Chest
Volume 132, Issue 3, September 2007, Pages 868-874
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ORIGINAL RESEARCH
ASTHMA
The Effect of Montelukast and Low-Dose Theophylline on Cardiovascular Disease Risk Factors in Asthmatics

https://doi.org/10.1378/chest.07-0831Get rights and content

Background

Recent studies have implicated the 5-lipoxygenase/leukotriene (LT) pathway in cardiovascular disease (CVD), which may have important implications for asthmatics because 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 in asthmatic patients.

Methods

Patients were randomized to receive either montelukast (10 mg/d), theophylline (300 mg/d), or placebo. A baseline run-in period of 7 to 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 month and 6 months after treatment.

Results

Patients with moderate-to-severe asthma receiving montelukast (n = 60) had significantly lower serum CRP compared to placebo (n = 73) after 1 month (1.7 mg/L vs 3.2 mg/L, respectively; p < 0.006) and 6 months of treatment (2.3 mg/L vs 3.5 mg/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 receiving inhaled corticosteroids as monotherapy for asthma.

Conclusions

Asthmatic patients receiving 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.

Section snippets

Study Subjects

The Effectiveness of Low Dose Theophylline as Add-On Therapy in the Treatment of Asthma (LODO) clinical trial was a recently completed, randomized, double-masked, placebo-controlled, parallel-designed trial of the effectiveness of montelukast and low-dose theophylline in the treatment of patients with poor asthma control.11 Briefly, 489 patients were recruited from 19 centers in the American Lung Association Asthma Clinical Research Centers. Participants were between the ages of 15 and 79

Results

Baseline characteristics of the 489 participants in the LODO clinical trial are shown in Table 1. The three treatment groups were well matched with respect to age, gender, ethnicity, obesity, and parameters related to asthma. In addition, there were no significant differences in the percentage of patients receiving various asthma medications among the three treatment groups (Table 1).

Overall, we observed a nonsignificant trend toward lower CRP and IL-6 levels in the montelukast and theophylline

Discussion

In the present study, we have provided evidence that asthma patients receiving the 5-LO pathway modifier montelukast or low-dose theophylline have lower blood risk factors associated with CVD compared to patients receiving placebo. Although these observations are from retrospective analyses of an already completed trial, they suggest that montelukast and low-dose theophylline could potentially reduce inflammatory CVD risk in asthmatics currently receiving these medications. This may be

ACKNOWLEDGMENT

We thank the patients for participating in the LODO clinical trial.

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    This work was supported by the American Lung Association Clinical Research Centers, the Nemours Research Foundation, and National Institutes of Health grants HL079353 (Dr. Allayee) and HL071394 (Dr. Lima). A portion of this work was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 (RR10600–01, CA62528–01, RR14514–01) from the National Center for Research Resources.

    The authors have no conflicts of interest to disclose.

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