Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction

Villarán, César; O’Neill, Shane; Helbling, Arthur; Noord, J.A. van; Lee, Tak H.; Chuchalin, Alexander; Langley, Stephen J.; Gunawardena, K A; Šuškovič, Stanislav; Laurenzi, Martino; Jasan, Jay; Menten, Joris; Leff, Jonathan A.

doi:10.1016/s0091-6749(99)70322-2

Cited by 171 publications

(108 citation statements)

References 26 publications

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“…However, the time effect of MNT during the first 4 weeks of treatment, which may be a window for the onset of early tolerance, has not been formally evaluated. VILLARAN et al [20] and EDELMAN et al [21] examined the effect of MNT and salmeterol on EIB over an 8-week period. Protection by MNT was evident at day 3 and persisted throughout the whole treatment period without development of tolerance, while the effect of salmeterol appeared to wane over time.…”

Section: Discussionmentioning

confidence: 99%

Lack of tolerance to the protective effect of montelukast in exercise-induced bronchoconstriction in children

Benedictis

Giudice²,

Forenza³

et al. 2006

Eur Respir J

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The effect over time of regular treatment with montelukast (MNT) in inhibiting exercise-induced bronchoconstriction (EIB) has never been evaluated in children. The aim of the present study was to examine the preventive effect of MNT against EIB in children at different time-points over a 4-week treatment period.Thirty-two asthmatic children (aged 6-12 yrs) were enrolled in a double-blinded, randomised, parallel group design to receive a 4-week treatment with MNT (5 mg chewable tablets administered once daily in the evening) or placebo. Exercise challenge was performed at baseline and after 3, 7 and 28 days of treatment, 20-24 h after dosing.MNT was significantly more protective than placebo against EIB at each time. The mean percentage drop of forced expiratory volume in one second (FEV1) was 24.6, 13.6, 12.0 and 11.6 for MNT, and 24.4, 22.4, 21.8 and 21.0 for placebo, at baseline and after 3, 7 and 28 days, respectively. For each drug, no significant difference in the percentage drop of FEV1 was found between different days.Regular treatment with montelukast provided significant protection against exercise-induced bronchoconstriction in asthmatic children over a 4-week period with no tolerance to the bronchoprotective effect.KEYWORDS: Exercise-induced bronchoconstriction, montelukast, tolerance E xercise-induced bronchoconstriction (EIB) is a common manifestation of asthma in children and can interfere in their daily activities. The pathogenetic mechanism of EIB is not completely clear, but the release of inflammatory mediators from airway mast cells appears likely [1]. Although leukotrienes (LTs) have been inconstantly recovered from urine after exercise [2], the evidence for the role of these mediators in EIB derives from the bronchoprotective effect of anti-LT drugs [3].Montelukast (MNT), a specific antagonist of cysteinyl-leukotriene (Cys-LT) receptors, showed a consistent effect against EIB in children when administered either as a single dose [4,5] or as regular treatment [6]. In adults, a 12-week treatment with MNT attenuated the fall in pulmonary function following exercise with no tolerance to the bronchoprotective effect [7]. No study has evaluated the effect over time of regular treatment with MNT in inhibiting EIB in children. The present authors therefore examined the effect of once-daily MNT on EIB at several time-points during a 4-week treatment period. PATIENTS AND METHODS SubjectsA total of 32 children aged 6-12 yrs with mild-tomoderate asthma [8] were enrolled into the current study. Patients were recruited from the Depts of Paediatrics, at the University of Perugia and the University of Naples, Italy. The study protocol was approved by the institutional review boards of the two participating centres. Informed consent was obtained from patients and their parents.At screening, all patients had a forced expiratory volume in one second (FEV1) of at least 75% of predicted and a decrease in FEV1 of at least 12% from the baseline after a standardised exercise challenge. Patients were not e...

