Montelukast inhibits interleukin-5 mRNA expression and cysteinyl leukotriene production in ragweed and mite-stimulated peripheral blood mononuclear cells from patients with asthma.

Important in the pathogenesis of asthma is the secretion of interleukin (IL)-5 by allergen-specific TH2 cells, which augments eosinophil functions, as well as subsequent synthesis of cysteinyl leukotrienes (CysLTs). Montelukast is an inhibitor of CysLT and also has been shown to decrease eosinophil counts in peripheral blood and sputum of patients with asthma. This study was performed to investigate the in vitro effects of montelukast, a leukotriene receptor antagonist, on CysLTs and IL-5 production and expression by peripheral blood mononuclear cells (PBMCs) stimulated with ragweed (RW) and mite (M) allergens. In this study 18 patients with allergic asthma (nine women and nine men, aged 27-67 years) were evaluated. PBMCs from these patients were cultured for 24 hours in the presence of phytohemagglutinin (15 micrograms/mL), RW antigen E (0.39 U/mL), or M (16.8 micrograms/mL) allergens with (1, 10, 50 microM) and without montelukast. Enzyme-linked immunosorbent assay was used to measure the concentration of CysLTs, regulated upon activation, normal T-cell expressed and secreted (RANTES), and IL-5 in the culture supernatants and total RNA was extracted from the cultured PBMCs. Reverse transcription-polymerase chain reaction was performed on the RNA samples using beta-actin polymerase chain reaction primers for a control and IL-5 specific primers for detecting IL-5 mRNA expression in the cells. Elevated CysLT levels were noted in 8 of 18 patients with RW (range, 8-580 pg/mL) and in 13 of 18 patients with M (range, 7-1613 pg/mL). Inhibition of CysLTs by 10 microM of montelukast was noted in 5 patients with RW and in 10 patients with M. Levels of RANTES in some patients were increased by both allergens without consistent inhibitory effects of montelukast. IL-5 secretion measured by Enzyme-linked immunosorbent assay was detected in only 1 of 11 patients. However, in seven of nine patients tested, IL-5 mRNA was induced by both RW and M, and montelukast at 10 microM completely blocked IL-5 mRNA expression. Therefore, montelukast may be anti-inflammatory by inhibiting IL-5 mRNA expression and reducing CysLT secretion by PBMCs from asthmatic patients.

A preliminary retrospective treatment and pharmacoeconomic analysis of asthma care provided by allergists, immunologists, and primary care physicians in a teaching hospital.

Allergy immunology specialists (AIs) differ from primary care physicians (PCP) in their treatment of asthma. A limited retrospective chart review of several visits over a 1-year period in 1997 evaluating the quality of asthma care by AIs vs. PCPs was conducted in an academic center. Data concerning quality, effectiveness and cost of asthma care was randomly collected from 15 AIs and 15 PCPs from charts at 3-month intervals over a 1-year period. Information obtained from data collection forms revealed that asthma patients evaluated by AIs had more visits and received a greater quantity of medication compared to those treated by PCPs. All 15 patients with persistent asthma followed by AIs were treated with inhaled corticosteroids at each visit in contrast to only 80% of those treated by PCPs. The total numbers of controller medications (i.e., inhaled corticosteroids, salmeterol, cromolyn, and theophylline) that were utilized, as recommended, by the National Asthma Expert Panel (NAEP) of the National Heart, Lung, and Blood Institute (NHLBI) guidelines were 70 by AIs vs. 24 by PCPs over three visits. Cromolyn was prescribed five times over three visits by AIs and not at all by PCPs. Recognition and treatment of coexisting allergic rhinitis was evident in only 13% of patients treated by PCPs as compared to 80% in those treated by AIS. (p < 0.0001). However, all patients treated by AIs were skin tested to explore the presence of allergic triggers, while no patients treated by PCPs were evaluated for IgE-mediated reactions. Treatment cost for allergic rhinitis was therefore higher, at $2039, for AIs as compared to $741 for PCPs. There were no peakflow values in charts obtained from PCPs. However, all charts from AIs had peakflow values, which improved during the course of therapy in 33% of patients. Total medication costs for asthma were higher for AIs @ $5,646.30 vs. $1,932.25 for PCPs. Total medication costs for allergic rhinitis plus asthma were higher for AIs @ $7615 vs. $2681 for PCPs. However, patients treated by AIs had more severe asthma and required more frequent visits. Ipratropium bromide was prescribed a total of four times over several visits by PCPs vs. only once by AIs. In comparing asthma care between AI specialists and PCPs, it was found that AI specialists treat more severe asthmatics, provide more frequent follow-up visits, utilize peak flow rates, prescribe more controller medications, and more often recognize and treat comorbid conditions such as allergic rhinitis that impact on asthma care. Thus, although treatment costs for AIs are higher, these costs are justified by a quality of care that is more consistent with national (NHLBI) guidelines.