A Randomized, Controlled Trial of Theophylline in Patients with Severe Chronic Obstructive Pulmonary Disease

Abstract

To assess the effects of theophylline in chronic obstructive pulmonary disease, we conducted a randomized, placebo-controlled, double-blind, crossover trial in 60 patients with severe but stable disease. The patients (mean age, 61 years) were studied before and after two months of placebo and two months of treatment with a sustained-release preparation of theophylline (10 mg per kilogram of body weight per day), administered orally. The two treatments were administered in a random order and separated by an eight-day washout period. After taking theophylline for two months (mean plasma concentration, 14.8 mg per liter), as compared with the two months of placebo, the patients had significant improvements in dyspnea, pulmonary gas exchange (partial pressure of arterial oxygen, 66 vs. 61 mm Hg [P less than 0.0001]; partial pressure of arterial carbon dioxide, 44 vs. 49 mm Hg [P less than 0.0001]), vital capacity (63 percent vs. 58 percent of the predicted value [P less than 0.0001]), and forced expiratory volume in one second (36 percent vs. 32 percent of the predicted value [P less than 0.0001]), with no significant change in airway resistance or functional residual capacity. Minute ventilation increased by a mean of 18 percent (P less than 0.0001) in the patients taking theophylline because of increased tidal volume, with no change in respiratory frequency. The respiratory-muscle performance of the patients taking theophylline improved by approximately 29 percent (P less than 0.0001), as indicated by a decline in the ratio of inspiratory pleural pressure during quiet breathing to maximal pleural pressure. We conclude that theophylline improves respiratory function and dyspnea in patients with severe chronic obstructive pulmonary disease and that these improvements are probably due to better respiratory-muscle performance.

The Effect of Acebrophylline vs Sustained Release Theophylline in Patients of COPD- A Comparative Study

“…Thirdly, shortness of breath (according to mMRC scale), was improved in 65% patients of group-1 and 45% patients of group-2. These findings are in agreement with the study by Giovanni Agliati [6], E. Pozzi [7], Danièle Murciano et al, [8], Donald A Mahler [9], and H.Weber [11]. There was no deterioration among patients of Acebrophylline group but breathlessness deteriorated in 35% patients on SR Theophylline.…”

Pulmonary Emphysema Induced by Cigarette Smoke Solution and Lipopolysaccharide in Guinea Pigs

“…It has been reported that longterm theophylline use for COPD patients results in improvement of pulmonary functions, indicating that theophylline has a beneficial effect on exacerbation of COPD. 25,26) Therefore, we examined the effect of theophylline on the functional structural changes in our model. …”

Combined Butalbital/Acetaminophen/Caffeine Overdose: Case Files of the Robert Wood Johnson Medical School Toxicology Service

“…The risk of side effects increases with higher theophylline concentrations, and the majority of seizures occur in patients with concentrations greater than 40 μg/mL [52][53][54]. Further reports suggest that peak serum theophylline concentrations were a predictor of toxicity [55][56][57]. Even so, no consensus guidelines existed for when to employ hemoperfusion, with threshold serum theophylline levels ranging from 330 (59.4) to 550 μmol/L (99 μg/mL) [10,58,59].…”

“…While caffeine is used for stimulant and mood-elevating effects in drinks such as coffee, it also has been used to treat neonatal apnea and headaches in combination with other analgesics. Theophylline has classically been used to treat bronchospastic airway diseases such as asthma and COPD, although it has generally fallen out of favor to pure β-adrenergic agonists due to their better safety profiles [2]. As a group, methylxanthines cause the release of catecholamines, which subsequently stimulate β 1 and β 2 receptors, accounting for their stimulant effects.…”