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Comparable reductions in hyperpnoea-induced bronchoconstriction and markers of airway inflammation after supplementation with 6·2 and 3·1 g/d of long-chain n-3 PUFA in adults with asthma

  • Neil C. Williams (a1), Kirsty A. Hunter (a1), Dominick E. Shaw (a2), Kim G. Jackson (a3), Graham R. Sharpe (a1) and Michael A. Johnson (a1)...

Although high dose n-3 PUFA supplementation reduces exercise- and hyperpnoea-induced bronchoconstriction (EIB/HIB), there are concurrent issues with cost, compliance and gastrointestinal discomfort. It is thus pertinent to establish the efficacy of lower n-3 PUFA doses. Eight male adults with asthma and HIB and eight controls without asthma were randomly supplemented with two n-3 PUFA doses (6·2 g/d (3·7 g EPA and 2·5 g DHA) and 3·1 g/d (1·8 g EPA and 1·3 g DHA)) and a placebo, each for 21 d followed by 14 d washout. A eucapnic voluntary hyperpnoea (EVH) challenge was performed before and after treatments. Outcome measures remained unchanged in the control group. In the HIB group, the peak fall in forced expiratory volume in 1 s (FEV1) after EVH at day 0 (−1005 (sd 520) ml, −30 (sd 18) %) was unchanged after placebo. The peak fall in FEV1 was similarly reduced from day 0 to day 21 of 6·2 g/d n-3 PUFA (−1000 (sd 460) ml, −29 (sd 17) % v. −690 (sd 460) ml, −20 (sd 15) %) and 3·1 g/d n-3 PUFA (−970 (sd 480) ml, −28 (sd 18) % v. −700 (sd 420) ml, −21 (sd 15) %) (P<0·001). Baseline fraction of exhaled nitric oxide was reduced by 24 % (P=0·020) and 31 % (P=0·018) after 6·2 and 3·1 g/d n-3 PUFA, respectively. Peak increases in 9α, 11β PGF2 after EVH were reduced by 65 % (P=0·009) and 56 % (P=0·041) after 6·2 and 3·1 g/d n-3 PUFA, respectively. In conclusion, 3·1 g/d n-3 PUFA supplementation attenuated HIB and markers of airway inflammation to a similar extent as a higher dose. Lower doses of n-3 PUFA thus represent a potentially beneficial adjunct treatment for adults with asthma and EIB.

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* Corresponding author: Dr N. C. Williams, email
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1. Carlsen K, Anderson S, Bjermer L, et al. (2008) Exercise‐induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN. Allergy 63, 387403.
2. Weiler JM, Anderson SD, Randolph C, et al. (2010) Pathogenesis, prevalence, diagnosis, and management of exercise-induced bronchoconstriction: a practice parameter. Ann Allergy Asthma Immunol 105, S1S47.
3. Hallstrand TS (2012) New insights into pathogenesis of exercise-induced bronchoconstriction. Curr Opin Allergy Clin Immunol 12, 4248.
4. Hallstrand TS, Altemeier WA, Aitken ML, et al. (2013) Role of cells and mediators in exercise-induced bronchoconstriction. Immunol Allergy Clin North Am 33, 313328.
5. Barnes PJ (2010) New therapies for asthma: is there any progress? Trends Pharmacol Sci 31, 335343.
6. Ramage L, Lipworth B, Ingram C, et al. (1994) Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol. Respir Med 88, 363368.
7. Kumar A, Mastana SS & Lindley MR (2016) n-3 Fatty acids and asthma. Nutr Research Rev 29, 116.
8. Calder PC (2010) Omega-3 fatty acids and inflammatory processes. Nutrients 2, 355374.
9. Arm JP, Horton CE, Mencia-Huerta JM, et al. (1988) Effect of dietary supplementation with fish oil lipids on mild asthma. Thorax 43, 8492.
10. Mickleborough TD, Murray RL, Ionescu AA, et al. (2003) Fish oil supplementation reduces severity of exercise-induced bronchoconstriction in elite athletes. Am J Respir Crit Care Med 168, 11811189.
11. Mickleborough TD, Lindley MR, Ionescu AA, et al. (2006) Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest 129, 3949.
12. Brannan JD, Bood J, Alkhabaz A, et al. (2015) The effect of omega-3 fatty acids on bronchial hyperresponsiveness, sputum eosinophilia, and mast cell mediators in asthma. Chest 147, 397405.
