Abstract
Allergic rhinitis represents a global health burden. The disease can seriously affect quality of life and is associated with multiple co-morbidities. Histamine and leukotrienes are important pro-inflammatory mediators in nasal allergic inflammation. Their actions on target cells are mediated through specific receptors and, consequently, molecules that block the binding of histamine and leukotrienes to their receptors have been important areas of pharmacological research.
The published literature of the pathophysiology of histamine and leukotrienes, and the effects of histamine H1-receptor antagonists (H1 antihistamines) and leukotriene antagonists in monotherapy or in combination therapy in the treatment of allergic rhinitis was reviewed. The presented results are based on the best available evidence.
The efficacy of H1 antihistamines and leukotriene antagonists (montelukast in particular) in allergic rhinitis has been established in numerous randomised placebo-controlled trials. Results from meta-analyses indicate that H1 antihistamines and leukotriene antagonists are equally effective in improving symptoms of allergic rhinitis and quality of life, but that both drugs are less effective than intranasal corticosteroids.
Data on the combination of H1 antihistamines and leukotriene antagonists in allergic rhinitis are limited. The available evidence shows that a combined mediator inhibition has additional benefits over the use of each agent alone, but is still inferior to intranasal corticosteroids. More well designed studies are needed to fully understand the benefits of a concomitant use of these agents.
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References
Johansson SG, Bieber T, Dahl R, et al. Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004; 113(5): 832–6
Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001; 108 Suppl. 5: S147–334
Spector SL. Overview of comorbid associations of allergic rhinitis. J Allergy Clin Immunol 1997; 99(2): S773–80
Meltzer EO. An overview of current pharmacotherapy in perennial rhinitis. J Allergy Clin Immunol 1995; 95 (5 Pt 2): 1097–110
Dale H, Laidlaw P. The physiological action of beta-imidazo-lethilamine. J Physiol (London) 1910; 41: 427–39
Ash AS, Schild HO. Receptors mediating some actions of histamine. Br J Pharmacol 1966; 27(2): 427–39
Taylor-Clark T, Foreman J. Histamine-mediated mechanisms in the human nasal airway. Curr Opin Pharmacol 2005; 5(3): 214–20
Naclerio RM, Proud D, Togias AG, et al. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med 1985; 313(2): 65–70
Simons FE. Advances in H1-antihistamines. N Engl J Med 2004; 351(21): 2203–17
Bachert C. Histamine: a major role in allergy? Clin Exp Allergy 1998; 28 Suppl. 6: 15–9
Jutel M, Akdis CA, Blaser K. Histamine in allergic inflammation and immune regulation. Int Arch Allergy Immunol 2005; 137(1): 82–92
Leurs R, Church MK, Taglialatela M. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy 2002; 32(4): 489–98
Bachert C. The role of histamine in allergic disease: re-appraisal of its inflammatory potential. Allergy 2002; 57(4): 287–96
Camelo-Nunes IC. New antihistamines: a critical view. J Pediatr (Rio J) 2006; 82 (5 Suppl.): S173–80
Simons FE. H1-receptor antagonists: comparative tolerability and safety. Drug Saf 1994; 10(5): 350–80
Pfizer. Cetirizine [prescribing information]. New York, 1997
McTavish D, Sorkin EM. Azelastine: a review of its pharmaco-dynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1989; 38(5): 778–800
Passalacqua G, Canonica GW, Bousquet J. Structure and classification of H1-antihistamines and overview of their activities. Clin Allergy Immunol 2002; 17: 65–100
Holgate ST, Canonica GW, Simons FE, et al. Consensus Group on New-Generation Antihistamines. Consensus Group on New-Generation Antihistamines (CONGA): present status and recommendations. Clin Exp Allergy 2003; 33(9): 1305–24
