ACHIEVING GUIDELINE-DEFINED ASTHMA CONTROL

Guideline-defined asthma control was achieved in 41% of patients with previously uncontrolled asthma who participated in a one-year, randomized, double-blind, clinical trial, according to an article in the October 15 American Journal of Respiratory and Critical Care Medicine. Because “most clinical studies assessing the efficacy of ‘controller’ therapies in asthma do not address whether control was achieved,” Eric D. Bateman, MD, of the University of Cape Town, in South Africa, and colleagues sought to assess the efficacy of fluticasone alone, or a combination of salmeterol and fluticasone, in achieving totally controlled asthma or well-controlled asthma.

A total of 3,421 patients ages 12 to 80 with uncontrolled asthma participated in the study and were divided into three groups—those who were corticosteroid-free, low-dose corticosteroid users, and moderate-dose corticosteroid users—and treated with either fluticasone alone or with a combination of salmeterol and fluticasone. Totally controlled asthma was defined as seven totally controlled weeks within eight consecutive weeks “with no exacerbations, emergency room criteria, or medication-related adverse event criteria for each day of each week.”

During phase I of the trial, “treatment was ‘stepped up’ every 12 weeks until totally controlled asthma was achieved or the highest dose of study drug reached (salmeterol/fluticasone 50/500 μg twice a day or fluticasone 500 μg twice a day).” During phase II, the “patients remained on the dose at which they achieved totally controlled asthma or the maximum dose of study medication” until the end of the one-year trial.

Results indicated that salmeterol/fluticasone was more efficacious in controlling asthma more rapidly and at a lower dose of corticosteroid than fluticasone alone. At the end of the one-year trial, totally controlled asthma was achieved in 690 patients taking salmeterol/fluticasone and in 468 patients taking fluticasone alone; well-controlled asthma was achieved in 1,204 patients taking salmeterol/fluticasone and in 988 patients taking fluticasone alone. According to the researchers, exacerbations “were virtually eliminated in patients who achieved guideline-defined control.”

Dr. Bateman and his colleagues said the results of the study suggest that treatment for asthma patients should be aimed at achieving total control. They said totally controlled asthma is a “realistic outcome for corticosteroid- naïve patients, and although it may not be achieved by the majority of patients previously on moderate or high doses of inhaled corticosteroids, by stepping up treatment and aiming for total control of asthma, considerable benefits are achieved in almost all patients.”

Bateman ED, Boushey HA, Bousquet J, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL Study. Am J Respir Crit Care Med. 2004;170:836-844.

CONCURRENT USE OF ERYTHROMYCIN AND CYP3A INHIBITORS INCREASES THE RISK OF SUDDEN DEATH

The concomitant use of oral erythromycin and cytochrome P-450 3A (CYP3A) inhibitors should be avoided, according to a study in the September 9 New England Journal of Medicine. Wayne A. Ray, PhD, of Vanderbilt University School of Medicine, and colleagues reviewed 1,476 cases of sudden death from cardiac causes and found an increased risk of sudden death in individuals who were concurrently using erythromycin and CYP3A inhibitors.

The investigators examined current use and former use of erythromycin and current use of amoxicillin, an antimicrobial agent that does not prolong cardiac repolarization. The CYP3A inhibitors that were examined included nitromidazole antifungal agents (ketoconazole, itraconazole, and fluconazole), diltiazem, verapamil, and troleandomycin.

Of the 1,476 individuals in the study cohort, “34% had medical encounters in the past year related to cardiovascular disease.” Approximately 25% of the subjects were 65 or older and 70% of the subjects were female. In addition, 58% of the subjects were white.

Results indicated that the risk of sudden death from cardiac causes was twice as high among subjects who currently used erythromycin as it was among those who did not use either erythromycin or amoxicillin. Furthermore, “there was no significant increase in the risk of sudden death among former users of erythromycin or current users of amoxicillin.”

The researchers also found that the risk of sudden death from cardiac causes in subjects who concurrently used erythromycin and CYP3A inhibitors was “five times as high as those who used neither CYP3A inhibitors nor study antibiotics.” They did not find an increase in the risk of sudden death among those who had formerly used CYP3A inhibitors or in those who concurrently used CYP3A inhibitors and amoxicillin.

“Given that there are alternatives to erythromycin and to most CYP3A inhibitors, the use of this combination should be avoided in clinical practice,” the researchers concluded.

Ray WA, Murray KT, Meredith S, et al. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351:1089-1096.

MULTIPLE SIBLINGS MAY PROTECT AGAINST ASTHMA

Children with one or more siblings may be less likely to develop asthma than are children without siblings, according to a study in the October Chest. Natalia Dik, MSc, and colleagues used the Cox proportional hazard model to identify characteristics associated with asthma in 170,960 children from Canada and found that having siblings seemed to lower the likelihood of developing asthma.

The children were selected from the Manitoba Population Health Research Repository, a database of medical records of approximately 1.2 million people in the province of Manitoba. The researchers followed the children from birth to age 6. They found that of the 170,960 children, 24,026 had been seen by a physician for asthma. “The incidence was highest in the first two years of life (2.6% and 2.9%, respectively) and declined to 2.0% in years 5 and 6.”

The researchers found that the hazard ratio for children with a sibling was 0.93, indicating that having a sibling was protective against developing asthma. They said that “when there were no time-dependent variables in the model, only children with four or more siblings had a significantly lower risk of asthma than those without siblings. When time-dependent variables were in the model, those with one sibling were protected, and protection increased almost linearly so that the hazard ratio for those with five and more siblings was 0.74.” The researchers also said “the siblings’ protective effect was greater in those with family history of asthma.”

The following characteristics were associated with an increased risk of asthma: male gender, having pediatricians as primary care providers, urban residence, lower birth weight, premature birth, cystic fibrosis, respiratory distress syndrome, upper or lower respiratory tract infection, maternal history of asthma, maternal age, and sibling history of allergy. In addition, being born during the months of July through December was associated with an increased risk of asthma, while being born during the months of January through March was associated with a lower risk.

Dik N, Tate RB, Manfreda J, Anthonisen NR. Risk of physician-diagnosed asthma in the first 6 years of life. Chest. 2004;126:1147-1153.

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