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Section: Discussionmentioning

confidence: 99%

Lack of tolerance to the protective effect of montelukast in exercise-induced bronchoconstriction in children

Benedictis

Giudice²,

Forenza³

et al. 2006

Eur Respir J

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“…As inhaled long-acting β 2 agonists rapidly loose their protective effect on exercise-provoked asthma when used on a regular basis (62)(63)(64), their use may not be advocated in subjects who exercise regularly in cold weather. For those subjects, leukotriene receptor antagonists may be more suitable since they are as effective as long-acting β 2 agonists in this setting (49,65) and do not loose their protective effect when used on a regular basis (63)(64)(65).…”

Section: Cold Air-provoked Short-term Responsesmentioning

confidence: 99%

“…For those subjects, leukotriene receptor antagonists may be more suitable since they are as effective as long-acting β 2 agonists in this setting (49,65) and do not loose their protective effect when used on a regular basis (63)(64)(65). In addition, the response to rescue short-acting β 2 agonists after exercise is fully maintained during regular treatment with leukotriene receptor antagonists, which may not be true during treatment with regular β 2 agonists (65,66).…”

Section: Cold Air-provoked Short-term Responsesmentioning

confidence: 99%

Cold air-provoked respiratory symptoms: the mechanisms and management

Koskela

2007

International Journal of Circumpolar Health

188

137

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Objectives. To describe the mechanisms and management of cold air-provoked respiratory symptoms. Study design. A literature review. Methods. The review includes human epidemiological studies, human and animal experimental studies, as well as human studies about management of the cold air-provoked respiratory symptoms. Results. Cold air is unlikely to be a causal factor initiating respiratory diseases but a symptom trigger. In the present review, the airway responses beyond these symptoms were divided into three types. The short-term responses are those that develop within minutes in response to sudden cooling of the airways. Subjects with asthma or rhinitis are especially prone to these responses. The long-term responses are those that develop in response to repeated and longstanding cooling and drying of the airways, usually in endurance athletes. Finally, there are the physiological, reflex-mediated lower-airway responses to cooling of the skin or upper airways. Conclusions. The mechanisms beyond cold air-provoked respiratory symptoms vary considerably and mainly depend on the individual's susceptibility and the ventilation level during the cold exposure. An understanding of these mechanisms is essential for successful management of the symptoms. (Int J Circumpolar Health 2007; 66(2) [91][92][93][94][95][96][97][98][99][100]

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“…Montelukast is an orally bioavailable cysteinyl leukotriene (LT) receptor antagonist that is effective, safe, well tolerated, and approved by the U.S. Food and Drug Administration for preventive therapy for the inflammatory component in asthma and allergic rhinitis in children 2 years and older (21)(22)(23)(24), with no demonstrable development of tolerance in long-term studies (25,26). We have recently found that the cloned human cysteinyl LT receptors 1 and 2 (LT1-R, LT2-R) (27,28) have increased expression in the tonsillar tissues of children with SA (29).…”

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confidence: 99%

Leukotriene Modifier Therapy for Mild Sleep-disordered Breathing in Children

Goldbart

Goldman

Veling

et al. 2005

Am J Respir Crit Care Med

284

157

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Background: Children with mild sleep-disordered breathing (SDB), who may not be recommended for adenotonsillectomy, frequently exhibit neurocognitive and behavioral morbidity, and may benefit from alternative therapeutic interventions, such as leukotriene modifier therapy. Methods: Twenty-four children with SDB completed an open-label intervention study for 16 weeks with daily montelukast therapy. Sleep studies and adenoid size estimates from lateral X-ray films of the neck were obtained before and after treatment. In a parallel study, adenoid and tonsillar tissues from children with obstructive sleep apnea or recurrent throat infections were subjected to quantitative polymerase chain reaction, immunohistochemistry, and Western blotting for gene and protein expression of leukotriene receptors LT1-R and LT2-R, and for concentrations of LTB4 and LTC4/D4/E4. Results: Montelukast treatment induced significant reductions in adenoid size and respiratory-related sleep disturbances, which were absent in 16 children with SDB who did not receive treatment. LT1-R and LT2-R mRNA was similarly abundant in adenoid tissues, but increased LT1-R and LT2-R protein expression and higher levels of LTB4 and LTC4/D4/E4 emerged in children with obstructive sleep apnea. Conclusions: Oral therapy with a leukotriene modifier appears to be associated with improved breathing during sleep. Double-blind, placebo-controlled trials will be needed to corroborate current findings and solidly establish antiinflammatory strategies, such as leukotriene modifiers, as therapeutic alternatives in children with SDB too mild to justify referral for adenotonsillectomy.

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Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction

Cited by 171 publications

References 26 publications

Lack of tolerance to the protective effect of montelukast in exercise-induced bronchoconstriction in children

Lack of tolerance to the protective effect of montelukast in exercise-induced bronchoconstriction in children

Cold air-provoked respiratory symptoms: the mechanisms and management

Leukotriene Modifier Therapy for Mild Sleep-disordered Breathing in Children

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