Conde Hernandez DJ, Palma Aqilar JL, Delgado Romero J. Comparison of azelastine nasal spray and oral ebastine in treatment of seasonal allergic rhinitis. Curr Med Res Opin 1995; 13(6): 299–304
Canonica GW, Ciprandi G, Petzold U, et al. Topical azelastine in perennial allergic conjunctivitis. Curr Med Res Opin 2003; 19(4): 321–9
Hore I, Georgalas C, Scadding G. Oral antihistamines for the symptom of nasal obstruction in persistent allergic rhinitis: a systematic review of randomized controlled trials. Clin Exp Allergy 2005; 35(2): 207–12
Stern MA, Wade AG, Ridout SM, et al. Nasal budesonide offers superior symptom relief in perennial allergic rhinitis in comparison to nasal azelastine. Ann Allergy Asthma Immunol 1998; 81(4): 354–8
Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ 1998; 317(7173): 1624–9
Schata M, Jorde W, Richarz-Barthauer U. Levocabastine nasal spray better than sodium cromoglycate and placebo in the topical treatment of seasonal allergic rhinitis. J Allergy Clin Immunol 1991; 87(4): 873–8
James IG, Campbell LM, Harrison JM, et al. Comparison of the efficacy and tolerability of topically administered azelastine, sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis. Curr Med Res Opin 2003; 19(4): 313–20
Wilson AM, O’Byrne PM, Parameswaran K. Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta-analysis. Am J Med 2004; 116(5): 338–44
Howarth PH, Stern MA, Roi L, et al. Double-blind, placebo-controlled study comparing the efficacy and safety of fexofenadine hydrochloride (120 and 180mg once daily) and cetirizine in seasonal allergic rhinitis. J Allergy Clin Immunol 1999; 104(5): 927–33
Van Cauwenberge P, Juniper EF. Comparison of the efficacy, safety and quality of life provided by fexofenadine hydrochloride 120mg, loratadine 10mg and placebo administered once daily for the treatment of seasonal allergic rhinitis. Clin Exp Allergy 2000; 30(6): 891–9
Kaiser HB, Rooklin A, Spangler D, et al. Efficacy of loratadine compared with fexofenadine or placebo for the treatment of seasonal allergic rhinitis. Clin Drug Invest 2001; 21: 571–8
van Cauwenberge P, Bachert C, Passalacqua G, et al. Consensus statement on the treatment of allergic rhinitis. EAACI Position paper. Allergy 2000; 55(2): 116–34
Murphy RC, Hammarstrom S, Samuelsson B. Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Natl Acad Sci U S A 1979; 76(9): 4275–9
Peters-Golden M, Gleason MM, Togias A. Cysteinyl leuko-trienes: multi-functional mediators in allergic rhinitis. Clin Exp Allergy 2006 Jun; 36(6): 689–703
Currie GP, Srivastava P, Dempsey OJ, et al. Therapeutic modulation of allergic airways disease with leukotriene receptor antagonists. Q J Med 2005; 98(3): 171–82
Salvi SS, Krishna MT, Sampson AP, et al. The anti-inflammatory effects of leukotriene-modifying drugs and their use in asthma. Chest 2001; 119(5): 1533–46
Knani J, Campbell A, Enander I, et al. Indirect evidence of nasal inflammation assessed by titration of inflammatory mediators and enumeration of cells in nasal secretions of patients with chronic rhinitis. J Allergy Clin Immunol 1992; 90: 880–9
Kojima T, Asakura K. A study of chemical mediators in patients with allergic rhinitis: 3. Release of histamine and leukotrienes from in vitro nasal mucosa. Nippon Jibiinkoka Gakkai Kaiho 1991; 94: 587–93
Garrelds IM, Koenders S, de Graaf-in ’t Veld C, et al. Relationship between nasal hyperreactivity, mediators and eosinophils in patients with perennial allergic rhinitis and controls. Clin Exp Allergy 1996; 26: 903–8
Wang D, Clement P, Smitz J, et al. Correlations between complaints, inflammatory cells and mediator concentrations in nasal secretions after nasal allergen challenge and during natural allergen exposure. Int Arch Allergy Immunol 1995; 106: 278–85
