Role of methylxanthines in the treatment of COPD
- Carlos A Vaz Fragoso, MD
Carlos A Vaz Fragoso, MD
- Associate Professor in Medicine (Geriatrics)
- Yale University School of Medicine
The value of methylxanthines (such as theophylline) in the management of patients with chronic obstructive pulmonary disease (COPD) is controversial. Current studies, in our view, continue to support a beneficial role in selected patients [1,2]. However, methylxanthines have a narrow therapeutic index; as a result, toxicity can be a significant problem with chronic use, and careful monitoring is essential.
The role of methylxanthines in the management of patients with COPD will be reviewed here. The role of theophylline in the treatment of asthma and the management of acute exacerbations of COPD and of stable COPD are discussed separately. (See "Theophylline use in asthma" and "Management of exacerbations of chronic obstructive pulmonary disease" and "Management of stable chronic obstructive pulmonary disease".)
EFFECTS ON FUNCTIONAL IMPAIRMENT
The majority of patients with chronic obstructive pulmonary disease (COPD) seek assistance because of functional impairment. Four independent determinants of functional impairment have been identified: dyspnea ratings, exercise capacity, respiratory mechanics, and respiratory muscle strength . Dyspnea ratings appear to influence general health status to a greater extent than do physiologic data , while performance in a standardized walking test correlates best with dyspnea ratings and the quality of life [3,5]. It is within this context that the clinical indications for theophylline in COPD can be evaluated. (See "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness".)
Dyspnea — One review of the efficacy of theophylline in COPD found that 6 of 10 studies cited showed an improvement in dyspnea . Furthermore, those studies that utilized the more sensitive dyspnea ratings demonstrated the greatest benefit. Five additional studies, employing either theophylline alone or combination therapy (theophylline plus aerosolized beta 2-agonists and anticholinergics) in patients with stable COPD, have subsequently been performed [7-11]. Two of these trials showed a beneficial effect of theophylline. One report, for example, randomized 38 patients with severe COPD who were treated with theophylline to either continued therapy or replacement of theophylline by placebo . The percentage of patients experiencing clinical deterioration was much lower in the group maintained on theophylline (15 versus 72 percent).
The three other studies found no beneficial effect of theophylline in the population as a whole, but noted improvement in some patients [9-11]. One report employing combination therapy concluded that, despite an overall lack of benefit, approximately one-third of patients were subjective responders in whom both dyspnea and forced expiratory volume in one second (FEV1) improved . In contrast, the subjective nonresponders failed to achieve a postbronchodilator increase in FEV1.
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