Effects of Montelukast Treatment and Withdrawal on Fractional Exhaled Nitric Oxide and Lung Function in Children With Asthma

Montuschi, Paolo; Mondino, Chiara; Koch, Pierluigi; Ciabattoni, Giovanni; Barnes, Peter J.; Baviera, Giuseppe

doi:10.1378/chest.07-1587

Cited by 67 publications

(52 citation statements)

References 18 publications

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“…Ample evidence supports the effectiveness of LTRAs against classic asthma [15,16,36], and their value against CVA has also been reported [18,19,20,37]. A placebo-controlled crossover study found that 2 weeks of treatment with zafirlukast significantly improved cough scores and capsaicin cough receptor sensitivity in 8 patients with CVA, while FEV 1 values remained unchanged [18].…”

Section: Discussionmentioning

confidence: 99%

“…Cysteinyl leukotriene (cys-LT) receptor antagonists (LTRAs) are antiasthma medications that reduce clinical symptoms and improve pulmonary function as well as airway inflammation in patients with classic asthma [15,16]. An uncontrolled observational study has shown that the LTRA montelukast reduces airway levels of cys-LTs in association with improvements in the quality of life of patients with classic asthma already under treatment with inhaled corticosteroids (ICS) [17].…”

Section: Introductionmentioning

confidence: 99%

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Clinical, Physiological and Anti-Inflammatory Effect of Montelukast in Patients with Cough Variant Asthma

Takemura¹,

Niimi²,

Matsumoto³

et al. 2011

Respiration

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Background: Cough variant asthma (CVA) is a phenotype of asthma presenting solely with coughing, characterized by airway hyperresponsiveness, eosinophilic inflammation and a cough response to bronchodilators. Leukotriene receptor antagonists (LTRAs) are antiasthma medications with anti-inflammatory and bronchodilatory properties. Although LTRAs exert antitussive effects in CVA, the mechanisms involved are unknown. Objectives: This study aimed to clarify the antitussive mechanisms of LTRAs in CVA patients. Methods: We prospectively observed the effect of montelukast (10 mg) daily for 4 weeks in 23 consecutive nonsmoking adults with anti-inflammatory treatment-naive CVA. We evaluated, before and after treatment, the cough visual analogue scale (VAS), pulmonary function (spirometry and impulse oscillation), methacholine airway responsiveness, cough receptor sensitivity, expressed by the concentration of capsaicin inducing 2 or more (C2) and 5 or more (C5) coughs, sputum eosinophil counts and levels of inflammatory mediators, including cysteinyl leukotrienes, leukotriene B₄, prostaglandin (PG) D₂, PGE₂, PGF₂_α and thromboxane B₂. We compared the baseline characteristics of the patients based on the symptomatic response to montelukast, defined as a decrease in the cough VAS of >25% (n = 15) or ≤25% (n = 8). Results: Montelukast significantly decreased the cough VAS (p = 0.0008), sputum eosinophil count (p = 0.013) and cough sensitivity (C2: p = 0.007; C5: p = 0.039), whereas pulmonary function, airway responsiveness and sputum mediator levels remained unchanged. Multivariate analysis showed that a better response to montelukast was associated solely with younger age (p = 0.032). Conclusion: The antitussive effect of montelukast in CVA may be attributed to the attenuation of eosinophilic inflammation rather than its bronchodilatory properties.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical, Physiological and Anti-Inflammatory Effect of Montelukast in Patients with Cough Variant Asthma

Takemura¹,

Niimi²,

Matsumoto³

et al. 2011

Respiration

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“…Figure 6 underscores the complexity of the physiological/pathological responses of histamine and leukotrienes in the upper airways. Both histamine and leukotrienes contribute to early-phase nasal congestive responses by eliciting a vasodilation of mucosal blood vessels and nasal edema [29][30][31] . In addition, H 1 receptor activation engenders vascular permeability, produces glandular secretions via parasympathetic reflexes and stimulates sensory nerves [31,32] .…”

Section: Discussionmentioning

confidence: 99%

Concomitant Activity of Histamine and Cysteinyl Leukotrienes on Porcine Nasal Mucosal Vessels and Nasal Inflammation in the Rat

