December 2000
SEATTLE - Additive therapy regimens and new combination medications that simplify dosing offer improved effectiveness and better patient compliance in the treatment of asthma, according to speakers at the American College of Allergy, Asthma and Immunology annual meeting here.
"We are at the threshold of an era in which combinations of long-acting ß-agonists and corticosteroids will be available worldwide for the treatment of asthma," said Robert P. Schleimer, PhD, professor of medicine at Johns Hopkins Asthma/Allergy Center in Baltimore.
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Both adrenaline and cortisol are produced by the adrenal gland and are released in response to stimuli, such as vigorous exercise and stress. The outpouring of these hormones during stress play a protective role, improving and modifying the cardiovascular system, the lungs and the immune system. The pharmacological effects are overtly distinct, he said.
Non-compliance
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"Acute bronchodilation, one of the most useful effects of long-acting ß-agonists, is not observed with corticosteroids. Likewise, the profound anti-inflammatory effects of steroids are not observed in most studies of ß-agonists in asthma. A number of studies have now established that the addition of a ß-agonist to an inhaled corticosteroid regimen improves lung function more than simply doubling the dose of the steroid," Schleimer said.
The revised National Institutes of Health guidelines recommend that patients with persistent asthma who are not adequately controlled on low to medium doses of inhaled corticosteroids, increase the inhaled steroid or add a second long-acting bronchodilator, including salmeterol (Serevent, Glaxo Wellcome) or a sustain-released theophylline preparation.
"A leukotriene modifier may also be considered, although this indication has not been firmly established," said Stanley P. Galant, MD, clinical professor of pediatrics, director of pediatric allergy & immunology at the University of California, Irvine. "Leukotriene modifiers and theophylline are two other classes of drugs that have been evaluated as adjuncts to inhaled corticosteroids in inadequately controlled patients."
One of the benefits of the combination is the convenience of having one rather than two delivery devices, which should increase a patient's adherence to an individual treatment plan.
Galant said there are four main reasons for poor patient compliance with inhaled medications:
"The fixed combination of long-acting ß-agonists and corticosteroids appears to address each of these issues, which should improve compliance. Because of the addition of a bronchodilator, patients will feel improvement within minutes, in addition to the steady improvement over a longer period. In addition, patients can be assured the safety profile has proven excellent in the proposed dosages of each," he said.
"The fixed combination with one inhaler has been shown to be equally effective to each given separately. Finally, the breath-activated dry powder inhaler is easier to use for most patients than a metered dose inhaler. A dose counter, multiple dosage per unit and several dosage forms should also help with compliance. The drawbacks for the fixed combination appear to be few," he said.
Evidence is accumulating that asthma is an inflammatory disease of the total lung. "Several investigators have demonstrated that the inflammatory process is not confined to the large airways, but also extends to the most peripheral small airways, including the alveoli," said Richard J. Martin, MD, head of the pulmonary division at National Jewish Medical & Research center and University of Colorado, Denver. "New formulations and delivery devices, which result in smaller particle size, target the large airways and also the small airways, where anti-inflammatory effects can be most beneficial."
There are an estimated 17 million Americans with asthma; 5.3 million are children. It is the leading serious chronic illness in children and the leading cause of school absences attributed to chronic conditions. Projected cost related to asthma in the United States is expected to total $14.5 billion this year.
Asthma usually starts during the first years of life. Studies show early intervention may prevent irreversible airway injury. Structural changes in the airway wall caused by chronic inflammation of asthma can lead to irreversible decline in lung function. Data suggest that anti-inflammatory medication, particularly inhaled corticosteroids, may be effective in preventing or reducing this process.
For more information:
- Schleimer RP. Molecular mechanisms and cellular targets.
- Stanley GP. Clinical basis for combination therapy.
- Martin RJ. Inhaled steroids: How do we really evaluate them?
- All presented at the American College of Asthma, Allergy & Immunology Annual Meeting. Nov. 3-8. Seattle.
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