Nearly 25 years had elapsed without the introduction of a single new class of therapy for the more than 15 million Americans who live with asthma. Then, in late 1996, medical care for patients with asthma was revolutionized by the introduction of a new class of drugs, leukotriene receptor antagonists (LTRAs), giving practitioners an additional option in asthma management.

Leukotrienes are chemical mediators that can cause airway constriction, swelling, and an influx of inflammatory cells into the lungs, all of which can contribute to an increase in asthma symptoms. Blocking leukotrienes may block asthma symptoms such as coughing and wheezing in many patients.

Despite the existence of these new controller therapies, incidence rates of asthma are on the rise. A report1 from the Centers for Disease Control and Prevention released in April 1998 indicated that the number of Americans with asthma has increased nearly 75 percent since 1980. In addition, nearly 5,000 Americans die each year from asthma.1

Efficacy studies of LTRAs already have demonstrated positive results. LTRAs have been shown to improve lung function and reduce daytime and nighttime asthma symptoms. They also have been shown to reduce the need for inhaled “rescue” medications commonly used to relieve acute symptoms of asthma.

Because LTRAs are administered as a pill, many practitioners have suggested that this form of medication may also increase asthma patients’ compliance with their medications. A scientific study2 presented at the 1998 annual meeting of the American Thoracic Society/American Lung Association showed that 55 percent of patients studied preferred LTRAs over common inhaled corticosteroids. In addition, 44 percent of patients in the study were not able to correctly use an inhaler.

The availability of LTRAs has spawned several studies to examine efficacy, patient compliance, and attitudes regarding oral vs inhaler therapy for the prevention of asthma symptoms. In a recent survey3 focusing on patient compliance and attitude issues, of the 400 patients studied, 55 percent said they were often frustrated by the need to take asthma medication. Commenting on inhaler therapy, 60 percent said they wished there were an easier way to take the medication. Yet 74 percent were unaware that a new class of drugs, in pill form, had been available for almost 2 years.

Asthma patients in this study had strong opinions about inhaler use; 81 percent said they would like to reduce their need for an inhaler. Inconvenience, terrible taste, and difficulty in achieving the correct dosage were listed as some of the reasons more than half of asthma patients said, if given a choice, they would prefer a pill. Although 93 percent of those surveyed said their physician explains how to properly take their asthma medication, a surprising 45 percent said they are not “perfect” in how they follow their physician’s instructions.

Enhancing Compliance
Patient compliance seems to improve with oral LTRA therapy. Patients are usually happy to take a pill rather than use the inhaler, and a twice-a-day schedule–one in the morning and one at night–is an easy one for most to remember.

The University of Pittsburgh’s Comprehensive Lung Center has a total practice of about 500 patients with moderate-to-severe asthma. Inhaler therapy has been a way of life for its patients; many lament about the inconvenience of inhalers and they frequently wish aloud for another option. Now that option is a reality, and a large number of patients currently use an LTRA in pill form for additional maintenance therapy.

Drug effectiveness can be assessed by looking at factors including peak flow, symptom score, and the need for “rescue” medications. Pulmonary function studies confirm this improvement, which can be credited, in part, to the mode of delivery. A pill is easier to take, and may have better compliance. Moreover, the action of an LTRA involves using the circulatory system to deliver medication to even the tiniest airways. This differs from the conventional inhaled steroid medication, which cannot reach the small airways and so does not always get the job done.

Patients using inhalers for both control and rescue therapy will sometimes overestimate their use of the maintenance inhaler and underestimate the amount of use of the rescue inhaler. Their compliance in taking maintenance medication which theoretically limits their need for rescue inhalers, is assessed through pulmonary function measurements.

Patient Education
Patient education is an important part of maximizing compliance no matter what medication is prescribed. Patients generally benefit from detailed one-on-one medication instructions given by a nurse clinician and/or asthma case manager. For those using inhaler therapy, this instruction is critically important. Patients must know how to deliver the optimum amount of inhaled medication, whether it is used for maintenance or, when asthma symptoms are present, as a rescue medication. Oral therapy, when appropriate, offers the advantage of convenience. A nurse clinician and asthma case manager may work closely with patients and family members to make sure that the benefits of the new drugs are fully explained.

LTRA As A Maintenance Drug
With the many benefits LTRAs seem to offer, the question arises as to why all patients do not take LTRAs as a maintenance drug. First, these drugs may not work for all patients. Clinical trials suggest that about two-thirds of patients will respond. The response rate for low-dose inhaled steroids may be similar to that of LTRAs. Second, for patients with moderate to severe asthma, LTRAs will supplement, not replace, inhaled steroids. Finally, some doctors are disinclined to change therapy in patients who are well controlled by their inhaled steroids. However, many patients who are not completely controlled by inhaled steroid therapy will benefit from the addition of an oral LTRA to their existing regimen, and those patients with mild persistent asthma (symptoms less than once daily) may prefer to use oral therapy over inhaled treatments. The safety profile of LTRA therapy is quite favorable, with essentially no detectable differences in adverse events between LTRA and placebo therapies. Thus, there is little to lose by assessing individual patients for possible benefit from use of LTRAs.

Maintenance oral LTRA treatment–either alone or in combination with inhaled therapy–does not eliminate the need for a rescue inhaler for any severity of asthma, mild intermittent through severe persistent disease. For rescue use, the inhaled route offers several advantages, including rapid onset of action, targeted delivery of drug to the airway, and good portability. However, it should be noted that the goal of asthma maintenance treatment is to minimize the need for rescue drug use.

William J. Calhoun, MD, is an associate professor of medicine and director of the Asthma Program at the University of Pittsburgh.

1. Centers for Disease Control and Prevention. Surveillance for Asthma–United States, 1960-1995. Washington, DC: US Department of Health and Human Services; 1998:47. SS-1.

2. Ringdal N. Problems with inhaler technique and patient preference for oral therapy–tablet Zafirlukast vs inhaled Beclomethasone. Am J Resp Crit Care Med. 1998;157:A416.

3. Asthma patient attitudes about medication compliance. Survey conducted by Wirthlin Worldwide, February 1998.