NEW YORK (Reuters Health) - Researchers report that treatment with oral cilomilast (Ariflo; GlaxoSmithKline), an investigational phosphodiesterase-4 inhibitor, significantly reduces the number of several key inflammatory cells in bronchial mucosa from patients with chronic obstructive pulmonary disease (COPD).
“This is the first demonstration of reduction by any agent of airway tissue inflammatory cells characteristic of COPD,” Dr. Peter Jeffery from Royal Brompton Hospital in London and colleagues note in their report in the October 15th American Journal of Respiratory and Critical Care Medicine.
An editorial in the journal calls the finding “great news on the anti-inflammatory front for a disease in desperate need of a novel treatment.”
GlaxoSmithKline received an approvable letter from the U.S. Food and Drug Administration for cilomilast for COPD in late October (See Reuters Health report Oct 28, 2003). The drug has been shown to improve lung function in COPD patients.
Researchers designed the current study to specifically look at the effects of cilomilast on inflammation in mild to moderate COPD. They randomized 59 such patients to cilomilast 15 mg twice daily or placebo for 12 weeks and obtained induced sputum and bronchial biopsies on two occasions.
Compared with placebo, analysis of variance of the change from baseline demonstrated significant reductions in counts of bronchial biopsy CD8+ T lymphocytes and CD68+ macrophages (p = 0.001 and p < 0.05, respectively).
Post hoc Poisson regression analysis confirmed significant reductions in the active treatment group compared with the placebo group in bronchial biopsy CD8+ and CD68+ cell counts (48% and 55%, respectively). Post hoc data also revealed reductions in subepithelial CD4+ cells (42%) and neutrophils (37%).
Cilomilast did not alter any sputum endpoint or FEV1 compared with placebo, although the trial was not statistically powered to show differences in clinical endpoints such as FEV1.
Dr. Jeffery and colleagues say there is “growing support” for the hypothesis that CD8+ T lymphocytes and CD68+ monocytes/macrophages are “the key effector cells responsible for the airway and lung damage of COPD and this distinct pattern of inflammation requires alternative anti-inflammatory treatment to that used in asthma.”
“Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in anti-inflammatory treatment of [COPD],” they conclude.
“We do not yet know whether the effects over a longer period of time may translate into attenuation of the accelerated rate of decline of lung function that characterizes patients with COPD and leads to disability and an early death,” Dr. Jeffery told Reuters Health.
Source: Am J Respir Crit Care Med 2003;168:914-915,976-982. [ Google search on this article ]
MeSH Headings:Enzyme Inhibitors: Enzymes, Coenzymes, and Enzyme Inhibitors: Phosphodiesterase Inhibitors: CD8-Positive T-Lymphocytes: Chemical Actions and Uses: Chemical Actions: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
