Recent innovations in asthma therapy.
Guidelines for the diagnosis and management of asthma have been published since 1990 and already new versions are being published. The recommendations for the treatment of asthma were organized around four components of effective asthma management: i) use of objective measures of lung function to assess the severity of asthma and to monitor the course of therapy, ii) environmental control measures to avoid or eliminate factors that precipitate asthma symptoms or exacerbations, iii) comprehensive pharmacologic therapy for long-term management designed to reverse and prevent the airway inflammation characteristic of asthma as well as pharmacologic therapy to manage asthma exacerbations, and iv) patient education that fosters a partnership among the patient, family and clinicians. Newly released medications include anti-leukotriene (LTs) agents which function either by blocking the interaction of LTs with receptors (receptor antagonists) or by inhibiting leukotriene synthesis (synthesis inhibitors). Representatives of the antagonists discussed here are zafirlukast, pranlukast and montelukast. Zafirlukast (20 mg twice daily) improves pulmonary function indices and days without symptoms and decreases the asthma exacerbation frequency. Pranlukast, the first leukotriene receptor antagonist to be marketed, improves lung function and symptoms when 450 mg twice daily is used. A study with montelukast demonstrated similar positive results irrespective of the use of concomitant inhaled corticosteroid. This indicates that leukotriene receptor antagonists may have additive effects to steroid therapy. They may also be a potential alternative to inhaled steroids, although more studies need to be performed before defining the role of receptor antagonists in the treatment of asthma. Zileuton, a leukotriene synthesis inhibitor, has been shown to improve lung function, reduce symptoms and reduce use of beta-agonists and asthma exacerbations. These positive effects are dose-dependent and liver function abnormalities seem to be a relevant issue during zileuton use in some patients. Other compounds that inhibit LTs synthesis are in development and, like zileuton, need more tests. Phosphodiesterases (PDE), enzymes that break down cAMP and cGMP, have been a target for new compounds developed to treat asthma. Inhibition of PDE enzymes increases intracellular cAMP or cGMP which then produces bronchodilation. Recent studies have also shown antiinflammatory effects by suppressing some PDE isoenzymes, including PDE III and PDE IV. These effects were detected by studies in vitro and in animal models. Clinical trials are necessary to determine which PDE inhibitors can be useful for the treatment of asthma.
Vianna
E O
EO
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Martin
R J
RJ