Oral Low-Dose Theophylline on Top of Inhaled Fluticasone-Salmeterol Does Not Reduce Exacerbations in Patients with Severe COPD: A Pilot Clinical Trial.
Chest. 2016 Apr 20;
Authors: Cosío BG, Shafiek H, Iglesias A, Yanez A, Cordova R, Palou A, Rodriguez-Roisin R, Peces-Barba G, Pascual S, Gea J, Sibila O, Barnes PJ, Agusti A
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation. In vitro and ex-vivo observations suggest that this inflammatory response is partially resistant to the effect of corticosteroids, and that low-dose theophylline can restore this response via enhancement of histone deacetylase activity (HDAC). Whether or not this occurs in vivo, and what are its potential clinical consequences is unclear.
OBJECTIVE: To determine if low-dose theophylline on top of inhaled long-acting beta-agonists /corticosteroids (ICS) treatment in COPD patients: (1) enhances HDAC activity and the anti-inflammatory effects of ICS in vivo; (2) reduces the concentration of inflammatory markers; and, (3) reduces exacerbation frequency.
METHODS: In this prospective, double-blind, placebo-controlled clinical trial, we randomized COPD patients (FEV1<50% predicted plus at least one hospitalization due to exacerbation in the previous year) to ICS plus theophylline 100 mg bid or matched placebo. We determined at baseline and at the end of 52 weeks follow-up: (1) HDAC activity in blood monocytes and sputum macrophages; (2) the concentration of several inflammatory markers (interleukin (IL)-8, IL-6, IL-1β and tumour necrosis factor alpha (TNFα)) in serum and sputum supernatant; and, (3) the rate of exacerbations and side effects.
RESULTS: 70 patients were randomized, 36 in the theophylline and 34 in the placebo arm. HDAC activity and levels of the inflammatory markers were not different in both arms either at baseline or after 52 weeks. Likewise, the rate of exacerbations during follow-up was similar in both groups.
CONCLUSIONS: The combination of low dose oral theophylline and ICS does not enhance the anti-inflammatory properties of ICS in vivo nor influence exacerbation rate.
PMID: 27107490 [PubMed - as supplied by publisher]