Salmeterol versus slow-release theophylline in patients with reversible obstructive pulmonary disease

Abstract

A 1-yr multicentre two-tailed randomized open study was conducted in 15 centres in Italy, with the aim of comparing the clinical efficacy (over 3 months) and tolerability (over 1 yr) of salmeterol with those of oral theophylline in patients with reversible chronic obstructive pulmonary disease (COPD). Patients with reversible COPD (forced expiratory volume in one second (FEV1) 50-80%, FEV1 after bronchodilator > 12%, n = 138) were randomized to receive salmeterol powder (50 micrograms b.i.d. with Diskhaler, n = 66) or individually dose-titrated slow-release oral theophylline capsules so as to obtain a serum concentration of theophylline ranging 10-20 micrograms.mL-1 (n = 72). During the 2-week run-in period, nonadmitted medications were discontinued and patients had to present with respiratory symptoms on at least four of the last seven days. Following randomization, patients were required to monitor daytime and night-time symptoms, additional use of as-required salbutamol, and morning and evening peak expiratory flow (PEF) for 3 months. Spirometric measurements and assessment of the quality of life were performed every 3 months for 1 yr. Salmeterol was proven to be statistically more effective than theophylline in: 1) increasing the maximum value of morning PEF; 2) increasing the percentages of days and nights without symptoms; 3) reducing the need for additional salbutamol during daytime and night-time; and 4) increasing quality of life in terms of physical and social activities, mental health and psychophysical energy, assessed 3 months after the beginning of treatment. Salmeterol was no more effective than theophylline in increasing: 1) forced vital capacity and FEV1 at the various measurements; 2) maximum evening PEF value; and 3) quality of life after the first 3 months of treatment. Neither treatment induced significant side-effects over the 1-yr treatment. This study confirms that inhaled salmeterol is more effective than oral theophylline in long term treatment of reversible obstructive pulmonary disease.