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This Article Full Text (PDF) Free All Versions of this Article: chest.07-0831v1 132/3/868    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Allayee, H. Articles by Lima, J. J. Search for Related Content PubMed PubMed Citation Articles by Allayee, H. Articles by Lima, J. J.

The Effect of Montelukast and Low-Dose Theophylline on Cardiovascular Disease Risk Factors in Asthmatics

¹Department of Preventive Medicine and ²Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9075 ³Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7073 ⁴Vermont Lung Center and Department of Medicine, College of Medicine, University of Vermont, Burlington, VT 05405-0075 ⁵Centers for Clinical Pediatric Pharmacology and Pharmacogenetics, Nemours Children's Clinic, Jacksonville, FL 32207 ⁶The American Lung Association Asthma Clinical Research Centers

hallayee{at}usc.edu

Abstract

Background -- Recent studies have implicated the 5-lipoxygenase/leukotriene (5-LO/LT) pathway in cardiovascular disease (CVD), which may have important implications for asthmatics since several drugs that target this pathway are currently used to treat asthma. We sought to determine whether montelukast, a cysteinyl LT antagonist, and low-dose theophylline, affected serum inflammatory and lipid CVD risk factors in a recently completed clinical trial of asthmatics.

Methods -- Patients were randomized to receive either montelukast (10mg/d), theophylline (300mg/d), or placebo. A baseline run-in period of 7-14 days was followed by treatment for 6 months. Serum levels of C-reactive protein (CRP), interleukin-6, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density cholesterol (HDL-C) were measured 1 and 6 months after treatment.

Results -- Patients with moderate to severe asthma on montelukast (n=60) had significantly lower serum CRP compared to placebo (n=73) after 1 month (1.7mg/L vs. 3.2mg/L, respectively; P < 0.006) and 6 months of treatment (2.3mg/L vs. 3.5mg/L, respectively; P < 0.04). At both time points, serum levels of all lipids were also significantly lower in the montelukast and theophylline groups compared to placebo but these effects were primarily observed in individuals who were also using inhaled corticosteroids as monotherapy for asthma.

Conclusions -- Asthmatics on montelukast and, to some extent, low-dose theophylline have lower levels of CVD-associated inflammatory biomarkers and lipid levels. These observations suggest these asthma medications may have some beneficial value in asthmatics with respect to CVD risk, although the effects on HDL-C levels should also be taken into consideration.

Key Words: 5-Lipoxygenase • cardiovascular disease • inflammation • leukotriene inhibitors • lipids