Recent advances in the management of asthma using leukotriene modifiers.
Asthma is a chronic inflammatory disease of the airways that affects approximately 100 million people worldwide. In order to reduce symptoms, improve pulmonary function, and decrease morbidity, current treatment guidelines emphasize the importance of controlling the underlying inflammation in patients with asthma. Leukotrienes are leukocyte-generated lipid mediators that promote airway inflammation. Recognition of the importance of leukotrienes in the pathogenesis of asthma has led to the development of leukotriene modifiers, the first new class of drugs for the treatment of asthma to become available in 25 years. Controlled clinical trials with the four currently used leukotriene modifiers (montelukast, zafirlukast, and zileuton in the US and pranlukast in Japan) have established their efficacy in improving pulmonary function, reducing symptoms, decreasing night-time awakenings, and decreasing the need for rescue medications. They exert anti-inflammatory effects that attenuate cellular infiltration and bronchial hyperresponsiveness and complement the anti-inflammatory properties of inhaled corticosteroids. In patients with moderate and severe asthma, they permit tapering of the corticosteroid dose. In patients with exercise-induced asthma, leukotriene modifiers limit the decline in and quicken the recovery of pulmonary functions without the tolerance issues seen with chronic long-acting beta(2)-adrenoceptor agonist use. In patients with aspirin (acetylsalicylic acid)-induced asthma, they improve pulmonary function and shift the dose response curve to the right, reducing the patient's response to aspirin. In patients with seasonal allergic rhinitis, with or without concomitant asthma, they improve nasal, eye, and throat symptoms as well as quality of life. Leukotriene modifiers are generally safe and well tolerated with adverse effect profiles similar to that of placebo. The one safety issue raised with leukotriene modifiers, Churg-Strauss Syndrome, appears to be the unmasking of an already present syndrome that is manifested when the leukotriene modifiers permit corticosteroid doses to be reduced. Although current treatment guidelines recommend their use in patients with mild persistent asthma, these guidelines were developed just as leukotriene modifiers were coming to the market, before much of the clinical efficacy data were published. Because asthma is a heterogeneous disease, the different asthma phenotypes respond differently to therapies; consequently asthma therapy needs to be individualized. Leukotriene modifiers increase the therapeutic options for patients with asthma and, based on recent data, it is expected that future guidelines will describe expanded uses for these agents in clinical circumstances where these drugs are effective.
Kemp
James P
JP
Department of Pediatrics, University of California School of Medicine, San Diego, California 92123, USA. JPK3355@aol.com
D000085:Acetates / Q000008:administration & dosage; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D002867:Chromones / Q000008:administration & dosage; D018849:Controlled Clinical Trials as Topic; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020024:Leukotriene Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D011804:Quinolines / Q000008:administration & dosage; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D002867:Chromones; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast; C047681:pranlukast; C063449:zileuton; D006918:Hydroxyurea