13. Reisman J, Schachter H, Dales R, et al. (2006) Treating asthma with omega-3 fatty acids: where is the evidence? A systematic review. BMC complement Altern Med 6, 1.
14. Weiler JM, Brannan JD, Randolph CC, et al. (2016) Exercise-induced bronchoconstriction update – 2016. J Allergy Clin Immunol 138, 12921295. e36.
15. Kumar A, Mastana SS & Lindley MR (2016) EPA/DHA dietary supplementation attenuates exercise-induced bronchoconstriction in physically active asthmatic males. Cogent Med 3, 1172696.
16. Mickleborough T & Lindley M (2014) The effect of combining fish oil and vitamin C on airway inflammation and hyperpnea-induced bronchoconstriction in asthma. J Allergy Ther 5, 2.
17. Tecklenburg-Lund S, Mickleborough TD, Turner LA, et al. (2010) Randomized controlled trial of fish oil and montelukast and their combination on airway inflammation and hyperpnea-induced bronchoconstriction. PLoS ONE 5, e13487.
18. Price OJ, Hull JH, Howatson G, et al. (2015) Vitamin D and omega-3 polyunsaturated fatty acid supplementation in athletes with exercise-induced bronchoconstriction: a pilot study. Expert Rev Respir Med 9, 369378.
19. Burns CP, Halabi S, Clamon G, et al. (2004) Phase II study of high‐dose fish oil capsules for patients with cancer‐related cachexia. Cancer 101, 370378.
20. Walser B & Stebbins CL (2008) Omega-3 fatty acid supplementation enhances stroke volume and cardiac output during dynamic exercise. Eur J Appl Physiol 104, 455461.
21. Williams NC, Johnson MA, Hunter KA, et al. (2015) Reproducibility of the bronchoconstrictive response to eucapnic voluntary hyperpnoea. Respir Med 109, 12621267.
22. Williams N, Hunter K, Johnson M, et al. (2013) A randomised placebo controlled trial to compare the effects of two dosages of omega-3 PUFA on exercise-induced bronchoconstriction (EIB). Br J Sports Med 47, e4e4.
23. Argyros GJ, Roach JM, Hurwitz KM, et al. (1996) Eucapnic voluntary hyperventilation as a bronchoprovocation technique: development of a standardized dosing schedule in asthmatics. Chest 109, 15201524.
24. Anderson SD, Argyros GJ, Magnussen H, et al. (2001) Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction. Br J Sports Med 35, 344347.
25. Parsons JP, Hallstrand TS, Mastronarde JG, et al. (2013) An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med 187, 10161027.
26. Boulet LP, FitzGerald JM & Reddel HK (2015) The revised 2014 GINA strategy report: opportunities for change. Curr Opin Pulm Med 21, 17.
27. Duffy P & Phillips Y (1991) Caffeine consumption decreases the response to bronchoprovocation challenge with dry gas hyperventilation. Chest 99, 13741377.
28. Vally H & Thompson P (2002) Alcoholic drinks and asthma. Clin Exp Allergy 32, 186191.
29. Yusof HM, Miles EA & Calder P (2008) Influence of very long-chain n-3 fatty acids on plasma markers of inflammation in middle-aged men. Prostaglandins Leukot Essent Fatty Acids 78, 219228.
30. Bahal SM, Romansky JM & Alvarez FJ (2003) Medium chain triglycerides as vehicle for palatable oral liquids: TECHNICAL NOTE. Pharm Dev Technol 8, 111115.
31. Miller MR, Hankinson J, Brusasco V, et al. (2005) Standardisation of spirometry. Eur Respir J 26, 319338.
32. Dweik RA, Boggs PB, Erzurum SC, et al. (2011) An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 184, 602615.
33. Alving K, Weitzberg E & Lundberg JM (1993) Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J 6, 13681370.
34. Junge W, Wilke B, Halabi A, et al. (2004) Determination of reference intervals for serum creatinine, creatinine excretion and creatinine clearance with an enzymatic and a modified Jaffe method. Clin Chim Acta 344, 137148.
35. Nauseef WM (2007) Isolation of human neutrophils from venous blood. Methods Mol Biol, 412, 1520.
36. Bligh EG & Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37, 911917.
37. Jackson KG, Bateman PA, Yaqoob P, et al. (2009) Impact of saturated, polyunsaturated and monounsaturated fatty acid-rich micelles on lipoprotein synthesis and secretion in Caco-2 cells. Lipids 44, 10811089.
