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Correspondence |

Evaluating the Effects of “Triple Therapy” With Inhaled Corticosteroids, Long-Acting β2-Agonists, and Leukotriene Modifiers in Asthma FREE TO VIEW

Graeme P. Currie, MD; Daniel K. C. Lee, MD; Daniel Menzies, MBChB; Brian J. Lipworth, MD
Author and Funding Information

Affiliations: Aberdeen Royal Infirmary, Aberdeen, Scotland,  Papworth Hospital, Cambridge, England,  Ninewells Hospital & Medical School, Dundee, Scotland

Correspondence to: Graeme P. Currie, MD, Department of Respiratory Medicine, Chest Clinic C, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, Scotland, UK; e-mail: graeme.currie@nhs.net



Chest. 2006;130(1):301-302. doi:10.1378/chest.130.1.301
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To the Editor:

Nathan et al1failed to show any additional benefit in lung function or symptoms when asthma patients (mean FEV1 81% predicted) with concomitant allergic rhinitis were treated with montelukast, 10 mg/d, for 4 weeks in conjunction with orally inhaled fluticasone, 100 μg bid, plus salmeterol. This finding is entirely in keeping with other data,2 in which the addition of montelukast, 10 mg/d, for 14 days conferred no significant improvement in terms of peak expiratory flow or symptom scores in patients with moderate-to-severe asthma maintained on inhaled corticosteroids and mostly receiving long-acting β2-agonists. Critically, in both studies,,12 no assessments of airway hyperresponsiveness or inflammatory biomarkers were made.3 Moreover, the relatively short duration of randomized treatment would have precluded any reduction in exacerbation frequency to be observed.

In another study4 in patients with persistent asthma (mean FEV1 80% predicted) receiving fluticasone, 250 μg bid, plus salmeterol, montelukast did in fact confer complementary effects on inflammatory biomarkers (exhaled nitric oxide and eosinophils) and airway hyperresponsiveness. In the same study,,4 and similar to the findings of Nathan et al,1 no additive effects were demonstrated in either peak expiratory flow or FEV1. This in turn illustrates that potentially beneficial effects of leukotriene modifiers on inflammatory biomarkers and airway hyperresponsiveness are dissociated from lung function in patients receiving long-acting β2-agonists, who are as a consequence likely to be maximally bronchodilated. When monitoring the effects of “triple therapy” with leukotriene modifiers in conjunction with inhaled corticosteroids and long-acting β2-agonists, it is imperative that a variety of end points are assessed before realistic conclusions can be made with certainty in both real life and within the realms of randomized controlled trials. Long-term clinical trials are required to investigate whether adding montelukast to inhaled corticosteroids and long-acting β2-agonists confers additive benefits—as might be predicted by its complimentary nonsteroidal antiinflammatory activity—in reducing exacerbations of asthma.

Dr. Currie has received funding from Merck and GlaxoSmithKline for attending postgraduate educational meetings and for giving talks. Dr. Lipworth has received funding from Merck Sharp & Dohme for attending conferences. Drs. Lee and Menzies have no conflicts of interest to disclose.

Nathan, RA, Yancey, SW, Waitkus-Edwards, K, et al (2005) Fluticasone propionate nasal spray is superior to montelukast for allergic rhinitis while neither affects overall asthma control.Chest128,1910-1920. [CrossRef] [PubMed]
 
Robinson, DS, Campbell, D, Barnes, PJ Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double-blind placebo-controlled trial.Lancet2001;357,2007-2011. [CrossRef] [PubMed]
 
Green, RH, Pavord, ID Leukotriene antagonists and symptom control in chronic persistent asthma.Lancet2001;357,1991-1992. [CrossRef] [PubMed]
 
Currie, GP, Lee, DK, Haggart, K, et al Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma..Am J Respir Crit Care Med2003;167,1232-1238. [CrossRef] [PubMed]
 

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References

Nathan, RA, Yancey, SW, Waitkus-Edwards, K, et al (2005) Fluticasone propionate nasal spray is superior to montelukast for allergic rhinitis while neither affects overall asthma control.Chest128,1910-1920. [CrossRef] [PubMed]
 
Robinson, DS, Campbell, D, Barnes, PJ Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double-blind placebo-controlled trial.Lancet2001;357,2007-2011. [CrossRef] [PubMed]
 
Green, RH, Pavord, ID Leukotriene antagonists and symptom control in chronic persistent asthma.Lancet2001;357,1991-1992. [CrossRef] [PubMed]
 
Currie, GP, Lee, DK, Haggart, K, et al Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma..Am J Respir Crit Care Med2003;167,1232-1238. [CrossRef] [PubMed]
 
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