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

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

背景：现有研究证实，鱼油（fish oil）与孟鲁司特（montelukast）均可减轻运动诱发性支气管收缩（exercise-induced bronchoconstriction, EIB）的严重程度。本研究旨在对比鱼油、孟鲁司特单药及联合给药对哮喘患者正常碳酸血症性自愿过度通气（eucapnic voluntary hyperpnea, EVH）诱导的气道炎症与支气管收缩的影响。
方法：本EIB模型研究纳入20例经证实存在过度通气诱发性支气管收缩（hyperpnea-induced bronchoconstriction, HIB）的哮喘受试者，开展随机双盲试验。所有受试者均维持日常饮食状态（预处理阶段，n=20），随后被随机分为两组：一组接受10mg活性孟鲁司特片剂+10粒安慰剂鱼油胶囊（n=10），另一组接受10粒安慰剂孟鲁司特片剂+10粒活性鱼油胶囊（每日给药，累计摄入3.2g二十碳五烯酸（eicosapentaenoic acid, EPA）与2.0g二十二碳六烯酸（docosahexaenoic acid, DHA），n=10），干预周期为3周。此后，所有受试者（联合治疗组，n=20）进入为期3周的联合干预阶段，每日服用10mg活性孟鲁司特片剂与10粒活性鱼油胶囊。
结果：与预处理阶段相比，孟鲁司特、鱼油单药及联合治疗均可显著抑制HIB（p<0.05），但各治疗组间无显著差异（p>0.017）；日常饮食（预处理）、鱼油单药、孟鲁司特单药及联合治疗组的一秒用力呼气容积（forced expiratory volume in 1 second, FEV1）下降百分比分别为-18.4±2.1%、-9.3±2.8%、-11.6±2.8%与-10.8±1.7%。三种治疗方案均可显著降低呼出气一氧化氮（fractional exhaled nitric oxide, FeNO）、呼出气冷凝液pH值及半胱氨酰白三烯水平（p<0.05）；与日常饮食相比，鱼油单药与联合治疗可显著降低EVH后尿液中9α,11β-前列腺素F2α水平（p<0.05），但各治疗组间上述生物标志物水平无显著差异（p>0.017）。
结论：尽管鱼油与孟鲁司特均可有效减轻气道炎症与HIB，但二者联合给药并未比单一干预方案带来更显著的保护作用。因此，鱼油补充可作为EIB的替代治疗方案。
试验注册：ClinicalTrials.gov 编号NCT00676468