Salmeterol More Effective for Asthma than Albuterol

By Patricia McGinley, FNP, MSN

Summary—An acute asthma attack can be frightening for patient and caretaker. The Centers for Disease Control and Prevention in Atlanta indicates 15 million U.S. citizens suffer from asthma, and the number is increasing. A specific definition of asthma eluded experts for decades, and available treatment was less than ideal for many patients. The recent report of a research study comparing the efficacy of albuterol, which must be administered frequently, and salmeterol, a longer-acting b2-agonist, offers hope for today’s asthmatics.

The Centers for Disease Control and Prevention estimates that 15 million Americans suffer from some form of asthma, a common respiratory disorder in adults and children, with a noted increase in the incidence over the past five years.1 Health care utilization by asthmatics has increased steadily over the past 15 years. In 1995, 1.8 million emergency department (ED) visits were due to asthma. The rate was 48.8 per 10,000 among whites and 228.9 per 10,000 visits among African-Americans. Hospitalization rates have risen as well, with 10.9 per 10,000 among whites and 35.5 per 10,000 visits among African-Americans.1

Attempts to define asthma precisely have been difficult, and some experts call it a syndrome rather than a disease. With the inception of pulmonary function testing in the 1950s, identification of pathologic components of asthma in the 1970s, and research focusing on bronchoscopic evaluation identifying inflammation with eosinophils and mucosal sloughing in the 1980s, medical science advanced to the latest current definition: Asthma is an inflammatory disease of the airways with reversibility of airflow obstruction and bronchial hyperresponsiveness as key components.2

Three Diagnostic Criteria

The National Institutes of Health in Bethesda, MD, has developed diagnostic criteria for asthma, including:
• history or presence of episodic symptoms of airflow obstruction;
• airflow obstruction that is at least partially reversible;
• and exclusion of other alternative diagnoses.3

Clinical manifestations of asthma include wheezing, cough, shortness of breath, and chest tightness. Management often includes the use of inhaled b2-adrenoceptor agonists such as albuterol, pirbuterol, and metaproterenol.

The New England Journal of Medicine recently reported a study comparing the use of a newer inhaled b2-agonist (salmeterol), albuterol, and a placebo. Salmeterol is a derivative of albuterol but has a longer binding capacity to the b2-adrenoreceptor protein, thus providing up to 12 hours of bronchodilation. It is dosed on a BID schedule instead of the QID schedule of shorter-acting albuterol.4

The multicenter randomized, placebo-controlled study compared the use of albuterol (180 mg four times daily) and salmeterol (42 mg twice daily) in the treatment of mild to moderate asthma. The 234 patients meeting criteria for inclusion in the study included 150 males and 84 females between ages 12 and 73. In addition to having a confirmed diagnosis of asthma, subjects had to be nonsmokers, at least 12 years old, and on a daily medication regimen to control the symptoms.

Study subjects received albuterol, salmeterol, or placebo once every 12 hours during the 12-week study period. Subjects were permitted to use albuterol supplementally for short-term relief of symptoms. Subjects using inhaled corticosteroids or cromolyn could enroll but had to maintain constant doses of these medications during the study. If asthma symptoms worsened between doses of the study medication, the subject’s usual "rescue" medications were taken as needed.

At the beginning of the study, each subject’s forced expiratory volume in one second (FEV1) was measured 30 minutes before and immediately after inhalation of the study drug and 12 hours later. These measurements were taken again four, eight, and 12 weeks into the study. Other measured variables included maintenance of a diary that recorded:
• the number of episodes of symptom exacerbations;
• use of rescue medications;
• and twice-a-day peak expiratory flow rate using a handheld peak flow meter.

Study Results

The study showed salmeterol to have advantages over albuterol and placebo in the management of asthma. A significant increase in the morning FEV1 was seen throughout the study period when salmeterol was compared with albuterol and placebo. When compared with pretreatment values, salmeterol resulted in a mean increase of 24 liters per minute, whereas albuterol showed a decrease of 6 liters per minute. Placebo resulted in an increase of 1 liter per minute.

In addition, there was a more sustained bronchodilation effect with salmeterol than with albuterol in which study subjects experienced less frequent and less severe breakthrough symptoms, thereby reducing the use of rescue medications. There was no evidence of a tolerance effect with the use of salmeterol over a long period of time.

The side effect profile for salmeterol was less than that of albuterol and placebo. Twelve percent of patients in the salmeterol group reported adverse effects, vs. 23% in the albuterol group and 20% in the placebo group. Reported side effects included headache, tremor, and tachycardia in the albuterol and salmeterol group; headache was most common in the placebo group.

Researchers concluded that salmeterol twice daily for the management of mild-to-moderate asthma is superior to albuterol given either as needed or four times daily.

Practice Implications

Once an individual is diagnosed with asthma, the key to better quality of life, less frequent utilization of health care resources such as ED visits and hospitalization, and less loss of time in work or school lies in the treatment regimen developed by the health care provider. The mainstay of therapy for patients with chronic, persistent asthma in the outpatient setting includes:
• reduction of environmental triggers;
• behavior changes;
• home peak flow monitoring;
• and therapeutic drug agents such as corticosteroids, theophylline, b2-agonists, leukotriene agonists, and cromalyn.

Management of asthma often includes the use of inhaled b2-adrenoceptor agonists such as albuterol, pirbuterol, and metaproterenol. The b2-agonists cause relaxation of the bronchial smooth muscle with duration of action between three and eight hours. These agents are used alone or in combination with corticosteroids or anti-inflammatory drugs. The selective b2-agonists are preferred due to a better side effect profile. However, if used more than every four hours, the selectivity of b2-receptor sites is diminished; therefore, b1-agonist effects are exhibited. The b2-agonists are prescribed on a QID schedule with instruction to increase utilization during periods of acute distress.

Intense patient and caregiver education on the nature of the disease, compliance with therapeutic regimens, and the need for follow-up care on a regular and emergency basis are crucial to successful management of the asthmatic patient. As with any chronic illness, the use of multiple drugs taken many times a day often leads to poor compliance and repeated exacerbations of symptoms.

This research study presents scientific evidence of a safe, effective medication that lasts longer than commonly used bronchodilators that have a QID dosing schedule. The use of salmeterol on a BID schedule is more convenient and has the potential for better compliance, thereby reducing the incidence of office and ED visits. Because the salmeterol study included adolescents, and the drug was proven safe, effective, and superior to albuterol, it offers a treatment modality more conducive to the busy lifestyle of this population. Clinicians may wish to consider salmeterol, especially for patients with compliance problems or those who don’t obtain the desired response from current medications.

References

1. Centers for Disease Control and Prevention. Asthma Rates in the U.S. Increase. Press Release, April 24, 1998. Web: http://www.cdc.gov/od/oc/media/pressrel/r980424.htm.

2 Barbee RA and Murphy S. The natural history of asthma. J Clin Immunol 1998;102(4), part 2:S65-66.

3. National Institute of Allergy and Infectious Diseases. Practical Guide for the Diagnosis and Management of Asthma. NIH Publication 97-4053, October 1997:4. Web: http://www.nhlbi.nih.gov/nhlbi/lung/asthma/prof/asthgdln.htm.

4. Pearlman D, Chervinsky P, Laforce C. A comparison of salmeterol with albuterol in the treatment of mild to moderate asthma. NEJM 1998;327:1420-1425.