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Theophylline in COPD: Still a Viable Option?
Q:Does theophylline still play a role in the treatment of chronicobstructive pulmonary disease (COPD), or has it been supersededby newer agents?
Q:Does theophylline still play a role in the treatment of chronicobstructive pulmonary disease (COPD), or has it been supersededby 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 thathelps strengthen diaphragmatic function and increase mucociliary clearance.1-4Of perhaps greater importance is the clinically significant anti-inflammatoryaction of theophylline on the airways.5 This is achieved at plasma levels of 5 to10 μg/mL-that is, lower than levels targeted for bronchodilation. These plasmalevels can be achieved at low dosages of theophylline, such as a singledaily dose of 400 to 600 mg. At low dosages, side effects are uncommon, andthere 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 phosphodiesterase4 inhibitors, some of which are currently in human clinical trials,are more specific agents that target key inflammatory cells-includingmacrophages, neutrophils, and cytotoxic T lymphocytes-involved in COPD.6Whether these agents will be more effective than theophylline has yet to bedetermined, but it is hoped that they will control basic airway inflammatoryprocesses in both COPD and asthma.Combination therapy. A recent study found that theophylline enhancedthe effectiveness of salmeterol in the management of COPD.7 The combinationtherapy provided significantly greater improvement in pulmonary functionthan either agent alone and was associated with a greater decrease in respiratorysymptoms (including dyspnea), albuterol use, and COPD exacerbations.Even small improvements in lung function with combination bronchodilatortherapy may result in meaningful improvements in disease control, quality oflife, and exacerbations. This appears to be true even in some patients whosesymptoms are not reversed by albuterol.5
References:
REFERENCES:
1.
McKay SE, Howie CA, Thomson AH, et al. Value of theophylline treatment in patients handicapped bychronic obstructive lung disease.
Thorax.
1993;48:227-232.
2.
Mahler DA, Matthay RA, Snyder PE, et al. Sustained-release theophylline reduces dyspnea in nonreversibleobstructive 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 ClinImmunol.
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 thetreatment of COPD.
Chest.
2001;119:1661-1670.
