The effect of montelukast, budesonide alone, and in combination on exercise-induced bronchoconstriction

Duong, MyLinh T.; Amin, Reshma; Baatjes, Adrian J; Kritzinger, Fiona; Qi, Ying; Meghji, Zahida; Lou, Wendy; Grasemann, Hartmut; O'Byrne, Paul M.; Subbarao, Padmaja

doi:10.1016/j.jaci.2012.02.051

Cited by 22 publications

(14 citation statements)

References 20 publications

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“…Leukotriene modifiers also reduce exerciseinduced bronchoconstriction 34,35 and have protective effects against the bronchoconstriction caused by exposure to pollutants. 36 Cromolyn sodium and nedocromil sodium also protect against exercise-induced bronchoconstriction, but inhaled β 2 -agonists are more effective.…”

Section: Pharmacotherapymentioning

confidence: 99%

Asthma and Exercise-Induced Bronchoconstriction in Athletes

2015

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egular exercise is one of the most effective means to maintain good health. A substantial proportion of the general population engages in competitive sports, including many people with asthma; when controlled, asthma does not restrict exercise performance. Indeed, exercise training can improve asthma symptoms, quality of life, exercise capacity, and pulmonary function, as well as reduce airway responsiveness. 1 Intense exercise imposes demands on the cardiorespiratory system. Cardiac output increases, as does minute ventilation, which can reach 200 liters per minute in high-level athletes. 2 At high minute ventilations, the airways are the site of intense respiratory heat and water exchange as they condition inspired air to body temperature and humidity levels. Furthermore, because mouth breathing is common during exercise, there is an increased penetration of allergens and pollutants-such as chloramines from chlorinated pools, ozone, and particulate matter from ambient air-into the lower airways. Therefore, it is not surprising that as compared with nonathletes, high-level endurance athletes have an increased prevalence of various respiratory ailments, such as asthma and rhinitis, and related coexisting conditions. 3-5 The term exercise-induced bronchoconstriction describes the transient narrowing of the airways after exercise, a phenomenon that occurs frequently among athletes who may not have a diagnosis of asthma or even have any respiratory symptoms. 5-8 Exercise-induced bronchoconstriction is a distinct form of airway hyperresponsiveness, which is defined as the tendency of airways to constrict more easily and more forcefully than normal airways in response to a wide variety of bronchoconstrictor stimuli. Airway hyperresponsiveness, which is a cardinal feature of asthma, is more common among endurance athletes-particularly winter-sports athletes and swimmers-than in the general population. 7,8 The mechanism of exercise-induced bronchoconstriction has not been established with certainty; both airway cooling resulting from conditioning of inspired air and postexercise rewarming of airways have been proposed as mechanisms. However, the key stimulus is probably airway dehydration as a result of increased ventilation, resulting in augmented osmolarity of the airway-lining fluid. 9 This is thought to trigger the release of mediators-such as histamine, cysteinyl leukotrienes, and prostaglandins-from airway inflammatory cells, which leads to airway smooth-muscle contraction and airway edema. However, uncontrolled airway inflammation can exacerbate this process and increase exercise-induced bronchoconstriction. 10 Furthermore, not only can osmotic and mechanical stress to the airways play a role in the acute response to exercise, but they may also be involved in the development of airway remodeling in athletes, probably through their effects on airway epithelial cells. 4,8,9 Finally, transient immunosuppression may also develop in athletes during periods of intense training, with increased susceptibility to respirat...

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Section: Pharmacotherapymentioning

confidence: 99%

Asthma and Exercise-Induced Bronchoconstriction in Athletes

2015

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“…The most effective therapy for EIA is regular use of ICS [122]. Early use of leukotriene inhibition may be equally effective [149,150].…”

Section: Subgroups With Treatment Implicationsmentioning

confidence: 99%

Clinically relevant subgroups in COPD and asthma

Turner

Tamási

Schleich³

et al. 2015

Eur Respir Rev

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As knowledge of airways disease has grown, it has become apparent that neither chronic obstructive pulmonary disease (COPD) nor asthma is a simple, easily defined disease. In the past, treatment options for both diseases were limited; thus, there was less need to define subgroups. As treatment options have grown, so has our need to predict who will respond to new drugs. To date, identifying subgroups has been largely reported by detailed clinical characterisation or differences in pathobiology. These subgroups are commonly called "phenotypes"; however, the problem of defining what constitutes a phenotype, whether this should include comorbid diseases and how to handle changes over time has led to the term being used loosely.In this review, we describe subgroups of COPD and asthma patients whose clinical characteristics we believe have therapeutic or major prognostic implications specific to the lung, and whether these subgroups are constant over time. Finally, we will discuss whether the subgroups we describe are common to both asthma and COPD, and give some examples of how treatment might be tailored in patients where the subgroup is clear, but the label of asthma or COPD is not. @ERSpublications Summary of subgroups of airways disease that can be found in COPD and asthma, and their management

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“…A number of pharmacological and nonpharmacological treatment approaches are recommended for the management of patients with EIA, which also include the cysLTR1 antagonists, especially montelukast or zafirlukast [5, 115–124]. Both montelukast and zafirlukast have been used either long term, particularly in asthmatic patients not controlled on baseline anti-asthma therapy, or even short term/acutely (e.g., single dose prior to exercise) and to provide useful protection against EIA, although there is some debate as to whether these agents are equivalent to or more or less effective than LABAs [5, 115–124]. …”

Section: Clinical Applications Of Cysltr1 Antagonistsmentioning

confidence: 99%

Cysteinyl Leukotriene Receptor-1 Antagonists as Modulators of Innate Immune Cell Function

Theron

Steel

Tintinger

et al. 2014

Journal of Immunology Research

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Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8+ cells. Recognition of the involvement of cysLTs in the immunopathogenesis of various types of acute and chronic inflammatory disorders, especially bronchial asthma, prompted the development of selective cysLT receptor-1 (cysLTR1) antagonists, specifically montelukast, pranlukast, and zafirlukast. More recently these agents have also been reported to possess secondary anti-inflammatory activities, distinct from cysLTR1 antagonism, which appear to be particularly effective in targeting neutrophils and monocytes/macrophages. Underlying mechanisms include interference with cyclic nucleotide phosphodiesterases, 5′-lipoxygenase, and the proinflammatory transcription factor, nuclear factor kappa B. These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophils in vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies.

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The effect of montelukast, budesonide alone, and in combination on exercise-induced bronchoconstriction

Cited by 22 publications

References 20 publications

Asthma and Exercise-Induced Bronchoconstriction in Athletes

Asthma and Exercise-Induced Bronchoconstriction in Athletes

Clinically relevant subgroups in COPD and asthma

Cysteinyl Leukotriene Receptor-1 Antagonists as Modulators of Innate Immune Cell Function

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