Randomized Controlled Trial of Fish Oil and Montelukast and Their Combination on Airway Inflammation and Hyperpnea-Induced Bronchoconstriction

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

The Effect of Omega-3 Fatty Acids on Bronchial Hyperresponsiveness, Sputum Eosinophilia, and Mast Cell Mediators in Asthma

“…6,18 The most obvious diff erence is that we used inhaled mannitol, a bronchial provocation challenge that has been derived from the understanding of the eff ects of dry air hyperpnea-induced BHR, which is a well-established alternative challenge stimulus to study EIB. There is strong evidence that the airway response to mannitol closely mimics central components of EIB, such as the activation of mast cells and eosinophils, resulting in the release of bronchoconstrictive mediators.…”

“…3 More recently, 3 weeks of omega-3s were reported to inhibit mild airway responses to exercise and eucapnic voluntary hyperventilation (EVH) in both elite athletes and symptomatic subjects with asthma. [4][5][6] Th is was observed in association with reductions in markers of airway infl ammation, such as reduced cytokine levels, reduced excretion of the urinary eicosanoids 11 b -prostaglandin F2 a (11 b -PGF 2 a ) and leukotriene E4 (LTE 4 ), and decreased sputum eosinophil counts, suggesting that the benefi ts of an omega-3-enriched diet on EIB was through antiinfl ammatory mechanisms.…”

The effects of short-term fish oil supplementation on pulmonary function and airway inflammation following a high-fat meal

“…Mickleborough and colleagues have demonstrated the protective effects of fish oil on exercise induced bronchoconstriction in asthmatic populations (Mickleborough et al 2006;Mickleborough et al 2003). In addition, Tecklenburg-Lund et al (2010) reduced airway inflammation in asthmatic subjects following a 3wk period of fish oil supplementation (Tecklenburg-Lund et al 2010). However, to date, it is unknown if fish oil supplementation for a similar 3 wk period will mitigate the airway inflammatory response elicited by a single HFM.…”

Exercise-Induced Asthma

“…Thus, the possibility exists for drug-diet interactions that confer greater anti-inflammatory benefits in the airway than either intervention alone. However, Tecklenburg-Lund et al (37) have shown recently that, whereas both fish oil and montelukast (Singulair A , Merck & Co., Inc., Whitehouse Station, NJ) taken in isolation are effective in attenuating airway inflammation and hyperpnea-induced bronchoconstriction in asthmatic subjects, treatment of both these agents in combination does not provide a greater anti-inflammatory effect or suppression of hyperpnea-induced bronchoconstriction than either treatment alone. On the basis of the available evidence (24,26,28,37), it is clear that fish oil supplementation should be considered an alternative treatment for exercise-induced bronchoconstriction.…”