Theophylline and Cardiac Stress in Patients with Dyspnea: An Observational Study

Abstract

Background/Aims: Appreciation of the anti-inflammatory actions of theophylline at low serum concentrations has revived the interest in this drug, but its cardiac side effects remain a concern. The serum level of N-terminal probrain natriuretic peptide (NT-proBNP) is a marker for cardiac stress. This study examined the association between theophylline intake and NT-proBNP. Methods: The effect of theophylline on NT-proBNP was prospectively evaluated by multiple regression analysis in 753 outpatients referred for pulmonary evaluation of dyspnea. Results: Of 548 patients with asthma, chronic obstructive pulmonary disease or respiratory muscle weakness, 107 were taking theophylline (median serum concentration 8.1 µg/ml). The theophylline users were older (mean 64.5 ± 11.6 vs. 56.5 ± 16.8 years, p < 0.01), had severer airway obstruction (p < 0.01) and had a higher prevalence of heart disease (33.6 vs. 23.1%, p = 0.02) than the patients not taking theophylline. Among the patients with heart disease (n = 138), the adjusted levels of NT-proBNP were lower (p < 0.01) in the theophylline-treated patients (n = 36) than in the patients not using theophylline (median 144.5 vs. 236.4 pg/ml). Theophylline had no effect on NT-proBNP in patients without heart disease. Conclusion: The results of this observational study call into question the traditional view that even low-dose theophylline therapy may be detrimental in patients with coexisting heart disease.