Abstract
BackgroundBoth fish oil and montelukast have been shown to reduce the severity of exercise-induced bronchoconstriction (EIB). The purpose of this study was to compare the effects of fish oil and montelukast, alone and in combination, on airway inflammation and bronchoconstriction induced by eucapnic voluntary hyperpnea (EVH) in asthmatics.MethodsIn this model of EIB, twenty asthmatic subjects with documented hyperpnea-induced bronchoconstriction (HIB) entered a randomized double-blind trial. All subjects entered on their usual diet (pre-treatment, n = 20) and then were randomly assigned to receive either one active 10 mg montelukast tablet and 10 placebo fish oil capsules (n = 10) or one placebo montelukast tablet and 10 active fish oil capsules totaling 3.2 g EPA and 2.0 g DHA (n = 10) taken daily for 3-wk. Thereafter, all subjects (combination treatment; n = 20) underwent another 3-wk treatment period consisting of a 10 mg active montelukast tablet or 10 active fish oil capsules taken daily.ResultsWhile HIB was significantly inhibited (p<0.05) by montelukast, fish oil and combination treatment compared to pre-treatment, there was no significant difference (p>0.017) between treatment groups; percent fall in forced expiratory volume in 1-sec was −18.4±2.1%, −9.3±2.8%, −11.6±2.8% and −10.8±1.7% on usual diet (pre-treatment), fish oil, montelukast and combination treatment respectively. All three treatments were associated with a significant reduction (p<0.05) in FENO, exhaled breathe condensate pH and cysteinyl-leukotrienes, while the fish oil and combination treatment significantly reduced (p<0.05) urinary 9α, 11β-prostaglandin F2 after EVH compared to the usual diet; however, there was no significant difference (p>0.017) in these biomarkers between treatments.ConclusionWhile fish oil and montelukast are both effective in attenuating airway inflammation and HIB, combining fish oil with montelukast did not confer a greater protective effect than either intervention alone. Fish oil supplementation should be considered as an alternative treatment for EIB.Trial RegistrationClinicalTrials.gov NCT00676468
Highlights
Exercise-induced bronchoconstriction (EIB) and exercise-induced asthma are terms used interchangeably that describe a transient narrowing of the airways during or following exercise [1] that can occur in patients with asthma [2] and elite athletes [3]
This study has shown that fish oil and montelukast were both effective in reducing the airway reactivity to hyperpnea with dry air, when fish oil was combined with montelukast no further attenuation in airway inflammation or hyperpnea-induced bronchoconstriction was observed
The degree of protection provided by montelukast on hyperpnea-induced bronchoconstriction in the present study is similar in magnitude to previous reports using an exercise challenge [11,12], which have shown that 2-hr following a single 10-mg dose of montelukast the maximum fall in post-exercise forced expiratory volume in 1-sec (FEV1) was reduced by approximately 52% [11] and 33% [12]
Summary
Exercise-induced bronchoconstriction (EIB) and exercise-induced asthma are terms used interchangeably that describe a transient narrowing of the airways during or following exercise [1] that can occur in patients with asthma [2] and elite athletes [3]. The mechanisms responsible for EIB likely involve multiple mechanistic pathways, it is generally accepted that exercise or dry air hyperpnea play an important role as an initiating stimulus through airway surface effects of water loss, which include mucosal cooling and dehydration [1] This transient dehydration causes an increase in airway surface liquid osmolarity which activates histamine, neuropeptides, and arachidonic acid metabolites such as cysteinyl (Cyst)- leukotrienes [(LTs) e.g., LTC4, D4 and E4)] and prostaglandins, from resident airway cells, resulting in bronchial smooth muscle contraction and subsequent airway obstruction [4]. The purpose of this study was to compare the effects of fish oil and montelukast, alone and in combination, on airway inflammation and bronchoconstriction induced by eucapnic voluntary hyperpnea (EVH) in asthmatics
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