Skoner DP, Lee L, Doyle WJ, et al. Nasal physiology and inflammatory mediators during natural pollen exposure. Ann Allergy 1990; 65: 206–10
Peters-Golden M, Henderson Jr WR. The role of leukotrienes in allergic rhinitis. Ann Allergy Asthma Immunol 2005; 94(6): 609–18
Meltzer EO. Role for cysteinyl leukotriene receptor antagonist therapy in asthma and their potential role in allergic rhinitis based on the concept of “one linked airway disease”. Ann allergy Asthma Immunol 2000; 84(2): 176–85
Mygind N, Dahl R, Bisgaard H. Leukotrienes, leukotriene receptor antagonists, and rhinitis. Allergy 2000 May; 55(5): 421–4
Ribeiro JD, Toro AA, Baracat EC. Antileukotrienes in the treatment of asthma and allergic rhinitis. J Pediatr (Rio J) 2006; 82 (5 Suppl.): S213–21
Walia M, Lodha R, Kabra SK. Montelukast in pediatric asthma management. Indian J Pediatr 2006; 73: 275–82
Chen ST, Lu KH, Sun HL, et al. Randomized placebo-controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2–6 yr. Pediatr Allergy Immunol 2006; 17: 49–54
Chervinsky P, Philip G, Malice MP, et al. Montelukast for treating fall allergic rhinitis: effect of pollen exposure in 3 studies. Ann Allergy Asthma Immunol 2004; 92(3): 367–73
Nayak AS, Philip G, Lu S, et al. Efficacy and tolerability of montelukast alone or in combination with loratadine in seasonal allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial performed in the fall. Ann Allergy Asthma Immunol 2002; 88(6): 592–600
Patel P, Philip G, Yang W, et al. Randomized, double-blind, placebo-controlled study of montelukast for treating perennial allergic rhinitis. Ann Allergy Asthma Immunol 2005; 95(6): 551–7
Rodrigo GJ, Yanez A. The role of antileukotriene therapy in seasonal allergic rhinitis: a systematic review of randomized trials. Ann Allergy Asthma Immunol 2006; 96(6): 779–86
Howarth PH. Mediators of nasal blockage in allergic rhinitis. Allergy 1997; 52 Suppl. 40: 12–8
Okuda M, Watase T, Mercuwa A, et al. The role of leukotriene D4 in allergic rhinitis. Ann Allergy 1988; 60: 537–40
Meltzer EO, Malmstrom K, Lu S, et al. Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: placebo-controlled clinical trial. J Allergy Clin Immunol 2000; 105(5): 917–22
Ciebiada M, Gorska-Ciebiada M, DuBuske LM, et al. Montelukast with desloratadine or levocetirizine for the treatment of persistent allergie rhinitis. Ann Allergy Asthma Immunol 2006; 97(5): 664–71
Kurowski M, Kuna P, Gorski P. Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic rhinitis: influence on clinical symptoms and nasal allergic inflammation. Allergy 2004; 59(3): 280–8
Wilson AM, Sims EJ, Orr LC, et al. Effects of topical cortico-steroid and combined mediator blockade on domiciliary and laboratory measurements of nasal function in seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2001; 87(4): 344–9
Wilson AM, Dempsey OJ, Sims EJ, et al. A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma. Clin Exp Allergy 2001; 31(4): 616–24
Pullerits T, Praks L, Ristoja V, et al. Comparison of a nasal glucocorticosteroid, antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol 2002; 109(6): 949–55
Di Lorenzo G, Pacor ML, Pellitteri ME, et al. Randomized placebo-controlled trial comparing fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis. Clin Exp Allergy 2004; 34(2): 259–67
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No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.
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Van Hoecke, H., Vandenbulcke, L. & Van Cauwenberge, P. Histamine and Leukotriene Receptor Antagonism in the Treatment of Allergic Rhinitis. Drugs 67, 2717–2726 (2007). https://doi.org/10.2165/00003495-200767180-00006
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DOI: https://doi.org/10.2165/00003495-200767180-00006