Randomized controlled trial of fish oil and montelukast and their combination on airway inflammation and hyperpnea-induced bronchoconstriction

Sandra Tecklenburg-Lund, Timothy D Mickleborough, Louise A Turner, Alyce D Fly, Joel M Stager, Gregory S Montgomery, Sandra Tecklenburg-Lund, Timothy D Mickleborough, Louise A Turner, Alyce D Fly, Joel M Stager, Gregory S Montgomery

Abstract

Background: Both 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.

Methods: In 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.

Results: While 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 F(E)NO, exhaled breathe condensate pH and cysteinyl-leukotrienes, while the fish oil and combination treatment significantly reduced (p<0.05) urinary 9α, 11β-prostaglandin F(2) after EVH compared to the usual diet; however, there was no significant difference (p>0.017) in these biomarkers between treatments.

Conclusion: While 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 registration: ClinicalTrials.gov NCT00676468.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. The percentage change in FEV…
Figure 1. The percentage change in FEV1 from pre- to post- EVH for the usual diet (pre-treatment) and across the three treatments.
Reductions in post-EVH in excess of 10% represent abnormal pulmonary function. Letters a and b refer to comparisons by treatment within respective time period. Different letters designate a significant difference (p

Figure 2. The percentage change in FEF…

Figure 2. The percentage change in FEF 25–75% from pre- to post- EVH for the…

Figure 2. The percentage change in FEF25–75% from pre- to post- EVH for the usual diet (pre-treatment) and across the three treatments.
Letters a and b refer to comparisons by treatment within respective time period. Different letters designate a significant difference (p

Figure 3. Mean fraction of exhaled nitric…

Figure 3. Mean fraction of exhaled nitric oxide (F E NO) concentration (ppb).

Different letters designate a…

Figure 3. Mean fraction of exhaled nitric oxide (FENO) concentration (ppb).
Different letters designate a significant difference (p

Figure 4. Mean exhaled breathe condensate (EBC)…

Figure 4. Mean exhaled breathe condensate (EBC) cysteinyl-leukotriene concentration (pg.mg −1 ).

* designates a significant difference…

Figure 4. Mean exhaled breathe condensate (EBC) cysteinyl-leukotriene concentration (pg.mg−1).
* designates a significant difference compared to pre-treatment (usual diet) pre-EVH. # designates a significant difference compared to pre-treatment (usual diet) post-EVH.

Figure 5. Mean urinary 9α, 11β-prostaglandin F…

Figure 5. Mean urinary 9α, 11β-prostaglandin F 2 concentration (ng.mg mmol creatinine −1 ).

* designates a significant…

Figure 5. Mean urinary 9α, 11β-prostaglandin F2 concentration (ng.mg mmol creatinine−1).
* designates a significant difference compared to pre-treatment (usual diet) pre-EVH. # designates a significant difference compared to pre-treatment (usual diet) post-EVH.
Similar articles
References
    1. Anderson SD, Kippelen P. Exercise-induced Bronchoconstriction: Pathogenesis. Curr Allergy Asthma Rep. 2005;5:116–122. - PubMed
    1. O'Byrne PM, Gauvreau GM, Brannan JD. Provoked models of asthma: what have we learnt? Clin Exp Allergy. 2009;39:181–192. - PubMed
    1. Lund TK, Pedersen L, Anderson SD, Sverrild A, Backer V. Are asthma-like symptoms in elite athletes associated with classical features of asthma? Br J Sports Med. 2009;43:1131–1135. - PubMed
    1. Hallstrand TS, Moody MW, Wurfel MM, Schwartz LB, Henderson WR, Jr, et al. Inflammatory Basis of Exercise-induced Bronchoconstriction. Am J Respir Crit Care Med. 2005;172:679–686. - PMC - PubMed
    1. Dahlen SE, Hedqvist P, Hammarstrom S, Samuelsson B. Leukotrienes are potent constrictors of human bronchi. Nature. 1980;288:484–486. - PubMed
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Figure 2. The percentage change in FEF…
Figure 2. The percentage change in FEF25–75% from pre- to post- EVH for the usual diet (pre-treatment) and across the three treatments.
Letters a and b refer to comparisons by treatment within respective time period. Different letters designate a significant difference (p

Figure 3. Mean fraction of exhaled nitric…

Figure 3. Mean fraction of exhaled nitric oxide (F E NO) concentration (ppb).

