New ProductsAdvair: Combination treatment with fluticasone propionate/salmeterol in the treatment of asthma☆
Section snippets
Overview
Several classes of medications are used in the treatment of asthma, including glucocorticoids, short-acting and long-acting β-adrenergic (LABA) bronchodilators, leukotriene modifiers, mast cell stabilizers, methylxanthines, and anticholinergics. These medications are often used in combination to optimize asthma control by improving pulmonary function, preventing symptoms, reducing the need for rescue medication, normalizing activity levels, preventing exacerbations, and minimizing the impact of
National heart lung and blood institute guidelines for the treatment of asthma
The National Heart Lung and Blood Institute Expert Panel 2 Guidelines to the Diagnosis and Management of Asthma classify asthma into 4 levels of severity based on symptoms and lung function measures assessed before the initiation of treatment: (1) mild intermittent asthma, (2) mild persistent asthma, (3) moderate persistent asthma, and (4) severe persistent asthma.1 Corresponding to the 4 levels of severity, a 4-step approach to asthma therapy has been defined. The medications used in this step
Importance of ICS therapy in the treatment of asthma
The importance of ICS therapy in the treatment of asthma cannot be overstated. Asthma is a chronic inflammatory disorder of the airways involving multiple cells and cellular elements including mast cells, eosinophils, T lymphocytes, neutrophils, and epithelial cells.1 The magnitude of the inflammation and the thickening of the subepithelial layer (airway remodeling) are generally correlated with the severity of asthma but have been observed to some degree even in mild intermittent asthma.2, 3
Efficacy of salmeterol
Salmeterol, a potent β2-adrenergic agonist, is the only long-acting bronchodilator currently available in the United States. Salmeterol provides superior bronchodilation in 12-hour serial pulmonary function studies in comparison to placebo33, 34, 35, 36, 37, 38 and albuterol administered every 6 hours.36, 37, 38, 39 Additionally, salmeterol provides significantly greater improvement than albuterol in predose FEV1 and morning PEF while reducing the requirement for rescue albuterol.36, 37, 38, 39
Evidence that LABAs may mask inflammation
Although long-acting inhaled β2-agonists clearly are the most effective bronchodilators to add to ICS therapy, concerns persist that by allowing the use of a lower dose of ICS, the underlying inflammation of asthma will be masked. This has been fueled by a crossover study where 13 patients taking at least 1500 μg/d of ICS for control of asthma were subjected to a steroid taper while receiving either salmeterol or placebo.85 As predicted, while receiving salmeterol, the patients were able to
Scientific rationale: Complementary action of ICS plus LABA
Considerable research effort has been aimed at characterizing the precise mechanisms of asthma and the contributions of various asthma treatments, fueled in part by the observed and otherwise unexplained clinical benefits of combination therapy with ICS and LABAs. The interactions between corticosteroids and β2-agonists in asthma have been excellently reviewed.92 Perhaps the most important finding in this regard has been the demonstration of the positive complementary actions of ICS and LABA
Studies of advair therapy
The clinical and scientific rationale for the combined use of ICS and LABA is well founded and compelling. No other single therapy or combination of other therapies has been shown to provide equal asthma control or to equally prevent the sequelae of uncontrolled asthma, including exacerbations and hospitalizations. Provided there is flexibility to vary the ICS dose, a combination ICS plus LABA product represents an important treatment advance. Furthermore, there is a compelling need for asthma
Conclusion
This article has reviewed the scientific and clinical rationale for and the efficacy and safety of Advair, a new combination inhaler for the treatment of asthma composed of the ICS fluticasone propionate and the long-acting β2-agonist salmeterol. For patients whose symptoms are inadequately controlled on low-dose ICS therapy, combination therapy provides better asthma control than increasing the dose of ICS. Combination treatment also provides superior asthma control than adding a leukotriene
Acknowledgements
The author thanks Amy Schaberg for her assistance with preparation of this manuscript.
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Reprint requests: Harold S. Nelson, MD, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206.