The Effect of Montelukast on Exhaled Nitric Oxide and Lung Function in Asthmatic Children 2 to 5 Years Old

Straub, Daniel; Minocchieri, Stefan; Moeller, Alexander; Hamacher, Jürg; Wildhaber, Johannes H.

doi:10.1378/chest.127.2.509

Cited by 65 publications

(44 citation statements)

References 35 publications

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“…Exhaled nitric oxide and other assessments of airways inflammation Elevated exhaled nitric oxide fractions (FeNO) have been found in wheezing infants, especially when they are atopic [70,71], and these normalise during treatment with ICSs [72] and montelukast [73,74]. FeNO in infants are affected by environmental exposures and genetic predisposition to atopy [75].…”

Section: Lung Function Testsmentioning

confidence: 99%

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

Brand¹,

Baraldi²,

Bisgaard³

et al. 2008

European Respiratory Journal

746

759

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There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis.Based on the limited evidence available, inhaled short-acting b 2 -agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop.Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit.Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

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Section: Lung Function Testsmentioning

confidence: 99%

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

Brand¹,

Baraldi²,

Bisgaard³

et al. 2008

European Respiratory Journal

746

759

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“…72 The interrupter technique has also been used to evaluate the response to cold air inhalation, inhaled fluticasone, 73 and oral montelukast therapy. 74 One issue with the interrupter technique is determining the best cutoff for bronchoconstrictor response. In adults, Sundblad and colleagues have shown that a 20% change in FEV 1 following methacholine corresponds to different levels of change of G aw (reciprocal of R int ) determined by the interrupter technique, depending on the underlying degree of bronchial responsiveness, in this case, to a 39% change in G aw in all subjects, but a 66% change in less responsive subjects and a 27% change in more responsive subjects.…”

Section: Measurement Of Airway Resistance By the Interrupter Techniquementioning

confidence: 99%

What Does Airway Resistance Tell Us About Lung Function?

2012

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SummarySpirometry is considered the primary method to detect the air flow limitation associated with obstructive lung disease. However, air flow limitation is the end-result of many factors that contribute to obstructive lung disease. One of these factors is increased airway resistance. Airway resistance is traditionally measured by relating air flow and driving pressure using body plethysmography, thus deriving airway resistance (R aw ), specific airway resistance (sR aw ), and specific airway conductance (sG aw ). Other methods to measure airway resistance include the forced oscillation technique (FOT), which allows calculation of respiratory system resistance (R RS ) and reactance (X RS ), and the interrupter technique, which allows calculation of interrupter resistance (R int ). An advantage of these other methods is that they may be easier to perform than spirometry, making them particularly suited to patients who cannot perform spirometry, such as young children, patients with neuromuscular disorders, or patients on mechanical ventilation. Since spirometry also requires a deep inhalation, which can alter airway resistance, these alternative methods may provide more sensitive measures of airway resistance. Furthermore, the FOT provides unique information about lung mechanics that is not available from analysis using spirometry, body plethysmography, or the interrupter technique. However, it is unclear whether any of these measures of airway resistance contribute clinically important information to the traditional measures derived from spirometry (FEV 1 , FVC, and FEV 1 /FVC). The purpose of this paper is to review the physiology and methodology of these measures of airway resistance, and then focus on their clinical utility in relation to each other and to spirometry.

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“…Taken together these assays clearly gave no evidence of any direct inhibitory effect of montelukast on NOS isoenzymes within the concentration range from 10 -7 to 10 -4 M, far exceeding that achieved during drug therapy (39). Therefore, alternative explanantions for the decreased NO levels measured in expired air from asthmatic subjects after treatment with montelukast should be considered (18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 95%

“…Since no acute inhibitory effect on NO synthesis, neither directly on the three NOS isoenzymes, nor a suppression of the expression of iNOS was found, alternative explanantions for the decreased NO levels measured in expired air from asthmatic subjects after treatment with montelukast must be considered (18)(19)(20)(21)(22)(23)(24)(25)(26)(27). They may be explained by changes in quantities or sites of NO generation, binding or more distal processes.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies in asthmatic subjects treated with montelukast have shown that such LTD 4 receptor blockade is associated with lower levels of exhaled NO (18)(19)(20)(21)(22)(23)(24)(25)(26)(27). In a murine allergic asthma model in which inflammation was induced by injection of ovalbumin, no evidence for a change in inducible NOS (iNOS) mRNA levels following montelukast treatment was observed (28).…”

Section: Introductionmentioning

confidence: 99%

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Montelukast exerts no acute direct effect on NO synthases

Hamacher¹,

Eichert²,

Braun³

et al. 2007

Pulmonary Pharmacology & Therapeutics

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The cysteinyl leukotrienes (CysLTs) LTC 4 , LTD 4 and LTE 4 are potent proinflammatory lipid mediators that play a central role in inflammation, contraction and remodelling of airways observed in asthmatics. Montelukast, a competitive inhibitor of the cysteinyl leukotriene-1 (CysLT 1 ) receptor attenuates asthmatic airway inflammation, contraction and remodelling. As a number of studies have shown that montelukast reduced exhaled nitric oxide (NO) levels, a marker of inflammation that correlates with the severity of asthma, we investigated whether or not a direct inhibition of NO synthase (NOS) by montelukast takes place.In an ex-vivo rat lung perfusion and ventilation model the NOS-dependent vasodilation effect after lipopolysaccharide (LPS) infusion was assessed with and without montelukast. Functional organ bath studies using isolated aortic rings from the same species aimed to assess effects of montelukast on the inducible and endothelial NOS isoenzymes (i-and eNOS) as well as on iNOS expression.Neuronal NOS (nNOS) was assessed by field stimulated rabbit corpus cavernosum, and isolated human iNOS enzyme activity was assessed for potential inhibition.Montelukast failed to cause vasoconstriction in LPS challenged rat lung, or to inhibit i-and eNOS activity as well as iNOS expression in aortic rings from the same species. Also the assays for nNOS in rabbit corpus cavernosum and on isolated human iNOS enzyme gave no evidence for a direct inhibition by montelukast in physiological and supraphysiological concentrations up to 10 -4 M.We therefore conclude that montelukast has no acute NOS inhibitor action. Its effect on exhaled NO is therefore probably indirectly mediated by a modulation of the asthmatic airway inflammation.

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The Effect of Montelukast on Exhaled Nitric Oxide and Lung Function in Asthmatic Children 2 to 5 Years Old

Cited by 65 publications

References 35 publications

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

What Does Airway Resistance Tell Us About Lung Function?

Montelukast exerts no acute direct effect on NO synthases

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