
Asthma has become a more tolerable disease with all the new therapies and treatments released in the past 20 years. This became more apparent to me in May when I attended a week-long camp for 7- to 14-year-olds with asthma.
Camp Breathe Easy at Twin Lakes in Rutledge, Ga., has existed for 24 years and is sponsored by the American Lung Association. In the program’s early years, campers required aerosol nebulizer treatment so frequently that the infirmary stayed open 24 hours a day to administer treatments.
This summer, the medical staff administered only five aerosol treatments, and no camper received more than one. Health issues like insect bites, athlete’s foot, ear infections, etc., were more prevalent than asthma attacks.
Despite the improvements in preventative therapies, asthma remains the top chronic illness facing children in the United States. Twelve percent of children under 18 have been diagnosed with asthma, according to the Centers for Disease Control and Prevention.
National guidelines are available that identify varying levels of asthma severity that require daily maintenance medication versus episodic treatment. However, physicians often fail to follow these recommendations, and patients often administer their prescribed drugs incorrectly or stop taking them due to bothersome side effects.
In addition, severe cases of asthma in the United States usually are treated as episodic, which results in the large number of asthma admissions to our nation’s hospitals. Most of these admissions can be avoided if physicians and patients work together to create and follow treatment plans that incorporate the most effective asthma control drugs.
ANTI-IGE FOR ALLERGIC ASTHMA
Throughout the past several years, the Food and Drug Administration has approved certain therapies for asthma management. Among them is the anti-IgE monoclonal antibody, an emerging treatment for allergic asthma that’s currently being studied.
The majority of asthma patients over the age of 3 have allergen-triggered asthma. Allergens are particles such as house dust or pollen that can trigger an allergic reaction. Some non-allergic triggers include air pollution, smoke, infection or emotions.
Allergen-triggered asthma patients react by producing high levels of a blood protein called IgE. IgE can instigate a chain of events that leads to an asthma attack. Without IgE, the allergic response is much less severe, if it occurs at all. The new anti-IgE antibody prevents IgE from attaching to allergen recognition cells. By preventing recognition of the allergens, the allergic response is interrupted.
In theory, the anti-IgE drug should help asthma sufferers. Published studies showed it to be superior to placebo in reducing inhaled steroid dose and improving quality of life for asthmatic patients. However, the effect on reducing exacerbations and hospitalizations was modest, and there was no significant change in lung function parameters.1-3
The FDA approved the anti-IgE drug for children age 12 and above based on premarketing studies that addressed safety and dosing. Because the number of patients used in these studies was small, the results may not reflect the true value of the drug therapy.
Results from post-marketing studies on more than 20,000 asthma patients won’t be published for months. The post-marketing studies will give a more accurate picture of the therapy because they’re done with a larger number of patients in real world clinical settings.
From my experience at Children’s Healthcare of Atlanta, which sees 3,000 asthma patients a year, only five patients have been prescribed anti-IgE drugs. This therapy also is expensive and not easily approved by most insurance companies.
CYTOKINE MODULATORS
Another emerging therapy is cytokine modulators. Asthma is a chronic disease characterized by inflammation and fibrosis of the airways. These chronic inflammatory changes are interceded by a series of cytokines from inflammatory cells, including lymphokines, pro-inflammatory cytokines, anti-inflammatory cytokines and chemokines.4
Cytokines play an important role in the coordination and persistence of inflammatory processes. Some appear to have an inhibitory or anti-inflammatory effect on allergic inflammation, or they block the messages to the inflammatory process. All asthma sufferers respond to cytokine modulators whether or not they have allergies.
The cytokine modulator therapy is beneficial because it interrupts the inflammatory process early enough to prevent an asthma attack. A readily available and commonly used therapy is leukotriene modifiers, which are long-term control asthma medications that reduce swelling inside the airways and relax smooth muscles around the airways.
A new use of leukotriene modifiers — intravenous monolucasts administration — reveals promising results for patients with asthma. A study showed an improvement in FEV1, which is a measure of airway obstruction, of 15 percent over 20 minutes following intravenous monolucasts administration.5
That 15-percent improvement is significant and could be added to other asthma therapies, so we could possibly see a reduction in need of hospitalization. It may be a part of asthma treatment in emergency rooms around the country soon.
COMBINATION THERAPIES
Another commonly used asthma therapy is corticosteroids, which reduce swelling and help other asthma medicines work better. Of great current interest is combination therapy, which is the use of corticosteroids and other controller medications simultaneously. Systemic corticosteroids such as prednisone also can interrupt an asthma attack after it has started. Inhaled corticosteroids are the most effective medications at preventing asthma exacerbations.
However, steroids are associated with multiple undesirable side effects such as decreased bone mineralization, hypertension and suppressed immune system when used in higher doses. By combining the corticosteroids with other drugs such as long-acting beta2-agonists, a patient with asthma can achieve optimum asthma control with minimum steroid exposure.
ALTERNATIVE APPROACHES
I generally don’t suggest alternative therapies to my patients; however, I don’t object to letting them explore other options. Studies on these alternative therapies often are tainted by biases and not very objective. For example, many herbal medications are proposed to have anti-asthma effects, but large-scale controlled studies don’t exist to prove this substantially.
As mentioned previously, allergies can trigger asthma, but an allergy to a food usually won’t cause asthma symptoms because the antigens from the allergy aren’t touching the airway. In regards to diet, if a patient notices a pattern of asthma symptoms from a certain food, then the patient naturally should avoid that particular food.
Another widely held belief around the world is that patients with asthma should eliminate dairy products from their diets. The theory is that dairy products increase mucus production, which is part of the asthma pathology in conjunction with bronchial swelling and muscle constriction.
No substantial evidence suggests whether this is true, but a study in Australia found that in 60 college-aged volunteers, who were deliber-ately infected with a cold virus, a high dairy diet versus a low dairy diet had no effect on mucus production.6
The goal for asthma therapies is that they be highly effective in preventing the asthma response but narrow in undesirable side effects. In addition, no one asthma case is the same, so each person reacts differently to certain preventative therapies. Therefore, researchers are attempting to target each asthma patient’s inflammatory profile so that they can treat them with the most appropriate therapy.
Dr. Harsch is a pediatric pulmonologist at Emory Children’s Center and an assistant professor for the department of pediatrics at Emory University School of Medicine, Atlanta.
For a list of references, please call Sharlene George at (610) 278-1400, ext. 1324, or visit www.advanceweb.com/respmanager.