Different letters designate a…

Figure 3. Mean fraction of exhaled nitric oxide (FENO) concentration (ppb).
Different letters designate a significant difference (p

Figure 4. Mean exhaled breathe condensate (EBC)…

Figure 4. Mean exhaled breathe condensate (EBC) cysteinyl-leukotriene concentration (pg.mg −1 ).

* designates a significant difference…

Figure 4. Mean exhaled breathe condensate (EBC) cysteinyl-leukotriene concentration (pg.mg−1).
* designates a significant difference compared to pre-treatment (usual diet) pre-EVH. # designates a significant difference compared to pre-treatment (usual diet) post-EVH.

Figure 5. Mean urinary 9α, 11β-prostaglandin F…

Figure 5. Mean urinary 9α, 11β-prostaglandin F 2 concentration (ng.mg mmol creatinine −1 ).

* designates a significant…

Figure 5. Mean urinary 9α, 11β-prostaglandin F2 concentration (ng.mg mmol creatinine−1).
* designates a significant difference compared to pre-treatment (usual diet) pre-EVH. # designates a significant difference compared to pre-treatment (usual diet) post-EVH.
Similar articles
References
    1. Anderson SD, Kippelen P. Exercise-induced Bronchoconstriction: Pathogenesis. Curr Allergy Asthma Rep. 2005;5:116–122. - PubMed
    1. O'Byrne PM, Gauvreau GM, Brannan JD. Provoked models of asthma: what have we learnt? Clin Exp Allergy. 2009;39:181–192. - PubMed
    1. Lund TK, Pedersen L, Anderson SD, Sverrild A, Backer V. Are asthma-like symptoms in elite athletes associated with classical features of asthma? Br J Sports Med. 2009;43:1131–1135. - PubMed
    1. Hallstrand TS, Moody MW, Wurfel MM, Schwartz LB, Henderson WR, Jr, et al. Inflammatory Basis of Exercise-induced Bronchoconstriction. Am J Respir Crit Care Med. 2005;172:679–686. - PMC - PubMed
    1. Dahlen SE, Hedqvist P, Hammarstrom S, Samuelsson B. Leukotrienes are potent constrictors of human bronchi. Nature. 1980;288:484–486. - PubMed
Show all 59 references
Publication types
MeSH terms
Associated data
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 3. Mean fraction of exhaled nitric…
Figure 3. Mean fraction of exhaled nitric oxide (FENO) concentration (ppb).
Different letters designate a significant difference (p

Figure 4. Mean exhaled breathe condensate (EBC)…

Figure 4. Mean exhaled breathe condensate (EBC) cysteinyl-leukotriene concentration (pg.mg −1 ).

* designates a significant difference…

Figure 4. Mean exhaled breathe condensate (EBC) cysteinyl-leukotriene concentration (pg.mg−1).
* designates a significant difference compared to pre-treatment (usual diet) pre-EVH. # designates a significant difference compared to pre-treatment (usual diet) post-EVH.

Figure 5. Mean urinary 9α, 11β-prostaglandin F…

Figure 5. Mean urinary 9α, 11β-prostaglandin F 2 concentration (ng.mg mmol creatinine −1 ).

* designates a significant…

Figure 5. Mean urinary 9α, 11β-prostaglandin F2 concentration (ng.mg mmol creatinine−1).
* designates a significant difference compared to pre-treatment (usual diet) pre-EVH. # designates a significant difference compared to pre-treatment (usual diet) post-EVH.
Figure 4. Mean exhaled breathe condensate (EBC)…
Figure 4. Mean exhaled breathe condensate (EBC) cysteinyl-leukotriene concentration (pg.mg−1).
* designates a significant difference compared to pre-treatment (usual diet) pre-EVH. # designates a significant difference compared to pre-treatment (usual diet) post-EVH.
Figure 5. Mean urinary 9α, 11β-prostaglandin F…
Figure 5. Mean urinary 9α, 11β-prostaglandin F2 concentration (ng.mg mmol creatinine−1).
* designates a significant difference compared to pre-treatment (usual diet) pre-EVH. # designates a significant difference compared to pre-treatment (usual diet) post-EVH.

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