All patients with persistent asthma require a controller medication. Inhaled corticosteroids (ICS) remain the single most effective therapy. Recently, researchers demonstrated that an intermittent, symptom-based short course of inhaled or oral corticosteroids produced similar increases in morning peak expiratory flow rates compared with daily controller medications (ICS or leukotriene modifiers).9 Daily ICS had a greater impact on inflammatory markers and symptoms but no difference in rate of asthma exacerbations.

For those unable or unwilling to use ICS, leukotriene modifiers/receptor agonists are reasonable.5-7 Long-acting β2-agonists should be added to ICS for those who remain symptomatic despite low-dose ICS therapy. Combination therapy is associated with fewer exacerbations than increasing doses of ICS. Adding a long-acting β2-agonist also decreases nocturnal asthma, improves lung function, and alleviates symptoms.    


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Leukotriene modifiers or sustained-released theophylline may be used instead of the long-acting β2-agonist. Theophylline has both bronchodilator and anti-inflammatory properties and therefore can be used as a controller medication. It has been shown to improve lung function and control nocturnal symptoms. Because of its side-effect profile and requirement for blood-level monitoring, theophylline is still considered an add-on medication.10 Leukotriene modifiers include cysteinyl leukotriene receptor antagonist agents (montelukast, zafirlukast) and a 5-lipoxygenase inhibitor (zileuton). They block airway smooth-muscle contraction and release of leukotrienes from mast cells and eosinophils. However, they are considered inferior to ICS as monotherapy and are less effective than long-acting β2-agonists as add-on therapy. Patients with aspirin- or nonsteroidal-induced asthma respond well to these agents.5-7   

In severe persistent asthma, the combination regimen uses high-dose ICS, and other oral agents are added for additional symptom control. Oral glucocorticosteroids are added only when all other agents have failed.5-7 
Other treatment modalities include second-generation antihistamines (H1-antagonists) for patients with allergic rhinitis; immunomodulators (methotrexate, cyclosporine), which can be given in refractory asthma but have a high side-effect profile; and IgE monoclonal antibody. Anti-IgE therapy may be considered as adjunctive therapy for adults with moderate-to-severe asthma who have clear evidence of allergies and elevated serum IgE levels. Use of monoclonal anti-IgE antibodies (omalizumab) is shown to reduce the dose of ICS and, when administered with ICS, result in 15% fewer exacerbations.11   

Future drug therapies are under investigation to prevent Th2 and eosinophil response. They include second-generation theophyllines to target phosphodiesterase subsites (PDE4), anti-Th2 (CD4+) receptors and anti-CD4+ monoclonal antibodies, anticytokine specific drugs and anti-interleukin antibodies, and drugs targeted against transcription regulatory factors. At this time, there still is no defined treatment once airway-wall remodeling has occurred. These new therapies hold promise for arresting the inflammatory response associated with asthma and improved control of symptoms.12

Conclusion

Current therapy for adult-onset asthma is based on severity stratification recommended by the NIH-NAEPP/GINA guidelines. ICS are the mainstay of treatment along with stepwise add-on therapy using long-acting bronchodilators. All patients should have a maintenance and acute exacerbation plan for improved management.

Dr. Hardin is assistant professor of internal medicine, Division of Pulmonary and Critical Care Medicine, University of California, Davis, School of Medicine, Sacramento, Calif., where Dr. Tharratt is professor of clinical medicine and anesthesiology, and Dr. Louie is professor of clinical internal medicine.

References

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  4. Bonekat HW, Hardin KA. Severe upper airway obstruction during sleep.  Clin Rev Allergy Immunol. 2003;25:191-210.
  5. National Asthma Education and Prevention Program. Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Md.: National Heart, Lung, and Blood Institute; 1997. NIH Publication no. 97-4051.
  6. National Asthma Education and Prevention Program. Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics 2002. Bethesda, Md.: National Heart, Lung, and Blood Institute; 2003. NIH Publication No. 02-5074.
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  10. Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med. 2003;167:813-818.
  11. Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108:184-190.
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