Effect of Montelukast on Exhaled Nitric Oxide and Nonvolatile Markers of Inflammation in Mild Asthma

Sandrini, Alessandra; Ferreira, Ivone; Gutiérrez, C.; Jardim, José Roberto; Zamel, Noé; Chapman, Kenneth R.

doi:10.1378/chest.124.4.1334

Cited by 81 publications

(58 citation statements)

References 31 publications

(28 reference statements)

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“…Furthermore, a circadian rhythm of exhaled H 2 O 2 was shown in healthy subjects with highest levels at 12:00 and 24:00 h and also in patients with COPD [13]. Increase in EBC H 2 O 2 level was found in asthma [22,58,60,[71][72][73], healthy smokers [35,39], COPD [34,44,45,59,65,74,75], bronchiectasis [76,77], CF [78,79] and acute respiratory distress syndrome (ARDS) [5,80,81], acute hypoxaemic respiratory failure [14], reperfusion injury [82], allergic rhinitis [83], common cold [84], post-operative period after lung resection [85], systemic sclerosis [86] and in experimental models of hypoxia/reoxygenation [87,88].…”

Section: Diseases States That Influence H 2 Omentioning

confidence: 90%

Exhaled breath condensate: methodological recommendations and unresolved questions

Ho¹,

Hunt²,

Barnes³

2005

Eur Respir J

1,159

1,315

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Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases.The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required.Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them.Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

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Section: Diseases States That Influence H 2 Omentioning

confidence: 90%

Exhaled breath condensate: methodological recommendations and unresolved questions

Ho¹,

Hunt²,

Barnes³

2005

Eur Respir J

1,159

1,315

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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: 94%

“…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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“…ICS and other anti-inflammatory therapies for asthma, including leukotriene receptor antagonists (LTRA) and omalizumab (anti-IgE), have been shown to reduce eNO both in children and adults [127][128][129][130].…”

Section: Exhaled No As a Biomarkermentioning

confidence: 99%