Effect of theophylline on erythrocytosis in chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) tend to develop secondary erythrocytosis to compensate for their chronic hypoxia. Theophylline has recently been shown to reduce hematocrit and erythropoietin blood levels in normal subjects and in patients with erythrocytosis after renal transplantation.

To determine whether theophylline may be used to lower the hematocrit in patients with COPD.

Two hundred four patients with COPD were studied retrospectively and 10 patients prospectively (8 starting treatment with the drug [group 1] and 2 who suspended its long-term use [group 2]) for the correlation between theophylline therapy and hematocrit and erythropoietin level.

In the patients studied retrospectively, lower hematocrits were found in the theophylline-treated than in the untreated patients (0.43 +/- 0.006 vs 0.46 +/- 0.007, respectively; P < .002). Twelve untreated patients and 2 of those treated with theophylline had hematocrits above 52%. Oxygen saturation levels were similar in both groups, and exclusion of patients with oxygen saturation lower than 88% did not change the pattern, suggesting that the effect of theophylline could not be entirely explained by improved oxygen availability. Seven of the 8 patients studied prospectively in group 1 (P < .02) and the 2 patients in group 2 showed inverse correlations between hematocrits and theophylline administration. A similar pattern was observed with serum erythropoietin levels in 5 of 7 patients studied. The effects were reproducible on rechallenge in 3 of the 4 patients in group 1 and the 2 patients in group 2.

Theophylline may have a beneficial effect in treatment and prevention of erythrocytosis in patients with COPD.