Lieber¹,

Jimenez²,

Hunter³

et al. 2010

Pharmacology

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Background: Histamine and cysteinyl leukotrienes are pivotal mast cell mediators which contribute considerably and likely complementary to the symptoms of allergic rhinitis. Currently, we sought to explore the direct actions of histamine and leukotriene D₄ (LTD₄), a cysteinyl leukotriene, on porcine nasal arteries and veins. We also studied combined blocks of histamine and cysteinyl leukotrienes using loratadine and montelukast in an in vivo model of allergy-mediated nasal inflammation. Methods: For the evaluation of the action of histamine and LTD₄ on arteries and veins, porcine nasal mucosa was isolated and cut into slices (100–300 µm thick). Real-time images of the nasal arteries and veins were recorded and vessel activities estimated by changes in cross-sectional area before and after the tested drugs. For the in vivo studies, the effect of loratadine and montelukast given alone and in combination was examined on upper airway inflammation in ovalbumin-sensitized and -challenged Brown Norway rats. Results: Both histamine (0.001–10 µmol/l) and LTD₄ (0.001–10 µmol/l) produced a concentration-dependent increase in the lumen area of nasal mucosa arteries and veins. Histamine (0.01 µmol/l) alone produced a 24 and 12% increase in cross-sectional areas of arteries and veins, respectively. LTD₄ (0.001 µmol/l) alone increased artery and vein dilation by about 17 and 9%, respectively. Combination treatment with histamine (0.01 µmol/l) and LTD₄ (0.001 µmol/l) increased vessel dilation by 65% (arteries) and 26% (veins). In our in vivo Brown Norway rat studies, oral loratadine (0.01–10 mg/kg) and montelukast (0.01–10 mg/kg) significantly reduced antigen-induced total nasal inflammatory cell infiltration in a dose-dependent manner. The antiinflammatory dose-response curve of loratadine was shifted to the left when studied in combination with montelukast (0.01 mg/kg). Similarly, the dose-response characteristics of montelukast (0.01–10 mg/kg) was shifted in the presence of loratadine (0.01 mg/kg). Conclusion: Our studies support the position that histamine and cysteinyl leukotrienes may act collaboratively to elicit allergic nasal pathologies such as upper airway inflammation and nasal vessel dilation (which may translate into increased nasal mucosal engorgement). Furthermore, the current results are supportive of the hypothesis that combined treatment of allergic rhinitis with an H₁ receptor antagonist and a CysLT₁ receptor antagonist may have greater benefit than sole treatment with these agents alone.

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“…For example, early studies showed that zileuton and cysLT1 antagonists reduced the numbers of eosinophils in lavage fl uid, sputum, and/or blood, both in the absence of [ 54 , 55 ] and following an experimental allergen challenge [ 56 ]. Many studies have reported a reduction in exhaled nitric oxide levels with montelukast therapy in adults and children [57][58][59]. Discussed earlier in this article was the ability of cysLT1 antagonists to blunt serum IgE levels and the allergen-induced accumulation in the airways of myeloid DCs and myofi broblasts [ 8 , 12 , 22 ].…”

Section: Do Anti-lt Drugs Inhibit Airway Infl Ammation In Humans?mentioning

confidence: 99%

Expanding roles for leukotrienes in airway inflammation

Peters‐Golden

2008

Curr Allergy Asthma Rep

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Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. Cysteinyl (cys) LTs C(4), D(4), and E(4) are long known to contribute to airway contractile responses via ligation of the cysLT1 receptor, and cysLT1 antagonists are beneficial in some patients with asthma. Research advances over the past several years suggest that cysLT1 also mediates the ability of cysLTs to modulate inflammation, immune responses, and airway remodeling. Although less is known about an additional receptor, cysLT2, emerging evidence indicates that it likely also contributes to cysLT actions promoting inflammation, vascular permeability, and perhaps fibrosis. LTB(4), best known as a neutrophil chemoattractant, is now recognized to exert other important effects contributing to inflammatory and immune responses. These recent data highlight a growing appreciation for LTs as pleiotropic effectors, which are integral components in the network of molecules that mediate the expression of asthma.

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Effects of Montelukast Treatment and Withdrawal on Fractional Exhaled Nitric Oxide and Lung Function in Children With Asthma

Cited by 67 publications

References 18 publications

Clinical, Physiological and Anti-Inflammatory Effect of Montelukast in Patients with Cough Variant Asthma

Clinical, Physiological and Anti-Inflammatory Effect of Montelukast in Patients with Cough Variant Asthma

Concomitant Activity of Histamine and Cysteinyl Leukotrienes on Porcine Nasal Mucosal Vessels and Nasal Inflammation in the Rat

Expanding roles for leukotrienes in airway inflammation

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