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What Role for an Old Drug?

What Role for an Old Drug?

Q:Does theophylline still play a role in the treatment of chronic obstructive pulmonary disease (COPD), or has it been superseded by newer agents?

A:Theophylline remains useful in the maintenance management of COPD. It is most commonly prescribed as an adjunct to an inhaled β-agonist, an anticholinergic, or a combination of these agents.

Anti-inflammatory effects. Theophylline is a weak bronchodilator that helps strengthen diaphragmatic function and increase mucociliary clearance.1-4Of perhaps greater importance is the clinically significant anti-inflammatory action of theophylline on the airways.5This is achieved at plasma levels of 5 to 10 μg/mL—that is, lower than levels targeted for bronchodilation. These plasma levels can be achieved at low dosages of theophylline, such as a single daily dose of 400 to 600 mg. At low dosages, side effects are uncommon, and there is no need to monitor blood levels unless the patient has symptoms (such as nausea or anorexia). Theophylline is a broad-spectrum phosphodiesterase inhibitor. The phosphodiesterase 4 inhibitors, some of which are currently in human clinical trials, are more specific agents that target key inflammatory cells—including macrophages, neutrophils, and cytotoxic T lymphocytes—involved in COPD.6Whether these agents will be more effective than theophylline has yet to be determined, but it is hoped that they will control basic airway inflammatory processes in both COPD and asthma.

Combination therapy. A recent study found that theophylline enhanced the effectiveness of salmeterol in the management of COPD.7The combination therapy provided significantly greater improvement in pulmonary function than either agent alone and was associated with a greater decrease in respiratory symptoms (including dyspnea), albuterol use, and COPD exacerbations. Even small improvements in lung function with combination bronchodilator therapy may result in meaningful improvements in disease control, quality of life, and exacerbations. This appears to be true even in some patients whose symptoms are not reversed by albuterol.5

References

REFERENCES:
1. McKay SE, Howie CA, Thomson AH, et al. Value of theophylline treatment in patients handicapped by chronic obstructive lung disease. Thorax. 1993;48:227-232.
2. Mahler DA, Matthay RA, Snyder PE, et al. Sustained-release theophylline reduces dyspnea in nonreversible obstructive airway disease. Am Rev Respir Dis. 1985;131:22-25.
3. Aubier M. Effect of theophylline on diaphragmatic and other skeletal muscle function. J Allergy Clin Immunol. 1986;78:787-792.
4. Ziment I. Theophylline and mucociliary clearance. Chest. 1987;92(suppl 1):38S-43S.
5. Lipworth BJ. Optimizing bronchodilator therapy for COPD. Chest. 2001;119:1628-1630.
6. Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med. 2000;343:269-280.
7. ZuWallack RL, Mahler DA, Reilly D, et al. Salmeterol plus theophylline combination therapy in the treatment of COPD. Chest. 2001;119:1661-1670.
 
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