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The effect of omega-3 fatty acids on bronchial hyperresponsiveness, sputum eosinophilia, and mast cell mediators in asthma.

Abstract

BACKGROUND

Omega-3 fatty acid supplements have been reported to inhibit exercise-induced bronchoconstriction (EIB). It has not been determined whether omega-3 supplements inhibit airway sensitivity to inhaled mannitol, a test for bronchial hyperresponsiveness (BHR) and model for EIB in people with mild to moderate asthma.

METHODS

In a double-blind, crossover trial, subjects with asthma who had BHR to inhaled mannitol (n = 23; 14 men; mean age, 28 years; one-half taking regular inhaled corticosteroids) were randomized to omega-3 supplements (4.0 g/d eicosapentaenoic acid and 2.0 g/d docosahexaenoic acid) or matching placebo for 3 weeks separated by a 3-week washout. The primary outcome was the provoking dose of mannitol (mg) to cause a 15% fall in FEV1 (PD15). Secondary outcomes were sputum eosinophil count, spirometry, Asthma Control Questionnaire (ACQ) score, serum triacylglyceride level, and lipid mediator profile in urine and serum.

RESULTS

PD15 (geometric mean, 95% CI) to mannitol following supplementation with omega-3s (78 mg, 51-119 mg) was not different from placebo (88 mg, 56-139 mg, P = .5). There were no changes in sputum eosinophils (mean ± SD) in a subgroup of 11 subjects (omega-3, 8.4% ± 8.2%; placebo, 7.8% ± 11.8%; P = .9). At the end of each treatment period, there were no differences in FEV1 % predicted (omega-3, 85% ± 13%; placebo, 84% ± 11%; P = .9) or ACQ score (omega-3, 1.1% ± 0.5%; placebo, 1.1% ± 0.5%; P = .9) (n = 23). Omega-3s caused significant lowering of blood triglyceride levels and expected shifts in serum fatty acids and eicosanoid metabolites, confirming adherence to the supplements; however, no changes were observed in urinary mast cell mediators.

CONCLUSIONS

Three weeks of omega-3 supplements does not improve BHR to mannitol, decrease sputum eosinophil counts, or inhibit urinary excretion of mast cell mediators in people with mild to moderate asthma, indicating that dietary omega-3 supplementation is not useful in the short-term treatment of asthma.

TRIAL REGISTRY

ClinicalTrials.gov; No.: NCT00526357; URL: www.clinicaltrials.gov.

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  • Authors+Show Affiliations

    ,

    Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, Hamilton, ON, Canada. Electronic address: john.brannan@sydney.edu.au.

    ,

    National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.

    ,

    Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, Hamilton, ON, Canada.

    ,

    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

    ,

    Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, Hamilton, ON, Canada.

    ,

    National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.

    ,

    Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.

    ,

    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.

    ,

    Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, Hamilton, ON, Canada.

    ,

    National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.

    Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, Hamilton, ON, Canada.

    Source

    Chest 147:2 2015 Feb pg 397-405

    MeSH

    Adult
    Asthma
    Bronchial Hyperreactivity
    Cross-Over Studies
    Dietary Supplements
    Dose-Response Relationship, Drug
    Double-Blind Method
    Eosinophilia
    Eosinophils
    Fatty Acids, Omega-3
    Female
    Forced Expiratory Volume
    Humans
    Leukocyte Count
    Male
    Mannitol
    Mast Cells
    Sputum
    Triglycerides
    Young Adult

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25321659

    Citation

    Brannan, John D., et al. "The Effect of Omega-3 Fatty Acids On Bronchial Hyperresponsiveness, Sputum Eosinophilia, and Mast Cell Mediators in Asthma." Chest, vol. 147, no. 2, 2015, pp. 397-405.
    Brannan JD, Bood J, Alkhabaz A, et al. The effect of omega-3 fatty acids on bronchial hyperresponsiveness, sputum eosinophilia, and mast cell mediators in asthma. Chest. 2015;147(2):397-405.
    Brannan, J. D., Bood, J., Alkhabaz, A., Balgoma, D., Otis, J., Delin, I., ... O'Byrne, P. M. (2015). The effect of omega-3 fatty acids on bronchial hyperresponsiveness, sputum eosinophilia, and mast cell mediators in asthma. Chest, 147(2), pp. 397-405. doi:10.1378/chest.14-1214.
    Brannan JD, et al. The Effect of Omega-3 Fatty Acids On Bronchial Hyperresponsiveness, Sputum Eosinophilia, and Mast Cell Mediators in Asthma. Chest. 2015;147(2):397-405. PubMed PMID: 25321659.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The effect of omega-3 fatty acids on bronchial hyperresponsiveness, sputum eosinophilia, and mast cell mediators in asthma. AU - Brannan,John D, AU - Bood,Johan, AU - Alkhabaz,Ahmad, AU - Balgoma,David, AU - Otis,Joceline, AU - Delin,Ingrid, AU - Dahlén,Barbro, AU - Wheelock,Craig E, AU - Nair,Parameswaran, AU - Dahlén,Sven-Erik, AU - O'Byrne,Paul M, PY - 2014/10/17/entrez PY - 2014/10/17/pubmed PY - 2015/4/22/medline SP - 397 EP - 405 JF - Chest JO - Chest VL - 147 IS - 2 N2 - BACKGROUND: Omega-3 fatty acid supplements have been reported to inhibit exercise-induced bronchoconstriction (EIB). It has not been determined whether omega-3 supplements inhibit airway sensitivity to inhaled mannitol, a test for bronchial hyperresponsiveness (BHR) and model for EIB in people with mild to moderate asthma. METHODS: In a double-blind, crossover trial, subjects with asthma who had BHR to inhaled mannitol (n = 23; 14 men; mean age, 28 years; one-half taking regular inhaled corticosteroids) were randomized to omega-3 supplements (4.0 g/d eicosapentaenoic acid and 2.0 g/d docosahexaenoic acid) or matching placebo for 3 weeks separated by a 3-week washout. The primary outcome was the provoking dose of mannitol (mg) to cause a 15% fall in FEV1 (PD15). Secondary outcomes were sputum eosinophil count, spirometry, Asthma Control Questionnaire (ACQ) score, serum triacylglyceride level, and lipid mediator profile in urine and serum. RESULTS: PD15 (geometric mean, 95% CI) to mannitol following supplementation with omega-3s (78 mg, 51-119 mg) was not different from placebo (88 mg, 56-139 mg, P = .5). There were no changes in sputum eosinophils (mean ± SD) in a subgroup of 11 subjects (omega-3, 8.4% ± 8.2%; placebo, 7.8% ± 11.8%; P = .9). At the end of each treatment period, there were no differences in FEV1 % predicted (omega-3, 85% ± 13%; placebo, 84% ± 11%; P = .9) or ACQ score (omega-3, 1.1% ± 0.5%; placebo, 1.1% ± 0.5%; P = .9) (n = 23). Omega-3s caused significant lowering of blood triglyceride levels and expected shifts in serum fatty acids and eicosanoid metabolites, confirming adherence to the supplements; however, no changes were observed in urinary mast cell mediators. CONCLUSIONS: Three weeks of omega-3 supplements does not improve BHR to mannitol, decrease sputum eosinophil counts, or inhibit urinary excretion of mast cell mediators in people with mild to moderate asthma, indicating that dietary omega-3 supplementation is not useful in the short-term treatment of asthma. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00526357; URL: www.clinicaltrials.gov. SN - 1931-3543 UR - https://www.unboundmedicine.com/medline/citation/25321659/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-3692(15)30173-2 DB - PRIME DP - Unbound Medicine ER -