38. Santanello N, Zhang J, Seidenberg B, et al. (1999) What are minimal important changes for asthma measures in a clinical trial? Eur Respir J 14, 2327.
39. Williams NC, Johnson MA, Shaw DE, et al. (2016) A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation. Br J Nutr 116, 798804.
40. Reiss TF, Hill JB, Harman E, et al. (1997) Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist. Thorax 52, 10301035.
41. Shapiro GG, Kemp JP, DeJong R, et al. (1990) Effects of albuterol and procaterol on exercise-induced asthma. Ann Allergy 65, 273276.
42. Nelson JA, Strauss L, Skowronski M, et al. (1998) Effect of long-term salmeterol treatment on exercise-induced asthma. N Engl J Med 339, 141146.
43. Anderson S, Rodwell L, Du Toit J, et al. (1991) Duration of protection by inhaled salmeterol in exercise-induced asthma. Chest 100, 12541260.
44. Bronsky EA, Yegen Ü, Yeh CM, et al. (2002) Formoterol provides long-lasting protection against exercise-induced bronchospasm. Ann Allergy Asthma Immunol 89, 407412.
45. Cheung D, Timmers MC, Zwinderman AH, et al. (1992) Long-term effects of a long-acting β2-adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma. N Engl J Med 327, 11981203.
46. Simons FE, Gerstner TV & Cheang MS (1997) Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Pediatrics 99, 655659.
47. Mickleborough T & Rundell K (2005) Dietary polyunsaturated fatty acids in asthma-and exercise-induced bronchoconstriction. Eur J Clin Nutr 59, 13351346.
48. Brannan JD & Lougheed MD (2012) Airway hyperresponsiveness in asthma: mechanisms, clinical significance, and treatment. Front Physiol 3, 460.
49. O’Sullivan S, Roquet A, Dahlen B, et al. (1998) Evidence for mast cell activation during exercise-induced bronchoconstriction. Eur Respir J 12, 345350.
50. Brannan JD, Gulliksson M, Anderson SD, et al. (2003) Evidence of mast cell activation and leukotriene release after mannitol inhalation. Eur Respir J 22, 491496.
51. Daviskas E, Anderson SD, Brannan JD, et al. (1997) Inhalation of dry-powder mannitol increases mucociliary clearance. Eur Respir J 10, 24492454.
52. Daviskas E, Anderson SD, Gonda I, et al. (1995) Changes in mucociliary clearance during and after isocapnic hyperventilation in asthmatic and healthy subjects. Eur Respir J 8, 742751.
53. Kippelen P, Fitch KD, Anderson SD, et al. (2012) Respiratory health of elite athletes – preventing airway injury: a critical review. Br J Sports Med 46, 471476.
54. Kippelen P, Tufvesson E, Ali L, et al. (2013) Urinary CC16 after challenge with dry air hyperpnoea and mannitol in recreational summer athletes. Respir Med 107, 18371844.
55. Romberg K, Bjermer L & Tufvesson E (2011) Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers. Respir Med 105, 3136.
56. Mickleborough TD, Vaughn CL, Shei R, et al. (2013) Marine lipid fraction PCSO-524™(lyprinol®/omega XL®) of the New Zealand green lipped mussel attenuates hyperpnea-induced bronchoconstriction in asthma. Respir Med 107, 11521163.
57. Simpson AJ, Bood JR, Anderson SD, et al. (2016) A standard, single dose of inhaled terbutaline attenuates hyperpnea-induced bronchoconstriction and mast cell activation in athletes. J Appl Physiol (1985) 120, 10111017.
58. Schubert R, Kitz R, Beermann C, et al. (2009) Effect of n-3 polyunsaturated fatty acids in asthma after low-dose allergen challenge. Int Arch Allergy Immunol 148, 321329.
59. Hamid Q, Springall DR, Polak J, et al. (1993) Induction of nitric oxide synthase in asthma. Lancet 342, 15101513.
60. Robbins R, Springall D, Warren J, et al. (1994) Inducible nitric oxide synthase is increased in murine lung epithelial cells by cytokine stimulation. Biochem Biophys Res Commun 198, 835843.
61. Barnes PJ (1995) Nitric oxide and airway disease. Ann Med 27, 389393.
62. Schmitz G & Ecker J (2008) The opposing effects of n-3 and n-6 fatty acids. Prog Lipid Res 47, 147155.
63. Accordino R, Visentin A, Bordin A, et al. (2008) Long-term repeatability of exhaled breath condensate pH in asthma. Respir Med 102, 377381.
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