title: The additive effect of theophylline on a combination of formoterol and tiotropium in stable COPD: a pilot study.
abstract: We explored the additive effect of titrated oral theophylline in patients with stable chronic obstructive pulmonary disease (COPD) who received both tiotropium, 18mug od, and formoterol, 12mug bid. Thirty-six patients with moderate-to-severe COPD were enrolled in this two-period trial. They were initially treated with formoterol+tiotropium for 4 weeks. After this first period, they were divided in two groups of 18 patients. Both groups continued with the initial treatment for further 4 weeks, but the first group received also placebo whereas the second group received oral theophylline. The combination therapy with formoterol+tiotropium induced a significant improvement in mean predose FEV(1) and FVC at the end of the first period, and a significant reduction in dyspnea score as measure by a visual analogic scale and in use of rescue salbutamol. The second period of treatment elicited a significant further improvement in lung function and reduction in dyspnea score and salbutamol use in both groups. On the contrary, differences in improvements in FEV(1) and FVC and reduction in dyspnea score and salbutamol use between theophylline and placebo arms at the end of the second treatment period were not significant, although 5 patients reported an important relief in dyspnea during the theophylline administration period. These findings question the importance of adding theophylline in stable COPD patients already treated with two long-acting bronchodilators, but also indicate the possibility that some of them can benefit from theophylline because of a symptomatic improvement.
authors.affiliation: Department of Respiratory Medicine, Unit of Pneumology and Allergology, A. Cardarelli Hospital, Naples, Italy. mcazzola@qubissoft.it
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Maria
authors.initials: M
authors.lastname: Gabriella Matera
mesh_terms: D000368:Aged; D000420:Albuterol / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004417:Dyspnea / Q000188:drug therapy / Q000209:etiology; D004983:Ethanolamines / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012602:Scopolamine Derivatives / Q000627:therapeutic use; D016037:Single-Blind Method; D013806:Theophylline / Q000627:therapeutic use*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D012602:Scopolamine Derivatives; D013806:Theophylline; D000420:Albuterol; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide