Theophylline and cardiac stress in patients with dyspnea: an observational study

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.

The effect of theophylline on NT-proBNP was prospectively evaluated by multiple regression analysis in 753 outpatients referred for pulmonary evaluation of dyspnea.

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.

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.